A Phase 3 Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Subjects With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy
Phase: PHASE3
Conditions: Multiple Myeloma
Sponsor: Janssen Research & Development, LLC

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 14 March 2024
Janssen Research & Development *
Clinical Protocol
A Phase 3 Study Comparing Daratumumab, VELCADE (bortezomib), Lenalidomide, and
Dexamethasone (D-VRd) with VELCADE, Lenalidomide, and Dexamethasone (VRd) in
Subjects with Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell
Transplant is Not Planned as Initial Therapy
Protocol 54767414MMY3019; Phase 3
Amendment 6
JNJ-54767414 (daratumumab)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries/territories. Therefore, the legal entity acting as the sponsor for Janssen Research &
Development studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP;
Janssen Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen
Sciences Ireland UC; or Janssen Research & Development, LLC. The term “sponsor” is used throughout
the protocol to represent these various legal entities; the sponsor is identified on the Contact Information
page that accompanies the protocol.
Studies conducted at sites in the United States (US) will be conducted under US Food and Drug
Administration Investigational New Drug (IND) regulations (21 CFR Part 312).
Studies conducted at sites in the European Economic Area (EEA) will be conducted under
Regulation [EU] No 536/2014.
EU TRIAL NUMBER:2023-507312-13
Status: 
Approved
Date: 
14 March 2024
Prepared by: Janssen Research & Development, LLC
EDMS number: 
EDMS-ERI-160761684; 9.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory
requirements.
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or
otherwise.
NCT03652064

JNJ-54767414 (daratumumab)
Clinical Protocol 54767414MMY3019 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved, Date: 14 March 2024
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 6 
14 March 2024
Amendment 5 
24 March 2022
Amendment 4  
1 October 2020
Amendment 3 
19 November 2019
Amendment 2 
18 January 2019
Amendment 1 
10 September 2018
Original Protocol 
17 July 2018
Amendment 6 (14 March 2024)
Overall Rationale for the Amendment: The overall rationale is to continue the study with limited data
collection after the planned final PFS analysis. Subjects who are benefitting from treatment with
daratumumab will have continued access to study treatment after the end of data collection. Additionally,
this amendment harmonizes changes previously included in Protocol Amendment 5/EEA-1. Specifically,
this amendment includes text to address country-specific changes for France and Czech Republic within
this global amendment. As a result, the Protocol Amendment 5/EEA-1 will be retired.
The changes made to the clinical protocol 54767414MMY3019 as part of Protocol Amendment 6 are listed
below, including the rationale of each change and a list of all applicable sections. Changes made in previous
protocol amendments are listed in Section 10.22 Appendix 22: Protocol Amendment History.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 SYNOPSIS  
1.3 Schedule of Activities (SoA) 
4.1 Overall Study Design  
4.4 End of Study Definition  
8.1.1 Overview  
9.2 Sample Size Determination  
Text was updated to specify that
investigator-assessed long term PFS, PFS2
and OS will continue to be collected after
the final PFS analysis until the end of data
collection, defined as 7 years after the last
subject was randomized into the study, or
earlier as per sponsor discretion.
To continue with limited data
collection after the planned
final PFS analysis until the end
of data collection.
1.3 Schedule of Activities (SoA) 
6.6.2.2 Daratumumab-Related 
Toxicity Management 
8.1.1 Overview  
8.1.4 End-of-Treatment Visit 
8.6 Pharmacokinetics and
Immunogenicity
8.6.1 Evaluations
8.6.4 Immunogenicity
Assessments
Text was updated to specify that
pharmacokinetic and immunogenicity
sampling will no longer be required for
subjects in Treatment Arm B after the
planned final PFS analysis.
To continue with limited data
collection after the planned
final PFS analysis.
4.4 End of Study Definition  
Text was updated to clarify the definition
of‘end of study’ and ‘end of data
collection’ so that subjects who are
benefitting from treatment with
daratumumab can continue to receive
study treatment after the end of data
collection.
To ensure that subjects
continue to have drug access
after end of data collection and
end of study.

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Clinical Protocol 54767414MMY3019 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 14 March 2024
Section Number 
and Name
Description of Change 
Brief Rationale
1.3 Schedule of Activities (SoA) 
8.2.1 Response Categories 
8.2.2 Myeloma Protein 
Measurements in Serum and 
Urine 
8.2.3 Albumin and Serum
Calcium Corrected for Albumin
8.3.6 Clinical Safety Laboratory
Assessments
10.20 Appendix 20:
Interpretation of The SEBIA
Hydrashift 2/4 Daratumumab
IFE Interference test
Text was updated to clarify that after the 
planned final PFS analysis, disease 
evaluations will be performed by the local 
laboratory instead of the central laboratory. 
To continue to monitor
investigator assessed PFS and
OS for the subjects in the study
after the planned final PFS
analysis.
8.2.1 Response Categories 
Text was updated to clarify that after the 
final PFS analysis, disease progression and 
response according to IMWG criteria will 
be determined by the investigator and the
computer algorithm will not be used.
To continue with limited data
collection after the planned
final PFS analysis.
7.2 Discontinuation of Study 
Treatment 
Text was updated to clarify that if a subject 
becomes pregnant, lenalidomide must be 
discontinued. Additionally, text was added 
to clarify that discontinuation of all study 
treatment is also acceptable if mandated by 
local regulations.
To clarify pregnancy
requirements with respect to
study treatment; to harmonize
protocol text with respect to EU
CTR requirements.
8.3.8.1 HBV Screening Serology 
Testing 
Text was updated to clarify that if required 
by local regulations, if the hepatitis B 
serologic status of a subject in Arm B is 
unknown, HBsAg, Anti-HBs, and Anti-
HBc testing is recommended if the subject
is still receiving daratumumab.
To harmonize protocol text
with respect to EU CTR
requirements.
1.1 SYNOPSIS  
5.3 Restrictions During Study 
Participation (Criterion 4) 
The brand name (Revlimid®) has been 
replaced by the generic drug name 
lenalidomide and references to the 
lenalidomide Global Pregnancy Prevention
plan have been included.
To accommodate the use of
generic lenalidomide in
countries when and if needed.
7.4 Lost to Follow-up  
Information has been added on the actions 
that must be taken if a subject fails to 
return to the study site for a required study
visit.
To align with information
included in the ICF.
8.4.1 Time Period and 
Frequency for Collecting 
Adverse Event and Serious 
Adverse Event Information
10.4 Appendix 4: Adverse
Events: Definitions and
Procedures for Recording,
Evaluating, Follow-up, and
Reporting
Information for reporting of SAEs has 
been updated. 
To clarify the current safety
reporting process for clinical
studies.
1.3 Schedule of Activities (SoA) 
6.1.2 Daratumumab 
Administration  
10.1 Appendix 1: Abbreviations 
Reference to the IPPI has been replaced by 
reference to the daratumumab SmPC, 
USPI, local prescribing information, or 
equivalent documentation. 
Commercial prescribing
information to be used for
additional guidance on
treatment preparation and
administration.
6.2.2 Injection-related Reactions 
Text was updated to clarify that if ocular 
symptoms occur, daratumumab has to be 
Added upon Health Authority
request.

JNJ-54767414 (daratumumab)
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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 14 March 2024
Section Number 
and Name
Description of Change 
Brief Rationale
interrupted and immediate ophthalmologic
evaluation has to be sought prior to
restarting daratumumab.
6.6.2.2 Daratumumab-Related 
Toxicity Management 
7.2 Discontinuation of Study 
Treatment 
Text was updated to clarify that ifa 
subject’s dose is held for more than 
28 days, the Sponsor has to be consulted to 
review safety, and efficacy, and to discuss
continuation on study.
To clarify treatment
continuation following
daratumumab delay.
1.3 Schedule of Activities (SoA) 
8.2.4 Bone Marrow Examination  
The window of yearly bone marrow 
sampling was extended from +/-1 month to 
+/-3 months. 
To allow more flexibility in the
window for sites to collect bone
marrow for MRD assessments.
8.4.5 Disease-Related Events 
and Disease-Related Outcomes 
Not Qualifying as Adverse 
Events or Serious Adverse
Events
Text was updated to clarify reporting of 
disease-related events and outcomes not 
qualifying as AEs or SAEs.
To align with the clinical
protocol template.
6.8.3 Prohibited Therapies 
11 REFERENCES  
Removed medications used for other 
indications that have anti-myeloma 
properties from the list of prohibited
therapies.
Amended to reflect the latest
research/data in the field.
7.2 Discontinuation of Study 
Treatment 
Deleted “the subject initiates treatment 
with a prohibited medication” as reason to 
discontinue a subject's study treatment.
Amended to reflect the latest
research/data in the field.
Clarified that for subjects who experience 
a second primary malignancy that cannot 
be treated by surgery alone, this scenario
should be discussed with the Sponsor.
Amended to reflect the latest
research/data in the field.
8.3.6 Clinical Safety Laboratory 
Assessments 
Text amended to refer serum chemistry 
and hematology to schedule of activities 
and to clarify that additional chemistry and
hematologic laboratory assessment
supporting the start and end dates of an AE
should be reported in the eCRF.
Amended to reflect the latest
research/data in the field.
Title page; 1.1 SYNOPSIS  
Added EU Trial Number 
To align with EU CTR
requirements.
1.1 SYNOPSIS  
Added text for benefit/risk. 
To align with EU CTR
requirements.
6 STUDY DRUG  
Added table (Table 3) providing 
designations of the study medicinal 
products (Investigational Medicinal
Product[s]/Non-investigational Medicinal
Product[s]/Auxiliary Medicinal Products).
To align with EU CTR
requirements.
4.2.1 Study-Specific Ethical 
Design Considerations 
5.1 Inclusion Criteria 
7.2 Discontinuation of Study
Treatment
8.3.2 Adverse Events
10.3 Appendix 3: Regulatory,
Ethical, and Study Oversight
Considerations
The term “legally acceptable 
representative” has been replaced by
“legally designated representative”.
To align with ICF v12.
7.3.1 Withdrawal from the Use 
of Study Samples 
8.1.1 Overview
The term “research sample” has been 
replaced with the term “study sample”.
To align with ICF v12.

JNJ-54767414 (daratumumab)
Clinical Protocol 54767414MMY3019 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 14 March 2024
Section Number 
and Name
Description of Change 
Brief Rationale
10.3 Appendix 3: Regulatory, 
Ethical, and Study Oversight 
Considerations 
Revised text regarding publication by 
Investigator and disclosure of results by 
the sponsor.
To align with the clinical
protocol template.
10.3 Appendix 3: Regulatory, 
Ethical, and Study Oversight 
Considerations 
Recording of the AE assessment and 
related follow-ups by the investigator 
should be kept as source documents. 
To clarify the current safety
reporting process for clinical
studies.
10.3 Appendix 3: Regulatory, 
Ethical, and Study Oversight 
Considerations
Added text regarding record retention 
under EU regulation. 
Update per EU CTR
requirement.
Title Page 
Added text on EU regulation; added EU 
Trial number; removed EudraCT number. 
Updates per EU CTR
requirement and local
requirements.
8.4.3. Regulatory Reporting 
Requirements for Serious 
Adverse Events 
Updated safety reporting text to use 
broader language (“safety information” 
and “Regulatory Authorities/IECs/IRBs”)
Update per EU CTR
requirement.
Throughout the protocol 
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted

JNJ-54767414 (daratumumab)
Clinical Protocol 54767414MMY3019 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
6
Status: Approved, Date: 14 March 2024
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 6
LIST OF IN-TEXT TABLES AND FIGURES.............................................................................................. 10
1. 
PROTOCOL SUMMARY................................................................................................................... 11
1.1. 
SYNOPSIS..................................................................................................................................... 11
1.2. 
Schema.......................................................................................................................................... 13
1.3. 
Schedule of Activities (SoA)........................................................................................................... 14
2. 
INTRODUCTION................................................................................................................................ 21
2.1. 
Background.................................................................................................................................... 21
2.1.1. 
Multiple Myeloma........................................................................................................................ 21
2.1.2. 
Treatment Options for Patients with Newly Diagnosed Multiple Myeloma................................. 21
2.1.3. 
VRd Followed by Lenalidomide as a Front-line Treatment Option for Multiple Myeloma.......... 22
2.1.4. 
Nonclinical Studies of Daratumumab in combination with lenalidomide and bortezomib .......... 23
2.1.5. 
Clinical Studies ........................................................................................................................... 25
2.1.5.1. 
Combination Therapy Studies ................................................................................................. 25
2.2. 
Overall Rationale for the Study...................................................................................................... 27
2.3. 
Benefit/Risk Assessment ............................................................................................................... 28
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 29
3.1. 
Objectives and Endpoints .............................................................................................................. 29
3.1.1. 
Objectives ................................................................................................................................... 29
3.1.2. 
Endpoints.................................................................................................................................... 30
3.1.3. 
Hypothesis.................................................................................................................................. 31
4. 
STUDY DESIGN ................................................................................................................................ 31
4.1. 
Overall Study Design ..................................................................................................................... 31
4.2. 
Scientific Rationale for Study Design............................................................................................. 33
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 37
4.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 38
4.4. 
End of Study Definition................................................................................................................... 38
5. 
STUDY POPULATION ...................................................................................................................... 39
5.1. 
Inclusion Criteria............................................................................................................................ 39
5.2. 
Exclusion Criteria........................................................................................................................... 41
5.3. 
Restrictions During Study Participation.......................................................................................... 43
5.4. 
Screen Failures.............................................................................................................................. 45
6. 
STUDY DRUG ................................................................................................................................... 45
6.1. 
Daratumumab ................................................................................................................................ 46
6.1.1. 
Daratumumab Subcutaneous Preparation ................................................................................. 46
6.1.2. 
Daratumumab Administration ..................................................................................................... 46
6.1.3. 
Guidelines for Prevention and Management of Injection Reactions .......................................... 47
6.1.3.1. 
Pre-administration Medication................................................................................................. 47
6.1.3.2. 
Post-administration Medication ............................................................................................... 47
6.2. 
Management of Injection-site and Injection-related Reactions...................................................... 48
6.2.1. 
Local Injection-site Reactions..................................................................................................... 48
6.2.2. 
Injection-related Reactions ......................................................................................................... 48
6.2.2.1. 
Injection-related Reactions of Grade 1 or Grade 2.................................................................. 49
6.2.2.2. 
Injection-related Reactions of Grade 3 or Higher.................................................................... 49
6.2.2.3. 
Recurrent Injection-related Reactions..................................................................................... 49
6.3. 
Bortezomib (Arms A and B) ........................................................................................................... 49
6.4. 
Lenalidomide (Arms A and B)........................................................................................................ 50
6.5. 
Dexamethasone (Arms A and B) ................................................................................................... 50

JNJ-54767414 (daratumumab)
Clinical Protocol 54767414MMY3019 Amendment 6
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 14 March 2024
6.6. 
Dose Delays and Dose Modification.............................................................................................. 51
6.6.1. 
Cycle Delay................................................................................................................................. 51
6.6.2. 
Daratumumab............................................................................................................................. 52
6.6.2.1. 
Daratumumab Dose Modification ............................................................................................ 52
6.6.2.2. 
Daratumumab-Related Toxicity Management......................................................................... 52
6.6.3. 
Lenalidomide .............................................................................................................................. 53
6.6.3.1. 
Renal Impairment .................................................................................................................... 53
6.6.4. 
Bortezomib.................................................................................................................................. 54
6.6.5. 
Dexamethasone.......................................................................................................................... 54
6.6.6. 
Dose Modification Guidelines ..................................................................................................... 55
6.7. 
Study Drug Compliance ................................................................................................................. 62
6.8. 
Concomitant Therapy..................................................................................................................... 62
6.8.1. 
Recommended Therapies .......................................................................................................... 62
6.8.1.1. 
Prevention of Deep Vein Thrombosis and Pulmonary Embolism ........................................... 62
6.8.1.2. 
Bisphosphonate Therapy and Denosumab............................................................................. 63
6.8.1.3. 
Therapy for Tumor Lysis Syndrome........................................................................................ 63
6.8.1.4. 
Prophylaxis for Bacterial Pneumonia and Pneumocystis Carinii Pneumonia......................... 63
6.8.1.5. 
Prophylaxis for Herpes Zoster Reactivation............................................................................ 63
6.8.1.6. 
Prevention of Steroid Induced Gastritis................................................................................... 64
6.8.1.7. 
Management of Hepatitis B Virus Reactivation....................................................................... 64
6.8.2. 
Permitted Therapies ................................................................................................................... 64
6.8.3. 
Prohibited Therapies................................................................................................................... 64
6.8.4. 
Subsequent Therapies................................................................................................................ 65
6.9. 
Long-term Follow-up ...................................................................................................................... 65
7. 
DISCONTINUATION OF STUDY DRUG AND SUBJECT
DISCONTINUATION/WITHDRAWAL............................................................................................... 66
7.1. 
Completion ..................................................................................................................................... 66
7.2. 
Discontinuation of Study Treatment............................................................................................... 66
7.3. 
Subject Discontinuation/Withdrawal from the Study...................................................................... 67
7.3.1. 
Withdrawal from the Use of Study Samples............................................................................... 67
7.4. 
Lost to Follow-up............................................................................................................................ 68
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 68
8.1. 
Study Procedures........................................................................................................................... 68
8.1.1. 
Overview..................................................................................................................................... 68
8.1.2. 
Screening Phase ........................................................................................................................ 69
8.1.3. 
Treatment Phase ........................................................................................................................ 69
8.1.4. 
End-of-Treatment Visit................................................................................................................ 70
8.1.5. 
Follow-up Phase......................................................................................................................... 70
8.1.6. 
Sample Collection and Handling ................................................................................................ 70
8.1.7. 
Study-specific Materials.............................................................................................................. 70
8.2. 
Efficacy Assessments .................................................................................................................... 71
8.2.1. 
Response Categories ................................................................................................................. 71
8.2.2. 
Myeloma Protein Measurements in Serum and Urine................................................................ 73
8.2.3. 
Albumin and Serum Calcium Corrected for Albumin.................................................................. 74
8.2.3.1. 
β2-microglobulin and Albumin................................................................................................. 74
8.2.4. 
Bone Marrow Examination.......................................................................................................... 74
8.2.5. 
Minimal Residual Disease Assessment...................................................................................... 75
8.2.6. 
Assessment of Lytic Disease...................................................................................................... 75
8.2.7. 
Assessment of Extramedullary Plasmacytomas ........................................................................ 76
8.3. 
Safety Assessments....................................................................................................................... 77
8.3.1. 
Home Health Care and Tele-Health Visits.................................................................................. 77
8.3.2. 
Adverse Events........................................................................................................................... 77
8.3.3. 
Physical Examination.................................................................................................................. 78
8.3.4. 
Vital Signs................................................................................................................................... 78
8.3.5. 
Electrocardiogram....................................................................................................................... 78
8.3.6. 
Clinical Safety Laboratory Assessments .................................................................................... 78

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8.3.7. 
Pulmonary Function Test............................................................................................................ 80
8.3.8. 
HBV Serology and DNA Testing................................................................................................. 80
8.3.8.1. 
HBV Screening Serology Testing............................................................................................ 80
8.3.8.2. 
HBV DNA Serial Testing.......................................................................................................... 81
8.3.9. 
Eastern Cooperative Oncology Group Performance Status....................................................... 81
8.4. 
Adverse Events and Serious Adverse Events ............................................................................... 81
8.4.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information.................................................................................................................................. 81
8.4.2. 
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 82
8.4.3. 
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 82
8.4.4. 
Pregnancy................................................................................................................................... 82
8.4.5. 
Disease-Related Events and Disease-Related Outcomes Not Qualifying as Adverse
Events or Serious Adverse Events ............................................................................................. 82
8.5. 
Treatment of Overdose .................................................................................................................. 83
8.6. 
Pharmacokinetics and Immunogenicity ......................................................................................... 83
8.6.1. 
Evaluations ................................................................................................................................. 84
8.6.2. 
Analytical Procedures................................................................................................................. 84
8.6.3. 
Pharmacokinetic Parameters and Evaluations........................................................................... 84
8.6.4. 
Immunogenicity Assessments .................................................................................................... 85
8.7. 
Pharmacokinetic/Pharmacodynamic Evaluations.......................................................................... 85
8.8. 
Biomarkers..................................................................................................................................... 86
8.9. 
Medical Resource Utilization.......................................................................................................... 87
8.10. 
Patient-reported Outcomes............................................................................................................ 87
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 88
9.1. 
Statistical Hypotheses.................................................................................................................... 88
9.2. 
Sample Size Determination ........................................................................................................... 88
9.3. 
Populations for Analyses................................................................................................................ 89
9.4. 
Statistical Analyses ........................................................................................................................ 89
9.4.1. 
General Analysis......................................................................................................................... 89
9.4.2. 
Efficacy Analyses........................................................................................................................ 89
9.4.3. 
Safety Analyses.......................................................................................................................... 90
9.4.4. 
Other Analyses ........................................................................................................................... 90
9.5. 
Medical Resource Utilization Analyses.......................................................................................... 91
9.6. 
Patient-reported Outcomes Analyses ............................................................................................ 91
9.7. 
Interim Analysis.............................................................................................................................. 92
9.8. 
Independent Data Monitoring Committee ...................................................................................... 92
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 93
10.1. 
Appendix 1: Abbreviations ............................................................................................................. 93
10.2. 
Appendix 2: Anticipated Events ..................................................................................................... 96
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations......................................... 98
10.4. 
Appendix 4: Adverse Events: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting............................................................................................................. 109
10.5. 
Appendix 5: Contraceptive and Barrier Guidance and Collection of Pregnancy Information...... 114
10.6. 
Appendix 6: IMWG Diagnostic Criteria........................................................................................ 116
10.7. 
Appendix 7: ECOG Performance Status Grade .......................................................................... 117
10.8. 
Appendix 8: Calculated and Measured Creatinine Clearance..................................................... 118
10.9. 
Appendix 9: Modified Diet in Renal Disease Formula................................................................. 119
10.10. Appendix 10: Serum Calcium Corrected for Albumin .................................................................. 120
10.11. Appendix 11: Asthma Guidelines................................................................................................. 121
10.12. Appendix 12: Antihistamines That May Be Used Predose .......................................................... 125
10.13. Appendix 13: Conversion Table for Glucocorticosteroid Dose .................................................... 126
10.14. Appendix 14: Body Surface Area Calculation.............................................................................. 127
10.15. Appendix 15: EORTC QLQ-C30.................................................................................................. 128
10.16. Appendix 16: EORTC QLQ-MY20............................................................................................... 130
10.17. Appendix 17: EQ-5D-5L............................................................................................................... 132
10.18. Appendix 18: New York Heart Association (NYHA) Functional Classification............................. 135

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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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10.19. Appendix 19: Individual and Myeloma-related Risk factors......................................................... 136
10.20. Appendix 20: Interpretation of The SEBIA Hydrashift 2/4 Daratumumab IFE Interference
test................................................................................................................................................ 137
10.21. Appendix 21: General Guidance on Study Conduct During the COVID-19 Pandemic ............... 138
10.22. Appendix 22: Protocol Amendment History................................................................................. 141
11. REFERENCES................................................................................................................................. 151
INVESTIGATOR AGREEMENT............................................................................................................... 154

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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 14 March 2024
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Schedule of Activities –Treatment and Follow-Up Phases...................................................... 14
Table 2: 
Schedule of Activities –Pharmacokinetic/Immunogenicity Sample Collection Times –
Arm B ONLY............................................................................................................................. 20
Table 3: 
Designations of Medicinal Products Used in the Study............................................................ 45
Table 4: 
Re-treatment criteria before the start of Cycles 1-8a ................................................................ 51
Table 5: 
Re-treatment criteria before the start of Cycle 9 and beyond................................................... 51
Table 6: 
Daratumumab-Related Toxicity Management.......................................................................... 53
Table 7: 
Dose Modification for Lenalidomide.......................................................................................... 53
Table 8: 
Dose Modification for Bortezomib............................................................................................. 54
Table 9: 
Dose Reductions for Dexamethasone...................................................................................... 54
Table 10: Dose modification Guidelines for Bortezomib, Lenalidomide, and Dexamethasone................ 56
Table 11: IMWG Consensus Recommendations for Multiple Myeloma Treatment Response
Criteria...................................................................................................................................... 72
Table 12: Criteria for Loss of Complete Response not Meeting Criteria for Disease Progression
(per Table 11) ........................................................................................................................... 73
Table 13: Bone Marrow Testing................................................................................................................ 75
FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 13
Figure 2: Daratumumab-Enhanced Multiple Myeloma Cell Killing by Key Multiple Myeloma
Chemotherapeutic Agents ........................................................................................................ 24
Figure 3: Dose-dependent Lysis of Multiple Myeloma Cells in Triple Chemotherapy Treatments.......... 24
Figure 4: Progression-free Survival According to MRD Status 10-5 in Studies MMY3003 and
MMY3004.................................................................................................................................. 34

JNJ-54767414 (daratumumab)
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Status: Approved, Date: 14 March 2024
1. 
PROTOCOL SUMMARY
1.1. 
SYNOPSIS
A Phase 3 Study Comparing Daratumumab, VELCADE (bortezomib), Lenalidomide, and Dexamethasone
(D-VRd) with VELCADE, Lenalidomide, and Dexamethasone (VRd) in Subjects with Untreated Multiple
Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy
EU TRIAL NUMBER:2023-507312-13
BENEFIT-RISK ASSESSMENT
The bortezomib, lenalidomide, and dexamethasone (VRd) backbone regimen to be used in this study is now
considered a standard of care regimen for newly diagnosed patients with multiple myeloma. Based on the
results of nonclinical studies, the mechanism of action, the route of administration, and results from
participants treated in daratumumab studies, the potential safety risks for daratumumab are systemic
administration-related reactions, cytopenia, and infections. Given the potential advantages of subcutaneous
(SC) administration, SC daratumumab will be used in this study. The safety and tolerability of SC
daratumumab has been demonstrated.
The addition of daratumumab to the VRd backbone regimen may improve initial disease control and long-
term outcomes. Additionally, daratumumab has been successfully combined with VRd, lenalidomide and
dexamethasone (Rd), and bortezomib and dexamethasone (Vd) in previous studies in various treatment
settings. Considering the measures taken to minimize risk to participants of this study, including an
Independent Data Monitoring Committee, the potential risks associated with the addition of daratumumab
to the VRd backbone are justified by the anticipated benefits for this patient population. Taken together,
there is a strong rationale for evaluating SC daratumumab in combination with VRd for the treatment of
patients with previously untreated multiple myeloma for whom initial transplant is not planned. More
detailed information about the known and expected benefits and risks of daratumumab may be found in the
Investigator’s Brochure.
OBJECTIVES AND ENDPOINTS
Objectives
Primary Objective
The primary objective is to determine if the addition of daratumumab to VELCADE (bortezomib),
lenalidomide, and dexamethasone (VRd) will improve overall minimal residual disease (MRD) negativity
rate compared with VRd alone.
Secondary Objectives
Key secondary objectives are:
To determine if the addition of daratumumab to VRd will improve clinical outcome as measured by:
Progression-Free Survival (PFS)
Durability of MRD negativity
Rate of complete response (CR) or better
To assess the safety profile of daratumumab + VRd (D-VRd)

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OVERALL DESIGN
This is a randomized, open-label, multicenter, Phase 3 study evaluating subjects with newly diagnosed
multiple myeloma and for whom transplant is not planned. Approximately 360 subjects (180/arm) will be
randomized 1:1. Subjects in Arm A will receive VRd alone for eight 21-day cycles followed by
lenalidomideand dexamethasone (Rd) until disease progression or unacceptable toxicity. Subjects in Arm B
will receive D-VRd for eight 21-day cycles followed by daratumumab, lenalidomide, and dexamethasone
(DRd) therapy until disease progression or unacceptable toxicity. Subjects will be stratified at
randomization by International Staging System (ISS) Stage and age/transplant eligibility.
DOSAGE AND ADMINISTRATION
Bortezomib will be given as a subcutaneous (SC) injection (1.3 mg/m2) on Days 1, 4, 8, 11 for 8 cycles.
Subjects will not receive bortezomib after Cycle 8. Lenalidomide will be administered PO at 25 mg on
Days 1 to 14 on a 21-day cycle for Cycles 1-8 and then Days 1 to 21 on a 28-day cycle for Cycle 9 and
beyond, until disease progression or unacceptable toxicity. Dexamethasone will be administered PO at
20 mg on Days 1, 2, 4, 5, 8, 9, 11, 12 during Cycles 1-8 and 40 mg Days 1, 8, 15, and 22 during Cycle 9
and beyond.
Daratumumab 1800 mg SC will be administered to subjects in Arm B once every week for Cycles 1 to 2,
then every 3 weeks for Cycles 3-8. For Cycle 9 and beyond, subjects will receive daratumumab 1800 mg
SC once every 4 weeks until documented disease progression or unacceptable toxicity.
Individual dose modification of daratumumab is not permitted, either a dose interruption or a dose delay is
recommended 
for 
managing 
daratumumab-related 
toxicities. Bortezomib, 
lenalidomide 
and
dexamethasone doses may be reduced, or the treatment schedule may be modified for the management of
study treatment-related toxicities.
EFFICACY EVALUATIONS
Assessment of tumor response and disease progression will be conducted in accordance with the
International Myeloma Working Group (IMWG) response criteria. Efficacy evaluations will include
measurements of tumor burden/residual disease, myeloma proteins, bone marrow examinations, skeletal
surveys, extramedullary plasmacytomas, and serum calcium corrected for albumin.
PHARMACOKINETIC AND IMMUNOGENICITY EVALUATIONS
Samples will be collected from all subjects in Arm B to assess both the serum concentration
(pharmacokinetics) of daratumumab and generation of anti-daratumumab antibodies (immunogenicity)
according to the Schedule of Activities. Samples will also be collected from all subjects in Arm B to
evaluate the immunogenicity of recombinant human hyaluronidase (rHuPH20) according to the Schedule
of Activities. After the planned final PFS analysis, pharmacokinetic and immunogenicity sampling will no
longer be required for subjects in Treatment Arm B.
BIOMARKER EVALUATIONS
Bone marrow samples will be collected from all subjects in both arms to evaluate MRD and high-risk
cytogenetics anomalies as outlined in the Schedule of Activities. Whole blood samples will be collected
from subjects as specified in the Schedule of Activities for processing to plasma and peripheral blood
mononuclear cells and may be used to evaluate mechanism of action of daratumumab in combination with
VRd.
SAFETY EVALUATIONS
Safety evaluations will include adverse event (AE) monitoring, physical examinations, electrocardiogram
(ECGs) monitoring, clinical laboratory parameters (hematology and chemistry), vital sign measurements,
and Eastern Cooperative Oncology Group (ECOG) performance status. All toxicities will be graded

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according to the National Cancer Institute Common Terminology Criteria for Adverse Events
(NCI-CTCAE) Version 5.
Based on the previous experience with daratumumab in humans, in vitro studies, and animal toxicological
findings, injection-related reactions (IRRs)/allergic reactions, hemolysis, and thrombocytopenia will be
closely monitored. As daratumumab is a biologic agent, immunogenicity also will be monitored.
STATISTICAL METHODS
The primary endpoint of the study is overall MRD negativity rate. The study is powered to test the
assumption that the addition of daratumumab will increase the overall MRD negativity rate by 15%.
The primary analysis of the overall MRD negativity rate will be performed approximately 18 months after
the last subject is administered his/her first dose of study treatment. The final PFS analysis will take place
when approximately 162 PFS events have been observed. An interim analysis for PFS is planned, when 98
PFS events (60% of total planned PFS events) are expected to have been accumulated.
1.2. 
Schema
Figure 1: 
Schematic Overview of the Study
Abbreviations: D-VRd=daratumumab in combination with bortezomib, lenalidomide, and dexamethasone;
OS=overall survival; PFS=progression-free survival; VRd=bortezomib, lenalidomide, and dexamethasone.

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Table 1: 
Schedule of Activities –Treatment and Follow-Up Phases
Notes
Screening Phase
Treatment
Phase
Follow-up
Phase
within 28 days
before
randomization
Cycles 1-8 
(21d cycles) 
Day 1 to Day 21 
Cycle 9 and beyond
(28d cycles)
Day 1 to Day 28
EOT
Within
30d after
last dose
Prior
to PDb
Post PD
(Q16wks)
± 2 wks
D1 
D8 
D15 
D1
A Low-dose full body CT used for skeletal disease evaluation cannot be used for baseline lung evaluation.
B For subjects who discontinue study treatment before PD, disease evaluations should continue at the frequency specified until confirmed PD, death, withdrawal of
consent to study participation, or end of study whichever occurs first.
C Subject’s neurological examination should be performed during the Screening phase by the treating physician (a neurologic specialist is not required).
D The visit window for these evaluations is 4 days instead of 3 days.
E A pregnancy test is required at the End-of-Treatment visit and 28 days following the last dose of lenalidomide for women with regular menstrual cycles or 14 and
28 days following the last dose of lenalidomide for women with irregular menstrual cycles.

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Table 2: 
Schedule of Activities –Pharmacokinetic/Immunogenicity Sample Collection Times –Arm B ONLY
Cycle 1 
Cycle 3 
Cycle 9 
Cycle 12 
Post-treatment
Day  
1 
4 
1 
4 
1 
1
Post-treatment
Week 8
Visit window
d=days, w=weeks
0a 
±1d  
0 a 
±1d  
0 a 
0 a 
±1w
Daratumumab pharmacokinetics 
(serum)a, c 
X 
predosea 
X 
X 
predosea 
X
X 
predosea 
X
predosea
X
Daratumumab immunogenicity 
(serum)b, c 
X 
predosea 
X 
predosea 
X
predosea
X
rHuPH20 immunogenicity 
(plasma)a, c 
X 
predosea 
X 
predosea 
X
predosea
X
Abbreviations: rHuPH20=recombinant human hyaluronidase; PK=pharmacokinetics: IRR=injection-related reaction
a 
Samples collected on daratumumab dosing days (i.e. C1D1, C3D1, C9D1, and C12 D1) Day 1 of a cycle) should be collected on the actual day of study drug
administration; sample collection on these days may occur up to 2 hours before (but not after) the start of daratumumab administration.
b 
No additional sample needed; will be taken from PK sample. In addition, when an IRR occurs associated with the second or later daratumumab administration, 2
separate blood samples should be obtained, if possible, for determination of anti-daratumumab antibodies and anti-rHuPH20 antibodies.
c 
After the planned final PFS analysis, pharmacokinetic and immunogenicity sampling will no longer be required for subjects in Treatment Arm B.

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2. 
INTRODUCTION
Daratumumab has multiple mechanisms of action, including the direct targeting of tumor cells by
selectively binding to cluster of differentiation 38 (CD38) molecules, immune mediated activity
with antibody-dependent cellular cytotoxicity, antibody dependent cellular phagocytosis and
complement-dependent cytotoxicity, decreased immunosuppression and CD38 enzymatic
inhibition. CD38 is highly expressed on myeloma cells but is expressed at relatively low levels on
normal lymphoid and myeloid cells and in some tissues of non-hematopoietic origin, making it a
relevant target for the treatment of multiple myeloma.
For the most comprehensive nonclinical and clinical information regarding daratumumab, refer to
the latest version of the Investigator’s Brochure (IB) for daratumumab. The term “sponsor” used
throughout this document refers to the entities listed in the Contact Information page(s), which
will be provided as a separate document.
2.1. 
Background
2.1.1. 
Multiple Myeloma
Multiple myeloma is characterized by uncontrolled and progressive proliferation of a plasma cell
clone. Patients with multiple myeloma produce a monoclonal protein (paraprotein) comprising
monoclonal protein (M-protein) and free light chain (FLC), which is an immunoglobulin (Ig) or a
fragment of one that has lost its function. The proliferation of myeloma cells causes displacement
of the normal bone marrow. Normal Ig levels are compromised, leading to susceptibility to
infections. Hypercalcemia, renal insufficiency or failure, and neurological complications are
frequently reported signs and symptoms of the disease.
2.1.2. 
Treatment Options for Patients with Newly Diagnosed Multiple
Myeloma
Treatment choices for multiple myeloma vary with age, performance status, comorbidity, the
aggressiveness of the disease, and related prognostic factors.35 Newly diagnosed patients with
multiple myeloma are typically categorized into 2 subpopulations usually defined by their age and
suitability for intensive treatment. Younger patients (ie, <65 years of age) typically receive an
induction regimen followed by treatment with high-dose chemotherapy and autologous stem cell
transplantation (ASCT), followed by consolidation therapy and maintenance treatment. For those
not considered suitable for high-dose chemotherapy and ASCT, longer-term treatment with
multi-agent combinations including alkylators, high-dose steroids, and novel agents are currently
considered standards of care.
The 
current 
standard 
of care 
combinations 
for 
nontransplant 
patients 
include
lenalidomide-dexamethasone 
(Rd),4 
bortezomib-melphalan-prednisone 
(VMP),43
bortezomib-cyclophosphamide-dexamethasone 
(VCD),26 
melphalan-prednisone-thalidomide
(MPT),16 and bortezomib-lenalidomide-dexamethasone (VRd)2,13
The Rd registration study (Front-line Investigation of Revlimid and Dexamethasone versus
Standard Thalidomide [FIRST]) is a large, randomized Phase 3 study (MM-020/IFM 07-01)

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comparing 2 active-treatment arms consisting of different durations of Rd to a third active control
arm of MPT in subjects newly diagnosed with multiple myeloma.14 In this study, 1,623 subjects
who were ineligible for ASCT were randomized to receive continuous Rd until disease progression
(Arm A); Rd for eighteen 28-day cycles (72 weeks) (Arm B); or MPT for up to twelve 42-day
cycles (72 weeks) (Arm C). Continuous treatment with Rd (Arm A) significantly improved the
primary endpoint of progression-free survival (PFS) versus fixed treatment duration of 18 months
with Rd (Arm B) (HR 0.70; 95% confidence interval [CI] 0.60-0.81) and versus MPT (Arm C)
(HR 0.69; 95% CI 0.59-0.79; p>0.00001).15 Based on this study, the paradigm of treatment until
disease progression was established.
2.1.3. 
VRd Followed by Lenalidomide as a Front-line Treatment Option for
Multiple Myeloma
Richardson and colleagues42 studied the use of VRd for subjects with newly diagnosed multiple
myeloma. Subjects were enrolled regardless of their eligibility for high-dose therapy and ASCT.
Sixty-six subjects were treated on this single-arm study. All subjects achieved a partial response
(PR) or better. Complete Response (CR) was achieved in 19 subjects (29%) with an additional
7 subjects (11%) in near CR (nCR). Importantly, this study showed that VRd was a feasible
induction regimen prior to ASCT.
A Phase 3 study conducted by the Intergroupe Francophone du Myélome (IFM) cooperative group
evaluated the VRd regimen in 700 newly diagnosed subjects with multiple myeloma who were
transplant eligible. All subjects received induction with 3 cycles of VRd and were then randomized
to receive either standard of care ASCT followed by 2 additional cycles of VRd or 5 additional
cycles of VRd alone. All subjects were given maintenance with lenalidomide for 1 year. The
median PFS was significantly improved in the subjects with transplant as part of their initial
therapy (50 months versus 36 months, HR 0.65, 95% CI 0.53-0.8; p value <0.001). However,
overall survival (OS) at 4 years did not differ between the 2 groups, 82% in VRd alone versus 81%
in the VRd transplant group. The CR rate was 48% in the VRd alone arm versus 59% in the VRd
transplant arm. The minimal residual disease (MRD) negativity rate as measured by 7-color flow
cytometry was 65% in the VRd alone arm versus 79% VRd transplant arm.2 This study showed
the depth of response with the VRd regimen with or without ASCT. Further, there was no
difference in OS between the 2 arms, suggesting that use of ASCT as salvage therapy is an
appropriate alternative approach to treatment.
The Southwest Oncology Group (SWOG) and the National Clinical Trial Network conducted a
randomized, open-label, Phase 3 study (SWOG S0777) “Bortezomib with lenalidomide and
dexamethasone versus lenalidomide and dexamethasone alone in subjects with newly diagnosed
myeloma without intent for immediate autologous stem cell transplant.”13 In this study,
525 subjects were randomized 1:1; 264 to VRd and 261 to Rd. In the 242 subjects in the VRd arm
and 229 subjects in the Rd arm, the median PFS was significantly improved in the VRd group
(43 months versus 30 months, HR 0.712, 95% CI 0.56-0.906; p=0.0018). The median OS was also
significantly improved in the VRd group (75 months versus 64 months; HR 0.709, 95%
CI: 0.524-0.959; p=0.025). The rate of the overall response rate (ORR) was 82% in the VRd arm
versus 72% in the Rd group. The CR rate was 15.7% in the VRd arm versus 8.4% in the Rd arm.

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Grade 3 or higher treatment-emergent adverse event (TEAEs) were experienced by 169 subjects
(75%) in the Rd arm and 198 subjects (82%) in the VRd arm. This study utilized IV bortezomib
treatment that likely resulted in a higher incidence of neurological toxicity for VRd versus Rd
alone (33% versus. 11% Grade 3 or worse neurological toxic effects), as well as premature
discontinuations during induction therapy (Cycles 1-8) (approximately 25% versus. 10%). This
study included a mixed age population (57% of subjects, <65 years of age). The improvement in
PFS and OS for the VRd arm versus the Rd arm showed a similar trend in subjects greater than 65
years of age.13 As such, this study demonstrates the benefit of the VRd regimen for treatment of
all newly diagnosed patients with multiple myeloma.
Based on the observed PFS benefit in both the Phase 3 IFM study and the SWOG 0777 study and
the OS benefit and tolerable safety profile observed in the SWOG077 study, the VRd regimen was
established as a standard care option for all patients with newly diagnosed multiple myeloma.27,33
2.1.4. 
Nonclinical Studies of Daratumumab in combination with
lenalidomide and bortezomib
In preclinical studies (GMB3003-070), the potential benefit of combining daratumumab with
multi-drug chemotherapy regimens was evaluated in fresh tumor cells from subjects with multiple
myeloma (data on file). Lysis of primary tumor cells was measured directly in bone marrow
mononuclear cell (BM-MNC) isolates obtained from subjects with multiple myeloma. Synergistic
tumor cell lysis was demonstrated when daratumumab was combined with lenalidomide or
bortezomib or both, even in samples from subjects who were refractory to lenalidomide and
bortezomib treatment. Treatment of BM-MNC with lenalidomide or bortezomib resulted in 10%
and 18% lysis, respectively. A combination of lenalidomide and bortezomib resulted in 25% lysis
of BM-MNC. When daratumumab was added to either lenalidomide or bortezomib, a 2-fold
increase in lysis was observed compared with lenalidomide or bortezomib alone. When
daratumumab was added to combinations of dexamethasone, lenalidomide and bortezomib or to
bortezomib, prednisone, and dexamethasone, the cell lysis was significantly increased (p<0.001)
compared with the triple combination alone (no daratumumab).45 Refer to Figure 2 and Figure 3.

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Figure 2: 
Daratumumab-Enhanced Multiple Myeloma Cell Killing by Key Multiple Myeloma
Chemotherapeutic Agents
BORT = bortezomib; DARA = daratumumab; LEN = lenalidomide; MM = multiple myeloma.
Figure 3: 
Dose-dependent Lysis of Multiple Myeloma Cells in Triple Chemotherapy Treatments
DARA = daratumumab; RDV= combination lenalidomide, bortezomib, and dexamethasone; MM = multiple
myeloma; MPV = bortezomib, prednisone, and dexamethasone.
P-values were calculated by a paired t-test. *P<0.05, ***P<0.001.
In conclusion, preclinical data, both from the literature and the sponsor’s ex vivo studies, support
the combination of daratumumab with bortezomib and lenalidomide in the treatment of multiple
myeloma.

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2.1.5. 
Clinical Studies
Daratumumab was initially developed as a treatment for multiple myeloma. There is a
comprehensive development plan across various hematologic malignancies.
In the EU, daratumumab is approved for the following indications:
As monotherapy for the treatment of adult patients with relapsed and refractory  multiple
myeloma, whose prior therapy included a proteasome inhibitor (PI) and an
immunomodulatory agent and who have demonstrated disease progression on the last therapy.
In combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for
the treatment of adult patients with multiple myeloma who have received at least one prior
therapy.
In the US, daratumumab is approved for the following indications:
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are
ineligible for autologous stem cell transplant and in patients with relapsed or refractory
multiple myeloma who have received at least one prior therapy.
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed
patients who are eligible for autologous stem cell transplant.
In combination with bortezomib and dexamethasone in patients who have received at least
one prior therapy.
As monotherapy, in patients who have received at least 3 prior lines of therapy including a
proteasome inhibitor (PI) and an immunomodulatory agent or who are double refractory to a
PI and an immunomodulatory agent.
In combination with pomalidomide and dexamethasone in patients who have received at least
two prior therapies including lenalidomide and a proteasome inhibitor.
In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who
are ineligible for autologous stem cell transplant.
2.1.5.1. 
Combination Therapy Studies
Two Phase 3 studies examined the safety and efficacy of intravenous (IV) daratumumab in
combination with bortezomib and lenalidomide containing therapies in the treatment of relapsed
multiple myeloma:
In Study MMY3003, subjects with multiple myeloma received IV daratumumab in
combination with lenalidomide and dexamethasone (DRd). At the time of the first interim
analysis, treatment with DRd resulted in a 63% reduction in the risk of disease progression or
death compared with Rd alone. The median PFS was not reached in the daratumumab group;
median PFS was 18.4 months in the Rd group. The ORR were 93% for the DRd group and
76% for Rd group. The safety profile was consistent with the known safety profile of
daratumumab and the backbone regimen. No new safety signals were identified.

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In Study MMY3004, subjects with  multiple myeloma received IV daratumumab in
combination with daratumumab, bortezomib, and dexamethasone (DVd). At the time of the
first interim analysis, treatment with DVd resulted in a 61% reduction in the risk for disease
progression or death compared with bortezomib-dexamethasone (Vd) alone. The median PFS
was not estimable in the DVd group; median PFS was 7.2 months in the Vd group. The ORRs
were 83% for the DVd group and 63% for the Vd group. The safety profile was consistent
with the known safety profile of daratumumab and the backbone regimen. No new safety
signals were identified.
Three Phase 3 studies examine the safety and efficacy of IV daratumumab in combination with
other therapies in previously untreated multiple myeloma:
In Study MMY3007, subjects with multiple myeloma received intravenous daratumumab
(Dara-IV) in combination with bortezomib, melphalan and dexamethasone (D-VMP). At the
time of the first interim analysis, treatment with D-VMP showed a 50% reduction in the risk
for disease progression or death compared with the combination of bortezomib, melphalan
and dexamethasone (VMP). The median PFS was not reached for the D-VMP group and was
18.1 months for the VMP group (HR=0.50, 95% CI: 0.38-0.65; p<0.0001). The ORRs were
91% for the D-VMP group and 75% for the VMP group. The safety profile was consistent
with the known safety profile of daratumumab and the backbone regimen. No new safety
signals were identified.
In Studies MMY3006 and MMY3008, subjects with multiple myeloma received IV
daratumumab in combination with VTd and DRd, respectively. Results of these studies are
not yet available.
Collectively, data from MMY3003, MMY3004, and MMY3007 demonstrate a favorable
benefit-risk profile of the triplet DVd and DRd regimens for the treatment of subjects with relapsed
or refractory multiple myeloma who have received at least 1 prior therapy and the quadruplet
regimen of daratumumab and VMP in transplant ineligible subjects with newly diagnosed multiple
myeloma.
Experience with daratumumab in combination with VRd
In Study MMY2004 (NCT02874742), IV daratumumab in combination with VRd, (D-VRd) is
being compared with VRd alone in subjects with newly diagnosed multiple myeloma eligible for
high-dose chemotherapy and ASCT. The primary endpoint of this study is stringent complete
response (sCR) rate post-consolidation. Subjects will receive 4 cycles of VRd induction therapy
followed by ASCT and 2 cycles of VRd consolidation therapy followed by maintenance therapy
until disease progression or unacceptable toxicity.
Sixteen subjects were enrolled in the safety run-in portion of the study and data for all 16 subjects
who completed 4 cycles of induction therapy is presented below.46 During Cycle 1, 3 subjects
experienced the following AEs that met the protocol-specified dose limiting criteria (DLT) criteria:
1 subject with Grade 3 fatigue on Day 15, 1 subject with Grade 3 gastroenteritis on Day 21, and
1 subject with Grade 3 pneumonitis (due to infection) and Grade 3 hypotension on Day 5. No
DLTs resulted in treatment discontinuation. All 16 subjects experienced at least 1 TEAE during
Cycles 1 to 4. Three subjects (19%) had at least 1 serious adverse event (SAE) and 2 subjects
(13%) had SAEs that were considered by the investigator to be related to daratumumab

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(gastroenteritis and pneumonitis). Eight subjects (50%) had Grade 3 or Grade 4 TEAEs, for
6 subjects (38%) these events were considered by the investigator to be related to daratumumab.
The most commonly reported Grade 3 or Grade 4 TEAEs were neutropenia and thrombocytopenia
(19% each), and lymphopenia and leukopenia (13% each). Six subjects (38%) experienced
infections, including 1 Grade 3 SAE of gastroenteritis. There were no adverse events (AEs) of
febrile neutropenia. No subject died or discontinued treatment due to TEAEs during the safety
run- in. Daratumumab IRRs (all Grade ≤2) were reported in 31% of subjects.
The safety profile was consistent with that previously reported for daratumumab as monotherapy
and the regimen of VRd. No new safety signals were identified with the addition of daratumumab
to VRd during the first 4 cycles of treatment in these 16 subjects with newly diagnosed multiple
myeloma. As per protocol, the study proceeded to the randomized phase and enrolled
approximately 200 subjects randomized 1:1 to D-VRd versus VRd. A pre-specified interim
analysis for safety after at least 50 subjects completed 4 cycles of induction treatment and stem
cell mobilization occurred on 04 April 2018, the Independent Data Monitoring Committee (IDMC)
recommended that the study continue without modification. Emerging data from this study will be
communicated to the IDMC (Section 9.8).
2.2. 
Overall Rationale for the Study
The treatment of newly diagnosed patients with multiple myeloma is evolving. Induction therapy
followed by transplant is not feasible in all patients due to age or patient frailty. Due to the
effectiveness of triplet and quadruplet therapies, some patients are deferring initial transplant. The
superiority of the VRd regimen has been established by the results of the Phase 3 study by Durie
and colleagues.13 This study demonstrated both increased PFS and OS in the VRd arm compared
with Rd alone. Further, the Phase 3 study by Attal and colleagues2 showed that a deep level of
response, CR and MRD negative status can be achieved with the VRd regimen without transplant.
While the treatment of newly diagnosed patients with multiple myeloma continues to improve,
patients still are not cured. The most active combination to date is the VRd regimen described
above. The sponsor has observed compelling clinical data with daratumumab in combination with
either bortezomib or lenalidomide in the relapsed/refractory setting, and bortezomib in the
frontline setting. The addition of daratumumab with VRd is anticipated to improve the response
rates and the depth of response and may lead to improved long-term outcomes in newly diagnosed
patients with multiple myeloma. Based upon the initial safety and efficacy observed in the ongoing
Phase 2 Study MMY2004 and continued positive results with daratumumab in various disease
settings in combination with both lenalidomide and bortezomib the Phase 3 D-VRd study will
proceed prior to completion of the Phase 2 D-VRd study. The initial PK of SC daratumumab
administration shows similar exposure to IV and improved safety with a lower IRR rate compared
with the IV formulation. The Phase 3 study of D-VRd will utilize the subcutaneous (SC)
formulation of daratumumab instead of the IV formulation utilized in the Phase 2 VRd study,
which is expected to provide similar exposure and is expected to limit additional toxicity to patients
treated with this quadruplet regimen, as injection-related reaction (IRR) is the primary toxicity for
daratumumab, and this toxicity is limited with the SC formulation.

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2.3. 
Benefit/Risk Assessment
The combination of VRd with subcutaneously administered daratumumab is anticipated to have a
positive benefit-risk profile when used for the treatment of patients with previously untreated
multiple myeloma and for whom transplant is not planned as frontline therapy, as proposed for
investigation in Study MMY3019. This assessment is based upon the following:
The VRd backbone regimen to be used in this study is now considered a standard of care
(SOC) regimen for newly diagnosed patients with multiple myeloma. Further details of studies
conducted using this regimen, which has demonstrated a positive benefit-risk profile, are
outlined in Section 2.1.3.
The addition of daratumumab to the VRd backbone regimen may improve initial disease
control and long-term outcomes. Daratumumab has been successfully combined with either
Rd or Vd in multiple myeloma patients. In Study MMY3003 (daratumumab + Rd) and
MMY3004 (daratumumab + Vd) a significant improvement was seen in PFS in the DRd and
DVd arms of the studies in relapsed/refractory subjects. In the newly diagnosed transplant
ineligible setting, Study MMY3007 (studying the combination of daratumumab with VMP
versus VMP) also showed a statistically significant improvement in PFS in the D-VMP arm
of the study (see Section 2.1.5.1 for further details). All 3 studies demonstrated that the safety
profiles were consistent with the known safety profile of daratumumab and the respective
backbone regimen and no new safety signals were identified. Preclinical synergism has also
been observed with daratumumab in combination with bortezomib and lenalidomide.
Data available from Study MMY2004 suggest that daratumumab can be combined safely with
VRd (see Section 2.1.5.1). The initial safety profile was consistent with that previously
reported for daratumumab as monotherapy and the regimen of VRd with the exception of
lower neurotoxicity due to use of SC bortezomib.
Given the potential advantages of SC administration, SC daratumumab will be used in this
study. As presented in Section 4.2, and in the current daratumumab IB, the safety and
tolerability of SC daratumumab has been demonstrated. Previous exposure-response analyses
have demonstrated a strong correlation between ORR and the maximum daratumumab Ctrough.
Analysis of the preliminary pharmacokinetic data indicated the 1800 mg Dara-SC dose
achieved maximum Ctrough values comparable with, or higher than, those observed for Dara-IV
16 mg/kg. Details are provided in Section 4.2.
The potential risks for the study will be mitigated with monitoring by the IDMC and the
sponsor’s medical monitor during the conduct of the study, as described throughout the
protocol (see Section 9.8).
In light of the above, there is a strong rationale for evaluating SC daratumumab in combination
with VRd for the treatment of patients with previously untreated multiple myeloma for whom
initial transplant is not planned. More detailed information about the known and expected benefits
and risks of daratumumab may be found in the Investigator’s Brochure.

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3. 
OBJECTIVES AND ENDPOINTS
3.1. 
Objectives and Endpoints
3.1.1. 
Objectives
The primary objective is to determine ifthe addition of daratumumab to VRd will improve overall
MRD negativity rate compared with VRd alone.
Secondary Objectives
The secondary objectives are:
To determine if the addition of daratumumab to VRd will improve clinical outcome as
measured by:
PFS
MRD negativity rate at 1 year
Durability of MRD negativity (defined in Section 3.1.2)
ORR, rate of very good partial response (VGPR) or better, and rate of CR or better
Time to response
Duration of response
Time to next treatment
Progression-free survival on the next line of therapy (PFS2; defined as time from
randomization to progression on the next line of therapy or death, whichever comes first)
OS
To evaluate medical resource utilization
To evaluate the pharmacokinetics (PK) of daratumumab
To determine the immunogenicity of daratumumab and recombinant human hyaluronidase
PH20 (rHuPH20)
To assess the safety profile of daratumumab + VRd (D-VRd)
To evaluate clinical efficacy (ie, overall MRD negativity rate and PFS) of daratumumab when
added to VRd in cytogenetic high-risk subgroups
To evaluate patient-reported outcomes (PROs).
Exploratory Objectives
The exploratory objectives are to determine:
Time to MRD negativity
Correlation of MRD negative status and clinical outcomes such as PFS and OS.

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3.1.2. 
Endpoints
Primary Endpoint
The primary endpoint of this study is:
Overall MRD negativity rate, which is defined as the proportion of subjects who have
achieved MRD negative status (at 10-5) by bone marrow aspirate after randomization and prior
to progressive disease (PD) or subsequent anti-myeloma therapy. Subjects who have achieved
MRD negative status on or after PD or after the switch to subsequent anti-myeloma therapy
before PD, will not be considered MRD negative in the primary endpoint analysis.
Secondary Endpoints
Secondary efficacy endpoints are:
PFS defined as the duration from the date of randomization to either progressive disease (PD)
or death, whichever comes first. Disease progression will be determined according to the
International Myeloma Working Group (IMWG) criteria (Table 11).12,40 For subjects who
have not progressed and are alive, data will be censored at the last disease evaluation before
the start of any subsequent anti-myeloma therapy.
MRD negativity rate at 1 year.
Durable MRD negativity rate is defined as the proportion of subjects who have achieved MRD
negative status (at 10-5) at 2 bone marrow aspirate examinations that are a minimum of 1 year
apart, without any examination showing MRD positive status in between.
Overall response rate is defined as the proportion of subjects who achieve PR or better
responses prior to subsequent anti-myeloma therapy in accordance with the IMWG criteria,
during or after the study treatment.
VGPR or better rate is defined as the proportion of subjects achieving VGPR and CR
(including sCR) prior to subsequent anti-myeloma therapy in accordance with the IMWG
criteria during or after the study treatment.
CR or better rate is defined as the proportion of subjects achieving CR or sCR prior to
subsequent anti-myeloma therapy in accordance with the IMWG criteria during or after the
study treatment.
Progression-free survival on the next line of therapy is defined as the time from randomization
to progression on the next line of treatment or death, whichever comes first. Disease
progression will be based on investigator judgment. Subjects who are still alive and not yet
progressed on the next line of treatment will be censored on the last date of follow-up.
Overall survival is measured from the date of randomization to the date of the subject’s death
due to any cause. If the subject is alive or the vital status is unknown, then the subject’s data
will be censored at the date the subject was last known to be alive.
Time to response is defined as the time between the randomization and the first efficacy
evaluation at which the subject meets all criteria for PR or better.

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Duration of response is calculated from the date of initial documentation of a response (PR or
better) to the date of first documented evidence of PD, as defined in the IMWG evaluation
before the start of any subsequent anti-myeloma therapy.
Clinical efficacy (ie, overall MRD negativity rate and PFS) of D-VRd in high-risk molecular
subgroups compared with VRd alone.
Pharmacokinetic concentrations of daratumumab.
Incidence of anti-daratumumab antibodies.
Prevalence and incidence of anti-rHuPH20 antibodies.
Mean change from baseline in the European Organization for Research and Treatment of
Cancer Quality of Life Questionnaire (EORTC QLQ) core 3-item (EORTC QLQ-C30) and
the multiple myeloma 20-item (EORTC QLQ-MY20), and EuroQol Five Dimension
Questionnaire (EQ-5D-5L) scales.
Refer to Section 8.2, Efficacy Assessments for evaluations related to endpoints.
3.1.3. 
Hypothesis
The primary hypothesis is that daratumumab added to VRd regimen will improve the overall MRD
negativity rate compared with VRd alone in subjects with newly diagnosed multiple myeloma for
whom hematopoietic stem cell transplant is not planned as initial therapy.
4. 
STUDY DESIGN
4.1. 
Overall Study Design
This is a randomized, open-label, multicenter, Phase 3 study evaluating subjects with newly
diagnosed multiple myeloma for whom hematopoietic stem cell transplant is not planned as initial
therapy. At randomization, subjects will be stratified by International Staging System (ISS) Stage
(I, II, or III, based on β-2 microglobulin and albumin by central laboratory), and age/transplant
eligibility (<70 years ineligible, or age <70 years and refusal to transplant, or age ≥70 years).
Approximately 360 subjects (180/arm) will be randomized in a 1:1 ratio in 2 arms. Subjects in
Arm A will receive VRd alone for eight 21-day cycles followed by Rd alone until disease
progression or unacceptable toxicity. Subjects in Arm B will receive D-VRd for eight 21-day
cycles and will continue to receive DRd therapy until disease progression or unacceptable toxicity.
The study will consist of 3 phases: A Screening Phase, a Treatment Phase (Intervention Phase),
and a Follow-up Phase (Postintervention Phase). The Screening Phase will be up to 28 days before
randomization. Subjects will receive either D-VRd or VRd for 8 cycles. No subject will receive
bortezomib after completion of the first 8 cycles of VRd. After completing 8 cycles of therapy,
subjects will continue with DRd or Rd until disease progression or unacceptable toxicity. Subjects
who discontinue treatment with any one component of study treatment (bortezomib, lenalidomide,
dexamethasone, or daratumumab) may continue to receive treatment with the other components
of study treatment, as assigned. Subjects will enter the Follow-up Phase once they have
documented disease progression, or unacceptable toxicity and all treatment is discontinued. In the
Follow-up Phase, subjects who discontinued before disease progression must continue to have

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disease evaluations according to the Schedule of Activities until confirmed PD, death, withdrawal
of consent, lost to follow-up, or the end of data collection. After disease progression is
documented, follow-up will be obtained at least every 16 weeks until the final PFS analysis.
Subsequent anticancer treatment, PFS2 (per investigator judgment), second primary malignancies,
and survival will also be recorded.
The primary analysis of the overall MRD negativity rate will be performed approximately
18 months after the last subject is administered his/her first dose of study treatment. The final
PFS analysis will take place when approximately 162 PFS events have been reached. An interim
analysis for PFS is planned, when 98 PFS events (60% of total planned PFS events) are expected
to have been accumulated. After the cut-off for the final PFS analysis, sponsor confirmation of
disease response and progression will no longer be required and will be based on investigator
assessment. Investigator-assessed long-term PFS, PFS2, and OS will continue to be collected until
end of data collection, which will be 7 years after the last subject is randomized into the study, or
earlier at sponsor discretion. Updates to the final Clinical Study Report for both efficacy and safety
will be provided in an addendum to the Clinical Study Report at study closure.
Assessment of tumor response and disease progression will be conducted in accordance with the
IMWG response criteria. An assessment of MRD will be conducted on bone marrow samples.
Safety evaluations will include AE monitoring, physical examinations, electrocardiogram (ECG)
monitoring, clinical laboratory parameters (hematology and chemistry), vital sign measurements,
and Eastern Cooperative Oncology Group (ECOG) performance status. Blood samples will be
drawn for assessment of pharmacokinetic and immunogenicity parameters.
An IDMC will be commissioned for this study to review safety and efficacy results before the final
analysis of PFS. After each review at the primary MRD analysis and the interim analysis of PFS,
the IDMC will make recommendations regarding the unblinding and the continuation of the study.
The IDMC will also review cumulative safety data after the first 100 subjects have been treated
for at least 1 cycle or discontinued, and thereafter every 6 months. Refer to Section 9.8, for details.
When data from the study are available, the benefit-risk assessment of D-VRd versus VRd will be
conducted by comparing between-treatment differences of key efficacy and safety endpoints.
Efficacy endpoints may include overall MRD negativity rate, durable MRD negativity rate, PFS,
duration of response, and improvement in PRO measures. Safety endpoints may include serious
infections (eg, pneumonia, lower respiratory tract infection), atrial fibrillation, diarrhea, infusion
reactions and other SAEs or events of special interest. Safety endpoints that show no
between-treatment differences will be noted but may be excluded from the benefit-risk analyses.
Adverse events (AEs) not in this list, but that show a clinically meaningful between-treatment
difference may be included. More detailed information about the known and expected benefits and
risks of daratumumab  can be found in the daratumumab IB. A diagram of the study design is
provided in Section 1.2, Schema.

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4.2. 
Scientific Rationale for Study Design
Rationale for Study Design
The VRd regimen in this study is based upon the SWOG S0777 study in newly diagnosed subjects
with multiple myeloma for whom transplant is not planned as frontline therapy, which utilized
eight 21-day cycles of induction therapy with VRd followed by Rd continuous therapy until PD.13
Continuous therapy with Rd until disease progression was demonstrated to be superior to a fixed
18-month duration of therapy in the FIRST study.4,41 In the current study, treatment with Rd will
continue until disease progression or unacceptable toxicity in Arms A and B. The SWOG S0777
study utilized IV bortezomib which resulted in 33% Grade 3 or higher neurologic toxicity in the
VRd arm compared with the Rd arm. For this study, bortezomib will be given via SC
administration which has been shown to decrease neurotoxicity versus IV administration.28
Rationale for MRD as a Primary Endpoint
Achievement of MRD negativity by flow or next generation sequencing (NGS) at a cutoff of both
10-4 and 10-5 has been correlated with improvement of both PFS and OS.20,21,30 These meta-and
pooled analyses of MRD data have demonstrated that MRD negative status is the strongest
independent prognostic biomarker for PFS and OS in newly diagnosed multiple myeloma. Based
upon the strength of these early analyses, the acceptance of MRD as a validated, clinical endpoint
may be achieved in the near future.
Furthermore, data from 2 studies utilizing daratumumab in combination with either Rd
(MMY3003) or Vd (MMY3004) in subjects with relapsed/refractory multiple myeloma have
shown over a 3-fold increase in the number of subjects who achieved MRD negative status
(Figure 4).3 Subjects achieving MRD negative status demonstrated improved PFS (Figure 4).
These studies utilized the FDA-approved clonoSEQ v2.0 MRD assay (Adaptive Biotechnologies®)
that is an analytically validated NGS assay. The use of the clonoSEQ assay allows for centralized
analysis and the consistent, accurate evaluation of MRD status that will support the primary
endpoint.

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Figure 4: 
Progression-free Survival According to MRD Status 10-5 in Studies MMY3003 and MMY3004
Study MMY3003 
Study MMY3004
In this study, minimal residual disease (MRD) initially will be evaluated at suspected CR when a
subject has achieved a deep clinical response. For subjects who achieve CR, have not progressed,
and remain on the study, additional landmark bone marrow aspirate samples will be obtained to
allow for the statistical analysis of the association of MRD with PFS/OS and to evaluate the
durability of MRD negativity in these subjects.
The primary endpoint will evaluate the overall MRD negativity rate in both arms thus capturing
the best overall MRD negativity rate between the 2 arms. Further secondary endpoints will assess
the durability of MRD negativity, thus assessing whether subjects who obtain MRD negativity are
able to maintain that depth of response. The sponsor will assess the impact of this durability of
MRD negativity on the long-term outcome of PFS. Further, the sponsor will assess whether
fixed-timepoints for evaluation of MRD negativity are as predictive of long-term outcome as the
overall MRD negative rate. The primary analysis for MRD at the 18-month timepoint was chosen
in order to mitigate the impact of Coronavirus Disease 2019 (COVID-19) on MRD sample
collection, and to ensure the maturity of MRD negativity at the primary analysis.
Rationale for Subcutaneous Daratumumab
A new formulation of daratumumab for subcutaneous (SC) administration has been developed to
avoid the long infusion time that frequently requires hospitalization with IV administration of
daratumumab and to lessen the rate and severity of infusion-related reactions observed with
IV daratumumab. Further, an enzyme rHuPH20 was used in the SC formulation in order to
facilitate the high-volume SC administration.
This SC formulation of daratumumab is currently being evaluated in Study MMY1004, an
open-label, multicenter, dose escalation Phase 1b Study. This study assessed the safety,
pharmacokinetics, and efficacy of SC administration of daratumumab plus rHuPH20
(DARA-PH20) in subjects with relapsed or refractory multiple myeloma. After a median treatment
duration of 5.6 months (clinical cutoff date of 13 Dec 2017), 25 subjects received at least 1 dose

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of 1800 mg Dara-SC in Study MMY1004.8 The infusion-related reaction rate was 16% and
consisted of Grade 1 or 2 chills, dyspnea, sneezing and allergic rhinitis, and two Grade 3 events of
hypertension. None of the IRR events led to treatment discontinuation. Injection-site reactions
occurred in 12% of subjects, all were Grade 1. The events were discoloration/injection-site
induration, hematoma, and erythema. The ORR was 52% with 28% VGPRs. Median PFS has not
been reached. The efficacy and AE profile are consistent with that of IV daratumumab with a lower
rate of infusion-related reactions. Based on this clinical data and supported by the pharmacokinetic
profile of Dara-SC, the safety and efficacy of Dara-SC appear equivalent to and may be better than
Dara-IV. The SC formulation is currently being further tested in Study, MMY3012, a Phase 3
study of Dara-IV versus Dara-SC in subjects with relapsed or refractory multiple myeloma.
Rationale for rHuPH20 Concentration
In this study, the concentration of rHuPH20 in Dara-SC will be 2000 U/mL; this is the same
concentration and total amount of rHuPH20 administered in Part 2 of Study MMY1004 with the
co-formulated drug product (Dara-CF). Products approved for commercial use, such as Herceptin
SC (trastuzumab) and MabThera SC (rituximab), also contain 2000 U/mL of rHuPH20.
Two studies in minipigs support the use of this concentration of rHuPH20 in SC daratumumab
(Dara-SC). In the first study, 20 mg/mL of human IgG in daratumumab formulation buffer was
formulated with 200, 500, or 800 U/mL of rHuPH20 and infused SC into the abdomen of sedated
animals at a rate of 2 or 4 mL/min using a syringe pump. The higher infusion rate (4 mL/min)
resulted in less local swelling and erythema. Erythema, when present, was mild and subsided by
the next day. Infusion pressures were similar for all concentrations of rHuPH20 at both infusion
rates (~40 to 60 mm Hg or 1 PSI). The second study evaluated 100 mg/mL daratumumab
formulated with 50, 500, 2000, or 5000 U/mL of rHuPH20. Sixteen (16) mL of each formulation
was infused SC into the abdomen of sedated animals at a rate of 3 mL/minute. Infusion pressures
showed a dose-dependent trend where pressures were reduced as the concentration of rHuPH20
increased. Formulations with ≥500 U/mL of rHuPH20 showed relatively small areas of local
swelling that was mainly soft to the touch with mild to no erythema. These all resolved by the
following day, with many resolving within an hour.
Rationale for Fixed Daratumumab Dose
Dara-IV exhibits a wide therapeutic window with no apparent relationship between drug exposure
in the therapeutic dose range and AEs of interest, which supports the feasibility of utilizing a fixed
dose approach. Simulations based on preliminary PK data from Part 1 of the MMY1004 study
where a mix-and-deliver SC presentation (Dara-MD) of the currently approved daratumumab IV
formulation was used indicated that across weight quartiles, similar exposure and variability was
predicted for each dosing approach (either Dara-MD 1800 mg or daratumumab IV 16 mg/kg).
Based on these simulations and the safety, efficacy, and PK data in Study MMY1004, fixed dosing
for SC administration is a feasible approach and will be used in this study.
Rationale for Daratumumab Dose Regimen
Previous exposure-response analyses have demonstrated a strong correlation between ORR and
the maximum daratumumab lowest drug concentration reached before the next dose is
administered (Ctrough)which occursat the end of weekly dosing (Cycle 3 Day 1 in the monotherapy

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schedule). These analyses have also demonstrated the lack of relationship between daratumumab
concentrations and AEs in the therapeutic dose range. Therefore, the dose of Dara-SC selected is
intended to achieve a similar or greater maximum Ctrough  compared with 16 mg/kg IV
administration.
As 03 Aug 2017, 18 subjects were evaluable for PK in Study MMY1004 Part 2. Analysis of the
preliminary pharmacokinetic data indicated the 1800 mg Dara-SC (co-formulated) dose achieved
maximum Ctrough  values comparable with, or higher than, those observed for Dara-IV 16 mg/kg.
The maximum Ctrough  mean value was 904.42 µg/mL for the 1800 mg Dara-SC cohort (n=18),
compared with 617.17 µg/mL in Study GEN501 Part 2 (n=27), and 573.49 µg/mL in
Study MMY2002 (n=73). The range of maximum Ctrough  observations for the SC cohort is
contained within the range observed following 16 mg/kg IV dosing and variability was similar
with a % coefficient of variance (CV) of 46 to 58% across the SC and IV doses. The observed
mean maximum observed concentration (Cmax) values following the last (8th) weekly dose for the
Dara-SC cohort was 1012.4 µg/mL, similar to the mean Cmax of 914.9 µg/mL observed after the
9th  dose for Dara-IV in Study MMY2002. The observed Cmax values from the Dara-SC cohort is
within the range observed for Dara-MD and 16 mg Dara-IV.
Study MMY1004 Part 2 also showed that 1800 mg Dara-SC can be administered subcutaneously
by manual injection with a median of 5 minutes (ranging from 2 to 11 minutes) and it is associated
with low incidence of IRRs, as noted above. The overall safety profile for the Dara-CF cohort is
consistent with previously reported safety profiles for daratumumab with daratumumab IV
administration and subcutaneous administration with Dara-MD. There are no new safety signals
with the Dara-SC administration. Therefore, based on the available safety and PK data, the dose
of 1800 mg Dara-SC is selected for study in Phase 3 studies, including this study.
The schedule utilized for this study begins with two 21-day cycles of weekly daratumumab dosing
to quickly achieve effective daratumumab concentrations, which is the same initial dosing
schedule (6 weeks of weekly dosing) as used in the MMY3007 study of daratumumab
(16 mg/kg IV) + VMP. The results from MMY3007 showed that the maximal trough concentration
was similar following the D-VMP dose regimen in subjects with newly diagnosed multiple
myeloma and the approved dose regimens in previous monotherapy and combination therapy
studies in subjects with relapsed or relapsed and refractory multiple myeloma, indicating 6 weeks
of weekly dosing in newly diagnosed multiple myeloma subjects is sufficient to achieve effective
concentrations. For Cycles 3-8 daratumumab will be given every-3-weeks and then every-4-weeks
for Cycle 9 and beyond; this progression to every-3-week and every-4-week dosing intervals is
similar to other approved daratumumab dosing schedules and is intended to maintain target
saturation.
Rationale for Pharmacokinetics and Immunogenicity Assessments
Data obtained from this study will provide information about the PK profile of Dara-SC in
combination with VRd in subjects with multiple myeloma. Therefore, samples will be obtained
from all subjects for PK assessments. Data may also be used for a population PK analysis to

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estimate additional PK parameters and provide information about the determinants of inter-subject
variability in this population.
Immunogenicity to daratumumab or rHuPH20 is possible. Therefore, the presence of
anti-daratumumab antibodies and anti-rHuPH20 antibodies (immunogenicity) will be determined
from PK samples collected from all subjects in Arm B.
Rationale for DNA and Biomarker Collection
Biomarker samples will be collected to evaluate the depth and durability of clinical response to
daratumumab through evaluation of MRD, using DNA sequencing of immunoglobulin genes
(FDA-approved clonoSEQ v2.0, Adaptive Biotechnologies®). Emerging data suggest that the
evaluation of circulating tumor DNA may be a less invasive method to identify biomarkers of
response than a bone marrow aspirate.
Rationale for Medical Resource Utilization
Medical resource utilization (MRU) data will be collected to determine the medical cost impact of
D-VRd and VRd treatment regimens. The data collected will be used to conduct exploratory
analyses that may be used to support the value story and cost-effectiveness modeling for market
access.
Rationale for Patient-reported Outcome Evaluations
The PRO  data complements data collected by clinical and laboratory findings to describe the
subject experience, directly reported by the subject. Patient-reported outcome data is supportive of
the clinical endpoints and captures inputs required for cost-effectiveness modeling. In addition,
the PRO data provides the patient perspective to communicate the value of treatment to patients,
clinicians, regulators, and payers.
4.2.1. 
Study-Specific Ethical Design Considerations
This study is designed to provide a highly efficacious regimen for the treatment of multiple
myeloma for subjects who are either transplant eligible or ineligible. VRd is established as a
standard treatment option for newly diagnosed myeloma. The improved outcomes of daratumumab
in combination with either of the components (DRd or DVd) in Phase 3 studies MMY3003 and
MMY3004 and the preclinical synergy observed with the combination indicates the potential for
improved outcome for daratumumab in combination with VRd. The safety profile of daratumumab
primarily consists of infusion-related reactions. This study will utilize SC daratumumab
administration, which demonstrated a lower IRR rate compared with IV daratumumab
administration. Based on the mode of action of daratumumab, infection could be a potential risk;
therefore, the protocol requires the review of hematological laboratory results prior to
daratumumab administration. CD38 is distributed in erythrocytes and platelets. Routine safety
laboratory measurement of red blood cells (RBC) and platelets will be closely monitored in this
study. An IDMC will be established to review safety data on a regular basis throughout the duration
of the study, and review both safety and efficacy results at primary analysis of the overall MRD
negativity rate and the interim analysis for PFS. Based on the data presented in Section 2.1.5 and
the addition of daratumumab to VRd is anticipated to provide benefit to subjects in this study.

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Potential subjects will be fully informed of the risks and requirements of the study, and, during the
study, subjects will be given any new information that may affect their decision to continue
participation. They will be told that their consent to participate in the study is voluntary and may
be withdrawn at any time with no reason given and without penalty or loss of benefits to which
they would otherwise be entitled. Only subjects who are fully able to understand the risks, benefits,
and potential AEs of the study, and provide their consent voluntarily will be enrolled. Note that as
specified in Appendix 3 (Section 10.3) a legally designated representative may provide consent on
behalf of the subject.
Blood volumes drawn for all phases of the study are provided in Section 8.1.1. The total blood
volume to be collected is considered to be acceptable for subjects with multiple myeloma
participating in a clinical study and reasonable over the time frame of the study.
4.3. 
Measures to Minimize Bias: Randomization and Blinding
Eligible subjects will be stratified by ISS (Stage I, II, or III, based on β-2 microglobulin and
albumin by central laboratory), and age/transplant eligibility (<70 years ineligible, or age
<70 years and refusal to transplant, or age ≥70 years), and then assigned randomly to 1 of
2 treatment groups in a 1:1 ratio based on an algorithm implemented in the interactive web
response system (IWRS) before the study. The randomization will be balanced by using randomly
permuted blocks. Based on the randomization code, the IWRS will assign a unique intervention
code, which will dictate the intervention assignment and matching study drug kit for the subject.
As this is an open study, blinding procedures are not applicable.
4.4. 
End of Study Definition
The end of data collection is defined as 7 years after the last subject is randomized, or earlier at
sponsor discretion. The sponsor will notify sites of the end of data collection, after which point no
additional eCRF data will be collected and the clinical database will be closed. Data collected in
the eCRF following the final PFS analysis up until the end of data collection will be reported in an
addendum to the Clinical Study Report. The final data from the study site will be sent to the
sponsor (or designee) after completion of the final subject assessment at that study site, in the time
frame specified in the Clinical Trial Agreement.
The sponsor will ensure that subjects who are still receiving treatment with daratumumab at the
end of data collection can continue to receive study treatment until and after the end of the study.
The end of study is defined as when one of the following occurs (whichever comes first):
When all subjects who are still receiving study treatment at the end of data collection have
access through another source such as a commercial availability, continued access through
a dedicated long-term extension study, or a patient access program.
When all subjects have discontinued daratumumab treatment.
By 31 October 2028.

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5. 
STUDY POPULATION
Screening for eligible subjects will be performed within 28 days before randomization. Refer to
Section 5.4, Screen Failures for conditions under which the repeat of any screening procedures is
allowed. The inclusion and exclusion criteria for enrolling subjects in this study are described
below. If there is a question about these criteria, the investigator must consult with the appropriate
sponsor representative and resolve any issues before enrolling a subject in the study. Waivers are
not allowed. For a discussion of the statistical considerations of subject selection, refer to
Section 9.2, Sample Size Determination.
5.1. 
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1. 
Newly diagnosed and not considered candidate for high-dose chemotherapy with stem
cell transplantation (SCT) due to:
Being age ≥65 years
or
age 18-65 years with presence of comorbid condition(s) likely to have a negative
impact on tolerability ofhigh-dose chemotherapy with SCT or who refuse high-dose
chemotherapy with SCT as initial treatment.
2. 
Diagnosis of multiple myeloma as documented per IMWG criteria: Monoclonal plasma
cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytoma and
documented multiple myeloma satisfying at least one of the CRAB (calcium, renal,
anemia, bone) criteria or biomarkers of malignancy criteria:
CRAB criteria:
1. Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than upper limit of
normal (ULN) or >2.75 mmol/L (>11 mg/dL)
2. Renal insufficiency: creatinine clearance <40mL/min or serum creatinine
>177 μmol/L (>2 mg/dL)
3. Anemia: hemoglobin >2 g/dL below the lower limit of normal or hemoglobin
<10 g/dL
4. Bone lesions: one or more osteolytic lesions on skeletal radiography, computed
tomography (CT), or positron emission tomography (PET)-CT
Biomarkers of Malignancy:
a. Clonal bone marrow plasma cell percentage ≥60%
b. Involved: uninvolved serum free light chain (FLC) ratio ≥100
c. >1 focal lesion on magnetic resonance imaging (MRI) studies
3. 
Must have measurable disease, as assessed by central laboratory, defined by any of
the following:

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IgG, IgA, IgM, IgD, or IgE multiple myeloma: Serum monoclonal paraprotein
(M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
Light chain multiple myeloma without measurable disease in serum or urine:
Serum Ig FLC ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
4. 
ECOG performance status score of 0, 1, or 2 (Appendix 7 [10.7])
5. 
Criterion modified per Amendment 2.
5.1 Criterion modified per Amendment 3
5.2 Clinical laboratory values meeting the following criteria during the
Screening Phase:
a. hemoglobin >7.5 g/dL ( 
mmol/L) (without prior RBC transfusion within 7 days
before the laboratory test; recombinant human erythropoietin use is permitted);
b. absolute neutrophil count (ANC) >1.0 x109/L (granulocyte colony stimulating
factor [G-CSF] use is permitted);
c. platelet count >70 x109/L for subjects in whom <50% of bone marrow nucleated
cells are plasma cells; otherwise platelet count >50 ×109/L (transfusions are not
permitted within 7 days);
d. aspartate aminotransferase (AST) ≤2.5 x ULN;
e. alanine aminotransferase (ALT) ≤2.5 x ULN;
f. total bilirubin ≤1.5 x ULN, except in subjects with congenital bilirubinemia, such
as Gilbert syndrome (direct bilirubin ≤2.0 x ULN);
g. Estimated creatinine clearance (CrCl) ≥30 mL/min. Creatinine clearance can be
calculated using the Cockcroft-Gault formula9 (Appendix 8 [Section 10.8]) or
eGFR (MDRD; Appendix 9 [Section 10.9]), or CKD-epi formula, or for subjects
with over- or underweight, CrCl may be measured from a 24-hours urine
collection using the formula provided in Appendix 8 [Section 10.8]). If
Cockcroft-Gault formula is used and body mass index (BMI) is ≥30 kg/m2 then
adjusted body weight should be used in calculation (Appendix 8 [Section 10.8]);
h. corrected serum calcium ≤13.5 mg/dL (≤3.4 mM/L); or free ionized calcium
≤6.5 mg/dL (≤1.6 mM/L) (Appendix 10 [Section 10.10])
Note: For criteria 6 to 11, contraceptive (birth control) use by men or women should be consistent
with local regulations regarding the acceptable methods of contraception for those participating in
clinical studies. Typical use failure rates may differ from those when used consistently and
correctly. Use should be consistent with local regulations regarding the use of contraceptive
methods for subjects in clinical studies.
6. Female subjects of reproductive childbearing potential must commit to either abstain
continuously from heterosexual sexual intercourse or to use 2 methods of reliable
birth control simultaneously during the Treatment Period, during any dose
interruptions, and for 3 months after the last dose of any component of the treatment

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regimen. Sexual abstinence is considered a highly effective method only if defined
as refraining from heterosexual intercourse during the entire period of risk associated
with the study drug. This birth control method must include one highly effective form
of contraception (tubal ligation, intrauterine device, hormonal [birth control pills,
injections, hormonal patches, vaginal rings or implants] or partner’s vasectomy) and
one additional effective contraceptive method (male latex or synthetic condom,
diaphragm, or cervical cap). Contraception must begin 4 weeks prior to dosing.
Reliable contraception is indicated even where there has been a history of infertility,
unless due to hysterectomy or bilateral oophorectomy (Appendix 5 [Section 10.5]).
7. 
A woman of childbearing potential must have 2 negative serum or urine pregnancy tests
at Screening, first within 10 to 14 days prior to dosing and the second within 24 hours
prior to dosing. For requirements during the Treatment Phase, refer to Section 5.3.
8. 
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for a period of 3 months after receiving the last dose of
any component of the treatment regimen.
9. 
Male subjects of reproductive potential who are sexually active with females of
reproductive potential must always use a latex or synthetic condom during the study and
for 3 months after discontinuing study treatment (even after a successful vasectomy).
10. Male subjects of reproductive potential must not donate sperm during the study or for
3 months after the last dose of study treatment.
11. Criterion modified per Amendment 6
11.1 Must sign an informed consent form (ICF) or their legally designated representative
must sign indicating that he or she understands the purpose of, and procedures required
for, the study and is willing to participate in the study.
12. Able to adhere to the prohibitions and restrictions specified in this protocol.
5.2. 
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating
in the study:
1. 
Frailty index of ≥2 according to Myeloma Geriatric Assessment score.31,35
2. Criterion modified per Amendment 3.
2.1 Prior therapy for multiple myeloma other than a short course of corticosteroids
(not to exceed 40 mg of dexamethasone, or equivalent per day, total of 160 mg
dexamethasone or equivalent).
3. Prior or concurrent invasive malignancy (other than multiple myeloma) within 5 years
of date of randomization (exceptions are adequately treated basal cell or squamous cell

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carcinoma of the skin, carcinoma in situ of the cervix or breast, or other non-invasive
lesion that in the opinion of the investigator, with concurrence with the sponsor’s
medical monitor, is considered cured with minimal risk of recurrence within 3 years).
4. Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National
Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Version 5.
5. Criterion modified per Amendment 3.
5.1 Focal radiation therapy within 14 days of randomization with the exception of
palliative radiotherapy for symptomatic pain management. Radiotherapy
within 14 days prior to randomization on measurable extramedullary
plasmacytoma is not permitted even in the setting of palliation for
symptomatic management.
6. Plasmapheresis within 28 days of randomization.
7. Clinical signs of meningeal involvement of multiple myeloma.
8. Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in
1 second (FEV1) <50% of predicted. (FEV1 testing is required for subjects suspected
of having COPD).
9. Moderate or severe persistent asthma within the past 2 years (see Appendix 11
[Section 10.11]), uncontrolled asthma of any classification. (Subjects who have
controlled intermittent asthma or controlled mild persistent asthma are allowed in the
study).
10. Criterion modified per Amendment 2.
10.1 Criterion modified per Amendment 3
10.2 Subject is:
a. Known to be seropositive for human immunodeficiency virus (HIV).
b. seropositive for hepatitis B (defined by a positive test for hepatitis B surface
antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg
negative but positive for antibodies to total hepatitis B core antigen [anti-HBc]
and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened
using real-time polymerase chain reaction (PCR) measurement of hepatitis B
virus (HBV) DNA levels. Those who are PCR positive will be excluded.
EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination
(anti-HBs positivity as the only serologic marker) AND a known history of prior
HBV vaccination, do not need to be tested for HBV DNA by PCR.
c. Known to be seropositive for hepatitis C virus (HCV; anti-HCV antibody
positive or HCV-RNA quantitation positive), except in the setting of a sustained

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virologic response (SVR), defined as aviremia at least 12 weeks after
completion of antiviral therapy.
11. Concurrent medical or psychiatric condition or disease (such as but not limited to,
systemic amyloidosis, POEMS, active systemic infection, uncontrolled diabetes, acute
diffuse infiltrative pulmonary disease) that is likely to interfere with study procedures
or results, or that in the opinion of the investigator would constitute a hazard if enrolled
in the study.
12. Has clinically significant cardiac disease, including:
Myocardial infarction within 6 months before signing the ICF, or unstable or
uncontrolled disease/condition related to or affecting cardiac function (eg, unstable
angina, congestive heart failure, New York Heart Association Class III-IV;
Appendix 18 [Section 10.18])
Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities
Screening 12-lead ECG showing a baseline QT interval as corrected by Frederica’s
formula (QTcF) >470 msec.
13. Received a strong CYP3A4 inducer within 5 half-lives prior to randomization.17
14. Allergy, hypersensitivity, or intolerance to boron or mannitol, corticosteroids,
monoclonal antibodies or human proteins, or their excipients (refer to the Investigator's
Brochure), or sensitivity to mammalian-derived products or lenalidomide.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening.
If a subject's clinical status changes (including any available laboratory results or receipt of
additional medical records) after screening but before the first dose of study drug is given such
that he or she no longer meets all eligibility criteria, then the subject should be excluded from
participation in the study. Section 5.4, Screen Failures, describes options for retesting. The
required source documentation to support meeting the enrollment criteria are noted in Appendix 3
(Section 10.3) Regulatory, Ethical, and Study Oversight Considerations.
5.3. 
Restrictions During Study Participation
Potential subjects must be willing and able to adhere to the following restrictions during the study
to be eligible for participation:
1. Refer to Section 6.8, Concomitant Therapy for details regarding prohibited and
restricted therapy during the study.
2. Agree to follow all requirements that must be met during the study as noted in the
Inclusion and Exclusion Criteria (eg, contraceptive requirements).
3. A woman of childbearing potential must remain on a highly effective method of birth
control (see inclusion criteria). Contraception must begin 4 weeks before initiating
treatment with daratumumab and lenalidomide, and continue during the Treatment

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Phase, during dose interruptions and continuing for at least 4 weeks after the last dose
of lenalidomide and 3 months following of the last dose of daratumumab. Reliable
contraception is indicated even where there has been a history of infertility, unless due
to hysterectomy. In addition, women must not donate ova during the study, for 4 weeks
after the last dose of lenalidomide, and for 3 months after the last dose of daratumumab.
All women must not breastfeed while taking lenalidomide and for at least 28 days after
the last dose of lenalidomide.
4. Criterion modified per Amendment 6
4.1 During the Treatment Phase, pregnancy tests are required weekly during Cycle 1
and then monthly in subsequent cycles in women with regular menstrual cycles or every
2 weeks in women with irregular menstrual cycles. A pregnancy test is also required at
the End-of-Treatment Visit and 28 days following the last dose of lenalidomide for
women with regular menstrual cycles or 14 and 28 days following the last dose of
lenalidomide for women with irregular menstrual cycles. Additional pregnancy tests
may be required, as specified in the local lenalidomide Risk Evaluation and Mitigation
Strategy (REMS) (where lenalidomide is supplied locally) or the Lenalidomide Global
Pregnancy Prevention Plan (where lenalidomide is supplied centrally and no local
lenalidomide REMS program exists).
In order to mitigate the risk of embryo-fetotoxicity associated with exposure
to lenalidomide, all investigators will prescribe lenalidomide according to the
following requirements:
All investigators at study centers will comply with either CELGENE’s Global
Lenalidomide Pregnancy Prevention Plan for subjects in clinical trials, or the
Lenalidomide Global Pregnancy Prevention Plan. This applies to countries
where study drug will be dispensed as Investigational Medicinal Product.
All investigators at study centers will comply with either the respective
CELGENE country-specific Revlimid Risk Minimization Program (ie,
pregnancy prevention program) as implemented in the post-marketing setting,
or the Lenalidomide Global Pregnancy Prevention Plan. This applies to
countries where study drug will be dispensed as Non-Investigational Medicinal
Product.
5. A man who has not had a vasectomy and who is sexually active with a pregnant woman
or a woman of childbearing potential must agree to use a barrier method of birth control
eg, condom with spermicidal foam/gel/film/cream/suppository during the study and for
at least 4 weeks after the study, All men must not donate sperm during the study, during
dose interruptions, or for at least 4 weeks after the last dose of lenalidomide, and for
3 months after the last dose of daratumumab. The exception to this restriction is that if
the subject’s female partner is surgically sterile, a second method of birth control is not
required.
6. Because of the embryo-fetal risk of lenalidomide all subjects must adhere to the local
lenalidomide REMS program (when lenalidomide is supplied locally), or the

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Lenalidomide Global Pregnancy Prevention Plan (when lenalidomide is supplied
centrally and no local lenalidomide REMS program exists).
7. Subjects must not donate blood during therapy, during dose interruptions and for at least
4 weeks following discontinuation of lenalidomide.
8. Typically, IV contrast is not used in CT scanning of subjects with secretory multiple
myeloma because of the risk to the kidney. If administration of IV contrast is necessary,
then adequate precautions including hydration are indicated.
5.4. 
Screen Failures
Subject Identification, Enrollment, and Screening Logs
The investigator agrees to complete a subject identification and enrollment log to permit easy
identification of each subject during and after the study. This document will be reviewed by the
sponsor study site contact for completeness.
The subject identification and enrollment log will be treated as confidential and will be filed by
the investigator in the study file. To ensure subject confidentiality, no copy will be made. All
reports and communications relating to the study will identify subjects by subject identification
and age at initial informed consent.
In cases where the subject is not randomized into the study, the date seen and age at initial informed
consent will be used.
Subjects who fail to meet the inclusion criteria or who fulfill any of the exclusion criteria (ie, screen
failures) may be rescreened once if their condition changes. Rescreening must be discussed with
and approved by the sponsor on a case-by-case basis. Subjects who are determined to be eligible
for the study after rescreening must sign a new ICF and then will be assigned a new screening
number.
6. 
STUDY DRUG
The study medicinal products and their designations are listed in Table 3.
Table 3: 
Designations of Medicinal Products Used in the Study
Designation 
Product
Investigational Medicinal Product(s) 
Daratumumab SC
Authorization status in the EU/EEA
Authorized 
Daratumumab SC
Unauthorized 
None
Non-investigational Medicinal
Product(s) (NIMP)/Auxiliary
Medicinal Product(s) (AxMP)
Bortezomib, Lenalidomide, Dexamethasone
Authorization status in the EU/EEA

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Table 3: 
Designations of Medicinal Products Used in the Study
Designation 
Product
Authorized 
Bortezomib, Lenalidomide,
Dexamethasone
Unauthorized 
None
6.1. 
Daratumumab
6.1.1. 
Daratumumab Subcutaneous Preparation
Dara-SC will be provided as a fixed-dosed (1800 mg), combination drug product containing
rHuPH20 drug substance (2000 U/mL) and daratumumab drug substance (120 mg/mL) in a single
vial. Manuals with detailed descriptions for preparation and administration of daratumumab will
be supplied to each pharmacy and site.
6.1.2. 
Daratumumab Administration
Daratumumab (1800 mg) will be administered by SC injection by manual push over approximately
3-5 minutes in the abdominal subcutaneous tissues in left/right locations, alternating between
individual doses. The volume of the SC solution will be 15 mL for the 1800 mg dose. Refer to the
SmPC, USPI, local prescribing information, or equivalent documentation for additional guidance
on study treatment handling, administration, and storage. All subjects will be observed for at least
6 hours after the end of the SC injection during Cycle 1 Day 1 and, if deemed necessary by the
investigator, after subsequent injections. Reasons for continued observation on subsequent
daratumumab injections may include but are not limited to the following: subjects with a higher
risk of respiratory complications (eg, subjects with mild asthma or subjects with COPD who have
an FEV1 <80% at screening or developed FEV1 <80% during the study without any medical
history), subjects with IRR with first injection of study drug, subject with a decreased condition
on day of dosing compared to prior dosing day. The dose of daratumumab will remain constant
throughout the study.
Daratumumab will be administered weekly in Cycles 1-2, every 3 weeks in Cycles 3-8, and every
4 weeks in Cycle 9 and beyond until the subject has progression or unacceptable toxicity. Every
effort should be made to keep subjects on the planned dosing schedule see Schedule of Activities
(Section 1.3) for acceptable window for treatment. However, doses given within 3 days of the
scheduled dose are permitted. Cycles 1-8 are 21 days and Cycle 9 and beyond are 28 days.
All daratumumab administrations will be in an outpatient setting. Subjects will receive
pre-injection medications and post-injection medications as outlined in Sections 6.1.3.1 and
6.1.3.2, respectively.

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As noted in the Schedule of Activities (Section 1.3), vital signs should be monitored extensively
on Cycle 1 Day  1 before, and after the first administration of daratumumab. For all other
administrations, vital signs should be measured before the start of injection and at the end of the
injection. If the subject experiences any significant medical event, then the investigator should
assess whether the subject should stay overnight for observation. If the subject has not experienced
a significant medical event but is hospitalized overnight only for observation, then the
hospitalization should not be reported as a SAE.
On dosing days where the VRd combination is given with daratumumab they should be
administered in the following order:
Lenalidomide, dexamethasone, daratumumab, and bortezomib.
If preference is to administer lenalidomide at night, the order should be: dexamethasone,
daratumumab, bortezomib, and lenalidomide.
Daratumumab will be manufactured and provided under the responsibility of the sponsor. Refer to
the daratumumab IB for a list of excipients.
6.1.3. 
Guidelines for Prevention and Management of Injection Reactions
6.1.3.1. 
Pre-administration Medication
To decrease the risk of IRRs, all subjects will receive the following medications 1 to 3 hours prior
to each study drug administration:
Paracetamol (acetaminophen) 650-1000 mg IV or orally (PO).
An antihistamine: diphenhydramine 25-50 mg IV or PO, or equivalent (see Appendix 12
[Section 10.12]) for list of antihistamines that may be used). Avoid IV promethazine.
Dexamethasone 20 mg Cycles 1-8 and 40 mg for Cycle 9 and beyond IV or PO on injection
days. For subjects older than  75 years or underweight (body mass index [BMI] <18.5),
dexamethasone 20 mg may be administered as appropriate (see Section 6.5). An equivalent
intermediate-acting or long-acting corticosteroid may substitute (see Appendix 13
(Section 10.13 for conversion table).
Montelukast 10 mg (or equivalent) is recommended on Cycle 1 Day 1 only up to 24 hours
prior to daratumumab injection.
If necessary, due to timing constraints, all PO pre-injection medications may be administered
outside of the clinic on the day of the injection, provided they are taken within 3 hours before the
injection.
6.1.3.2. 
Post-administration Medication
For subjects with a higher risk of respiratory complications (e.g., subjects with mild asthma or
subjects with COPD who have an FEV1 <80% at screening or developed FEV1 <80% during the
study without any medical history), the following post-injection medications should be considered:

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Antihistamine
Short-acting β2 adrenergic receptor agonist such as salbutamol
Control medications for lung disease (eg, inhaled corticosteroids ± long-acting β2 adrenergic
receptor agonists for subjects with asthma; long-acting bronchodilators such as tiotropium or
salmeterol ± inhaled corticosteroids for subjects with COPD).
In addition, subjects at-risk for respiratory complications may be hospitalized for monitoring for
up to 2 nights after an injection after daratumumab administration. If subjects are hospitalized,
then their FEV1 should be measured before discharge. If these subjects are not hospitalized, then
a follow-up telephone call should be made to monitor their condition within 48 hours after all
injections. If the subject has not experienced a significant medical event but is hospitalized
overnight only for observation, then the hospitalization should not be reported as a SAE.
Investigators may prescribe bronchodilators, antihistamines, and corticosteroids that are deemed
necessary to provide adequate supportive care in the event that bronchospasm occurs after a subject
is released from the hospital/clinic. If, after 4 full doses, an at-risk subject experiences no major
IRR, then these post-injection medications may be stopped.
6.2. 
Management of Injection-site and Injection-related Reactions
6.2.1. 
Local Injection-site Reactions
In Study MMY1004 Part 1, SC administration of daratumumab in abdominal SC tissue was
associated with local injection-site reactions, such as induration and erythema, in some subjects.
The reactions usually resolved within 60 minutes. Local injection-site reactions should be managed
per institutional standards.
6.2.2. 
Injection-related Reactions
Subjects should be observed carefully during daratumumab administrations. Trained study staff at
the clinic should be prepared to intervene in case of any IRRs, and resources necessary for
resuscitation (e.g., agents such as epinephrine and aerosolized bronchodilator, medical equipment
such as oxygen tanks, tracheostomy equipment, and a defibrillator) must be available at the
bedside. Attention to staffing should be considered when multiple subjects will be dosed at the
same time.
If an IRR develops, then daratumumab administration should be temporarily interrupted. Subjects
who experience AEs during daratumumab administration must be treated for their symptoms.
Subjects should be treated with paracetamol (acetaminophen), antihistamine, or corticosteroids, as
needed. Intravenous saline may be indicated. For bronchospasm, urticaria, or dyspnea, subjects
may require antihistamines, oxygen, corticosteroids, or bronchodilators. For hypotension, subjects
may require vasopressors. If ocular symptoms (including choroidal effusion, acute myopia, and
acute angle closure glaucoma) occur, interrupt daratumumab and seek immediate ophthalmologic
evaluation prior to restarting daratumumab. In the event of a life-threatening IRR (which may
include pulmonary or cardiac events) or an anaphylactic reaction, daratumumab should be
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6.2.2.1. 
Injection-related Reactions of Grade 1 or Grade 2
If the investigator assesses a Grade 1-2 IRR AE to be related to administration of study drug, then
the daratumumab administration should be paused. When the subject's condition is stable,
daratumumab administration may be restarted at the investigator's discretion. Refer to the sIPPM
for further details regarding continuation of daratumumab administration.
If the subject experiences a Grade 2 or higher event of laryngeal edema, or a Grade 2 or higher
event of bronchospasm that does not respond to systemic therapy and does not resolve within
6 hours from onset, then the subject must be permanently discontinued from daratumumab
treatment.
6.2.2.2. 
Injection-related Reactions of Grade 3 or Higher
For IRR AEs (other than laryngeal edema or bronchospasm) that are Grade 3, the daratumumab
administration must be stopped and the subject must be observed carefully until resolution of the
AE or until the intensity of the event decreases to Grade 1, at which point the daratumumab
administration may be restarted at the investigator’s discretion. Refer to the sIPPM for further
details regarding continuation of daratumumab administration.
If the intensity of the AE returns to Grade 3 after restart of the daratumumab administration, then
the subject must be permanently discontinued from daratumumab treatment.
For IRR AEs that are Grade 4, the daratumumab administration must be stopped and the subject
permanently discontinued from daratumumab treatment.
6.2.2.3. 
Recurrent Injection-related Reactions
If a Grade 3 IRR (or Grade 2 or higher event of laryngeal edema, or a Grade 2 or higher event of
bronchospasm) recurs during or within 24 hours after a subsequent daratumumab administration,
the subject must be permanently discontinued from daratumumab treatment.
6.3. 
Bortezomib (Arms A and B)
The amount (in mg) of bortezomib to be administered will be determined by body surface area,
calculated per a standard nomogram, there is no maximum dose (Appendix 14 ([Section 10.14]).
The calculated dose of bortezomib may be rounded to the nearest tenth of a mg (or as per
institutional practice).
Subjects will receive 1.3 mg/m2 bortezomib as a subcutaneous injection twice weekly on Days 1,
4, 8, and 11 of each 21-day cycle for Cycles 1-8. For subjects who experience injection-site
reactions at the subcutaneous administration site, bortezomib may be administered by IV injection
(see local prescribing information). Subjects will not receive bortezomib after the first 8 cycles of
treatment. On treatment days when both bortezomib and daratumumab are administered,
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If a subject’s weight changes by more than 10% from baseline, the weight used for drug
calculations should be adjusted and the dose of bortezomib will be re-calculated. Bortezomib
dosing may be delayed up to 48 hours, however subsequent doses must be adjusted to account for
the delay. Note that there should be approximately 3 days between doses of bortezomib. Skipped
doses of bortezomib will not be made up later in the cycle.
For subjects with unacceptable toxicity at the local injection-site despite dose modifications or
change in injection concentration, bortezomib can be administered intravenously as a 3 to
5 seconds bolus injection. Refer to local prescribing information for further details on either SC or
IV administration.
6.4. 
Lenalidomide (Arms A and B)
In Cycles 1 through 8, lenalidomide will be self-administered at a dose of 25 mg orally each day
on Days 1 through 14 of each 21-day cycle for subjects with CrCl ≥60 mL/min. During Cycles 9
and beyond, lenalidomide 25 mg will be administered daily on Days 1-21 of each 28-day cycle.
Lenalidomide will be continued until disease progression or unacceptable toxicity whichever
occurs first. See Section 6.6.3.1, Renal Impairment for lenalidomide dose adjustments in subjects
with renal impairment.
On daratumumab administration  days, it is recommended that lenalidomide should be
administered either prior to or at the same time (preferred) as pre-injection medication. If a daily
lenalidomide dose is missed, it may be taken if <12 hours have elapsed since the time that it should
have been taken. Otherwise, the missed lenalidomide dose should be skipped.
Lenalidomide should be taken as a single dose at the same time daily. Lenalidomide can be taken
with or without food. Breaking or dividing the lenalidomide capsule is strongly discouraged.
6.5. 
Dexamethasone (Arms A and B)
Dexamethasone (or equivalent in accordance with local standards; see Appendix 13 (Section 10.13)
for conversion table) will be self-administered orally, 20 mg on Days 1, 2, 4, 5, 8, 9, 11, 12 of each
21-day cycle for Cycles 1-8. For subjects older than 75 years or underweight (BMI <18.5), the
dexamethasone dose may be administered at a dose of 20 mg on days 1, 4, 8, and 11. For subjects in
Arm B, the dexamethasone 20 mg oral or IV dose administered as a pre-injection medication on
daratumumab injection days, replaces the oral dexamethasone dose for that day.
In Cycle 9 and beyond dexamethasone, will be self-administered orally at a total dose of 40 mg on
Days 1, 8, 15, 22 of each 28-day cycle. For subjects older than 75 years or underweight (BMI <18.5),
the dexamethasone dose may be administered at a dose of 20 mg weekly. For subjects in Arm B, the
dexamethasone 40 mg oral or IV dose administered as a pre-injection medication on daratumumab
infusing days Day 1 of each cycle replaces the oral/IV dexamethasone dose for that day.
Dexamethasone will be administered until the subject experiences’ disease progression or
unacceptable toxicity during the treatment phase.

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If a weekly dexamethasone dose is missed, it may be taken if <4 days have elapsed since the
time that it should have been taken. If the next dose is scheduled to be taken within 3 days, the
missed dexamethasone dose should be skipped.
Dexamethasone tablets are to be taken with or immediately after a meal or snack, preferably in the
morning.
6.6. 
Dose Delays and Dose Modification
Any dose/dosage adjustment should be overseen by medically-qualified study site personnel
(principal or sub investigator unless an immediate safety risk appears to be present).
Study drug administration must be captured in the source documents and the electronic case report
form (eCRF).
6.6.1. 
Cycle Delay
On the first day of each new treatment cycle and before each daratumumab dose, the subject will
be evaluated by the treating physician for possible toxicities that may have occurred after the
previous dose(s). Toxicities are to be assessed according to NCI-CTCAE, Version 5. Dose
modifications or delays will be made based on the toxicity experienced during the previous cycle
of therapy or newly encountered on Day 1 of a cycle. For any neurological deficits that develop,
it is strongly recommended that these be evaluated by the same physician who performed the
neurological assessment at baseline. The parameters in Table 4 must be met on the first day of a
new cycle (ie, the following represent baseline inclusion criteria levels):
Table 4: 
Re-treatment criteria before the start of Cycles 1-8a
Laboratory parameter 
Requirements before each study agent administration
ANC  
1.0 x109/L
Platelet count 
70 x109/L
Hemoglobin  
7.5 g/dL (≥4.96 mmol/L)
a 
Refer to Table 10 or management of neurotoxicity.
Retreatment criteria before the start of Cycle 9 and beyond are provided in Table 5.
Table 5: 
Re-treatment criteria before the start of Cycle 9 and beyond
Laboratory parameter 
Requirements before each study agent administration
ANC 
1.0 x109/L
Platelet count 
50 x109/L
Hemoglobin  
7.5 g/dL (≥4.96 mmol/L)
If the above parameters are not met, the start of the next cycle will be held for a minimum of
1 week from the planned start of a new cycle and a maximum of 28 days until recovery to the
specified levels. Supportive care medications including transfusions should be administered at the
investigator discretion. During the cycle delay, daratumumab, bortezomib, dexamethasone and
lenalidomide, (all applicable) must be held.

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If there is a delay in the start of a new cycle (ie, none of the study medications are given during
this period) for more than 28 days due to insufficient recovery from toxicity, subjects will
discontinue taking the study drugs permanently unless continuation is approved by the medical
monitor. If the PRO assessment is completed and then the cycle is delayed, the PRO data does not
need to be collected again when the drugs are resumed. If subject permanently discontinues therapy
procedures should be performed as outlined in the Schedule of Activities (Section 1.3).
6.6.2. 
Daratumumab
6.6.2.1. 
Daratumumab Dose Modification
Individual dose modification of daratumumab is not permitted. Dose delay is recommended as the
primary method for managing daratumumab-related toxicities.
6.6.2.2. 
Daratumumab-Related Toxicity Management
Refer to Section 6.1.3 for details on management of IRRs. If any ofthe following criteria are met
and the toxicity is more than expected for the backbone therapy (lenalidomide, bortezomib,
dexamethasone), or underlying multiple myeloma, the daratumumabinjectionmustbeheldtoallow
forrecoveryfromtoxicity as noted below. If attribution is unclear, then daratumumab should be
held until recovery from toxicity as noted below.
The criteria for a dose delay are:
Grade 4 hematologic toxicity, except for Grade 4 lymphopenia
Grade 3 thrombocytopenia with bleeding
Febrile neutropenia ofany grade
Neutropenia with infection, ofany grade
Grade 3 or higher non-hematologic toxicities with the following exceptions:
Grade 3 nausea that responds to antiemetic treatment within 7 days
Grade 3 vomiting that responds to antiemetic treatment within 7 days
Grade 3 diarrhea that responds to antidiarrheal treatment within 7 days
Grade 3 fatigue or asthenia that was present at baseline and lasts for <7 days after the
last administration of daratumumab
Grade 3 or 4 electrolyte disturbances which can be managed with replacement therapy
Grade 3 asthenia that was present at baseline or that lasts for <7 days after the last
administration of daratumumab
Administration of daratumumab may be restarted upon recovery from toxicity to Grade 2 or
baseline, with the exception that Grade 2 laryngeal edema or Grade 2 bronchospasm must be fully
recovered.

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Other than on Day 1 of a cycle, if daratumumab  administration does not commence within the
pre-specified window (Table 6) of the scheduled administration date, then the dose will be
considered a missed dose. Administration may resume at the next planned dosing date.
Table 6: 
Daratumumab-RelatedToxicity Management
Cycles 
Frequency  
Missed Dose 
Dosing Resumption
1-2 
Weekly (every 1 week) 
>3 days 
Next planned weekly dosing date
3-8 
Every cycle (every 3 weeks) 
>7 days 
Next planned every 3-week dosing date
9+ 
Every cycle (every 4 weeks) 
>14 days 
Next planned every 4-week dosing date
A missed dose will not be made up. If a dose delay  occurs, then  pharmacokinetic blood
samples should be collected on the actual day of study drug administration, not on the original
scheduled administration day. After the planned final PFS analysis, pharmacokinetic and
immunogenicity sampling will no longer be required for subjects in Treatment Arm B.
If a dose is delayed, the dose schedule within cycle should be maintained. If an AE deemed to be
related to daratumumab requires a dose hold of more than 28 days, consult with the Sponsor to
review safety, and efficacy, and to discuss continuation on study. If not approved, the subject
should be discontinued from daratumumab and proceed to End-of-Treatment Visit. If
daratumumab is held or discontinued, treatment with bortezomib, lenalidomide, and
dexamethasone may continue.
6.6.3. 
Lenalidomide
Dose adjustments of lenalidomide will follow the approved labeling as noted in Table 7.
Table 7: 
Dose Modification for Lenalidomide
Starting 
Dose 
First Dose 
Reduction  
Second Dose
Reduction
Third Dose 
Reduction  
Fourth Dose 
Reduction
Fifth Dose reduction
Lenalidomide 
25 mg 
Lenalidomide
20 mg 
Lenalidomide
15 mg
Lenalidomide 
10 mg 
Lenalidomide 
5 mg 
Discontinue
Lenalidomide
Dose adjustments should be based on the highest grade of toxicity that is ascribed to lenalidomide
as noted in Table 10. If lenalidomide is held or discontinued, treatment with daratumumab (Arm
B only), bortezomib, and dexamethasone may continue.
6.6.3.1. 
Renal Impairment
Adjustments to the dose of lenalidomide is recommended to provide appropriate drug exposure in
subjects with moderate or severe renal impairment, because lenalidomide is primarily excreted
unchanged by the kidney. Lenalidomide dose adjustment should be instituted for subjects with a
CrCl <60 mL/min. The recommended doses for subjects with multiple myeloma and renal
impairment are shown in Table 10. To be enrolled in the study, subjects must have CrCl
≥30 mL/min. If during treatment a subject’s renal status changes, the dose should be adjusted as
shown in Table 10. In the event of a dose adjustment, lenalidomide doses may be re-escalated at
the investigator’s discretion.

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6.6.4. 
Bortezomib
Dose adjustments should be based on the highest grade oftoxicity that is ascribed to bortezomib.
Bortezomib therapy should be withheld at the onset of any Grade 3 or Grade 4 non-hematological
or Grade 4 hematological toxicities excluding neuropathy  as discussed in Table 10.
Once the symptoms ofthe toxicityhave resolved, bortezomib therapy may be reinitiated at a 25%
reduced dose per approved labeling, as follows (Table 8):
Table 8: 
Dose Modification for Bortezomib
Starting Dose 
First Dose Reduction 
Second Dose Reduction 
Third Dose Reduction
Bortezomib 1.3 mg/m2 
Bortezomib 1.0 mg/m2 
Bortezomib 0.7 mg/m2 
Discontinue bortezomib
A dose of bortezomib  may  be delayed up  to 48 hours; however, subsequent doses must be
adjusted as all bortezomib doses should be approximately 3 days apart. Doses that are delayed
>48 hours or need to be withheld are skipped and will not be made up later in the cycle. Dose
adjustments for toxicity should be followed as outlined in Table 10. If bortezomib is held or
discontinued, treatment with daratumumab (Arm B only), lenalidomide, and dexamethasone may
continue.
6.6.5. 
Dexamethasone
Dexamethasone may be reduced, if necessary, according to Table 9. For other Grade 3 or 4
non-hematologic and non-renal toxicities judged by the investigator to be related to
dexamethasone alone, treatment with dexamethasone should be interrupted and restarted at the
next lower dose level once the toxicity has resolved to Grade 2 or less. Treatment with
daratumumab (Arm B only), bortezomib, and lenalidomide may continue. For complete details on
dexamethasone, refer to the most current local product prescribing information.
If weekly dexamethasone dosing has been reduced below 10 mg due to AEs during study, a
minimum of dexamethasone 10 mg IV or PO should continue to be administered prior to
daratumumab injections.
Dexamethasone will be reduced or discontinued according to the guidelines presented in Table 9.
Table 9: 
Dose Reductions for Dexamethasone
First Dose Reduction 
Second Dose Reduction 
Third Dose Reduction
Reduce dexamethasone by 50% from 
starting dose 
Skip dexamethasone on days when 
daratumumab is not given in Arm B,
or corresponding days for Arm A.
Discontinue dexamethasone

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6.6.6. 
Dose Modification Guidelines
Dose modification guidelines for bortezomib, lenalidomide, and dexamethasone are provided in
Table 10.
Note that the dose modifications in Table 10 are suggested, but physician discretion and clinical
judgment should prevail.

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Table 10: 
Dose modification Guidelines for Bortezomib, Lenalidomide, and Dexamethasone
Body System
NCI-CTC Adverse Event and or
Symptom and Category
Bortezomib 
Lenalidomide 
Dexamethasone
e
The neurotoxicity-directed questionnaire is a useful tool for determining the presence and intensity of neuropathic pain and/or peripheral neuropathy from the subject’s perspective.
Neuropathic symptoms are more prominent than abnormalities on the clinical examination. After the subject completes the neurotoxicity-directed questionnaire, the questionnaire
should be reviewed to assist with the evaluation of the onset and intensity of peripheral neuropathy and other neurotoxicities that may require intervention or dose modification.
f
CrCl = creatinine clearance. Estimated by creatinine clearance as calculated by the Cockcroft-Gaultformula and adjusted for body weight in subjects with a body mass index
>30 kg/m2. The eGFR (MDRD) or CKD-epi formulas can also be utilized to assess renal function.

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6.7. 
Study Drug Compliance
Study drug (daratumumab) and the components of the backbone regimens (VRd) will be administered
or prescribed by qualified site staff, and the details of study drug and the components of VRd
administration will be recorded in the eCRF. Study drug accountability and additional study drug
additional details are provided in the sIPPM or equivalent document.
6.8. 
Concomitant Therapy
Throughout the study, investigators may prescribe any concomitant medications or treatments
deemed necessary to provide adequate supportive care except for those listed in Section 6.8.3. The
sponsor must be notified in advance (or as soon as possible thereafter) of any instances in which
prohibited therapies are administered.
For subjects who may need stem cell transplant at a later time, stem cell harvest following
mobilization with G-CSF or plerixafor or cyclophosphamide or any combination of the 3 is
permitted after Cycle 4 while on study treatment. Autologous stem cell transplantation cannot be
initiated as part of initial therapy.
Routine systemic use of concomitant medications will be collected in the eCRF and recorded in
the source documents beginning with signing of the ICF to 30 days after the last dose of the last
study treatment or until the start of subsequent anticancer treatment, if earlier. Concomitant
medications to manage AEs and SAEs will be recorded as per Appendix 4 (Section 10.4).
6.8.1. 
Recommended Therapies
6.8.1.1. 
Prevention of Deep Vein Thrombosis and Pulmonary Embolism
Lenalidomide has been associated with an increased risk of deep vein thrombosis and pulmonary
embolism. Therefore, prophylaxis of venous thromboembolism for all subjects is recommended
according to IMWG guidelines (Appendix 19 [Section 10.19]).38 Both individual and
myeloma-related risks of venous thromboembolism should be considered in determining the type
of thromboprophylaxis.
In summary:
Individual and Myeloma-related Risk factors:
If no risk factor, or any one risk factor is present, then aspirin 81-325 mg once daily is
recommended or dose per institutional standards.
If 2 or more risk factors are present, low molecular weight heparin (equivalent of
enoxaparin 40 mg once daily) or full dose warfarin, a target international normalized ratio
of 2-3, is recommended until the risk factors are resolved.

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6.8.1.2. 
Bisphosphonate Therapy and Denosumab
Bisphosphonate therapy is strongly recommended for all subjects with evidence of lytic
destruction of bone or with osteopenia. Bisphosphonate therapy should be continued per treatment
guidelines.29,32 Commercially available IV bisphosphonates (pamidronate and zoledronic acid) are
preferred when available, and should be used according to the manufacturer’s prescribing
information, for subjects with osteolytic or osteopenic myelomatous bone disease. Oral
bisphosphonates may be used as alternatives if IV bisphosphonates are not available at the study
site. It is preferred that investigators should use the same route of bisphosphonate therapy for all
subjects at their sites.
Subjects who are currently using bisphosphonate therapy when they enter the study should
continue the same treatment. Subjects with an indication for bisphosphonates who are not using it
at the time of randomization should start a bisphosphonate as soon as possible during Cycle 1 or 2
of treatment. Investigators should not start a bisphosphonate later during the study, unless it has
been agreed with the sponsor that there is no sign of disease progression.
Denosumab is permitted as an alternative to bisphosphonate therapy and should be started as soon
as possible during Cycle 1 or 2 of treatment. Investigators should not start denosumab later during
the study, unless it has been agreed with the sponsor that there is no sign of disease progression.
6.8.1.3. 
Therapy for Tumor Lysis Syndrome
Subjects should be monitored for symptoms of tumor lysis syndrome. Management of tumor lysis
syndrome, including increasing hydration and treating hyperkalemia, hyperuricemia, and
hypocalcemia, is highly recommended. It is also recommended that high-risk subjects, ie, those
with a high tumor burden, be treated prophylactically in accordance with local standards
(eg, increased hydration; allopurinol 300 mg daily and medication to increase urate excretion).
Subjects are to be provided prophylactic therapy to manage injection reactions during the
Treatment Phase, as described in Section 6.1.3.1.
6.8.1.4. 
Prophylaxis for Bacterial Pneumonia and Pneumocystis Carinii
Pneumonia
Antibacterial prophylaxis for bacterial pneumonia should be considered, as per institutional
guidelines, especially in patients with a history of respiratory disorders.
Pneumocystis carinii pneumonia prophylaxis should be considered, as per institutional guidelines.
6.8.1.5. 
Prophylaxis for Herpes Zoster Reactivation
Prophylaxis for herpes zoster reactivation is recommended during the Treatment Phase and
continue for 3 months following treatment with daratumumab. Initiate antiviral prophylaxis to
prevent herpes zoster reactivation within 1 week after starting study treatment and continue for
3 months following study treatment. Acceptable antiviral therapy includes acyclovir (eg, 400 mg
given orally 3 times a day, or 800 mg given orally 2 times a day or per institutional standards),
famcyclovir (eg, 125 mg given, twice a day or per institutional standards), or valacyclovir
(eg, 500 mg given orally, twice a day or per institutional standards).

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6.8.1.6. 
Prevention of Steroid Induced Gastritis
Dexamethasone and other corticosteroids may induce gastritis. Medications to prevent gastritis are
permitted per institutional guidelines. For eg, proton pump inhibitors (omeprazole or equivalent)
or sucralfate, or H2 blockers (ranitidine or equivalent) may be used.
6.8.1.7. 
Management of Hepatitis B Virus Reactivation
Primary antiviral prophylaxis is permitted as per local standard of care. Per protocol, HBV DNA
testing by PCR is mandatory for subjects at risk for HBV reactivation see Section 8.3.8.
For subjects who are diagnosed with HBV reactivation while on treatment, study treatment should
be interrupted until the infection is adequately controlled. If the benefits outweigh the risks, study
treatment may be resumed with concomitant antiviral prophylaxis as per local standard of care.
Consult a liver disease specialist as clinically indicated.
6.8.2. 
Permitted Therapies
Subjects are to receive full supportive care during the study. The following medications and
supportive therapies are examples of support therapies that may be used during the study:
Colony stimulating factors, erythropoietin, and transfusion of platelets and red cells
Loperamide is recommended for the treatment of diarrhea, starting at the time of the first
watery stool. The loperamide dose and regimen is according to institutional guidelines.
Prophylactic loperamide is not recommended
Prevention of constipation (e.g., adequate hydration, high-fiber diet, and stool softeners, if
needed)
Adequate hydration is recommended for prevention of myeloma-related kidney disease
Prophylactic antiemetics, except for corticosteroids
An emergency short course of corticosteroid (equivalent of dexamethasone 40 mg/day for a
maximum 4 days) is permitted before treatment
G-CSF/plerixafor for mobilization of stem cells
Single dose of cyclophosphamide for mobilization of stem cells
Vaccination is recommended per local guidelines (including annual influenza and inactivated
SARS CoV-2 vaccines); however, some types of vaccines (eg, live, attenuated or with
suspected replication capabilities) are not permitted. mRNA-based vaccines are permitted.
Note that antibody responses to vaccines may be suboptimal during study treatment.1
Other symptoms may be managed according to institutional guidelines provided prohibited
therapies are not administered (see Section 6.8.3).
6.8.3. 
Prohibited Therapies
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which prohibited therapies are administered. Use of the treatments listed below is prohibited
during the study:

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Concomitant administration of strong CYP3A4 inducers is prohibited with the use of
bortezomib. Administration of strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir) should
be avoided and is not recommended in subjects receiving bortezomib. If a strong CYP3A4
inhibitor must be given in combination with bortezomib, monitor subjects for signs of
bortezomib toxicity and consider a bortezomib dose reduction. For an ongoing list of CYP3A
inhibitors and inducers, see Flockhart et al.17
Other agents that target CD38.
Approved or investigational treatments for multiple myeloma (including but not limited to
conventional chemotherapies, immunomodulatory drugs, or PIs.
Concomitant administration of investigational agents is prohibited, including administration
of commercially available agents with activity against or under investigation for multiple
myeloma.
Systemic corticosteroids (>10 mg dexamethasone per day or equivalent, or a total maximum
dose of 140 mg dexamethasone or equivalent in 14 days) other than those given for IRRs as
described in Section 6.2.2.
Non-steroidal anti-inflammatory agents should be avoided as they may exacerbate
myeloma-related kidney disease.
In the absence of disease progression, should a subject require emergency orthopedic surgery or
radiotherapy, upon recovery the subject may continue treatment after consultation with, and
approval by, the sponsor’s medical monitor. Such emergency radiotherapy may consist of
localized radiotherapy for pain control or for stabilization of an extensive bone lesion at high-risk
of pathologic fracture or damage to surrounding tissues in a subject in whom delay of systemic
therapy is not appropriate. Such radiotherapy is to occur within the first 2 cycles of treatment and
the absence of evidence of disease progression is to be reviewed and approved by the sponsor.
6.8.4. 
Subsequent Therapies
It is not permissible to start other anti-myeloma therapy until disease progression is confirmed by
IMWG criteria. Subjects who discontinue study treatment for reasons other than disease
progression should not start subsequent treatment until documented disease progression; following
study treatment discontinuation, these subjects should be monitored for disease progression
according to the Schedule of Activities (Section 1.3).
After confirmation of disease progression, subsequent therapy is left to the investigator’s
discretion. Subsequent therapy for multiple myeloma (including start and end date and best
response) should be documented in the appropriate section of the CRF.
6.9. 
Long-term Follow-up
The Follow-up Phase will begin once a subject permanently discontinues treatment with study
medications. See Section 6.8.4 above regarding subsequent therapy for multiple myeloma.
Telephone contact will be made to determine survival as per the schedule of events table until the
study end unless the subject has died, is lost to follow-up, or has withdrawn consent. If the
information on safety or survival is obtained via telephone contact, written documentation of the

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communication must be available for review in the source documents. If the subject has died, the
date and cause of death will be collected and documented on the CRF. Investigators may contact
the subject to obtain long-term follow-up information regarding the subject's safety or survival
status as noted in the ICF (refer to Informed Consent in Appendix 3 [Section 10.3]), Regulatory,
Ethical, and Study Oversight Considerations).
7. 
DISCONTINUATION OF STUDY DRUG AND SUBJECT
DISCONTINUATION/WITHDRAWAL
7.1. 
Completion
A subject will be considered to have completed the study if he or she has finished all
protocol specified procedures before the end of the study, has not been lost to follow-up, and has
not withdrawn consent for study participation before the end of the study.
7.2. 
Discontinuation of Study Treatment
Subjects who need to discontinue treatment with any component of study treatment (bortezomib,
lenalidomide, dexamethasone, or daratumumab) may continue to receive treatment with the other
components of study treatment, as assigned.
A subject will not be automatically withdrawn from the study if he or she must discontinue study
treatment before the end of the treatment regimen; instead, the subject will enter the Follow-up
Phase. The End-of-Treatment Visits and Follow-up visit assessments should continue as specified
in the Schedule of Activities (Section 1.3).
A subject's study treatment must be discontinued if:
The investigator believes that for safety reasons or tolerability reasons (eg, AE, IRR as
described in Section 6.2) it is in the best interest of the subject to discontinue study drug.
If the subject’s dose is held for more than 28 days, or if 3 consecutive planned doses of
daratumumab are missed for reasons other than toxicity, consult with the Sponsor to
review safety, and efficacy, and to discuss continuation on study. If not approved, the
subject should be discontinued from study treatment and proceed to End of Treatment
visit.
The subject becomes pregnant, unless the subject (or the subject's legally designated
representative), investigator, and sponsor agree the benefits outweigh the risks to the fetus and
continuation of study treatment is in the best interests of the subject, except for lenalidomide
(which must be permanently discontinued if a subject becomes pregnant). Refer to Appendix 5
(Section 10.5 Contraceptive Guidance and Collection of Pregnancy Information.
Discontinuation of all study treatment is also acceptable if mandated by local regulations.
The subject (or the subject’s legally designated representative) withdraws consent for
administration of study treatment.
The subject received concurrent (non-protocol) treatment for multiple myeloma prior to
disease progression.
The subject experiences unacceptable toxicity, including IRR described in Section 6.2.

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The subject experiences disease progression (as outlined below).
The subject experiences a second primary malignancy that cannot be treated by surgery alone.
This scenario should be discussed with the Sponsor. However, a subject who develops a
malignancy that can be cured surgically may continue to receive the assigned study treatment
and should continue to be followed for subsequent progression of multiple myeloma.
The primary reason for discontinuation of study treatment is to be recorded in the eCRF.
Study treatment will continue until confirmation of disease progression. Before subjects are
discontinued from study treatment because of suspected disease progression:
1. The investigator (or designee) will provide documentation of disease progression (for
example, by completing a disease progression form or by contacting the IWRS) as soon as
possible and within 48 hours of confirmation of disease progression.
2. The sponsor's medical monitor will review the provided documentation and confirm disease
progression has occurred per IMWG criteria (see Section 8.2.1, Response Categories) and that
study treatment should be discontinued.
3. After confirmation of disease progression by the sponsor, the subject will discontinue study
treatment and enter the Follow-up Phase.
7.3. 
Subject Discontinuation/Withdrawal from the Study
A subject will not be automatically withdrawn from the study if they discontinue study drug before
the end of the treatment regimen.
A subject will be withdrawn from the study for any of the following reasons:
Lost to follow-up
Withdrawal of consent for study participation
Death
The study investigator or sponsor, for any reason, stops the study or stops the subject’s
participation in the study
When a subject withdraws before completing the study, the reason for withdrawal is to be
documented in the CRF and in the source document. Study drug assigned to the withdrawn subject
may not be assigned to another subject. Additional subjects will not be entered to ensure the
protocol-specified number of subjects complete the study. If a subject discontinues study treatment
and withdraws from the study before the end of the Treatment Phase, End-of-Treatment
assessments should be obtained. If the reason for withdrawal from the study is withdrawal of
consent, then no additional assessments are allowed.
7.3.1. 
Withdrawal from the Use of Study Samples
The subject may withdraw consent for use of study samples (refer to Appendix 3 [Section 10.3]).
In such a case, samples will be destroyed after they are no longer needed for the clinical study.
Details of sample retention are presented in the ICF.

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7.4. 
Lost to Follow-up
A subject will be considered lost to follow-up if the subject repeatedly fails to return for scheduled
visits and is unable to be contacted by the study site. A subject cannot be deemed lost to follow-up
until all reasonable efforts made by the study site personnel to contact the subject are deemed
futile. The following actions must be taken if a subject fails to return to the study site for a required
study visit:
The study site personnel must attempt to contact the subject to reschedule the missed visit
as soon as possible, to counsel the subject on the importance of maintaining the assigned
visit schedule, to ascertain whether the subject wishes to or should continue in the study.
Before a subject is deemed lost to follow-up, the investigator or designee must make every
reasonable effort to regain contact with the subject (where possible, 3 telephone calls,
emails, fax, and, if necessary, a certified letter to the subject’s last known mailing address,
or local equivalent methods). Locator agencies may also be used as local regulations
permit. These contact attempts should be documented in the subject’s medical records.
Should the subject continue to be unreachable, they will be considered to have withdrawn
from the study.
8. 
STUDY ASSESSMENTS AND PROCEDURES
8.1. 
Study Procedures
8.1.1. 
Overview
The Schedule of Activities summarize the frequency and timing of assessments applicable to this
study. Study assessments will be performed only after written informed consent is obtained. Every
effort should be made to keep subjects on the study schedule as planned from Cycle 1 Day 1. At
each visit, study assessments should be completed before the administration of any treatment. Any
missed visits, tests not performed, or examinations that are not conducted must be reported as such
in the eCRF.
During the treatment phase and prior to PD, the PRO measures will be completed using an
electronic tablet (ePRO), unless the subject is unable to complete the visit in-person. Site-assisted,
telephone-based collection of the PRO responses can be done if the subject is unable to come to
the site due to the coronavirus pandemic, and paper PRO assessments can be completed as part of
the home health care visits. All visit-specific PRO assessments should be completed before any
tests, procedures, or other consultations for that visit to prevent influencing subject perceptions. If
the subject is unable to complete the PRO assessments, the reason for not completing the
questionnaires will be documented (ie, too ill, subject refused, etc). Refer to Section 8.10 for
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Urine and blood collections should be kept as close to the specified time as possible. Other
measurements may be done earlier than specified, if needed. Additional pregnancy tests may be
performed, as determined necessary by the investigator or required by local regulation, to establish
the absence of pregnancy at any time during the subject's participation in the study.
The total blood volume for the study is estimated at approximately 50 mL during screening,
approximately 360 mL in the Treatment Phase (Cycles 1-8). In Cycle 9 and beyond, the blood
volume is estimated to be approximately 600 mL during the first two and a half years, then
approximately 180 mL per year until disease progression, and approximately 10 mL per visit in
the pre-PD Follow-up Phase. This includes laboratory assessments associated with safety, efficacy,
and pharmacokinetic evaluations, as well as scientific study samples. At the End-of-Treatment
Visit, approximately 10 mL of blood will be collected and approximately 10 mL will be collected
for pharmacokinetic testing in the Post-treatment Phase. After the planned final PFS analysis,
pharmacokinetic and immunogenicity samples will no longer be collected from subjects in
Treatment Arm B. Unscheduled samples may be taken for safety reasons (eg, IRR) or repeat
samples may be taken due to technical issues with the samples. After the planned final PFS
analysis, pharmacokinetic and immunogenicity samples will no longer be collected from subjects
in Treatment Arm B for safety reasons.
8.1.2. 
Screening Phase
The signed ICF must be obtained before any study-specific procedures are performed. The
Screening Phase begins when the first screening assessment is conducted. During the Screening
Phase, eligibility criteria will be reviewed by the investigator or the delegate and a complete
clinical evaluation will be performed as specified in the Schedule of Activities (Section 1.3).
Screening procedures will be performed within 28 days before randomization; however, results of
tests such as hematology or chemistry to document CRAB criteria, skeletal survey or other
radiologic tests (eg, CT scans or MRI) to document baseline lytic lesions or size of known or
suspected extramedullary plasmacytomas, ECG, chest x-rays or full chest CT scans, spirometry,
or bone marrow aspirate/biopsy performed within 6 weeks (42 days) before randomization as
routine SOC for the subject’s disease can be used. A negative pregnancy test for women of
childbearing potential must be documented within 10 to 14 days and again within 24 hours before
the first dose ofany component of the treatment regimen. If approved by the sponsor, subjects who
are screen failures may be rescreened if their condition changes (see Section 5.4 for details).
8.1.3. 
Treatment Phase
Details of the procedures performed during the Treatment Phase are outlined in the Schedule of
Activities. The Treatment Phase begins on Cycle 1 Day 1 and continues until disease progression
or for the other reasons outlined in Section 7.3. Subjects will be monitored closely for AEs,
laboratory abnormalities, and clinical response. Clinical evaluations and laboratory studies may be
repeated more frequently, if clinically indicated. If disease progression is diagnosed, then the
subject will discontinue the study drugs, complete the End-of-Treatment Visit, and enter the
Follow-up Phase.

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8.1.4. 
End-of-Treatment Visit
Unless a subject withdraws consent for study participation, or is lost to follow-up, an
End-of-Treatment Visit should be performed within 30 days after the last dose of all components
of the treatment regimen have been discontinued. Every effort should be made to conduct the
End-of-Treatment Visit before the subject starts subsequent therapy. Posttreatment PK and
immunogenicity samples from subjects in Arm B still should be collected, even if a subsequent
therapy has been initiated. After the planned final PFS analysis, pharmacokinetic and
immunogenicity samples will no longer be collected from subjects in Treatment Arm B. If a subject
is unable to return to the site for the End-of-Treatment Visit, then the subject should be contacted
to collect AEs and concomitant therapies that occur within 30 days after the last dose of any
component of the treatment regimen. Additional information on reporting of AEs can be found in
Appendix 4 (Section 10.4).
8.1.5. 
Follow-up Phase
The Follow-up Phase begins when a subject permanently discontinues treatment with study
medications. For all subjects who complete or discontinue study drug without disease progression,
disease evaluations should continue to be performed as specified in the Schedule of Activities until
documented disease progression. Thereafter subsequent anticancer treatment and response to
treatment including date of subsequent progression (PFS2) will be recorded and survival status
will be obtained. In accordance with the 2016 IMWG consensus recommendations for the purposes
of the study a line of subsequent therapy is defined as one or more cycles of a planned treatment
program. 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 a disease progression, relapse, or
toxicity.40
If the information is obtained via telephone contact, written documentation of the communication
must be available for review in the source documents. If the subject has died, then the date and
cause of death will be collected and documented in the eCRF.
8.1.6. 
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the CRF or laboratory
requisition form. Refer to the Schedule of Activities for the timing and frequency of all sample
collections. Instructions for the collection, handling, storage, and shipment of samples are found
in the Laboratory Manual that will be provided. Collection, handling, storage, and shipment of
samples must be under the specified, and where applicable, controlled temperature conditions as
indicated in the Laboratory Manual.
8.1.7. 
Study-specific Materials
The investigator will be provided with the following supplies:
Study protocol
IWRS Manual
Investigational Product Manual

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Investigator Brochure for daratumumab
Site Investigational Product Procedures Manual
Laboratory manual and laboratory kits
PRO questionnaires and completion guidelines
Sample ICF
Trial Center File, and corresponding site-specific documentation
Subject study tools (including emergency ID card etc, as required)
Investigator study tools and quick reference cards, as required.
8.2. 
Efficacy Assessments
Assessment of tumor response and disease progression will be conducted in accordance with the
IMWG response criteria. Efficacy evaluations will include measurements of tumor burden/residual
disease, myeloma proteins, bone marrow examinations, skeletal surveys, extramedullary
plasmacytomas, and serum calcium corrected for albumin.
8.2.1. 
Response Categories
Disease evaluations must be performed as outlined in the Schedule of Activities (Section 1.3) on
the scheduled assessment day (±7 days). Disease evaluations scheduled for treatment days should
be collected before study drug is administered. Disease evaluations will be performed by a central
laboratory until the final PFS analysis (unless otherwise specified). In exceptional circumstances
up to the final PFS analysis, the local laboratory results of blood and urine M-protein
measurements may be used to determine disease response and progression. After the final PFS
analysis, disease evaluations will no longer be performed by the central laboratory, and local
laboratory results of blood and urine M-protein measurements should be used by investigators to
determine disease response and progression.
This study will use the IMWG consensus recommendations for multiple myeloma treatment
response criteria40 presented in Table 11. For quantitative immunoglobulin at baseline, M-protein,
and immunofixation measurements in serum and 24-hour urine, the investigator will use results
provided by the central laboratory until the final PFS analysis, after which time the investigator
will use local results. The criteria for loss of CR without disease progression is presented in
Table 12. During the time period when results are provided by the central laboratory, subjects with
suspected daratumumab interference on serum M-protein quantitation by electrophoresis (SPEP)
and immunofixation, a Hydrashift interference test will be performed (Section 8.2.2; Appendix 20
[Section 10.20). Subjects with confirmed daratumumab interference who meet all other clinical
criteria for CR or sCR will be considered CR/sCR.

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Table 11: 
IMWG Consensus Recommendations for Multiple Myeloma Treatment Response Criteria
Response 
Response Criteria
Stringent complete 
Response (sCR) 
CR as defined below, plus
Normal FLC ratio, and
Absence of clonal PCs by immunohistochemistry, immunofluorescencea or 2- to 4-color flow
cytometry
Complete 
response (CR)* 
Negative immunofixation on the serum and urine, and
Disappearance of any soft tissue plasmacytomas, and
<5% PCs in bone marrow
Very good partial 
Response 
(VGPR)* 
Serum and urine M-component detectable by immunofixation but not on
electrophoresis, or
≥90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours
Partial response 
(PR) 
≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to
<200 mg/24 hours
If the serum and urine M-protein are not measurable, a decrease of ≥50% in the difference between
involved and uninvolved FLC levels is required in place of the M-protein criteria
If serum and urine M-protein are not measurable, and serum free light assay is also not measurable,
≥50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone
marrow plasma cell percentage was ≥30%
In addition to the above criteria, if present at baseline, a ≥50% reduction in the size of soft tissue
plasmacytomas is also required.
Stable disease 
(SD)
Not meeting criteria for CR, VGPR, PR, or PD
Progressive 
disease (PD)† 
Increase of 25% from lowest response value in any one of the following:
Serum M-component (absolute increase must be ≥0.5 g/dL)
Urine M-component (absolute increase must be ≥200 mg/24 hours)
Only in subjects without measurable serum and urine M-protein levels: the difference between
involved and uninvolved FLC levels (absolute increase must be >10 mg/dL)
Only in subjects without measurable serum and urine M-protein levels and without measurable
disease by FLC levels, bone marrow PC percentage (absolute increase must be ≥10%)
Bone marrow plasma cell percentage: the absolute increase 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/dL) that can be attributed
solely to the PC proliferative disorder
Abbreviations: CR=complete response; FLC=free light chain; PC=plasma cell; PR=partial response; VGPR=Very good
partial response; SD=stable disease.
All response categories (CR, sCR, VGPR, PR, and PD) require 2 consecutive assessments made at any time before the
institution of any new therapy; CR, sCR, VGPR, PR, and SD categories also require no known evidence of progressive or
new bone lesions if radiographic studies were performed. VGPR and CR categories require serum and urine studies
regardless of whether disease at baseline was measurable on serum, urine, both, or neither.
Radiographic studies are not required to satisfy these response requirements. Bone marrow assessments need not be
confirmed. For PD, serum M-component increases of more than or equal to 1 g/dL are sufficient to define relapse if
starting M-component is ≥5 g/dL.
* Clarifications to IMWG criteria for coding CR and VGPR in subjects in whom the only measurable disease is by serum
FLC levels: CR in such subjects indicates a normal FLC ratio of 0.26 to 1.65 in addition to CR criteria listed above. VGPR
in such subjects requires a >90% decrease in the difference between involved and uninvolved FLC levels.
† Clarifications to IMWG criteria for coding PD: Bone marrow criteria for PD are to be used only in subjects without
measurable disease by M-protein and by FLC levels; “25% increase” refers to M-protein, FLC, and bone marrow results,
and does not refer to bone lesions, soft tissue plasmacytomas, or hypercalcemia and the “lowest response value” does not
need to be a confirmed value.
a 
Presence/absence of clonal cells is based upon the kappa/lambda ratio. An abnormal kappa/lambda ratio by
immunohistochemistry or immunofluorescence requires a minimum of 100 plasma cells for analysis. An abnormal ratio
reflecting presence of an abnormal clone is kappa/lambda of >4:1 or <1:2.
Reference: Rajkumar 201140

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Table 12: 
Criteria for Loss of Complete Response not Meeting Criteria for Disease Progression (per
Table 11)
Loss of CR 
One or more of the following criteria:
Reappearance of serum M-protein by immunofixation or electrophoresis
Reappearance of urine M-protein by immunofixation or electrophoresis
Development of≥5% plasma cells in the bone marrow
Abbreviation: CR=complete response.
For continuation of treatment, the IMWG response will be determined on an ongoing basis by the
investigator. For data analysis and reporting up to the final PFS analysis, however, the sponsor
will use a validated computer algorithm that has been shown to provide consistent review of the
data necessary to determine disease progression and response according to the IMWG criteria.
After the final PFS analysis, the disease progression and response according to IMWG criteria will
be determined by the investigator and the computer algorithm will not be used.
8.2.2. 
Myeloma Protein Measurements in Serum and Urine
Blood and 24-hour urine samples for M-protein measurements will be sent to and analyzed by a
central laboratory until the final PFS analysis. After the final PFS analysis, blood and 24-hour
urine samples for M-protein measurements should be sent to and analyzed by a local laboratory.
Serum M-protein quantitation by electrophoresis (SPEP)
Serum immunofixation (SIFE) at screening and thereafter when M-protein is non-quantifiable
up to confirmation of CR
24-hour urine M-protein quantitation by electrophoresis (UPEP)
Urine immunofixation (UIFE) at screening and thereafter when a M-protein is
non-quantifiable up to confirmation of CR
Free light chain assessment for subjects with light chain only myeloma AND for all subjects
to confirm sCR
Serum QIgs: All subjects will be evaluated for IgG, IgA, IgM, IgE, and IgD at Screening.
Blood and 24-hour urine samples will be collected as specified in the Schedule of Activities
(Section 1.3) until the development of confirmed disease progression. Disease progression based
on 1 of the laboratory tests alone must be confirmed by at least 1 repeat investigation. Disease
evaluations will continue until disease progression or unacceptable toxicity is confirmed. Serum
and urine immunofixation tests will be performed at screening and thereafter when serum or
24-hour urine M-protein electrophoresis [by SPEP or UPEP] is negative or non-quantifiable. For
subjects with light chain multiple myeloma, both serum and urine immunofixation tests will be
performed at every cycle.
As an IgG1 kappa immunoglobulin, daratumumab has been shown to interfere with serum protein
electrophoresis (SPE) and immunofixation (IFE).25 During the period of central laboratory
analysis, subjects with daratumumab interference on serum immunofixation (IFE), the SEBIA
Hydrashift 2/4 Daratumumab IFE Interference test (Appendix 20 [Section 10.20]) will be used to
distinguish a positive SPEP/IFE due to the presence of daratumumab versus the presence of the

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underlying (endogenous) monoclonal protein. This assay will be implemented as part of response
criteria by central laboratory assessment. For those subjects who meet all other clinical criteria for
CR/sCR, with confirmed daratumumab interference on SPE/IFE, will be considered CR/sCR.
Note: All attempts should be made to determine eligibility of the subject based on the central
laboratory results of screening blood and urine M-protein measurements. In exceptional
circumstances, the local laboratory results of blood and urine M-protein measurements may be
used to determine eligibility, but only if the results are clearly (eg, 25% or more) above the
thresholds for measurability. In such cases, central laboratory results are still required to be
obtained in order to establish baseline values and confirm the results from the local laboratory.
8.2.3. 
Albumin and Serum Calcium Corrected for Albumin
Blood samples for calculating serum calcium corrected for albumin will be collected and analyzed
at the central laboratoryup until the final PFS analysis, and at local laboratories after this timepoint,
as specified in the Schedule of Activities until the development of confirmed disease progression.
Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L) may
indicate disease progression or relapse if it is not attributable to any other cause (see disease
response criteria in Table 11). Calcium binds to albumin and only the unbound (free) calcium is
biologically active; therefore, the serum calcium level must be adjusted for abnormal albumin
levels (“corrected serum calcium”). The formula for adjustment is presented in Appendix 10
(Section 10.10).
Measurement of free ionized calcium is an acceptable alternative to corrected serum calcium for
determining hypercalcemia. Free ionized calcium levels greater than the ULN (local laboratory
reference ranges) are hypercalcemic for purposed of safety and efficacy reporting in this study.
8.2.3.1. 
β2-microglobulin and Albumin
Blood samples for β2 microglobulin and albumin are to be collected at Screening and will be
analyzed 
by 
the 
central 
laboratory 
and 
used 
for 
the 
assessment 
of ISS
staging at study entry.
8.2.4. 
Bone Marrow Examination
Bone marrow aspirate, or bone marrow biopsy, or both  will be performed at screening for clinical
staging (morphology, central fluorescence in situ hybridization (FISH) evaluation of high-risk
cytogenetic anomalies (del17p, t[4;14]) and t[14;16]), and immunohistochemistry [IHC] or
immunofluorescence or flow cytometry), to establish baseline multiple myeloma clonality, to
monitor for MRD, and to perform molecular subtyping. FISH evaluation of amp(1q21) may be
performed as an exploratory risk anomaly. Clinical staging will be performed locally; however, a
portion of the bone marrow aspirate/biopsy must be sent to the central lab for analysis of MRD
and molecular subtyping. Morphology and IHC or immunofluorescence or flow cytometry will be
performed locally. A fresh bone marrow aspirate at screening is required to be sent to the central
laboratory (archived samples will not be accepted) for MRD and cytogenetic evaluation. A core
bone marrow biopsy/aspirate will be performed to confirm sCR and CR. If a bone marrow core
biopsy cannot be obtained or is not available, morphologic review of the bone marrow aspirate

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smear may be reviewed by the local laboratory for confirmation of CR. Bone marrow aspirates are
acceptable for determination of loss of CR (IHC or immunofluorescence) and to monitor for MRD
(Table 13).
While archived samples will not be accepted for MRD or cytogenetic evaluation at screening,
archived samples may be requested to be sent to the central laboratory, if available, in cases in
which there is difficulty in establishing baseline clonality for MRD or if screening baseline
cytogenetics are not evaluable.
Table 13: 
Bone Marrow Testing
Local Testing 
Central Testing
Screening 
Disease characterization(morphology, 
and either immunohistochemistry, 
immunofluorescence, or flow 
cytometry). 
A fresh bone marrowaspirate will be collected at
Screening and sent to a central laboratory to use for
MRD index clone identification, while a second
portion of the bone marrow aspirate will be used for
cytogenetic analysis by conventional FISH.
During 
Treatment 
At time ofsuspected CR/sCR: 
Evaluate Plasma cell percentage in the 
bone marrow to confirm CR  
Evaluate clonality ofplasma cells (by
flow cytometry, IHC or IF) a in the
bone marrow to confirm sCR
(IfsCRcriteria are not met, repeat
local testing for sCRwith subsequent
bone marrow testing.)
A portion ofbone marrow aspirates collected at
time ofsuspected CR and for subjects who
achieve CR, have not progressed, and remain on
study, additional bone marrow aspirate will be
obtained for MRD at 12,18, 24, 30 and
36 months post Cycle 1 Day 1 (± 1 month) and
yearly thereafter (±3 months)b
Abbreviations: CR=complete response; FISH=fluorescence in situ hybridization; IHC=immunohistochemistry;
IF= immunofluorescence; MRD=minimal residual disease; sCR=stringent complete response
a 
Immunohistochemistryor immunofluorescence(both require kappa/lambda ratio from analysis of>100 cells) or 2-to 4-color
flow cytometryare acceptable methods to evaluate plasma cell clonality.
b 
Ifone ofthese time points occurs within 1 month ofsuspected CR/sCR, a repeat bone marrow will not be requested. These bone
marrow tests will only be required if subject’s response is near CR or better by blood and urine evaluations.
8.2.5. 
Minimal Residual Disease Assessment
Bone marrow samples will be collected when a bone marrow aspirate is performed at Screening
and at the subsequent timepoints outlined in Table 13 and Schedule of Activities (Section 1.3). If
a sample is unevaluable, every effort should be taken to repeat BM assessment if not within
2 months of another pre-specified collection.
8.2.6. 
Assessment of Lytic Disease
A complete skeletal survey (including skull, entire vertebral column, pelvis, chest, humeri, femora,
and any  other bones for which  the investigator suspects involvement by disease) is to be
performed and evaluated by the local radiologist. An alternative (eg low-dose CT) may be used
in accordance with local SOC. Note that the same methodology used at Screening should be used
throughout the study for comparison purposes. During the Treatment Phase and before disease
progression is confirmed, imaging should be performed whenever clinically indicated based on

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symptoms, to document response or progression. Magnetic resonance imaging may be included
as an additional assessment at the discretion ofthe investigator; however, focal lesions identified
by MRI alone cannot be counted as lytic disease unless they meet IMWG diagnostic criteria (SLiM
[S=≥Sixty-percent (≥60%) clonal BM plasma cells; Li=serum free Light chain ratio involved:
uninvolved ≥100; M=>1 focal lesion (≥5 mm each) detected by MRI studies] criteria) for MRI
bone lesions. If a radionuclide bone scan was used at Screening in addition to the complete skeletal
survey, then  both  methods must be used to document disease status. These tests must be
performed at the same time. However, a radionuclide bone scan  does not replace a complete
skeletal survey.
Some subjects present with  disease progression  manifested by symptoms of pain  due to bone
changes. In this case, disease progression may be documented, in these cases, by skeletal survey
or other imaging tests, depending on the symptoms that the subject experiences. Ifthe diagnosis
ofdisease progression is obvious by imaging investigations, then no repeat confirmatory imaging
is necessary. In instances when changes are subtler, repeat imaging should be performed in 1 to
3 weeks.
8.2.7. 
Assessment of Extramedullary Plasmacytomas
Sites ofknown extramedullary plasmacytomas must be documented during the Screening Phase.
Clinical examination  or MRI may  be used  to document extramedullary  sites of disease.
Computed tomography scan  evaluations are an  acceptable alternative if there is no
contraindication to the use ofIV contrast. Positron emission tomography scan or ultrasound tests
are not acceptable to document the size of extramedullary plasmacytomas.
Extramedullary plasmacytomas should be assessed for all subjects with  a history  of
plasmacytomas or if clinically indicated at Screening, by  clinical examination  or radiologic
imaging. Assessment of measurable sites of extramedullary disease will be performed and
evaluated locally every  4 weeks (by  physical examination) for subjects with  a history  of
plasmacytomas or as clinically indicated during treatment for other subjects until development of
confirmed CR  or confirmed disease progression. If assessment can  only be performed using
imaging, then evaluation ofextramedullary plasmacytomas should be done every 12 weeks. For
every subject, the methodology used forevaluation ofeach disease site should be consistent across
all visits. Irradiated or excised lesions will be considered not measurable and will be monitored
only for disease progression.
To qualify for PR, the sum  of products of the perpendicular diameters of the existing
extramedullary plasmacytomas must have decreased by at least 50%, and new plasmacytomas
must not have developed (see the disease response criteria in Table 11). To qualify for disease
progression, either the sum  of products of the perpendicular diameters of the existing
extramedullary  plasmacytomas must have increased by  at least 50%  or a new plasmacytoma
must have developed. In the cases where not all existing extramedullary  plasmacytomas are
reported, but the sum of products ofthe perpendicular diameters ofthe reported plasmacytomas
have increased by at least 50%, this will also qualify as disease progression.

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8.3. 
Safety Assessments
Safety evaluations will include AE monitoring, physical examinations, ECGs monitoring, clinical
laboratory parameters (hematology and chemistry), vital sign measurements, and ECOG
performance status. All toxicities will be graded according to the NCI-CTCAE Version 5.
Clinically relevant changes occurring during the study must be recorded on the AE section of the
CRF. Clinically significant abnormalities persisting at the end of the study/early withdrawal will
be followed by the investigator until resolution or until a clinically stable endpoint is reached.
Adverse events will be reported and followed by the investigator as specified in Section 8.4,
Adverse Events and Serious Adverse Events and Appendix 4 (Section 10.4), Adverse Events:
Definitions and Procedures for Recording, Evaluating, Follow-Up, and Reporting.
Based on the previous experience with daratumumab in humans, in vitro studies, and animal
toxicological findings, IRRs/allergic reactions, hemolysis, and thrombocytopenia will be closely
monitored. As a biologic agent, immunogenicity also will be monitored. Any of the safety
monitoring assessments may be performed more frequently, and AEs should be evaluated by the
investigator according to the standard practice, if clinically indicated.
The study will include the following evaluations of safety and tolerability according to the time
points provided in the Schedule of Activities (Section 1.3).
8.3.1. 
Home Health Care and Tele-Health Visits
In exceptional circumstances, home health care (with approval from the sponsor) and tele-health
visits may be implemented per the clinical judgement of the investigator, where feasible and
permissible by local policy and regulations.
Subjects for whom there is no safety concern may have home health care and tele-health
(conducted via phone or video conference) visits.
Study procedures such as subject reconsenting, PRO collection, Eastern Cooperative Oncology
Group assessment, AE and concomitant medication reporting, review of body systems, and
collection of information on the subject’s current health status (as outlined per the SoA in
Section 1.3) may be performed with home health care and tele-health visits. Protocol-specified
laboratory assessments for efficacy (central laboratory) and safety (central and local laboratories)
may be collected during home health care visits. All assessments should be followed with in-
person examination, as applicable.
Where local laboratories are used, it is important to ensure appropriate documentation of
laboratory reference ranges. Source documentation and if applicable the appropriate case report
forms should be completed and detail how each assessment was collected (eg, remote vs on-site,
central vs local laboratory, vital signs taken at home by delegated in-home nursing, etc.).
8.3.2. 
Adverse Events
Adverse events (with the exception of progression of multiple myeloma) will be reported by the
subject (or, when appropriate, by a caregiver, surrogate, or the subject's legally designated

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representative) from the time a signed and dated informed consent is obtained until 30 days
following the last dose of any component of the treatment regimen. Expected progression of
disease should not be considered an AE (or SAE).
8.3.3. 
Physical Examination
A complete physical examination (including neurological examination) should be performed
during the Screening Phase. Height will be measured at screening only; weight will be measured
regularly as specified in the Schedule of Activities. Thereafter, only a symptom and disease
directed physical examination is required. Abnormalities will be recorded in the appropriate
sections of the eCRF.
8.3.4. 
Vital Signs
Vitals signs (heart rate, temperature, blood pressure) will be assessed as specified in the Schedule
of Activities (Section 1.3). It is recommended that blood pressure (sitting) and heart rate
measurements be preceded by at least 5 minutes of rest in a quiet setting without distractions
(eg, television, cell phones).
The measurements of vital signs at Screening and Cycle 1 Day 1 will be recorded in the eCRF.
Adverse events associated with monitoring of vital signs while on treatment will be recorded as
AEs in the eCRF. All measurements of vital signs (except Screening and Cycle 1 Day1) will be
recorded in the source documents.
8.3.5. 
Electrocardiogram
12-lead ECGs will be performed as specified in the Schedule of Activities (Section 1.3). When
possible, ECGs should be taken immediately before chemistry and PK assessments. During the
collection of ECGs, subjects should be in a quiet setting without distractions (eg, television, cell
phones). Subjects should rest in a supine position for at least 5 minutes before ECG collection and
should refrain from talking or moving arms or legs. If blood sampling or vital sign measurement
is scheduled for the same time point as ECG recording, it is recommended that the procedures are
performed in the following order: ECG(s), vital signs, blood draw.
8.3.6. 
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry and hematology will be collected as noted in SoA. The
investigator must review the laboratory results, document this review, and record any clinically
relevant changes occurring during the study in the AE section of the eCRF. The laboratory reports
must be filed with the source documents. Any additional chemistry and hematologic laboratory
assessment supporting the start and end dates of an AE should be reported in the eCRF.
The following tests will be performed by the local laboratory unless otherwise noted.
Hematology Panel
-hemoglobin 
-absolute neutrophil count
-white blood cell count 
-absolute lymphocyte count
-platelet count

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Serum Chemistry Panel
During Cycles 1-8
-blood urea nitrogen or urea 
-alkaline phosphatase
-creatinine 
-lactic acid dehydrogenase (LDH)
-glucose 
-uric acid
-ALT  
-total protein
-AST  
-sodium
-creatinine clearance (calculated or measured) 
-potassium
-total bilirubin; direct bilirubin (not required except in case of
congenital bilirubinemia, such as Gilbert disease)
During Cycle 9 and beyond
-AST  
-creatinine clearance (calculated or measured)
-ALT  
-blood urea nitrogen or urea
- total bilirubin (direct bilirubin if total bilirubin
abnormal)
Serum or Urine Pregnancy Testing
For women of childbearing potential only. Lenalidomide is a thalidomide analog and is
contraindicated for use during pregnancy. Birth defects have been observed in preclinical studies
of lenalidomide similar to thalidomide in humans. Therefore, strict monitoring for pregnancy must
be conducted during Screening and throughout the Treatment Phase as per the Schedule of
Activities (Section 1.3). Pregnancy testing is only required for women of childbearing potential.
Any subject who becomes pregnant during the study must be discontinue study treatment
immediately and the subject should be referred to an obstetrician experienced in reproductive
toxicity for further evaluation and counseling (Section 8.4.4)
Calcium and Albumin Adjusted Calcium:
These parameters will be part of the efficacy evaluations as specified in Section 8.2.3, and will be
analyzed by the central laboratory until the final PFS analysis (local laboratory assessments may
be accepted prior to the final PFS analysis in exceptional circumstances if central laboratory is not
evaluable). After the final PFS analysis, local laboratory assessments should be used. Measurement
of calcium and albumin should follow the schedule for disease assessments. Measurement of free
ionized calcium is an acceptable alternative to corrected serum calcium for determining
hypercalcemia.
Daratumumab Interference with Indirect Antiglobulin Test Results:
Blood type, Rh, and Indirect Antiglobulin Test (IAT) should be done before the first dose of
daratumumab. Subject RBC phenotyping (standard or extended) is an alternative option to the IAT
test, if locally required. Either method must be completed prior to first daratumumab
administration.
Daratumumab interferes with the IAT, which is a routine pre-transfusion test performed to identify
a patient’s antibodies to minor antigens so that suitable donor blood can be given for transfusion.
Daratumumab does not interfere with ABO/RhD typing. CD38 is expressed at very low levels on
erythrocytes. Daratumumab binds to the CD38 on erythrocytes, which results in a positive IAT

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(Indirect Coombs Test). This positive result masks the detection of antibodies to minor antigens
and may prevent or delay blood banks from issuing donor blood for transfusion. This effect occurs
during daratumumab treatment and for up to 6 months after treatment ends. Subjects will receive
a patient identification wallet card for the study that includes the blood profile (ABO, Rh, and IAT)
determined before the first injection of daratumumab along with information on the IAT
interference for health care providers/blood banks. Subjects are to carry this card throughout the
treatment period and for at least 6 months after treatment ends. Blood banks can eliminate the
daratumumab IAT interference by treating reagent RBCs with dithiothreitol (DTT).6,7
Possible methods for blood banks to provide safe RBCs for transfusion to subjects receiving
daratumumab include:
a) Providing ABO/RhD compatible, phenotypically or genotypically matched units
b) Providing ABO/RhD compatible, K-negative units after ruling out or identifying
alloantibodies using dithiothreitol (DTT)-treated reagent RBCs
Un-crossmatched, ABO/RhD compatible RBC units should be administered if transfusion is
needed emergently as per local blood bank practice.
Despite daratumumab binding to CD38 on erythrocytes, no indication of clinically significant
hemolysis has been observed in daratumumab studies. For additional details, refer to the
Daratumumab IB.
8.3.7. 
Pulmonary Function Test
Subjects with known or suspected COPD must have a FEV1 test during screening. Refer to
Section 6.1.3.2 for details on subjects with higher risk of respiratory complications.
8.3.8. 
HBV Serology and DNA Testing
8.3.8.1. 
HBV Screening Serology Testing
All subjects will be tested locally for hepatitis B surface antigen (HBsAg), hepatitis B surface
antibody (Anti-HBs), and hepatitis B core antibody (Anti-HBc) at Screening. Additionally,
subjects ongoing in the Treatment Phase who are within 6 months of starting study treatment when
Protocol Amendment 2 is implemented will be required to have HBV serology performed locally
upon signing the updated ICF. If required by local regulations, if the hepatitis B serologic status
of a subject in Arm B (D-VRd) is unknown, HBsAg, Anti-HBs, and Anti-HBc testing is
recommended if the subject is still receiving daratumumab (or is within 6 months after the last
dose).
HBV serology is not required at Screening or for subjects ongoing in the Treatment Phase who are
within 6 months of starting study treatment if this was performed as part of standard of care within
3 months prior to first dose.

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8.3.8.2. 
HBV DNA Serial Testing
Subjects who are positive for Anti-HBc and/or Anti-HBs will undergo testing for hepatitis B DNA
by PCR. Subjects with serologic findings suggestive of HBV vaccination (Anti-HBs positivity as
the only serologic marker) and a known history of prior HBV vaccination do not need to be tested
for HBV DNA by PCR. During and following study treatment, subjects who have history of HBV
infection will be closely monitored for clinical and laboratory signs of reactivation of HBV as
specified in the Schedule of Activities (Table 1). Where required by local law, the result of HBV
testing may be reported to the local health authorities.
8.3.9. 
Eastern Cooperative Oncology Group Performance Status
Eastern Cooperative Oncology Group (ECOG) performance status will be used to evaluate the
effect of the disease status on the activities of daily living. When scheduled, ECOG Performance
Status assessments should be obtained prior to any other study procedures planned for the same
day whenever possible.
8.4. 
Adverse Events and Serious Adverse Events
Timely, accurate, and complete reporting and analysis of safety information from clinical studies
are crucial for the protection of subjects, investigators, and the sponsor, and are mandated by
regulatory agencies worldwide. The sponsor has established Standard Operating Procedures in
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety
information; all clinical studies conducted by the sponsor or its affiliates will be conducted in
accordance with those procedures.
For further details on AEs and SAEs (Definitions and Classifications; Attribution Definitions;
Severity Criteria; Special Reporting Situations; Procedures) as well as product quality complaints,
refer to Appendix 4 (Section 10.4), Adverse Events: Definitions and Procedures for Recording,
Evaluating, Follow-Up, and Reporting.
8.4.1. 
Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from the
time a signed and dated ICF is obtained until completion of the subject's last study-related
treatment, which may include contact for follow-up of safety. Serious adverse events, including
those spontaneously reported to the investigator within 30 days after the last dose of any
component of the treatment regimen, must be reported using the Serious Adverse Event Form. The
sponsor will evaluate any safety information that is spontaneously reported by an investigator
beyond the time frame specified in the protocol. The sponsor will evaluate treatment-related SAEs
during the Follow-up Phase of the study.
Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate sponsor contact person
by study site personnel immediately, but no later than 24 hours after their knowledge of the event.

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Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event
Form, which must be completed and signed by a physician from the study site and transmitted to
the sponsor immediately, but no later than 24 hours after their knowledge of the event. The initial
and follow-up reports of a SAE should be made by facsimile (fax).
8.4.2. 
Follow-up of Adverse Events and Serious Adverse Events
Adverse events, including pregnancy, will be followed by the investigator as specified in
Appendix 4 (Section 10.4), Adverse Events: Definitions and Procedures for Recording,
Evaluating, Follow-up, and Reporting.
8.4.3. 
Regulatory Reporting Requirements for Serious Adverse Events
The sponsor assumes responsibility for appropriate reporting of safety information to the
regulatory authorities/IECs/IRBs. The sponsor will also report to the investigator (and the head of
the investigational institute where required) all suspected unexpected serious adverse reactions
(SUSARs). For anticipated events reported as individual SAEs the sponsor will make a
determination of relatedness in addition to and independent of the investigator’s assessment. The
sponsor will periodically evaluate the accumulating data and, when there is sufficient evidence
and the sponsor has determined there is a reasonable possibility that the treatment caused a serious
anticipated event, they will submit a safety report in narrative format to the investigators (and the
head of the institute where required). The sponsor assumes responsibility for appropriate reporting
of anticipated events to the regulatory authorities according to requirements of the countries in
which the studies are conducted. The investigator (or sponsor where required) must report
SUSARs to the appropriate Independent Ethics Committee/Institutional Review Board (IEC/IRB)
that approved the protocol unless otherwise required and documented by the IEC/IRB.
8.4.4. 
Pregnancy
All initial reports of pregnancy in female subjects or partners of male subjects must be reported to
the sponsor by the study site personnel within 24 hours of their knowledge of the event using the
appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous
abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs and
must be reported using the Serious Adverse Event Form. Any subject who becomes pregnant
during the study must discontinue study treatment immediately and the subject should be referred
to an obstetrician experienced in reproductive toxicity for further evaluation and counseling.
Pregnancies in partners of male subjects included in the study will be reported as noted above,
because the effect of the study drug on sperm is unknown. Follow-up information regarding the
outcome of the pregnancy and any postnatal sequelae in the infant will be required.
8.4.5. 
Disease-Related Events and Disease-Related Outcomes Not
Qualifying as Adverse Events or Serious Adverse Events
All events that meet the definition of an SAE will be reported as SAEs, regardless of whether they
are protocol-specific assessments.
Expected progression of disease, which is part of the natural course of the disease under study,
should not be considered or reported as an adverse event (or serious adverse event).

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Death or hospitalization that is attributed by the investigator to progression of disease should not
be considered nor reported as an adverse event (or serious adverse event).
Of note, worsening of disease (and associated hospitalization or death) determined by the
investigator to be caused by the study treatment should be reported per the usual reporting
requirements (refer to Adverse Event Definitions and Classifications in Appendix 4: Adverse
Events: Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting).
Progression of disease and death due to disease progression should be documented on the
appropriate eCRF forms (eg, the Disease Progression form and the Death form).
Signs or symptoms of disease progression that are of clinical significance, such as spinal cord
compression, vena cava superior syndrome, major vessel rupture, efflux obstruction or organ
failure, should be documented on the appropriate eCRF forms (eg, the Symptomatic Progression
Form).
Known consequences of the underlying disease under investigation (eg, symptoms) and events
common in the study population independent of drug therapy are AEs. If they are considered
drug-related they will be recorded and reported (if appropriate) as per current legislation to Health
Authorities and Ethics Committees. If they are considered disease-related or not related to the
study drugs they will be exempt from expedited reporting.
8.5. 
Treatment of Overdose
No MTD has been reached for daratumumab. However, if the dose exceeds the maximum tested
dose of 2000 mg, then it will be considered as an overdose in this study.
In the event of an overdose, the investigator or treating physician should:
Contact the medical monitor immediately.
Closely monitor the subject for AE/SAE and laboratory abnormalities until daratumumab can
no longer be detected systemically (at least 3 months).
Document the quantity of the excess dose as well as the duration of the overdosing in the CRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in
consultation with the medical monitor based on the clinical evaluation of the subject.
8.6. 
Pharmacokinetics and Immunogenicity
Serum samples will be used to evaluate the PK and immunogenicity of daratumumab. Plasma
samples will be used to evaluate the immunogenicity of rHuPH20. Samples collected for PK and
immunogenicity analysis may additionally be used to evaluate safety or efficacy aspects that
address concerns arising during or after the study period. Genetic analyses will not be performed
on these serum samples. Subject confidentiality will be maintained. After the final PFS analysis,
pharmacokinetic and immunogenicity samples will no longer be collected from subjects in
Treatment Arm B.

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8.6.1. 
Evaluations
Samples will be collected from all subjects in Arm B to assess both the serum concentration
(pharmacokinetics) of daratumumab and generation of anti-daratumumab antibodies
(immunogenicity) according to the Schedule of Activities (Section 1.3). At specified time points,
venous blood samples (5 mL per sample) will be collected and the serum will be divided into
3 aliquots (1 aliquot for pharmacokinetic analysis, 1 aliquot for immunogenicity assessment [when
appropriate], and 1 aliquot as a back-up). Samples will also be collected from all subjects in Arm B
to evaluate the immunogenicity of rHuPH20 according to the Schedule of Activities (Section 1.3).
After the final PFS analysis, pharmacokinetic and immunogenicity samples will no longer be
collected from subjects in Treatment Arm B.
The exact dates and times of blood sampling must be recorded. Refer to the Laboratory Manual or
equivalent document for sample collection requirements. Collected samples must be stored under
the specified and controlled conditions for the temperatures indicated in the Laboratory Manual.
Samples collected for determining serum concentrations/immunogenicity of daratumumab or
immunogenicity of rHuPH20 in this study may be retained to address questions about drug
characteristics.
8.6.2. 
Analytical Procedures
Pharmacokinetics
Serum samples will be analyzed to determine concentrations of daratumumab or generation of
anti-daratumumab or anti-rHuPh20 antibodies using a validated, specific, and sensitive
immunoassay method by or under the supervision of the sponsor.
Immunogenicity
For the daratumumab immunogenicity assessments, serum samples will be screened for antibodies
binding to daratumumab and serum titer will also be determined from confirmed positive samples.
Other immunogenicity analyses (eg, assessment of neutralizing capabilities) may be performed to
further characterize the immune responses that are generated.
For the rHuPH20 immunogenicity assessments, plasma samples will be screened for antibodies
binding to rHuPH20 and will be assessed in confirmatory and titer assays as necessary.
Neutralizing antibody assessments may also be performed to further characterize immune
responses that are generated.
8.6.3. 
Pharmacokinetic Parameters and Evaluations
Pharmacokinetic samples to determine serum concentration of daratumumab will be obtained from
subjects in Arm B. The pharmacokinetic parameters are defined as:
Cmax  
Maximum observed concentration
Cmin  
Minimum observed concentration

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The pharmacokinetic evaluations include Cmin  and Cmax  which will be determined based on the
assigned collection timepoints. If there are sufficient data, population pharmacokinetic analysis of
serum concentration-time data of daratumumab may be performed and may include data from
other clinical studies. If performed, details will be provided in a population pharmacokinetic
analysis plan and results of the analysis will be presented in a separate report.
8.6.4. 
Immunogenicity Assessments
Serum from venous blood samples collected from all subjects in Arm B will be assessed for the
generation of anti-daratumumab antibodies (immunogenicity) according to the Schedule of
Activities. Daratumumab concentration will be evaluated at all immunogenicity time points to
ensure appropriate interpretation of immunogenicity data. When both daratumumab serum
concentration and immunogenicity analyses are specified, they will be performed on aliquots from
the same blood draw and no additional sampling is required. Plasma samples will also be collected
from all subjects receiving daratumumab (Arm B) and assessed for anti-rHuPH20 antibodies.
Procedures for sample collection, preparation, identification, storage, and shipment will be
provided in the Laboratory Manual or equivalent document.
When an IRR occurs associated with the second or later daratumumab administration, 2 blood
samples should be obtained, if possible, for determination of antibodies to daratumumab and
antibodies to rHuPH20. No unscheduled samples need to be collected for injection reactions
associated with the first administration of daratumumab. Daratumumab serum concentration will
also be determined from  the daratumumab injection reaction sample for interpreting
immunogenicity data. If the injection reaction results in treatment discontinuation, then subjects
should undergo all scheduled safety and efficacy evaluations. Procedures for sample collection,
preparation, identification, storage, and shipment will be provided in the Laboratory Manual or
equivalent document. Samples collected for the analysis of daratumumab immunogenicity/serum
concentration or rHuPH20 immunogenicity may be used to evaluate safety or efficacy questions
that arise during or after the study period or for the evaluation of relevant biomarkers by the
sponsor or sponsor’s designee.
Subjects who discontinue treatment or withdraw from the study before confirmation of PD should
have samples collected at the time of early discontinuation. Subjects who discontinue treatment
will also be asked to return for immunogenicity evaluation during the Follow-up Phase. After the
final PFS analysis, pharmacokinetic and immunogenicity samples will no longer be collected from
subjects in Treatment Arm B. These samples will be tested by the sponsor or sponsor's designee.
8.7. 
Pharmacokinetic/Pharmacodynamic Evaluations
If sufficient data are available, then other pharmacokinetic/pharmacodynamic modeling may be
performed, including exploring the relationship between serum concentrations of daratumumab
and endpoints of clinical efficacy and safety. If these analyses are performed, then the details and
results will be presented in a separate report.

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8.8. 
Biomarkers
As permitted by local rules and regulations, bone marrow aspirates in the D-VRd and VRd cohorts
will be collected at screening and following treatment as outlined in the Schedule of Activities
(Section 1.3) for MRD monitoring. Baseline fresh bone marrow aspirate samples will be subjected
to DNA sequencing to establish a multiple myeloma clone for MRD monitoring (calibration) and
for cytogenetic evaluation by the central laboratory. A fresh bone marrow aspirate at screening is
required (archived samples will not be accepted). Fresh bone marrow aspirates will be utilized for
assessment of MRD by NGS of immunoglobulin (Ig) heavy and light chains as specified. For this
study only the FDA-approved next generation sequencing (NGS) clonoSEQ v2.0 (Adaptive
Biotechnologies®) methodology will be employed for assessing MRD. A portion of the screening
bone marrow aspirate will be evaluated by central lab fluorescent in situ hybridization for high-risk
cytogenetic anomalies of t (4;14); t (14;16); and del17p. amp(1q21) will be evaluated as an
exploratory risk marker.
Whole blood samples will be collected from subjects as specified in the Schedule of Activities for
processing to plasma and peripheral blood mononuclear cells. These samples may be used to
evaluate the impact of VRd on daratumumab’s immunomodulatory mechanism of action where
specific subsets of immune cells such as cytotoxic T cells, regulatory T cells, and activated natural
killer cells may be evaluated by flow cytometry or cytometry/time-of-flight mass spectrometry
and T-cell receptor sequencing. Proteomic or genomic analysis may also be used to evaluate
baseline and changes in proteins or tumor associated DNA in circulation to evaluate potential
biomarkers of response and resistance.
Stopping Analysis
Biomarker analyses are dependent upon the availability of appropriate biomarker assays and
clinical response rates. Biomarker analysis may be deferred or not performed, if during or at the
end of the study, it becomes clear that the analysis will not have sufficient scientific value for
biomarker evaluation, or if there are not enough samples or responders to allow for adequate
biomarker evaluation. In the event the study is terminated early or shows poor clinical efficacy,
completion of biomarker assessments is based on justification and intended utility of the data.
Additional Collections
If it is determined at any time before study completion that additional material is needed from a
formalin-fixed, paraffin-embedded (FFPE) tumor sample for the successful completion of the
protocol-specified analyses, the sponsor may request that additional material be retrieved from
existing samples. Also, based on emerging scientific evidence, the sponsor may request additional
material from previously collected tumor samples during or after study completion for a
retrospective analysis. In this case, such analyses would be specific to research related to the study
drug(s) or diseases being investigated.

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8.9. 
Medical Resource Utilization
Medical resource utilization data, associated with medical encounters, will be collected in the
eCRF by the investigator and study site personnel for all subjects throughout the study.
Protocol-mandated procedures, tests, and encounters are excluded. Data collected will include:
Number and characteristic of diagnostic and therapeutic tests and procedures (inpatient and
outpatient)
Number and duration of hospitalization (total days length of stay [days], including duration
by each hospital unit (intensive care unit)
Number and duration of medical care encounters, including surgeries, and other selected
procedures (inpatient and outpatient)
Outpatient medical encounters and treatments (including physician, nurse practitioner,
emergency room visits, tests and procedures, and medications)
Refer to the eCRF completion guidelines.
8.10. Patient-reported Outcomes
Subject’s HRQoL, symptoms, functioning, and general well-being will be captured using 3 PRO
measures: the EORTC QLQ-C30 (Appendix 15 [Section 10.15]), EORTC QLQ-MY20
(Appendix 16 [Section 10.16]), and the EQ-5D-5L (Appendix 17 [Section 10.17]). The PRO
measures will be electronically (ePRO) collected to understand the change in PRO endpoints.
These measures will be administered according to the Schedule of Activities to understand how
subjects self-reported health state changes over time and the difference between treatment arms
during treatment, maintenance, and post-progression.
The PRO measures will be provided in the local language. If a subject requires assistance
completing the PRO, a study coordinator may assist but should not prompt the subject in selecting
their response. At completion, the study coordination should check that the questionnaires are
completed or document why they are missing. Full training documentation will be provided to site
coordinators before the start of data collection.
The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales (physical functioning,
role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global
Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single
items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The
recall period is 1 week (“past week”) and responses are reported using a verbal rating scale. Item
and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL,
better functioning, and more (worse) symptoms. The EORTC QLQ-C30 has been widely used
among cancer patients. Reliability, validity, and clinically meaningful change have been
demonstrated in multiple myeloma patients.47,48 The EORTC Multiple Myeloma Module
(QLQ-MY20) has been designed to use alongside the EORTC QLQ-C30 to address issues of more
relevance to myeloma patients.10 The 20-items make up 4 scales: disease symptoms, side effects
of treatment, future perspective, and body image. Recall, response options, and interpretation is
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administration time is approximately 30 minutes. Key PRO endpoints include the GHS, Physical
Functioning, Fatigue, and Pain subscales from the EORTC QLQ-C30 and the Disease Symptoms
from the EORTC QLQ-MY20.
The EQ-5D-5L is a generic measure of health status. For purposes of this study, the EQ-5D-5L
will be used to generate utility scores for use in cost-effectiveness analyses. The EQ-5D-5L is a
5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities,
pain/discomfort and anxiety/depression plus a visual analog scale rating “health today” with
anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).18  The
scores for the 5 separate questions are categorical and are cannot be analyzed as cardinal numbers.
However, the scores for the 5 dimensions are used to compute a single utility score ranging from
zero (0.0) to 1 (1.0) representing the general health status of the individual. The EQ-5D-5L asks
respondents to select their response based on their current health (“today”) and takes less than
5 minutes to complete.
The EQ-5D-5L will be performed until death or study end. Following disease progression, sites
should attempt to administer the EQ-5D-5L every 16 weeks, unless death or study end occurs first.
Subjects who visit the site for the follow-up assessments should complete the EQ-5D-5L
questionnaire at that time. If the EQ-5D-5L is conducted via a telephone call with the subject, then
the subject’s questionnaire responses will be read over the telephone to the site staff who will
record the data in the EQ-5D-5L. If the subject is unable to complete the EQ-5D-5L during the
Long-Term Follow-up Phase, the reason for not completing the questionnaire will be documented
(i.e., too ill, subject refused).
9. 
STATISTICAL CONSIDERATIONS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general
description of the statistical methods to be used to analyze the efficacy and safety data is outlined
below. Specific details will be provided in the Statistical Analysis Plan (SAP).
9.1. 
Statistical Hypotheses
The null hypothesis is that there is no difference in overall MRD negativity rate between
daratumumab in combination with VRd and VRd alone in subjects with newly diagnosed multiple
myeloma who are not intended for initial transplant.
9.2. 
Sample Size Determination
Based on the available data from CASTOR, POLLUX, and ALCYONE, approximately 64% of
MRD negative subjects at a threshold of 10-4 were also MRD negative at 10-5. The IFM2009-TE
NDMM study showed a 49% overall MRD negativity rate at 10-4 for all the VRd subjects without
transplant. Thus, the anticipated overall MRD negative rate (10-5) for the control arm in this study
is estimated to be at most 35%. This study assumes a 15% absolute increase in overall MRD
negativity rate (50% daratumumab plus VRd versus. 35% VRd alone). A sample size of 360
subjects (180 each arm) is needed to achieve a power of 80% to detect such a treatment difference
at a 2-sided alpha of 0.05.

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The final PFS analysis will take place when approximately 162 PFS events have been observed,
which will provide approximately 80% power to detect a 37% reduction in the risk of progression
or death (HR=0.63, translating to an improvement in median PFS from 43 months to 68 months)
with a log-rank test at a 2-sided alpha of 0.05. To ensure adequate power for PFS, an adaptive
approach may be used to determine the timing of the final PFS analysis. If the observed HR for
PFS at the interim analysis (ie, 60% of events) is higher than expected (eg, 0.7 or higher), the final
analysis of PFS may be delayed until approximately 205 events have been observed (roughly 3
years later). To control the overall type I error rate, the inverse normal test with the same fixed
weights as originally planned will be used to combine the log-rank statistics before and after the
interim analysis. Investigator-assessed long-term PFS, PFS2, and OS will continue to be collected
after the final PFS analysis until the end of data collection, using local disease assessments.
Updates to the final Clinical Study Report for both efficacy and safety will be provided in an
addendum to the Clinical Study Report at study closure.
9.3. 
Populations for Analyses
The primary analysis population will be the intent-to-treat (ITT) population, which will include all
randomized subjects. Safety will be evaluated for the population of all treated subjects.
Pharmacokinetic analyses will be performed on the pharmacokinetic-evaluable population.
9.4. 
Statistical Analyses
9.4.1. 
General Analysis
Continuous variables will be summarized using descriptive statistics such as mean, standard
deviation, and range. Categorical variables will be summarized using frequency tables. For
time-to-event variables, the Kaplan-Meier method will be used for descriptive summaries.
9.4.2. 
Efficacy Analyses
Response to study treatment and PD will be evaluated by a validated computer algorithm that has
been used in the previously reported Phase 2 and Phase 3 studies.11,23,37
Primary Endpoint
The primary endpoint, overall MRD negativity rate, will be compared between the 2 treatment
groups using the stratified Cochran Mantel Haenszel test based on the ITT population (ISS staging
and age/transplant eligibility as stratification factors). A Mantel-Haenszel odds ratio, along with
its 2-sided 95% CI, will be calculated.
Secondary Endpoints
If the primary endpoint of overall MRD negativity rate is statistically significant, the key secondary
endpoints (ie, CR or better rate, PFS, and durable MRD negativity rate) will be sequentially tested,
each with an overall two-sided alpha of 0.05, by utilizing a hierarchical testing approach as
proposed by Tang and Geller (1999)44 that strongly controls family wise Type I error rate.
Time-to-event efficacy endpoints, including PFS, PFS2 and OS will be compared between the
2 treatment groups using a stratified log-rank test. The Kaplan-Meier method will be used to

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estimate their distribution in each treatment group. Hazard ratio and its 95% CI will be estimated
based on a stratified Cox’s regression model with treatment as the sole explanatory variable.
For the binary secondary endpoints, including durable MRD negativity rate, rate of CR or better,
rate of VGPR or better and ORR, will be analyzed similarly to overall MRD negativity rate. The
time to response will be provided descriptively for each treatment arm without formal statistical
comparison.
9.4.3. 
Safety Analyses
Adverse Events
The verbatim terms used in the CRF by investigators to identify AEs will be coded using the
Medical Dictionary for Regulatory Activities (MedDRA). Treatment-emergent adverse events are
AEs with onset during the Treatment Phase or that are a consequence of a pre-existing condition
that has worsened since baseline. All reported AEs will be included in the analysis. For each AE,
the percentage of subjects who experience at least 1 occurrence of the given event will be
summarized by treatment group. In addition, comparisons between treatment groups will be
provided if appropriate.
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those
subjects who die, who discontinue study drug due to an AE, or who experience a severe or a serious
AE.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Reference ranges and markedly
abnormal results (specified in the SAP) will be used in the summary of laboratory data. Descriptive
statistics will be calculated for each laboratory analyte at baseline and for observed values and
changes from baseline at each scheduled time point. Changes from baseline results will be
presented in pre- versus posttreatment cross-tabulations (with classes for below, within, and above
normal ranges). A listing of subjects with any laboratory results outside the reference ranges will
be provided. A listing of subjects with any markedly abnormal laboratory results will also be
provided.
9.4.4. 
Other Analyses
Pharmacokinetic Analytical Procedures
Pharmacokinetic analyses will be performed on the pharmacokinetic-evaluable population,
defined as subjects assigned to Arm B who have received at least 1 dose of daratumumab and have
at least one pharmacokinetic sample concentration value after the first administration of
daratumumab.
All concentrations below the lowest quantifiable concentration or missing data will be labeled as
such in the concentration database. Concentrations below the lowest quantifiable concentration
will be treated as zero in the summary statistics.

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Descriptive statistics will be used to summarize daratumumab  serum concentrations at each
sampling time point. The PK parameters Cmin, and Cmax will be defined by planned timepoint.
If sufficient data are available, then population pharmacokinetic analysis of serum
concentration-time data of daratumumab may be performed using nonlinear mixed effects
modeling and may include data from other studies. If the population pharmacokinetic analysis is
conducted, details will be given in a population pharmacokinetic analysis plan and the results of
the analysis will be presented in a separate report.
Immunogenicity Analyses
The incidence of anti-daratumumab antibodies will be summarized for all subjects who receive at
least 1 dose of daratumumab and have daratumumab at least 1 sample obtained after the first dose
of daratumumab. The prevalence and incidence of anti-rHuPH20 antibodies will be summarized
for all subjects who receive a dose of daratumumab and have at least 1 sample for detection of
anti-rHuPH20 antibodies obtained after the first dose of daratumumab. A listing of subjects who
are positive for anti-daratumumab antibodies or anti-rHuPH20 antibodies will be provided.
Biomarkers Analyses
MRD negativity rate is the primary endpoint and the analysis method is described in Section 9.4.2.
Baseline bone marrow aspirate samples will be evaluated by the FDA-approved clonoSEQ v2.0
MRD assay  to establish the myeloma clone (calibration) and for MRD monitoring. MRD
assessment by NGS is an emerging tool in the assessment of patients with multiple myeloma and
for cytogenetics evaluations.19 Several studies have demonstrated that MRD status is correlated
with PFS and OS.24 In this study, bone marrow samples will be collected when a bone marrow
aspirate is performed at Screening and at the subsequent timepoints outlined in Table 13 and
Schedule of Activities (Section 1.3). Whole blood sample will be collected from subjects as
outlined in the Time and Events Schedule and processed to plasma and PBMCs and may be used
to evaluate daratumumab’s immunomodulatory mechanism of action.
Pharmacokinetic/Pharmacodynamic Analyses
Pharmacokinetic/pharmacodynamic modeling may be performed, including exploring the
relationship between serum concentrations of daratumumab and endpoints of clinical efficacy or
safety. Details and results of any analysis performed will be presented in a separate report.
9.5. 
Medical Resource Utilization Analyses
Medical resource utilization will be descriptively summarized by treatment group. Additional
analyses may be conducted; details and results of any additional analyses will be presented in a
separate report.
9.6. 
Patient-reported Outcomes Analyses
The EORTC QLQ-C30 and EORTC QLQ-MY20 scale scores, and EQ-5D-5L utility and visual
analog scores will be descriptively summarized by treatment group at each time point.
Within-group and between-group treatment effects of the PRO endpoints will be assessed by

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change from baseline using mixed models for repeated measures for exploratory purpose. Full
details of statistical analyses will be provided in the SAP.
Benefit-risk Analyses
For benefit-risk (B-R) analyses, between treatment differences will be shown with absolute rate or
other difference measures and corresponding 95% CIs. Both continuous and dichotomized
versions of continuous endpoints will be shown. Results will be displayed in tabular and forest
plot form. Additional details will be provided in the separate benefit-risk SAP.
9.7. 
Interim Analysis
There is no interim analysis planned for the overall MRD negativity rate. After the primary analysis
of MRD negativity rate, disease assessment will continue for the secondary endpoint PFS, for
which one interim analysis is planned after approximately 98 events (ie, 60% of the total
162 events) have been accumulated. The significance levels at this interim analysis of PFS to
establish the superiority (or declare the futility) of daratumumab plus VRd over VRd alone will be
determined based on the observed number of PFS events at this analysis using the
O’Brien-Fleming boundaries as implemented by the Lan-DeMets alpha- and beta-spending
method.
9.8. 
Independent Data Monitoring Committee
An IDMC will be established according to regulatory agency guidelines. The IDMC will start the
safety review after the first 100 subjects have been treated for at least 1 cycle or discontinued, and
subsequently perform a periodic safety review every 6 months. At the primary analysis of the
overall MRD negativity rate and the interim analysis for PFS, the IDMC will review both safety
and efficacy results and make recommendations regarding the unblinding and continuation of the
study. More details are specified in a separate IDMC charter. Emerging data from all ongoing
daratumumab studies will be communicated to the IDMC, where applicable.

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations
ADR  
Adverse drug reaction
AE 
Adverse event
ALT  
alanine aminotransferase
ANC  
absolute neutrophil count
Anti-HBc 
hepatitis B core antigen
Anti-HBs 
hepatitis B surface antigen
ARC  
Anticipated Event Review Committee
ASCT  
autologous stem cell transplantation
AST  
aspartate aminotransferase
BMI 
body mass index
BM-MNC  
bone marrow mononuclear cell
B-R  
benefit-risk
CD38  
cluster of differentiation 38
CDC  
Centers for Disease Control
CI 
confidence interval
Cmax  
maximum observed concentration
Cmin  
minimum observed concentration
COPD  
chronic obstructive pulmonary disease
COVID-19 
Coronavirus Disease 2019
CR  
complete response
CRAB  
calcium, renal, anemia, bone
CrCl 
creatinine clearance
CRF  
case report form
CT  
computed tomography
Ctrough  
concentration at the end of a dosing interval at steady state
CV  
coefficient of variance
Dara-CF  
co-formulated product of daratumumab and rHuPH20
Dara-IV  
intravenous daratumumab
Dara-MD  
mix-and-deliver formulation of daratumumab
Dara-SC  
subcutaneous daratumumab
DLT  
dose limiting criteria
DRd 
daratumumab + lenalidomide + dexamethasone
DVd 
daratumumab + bortezomib
D-VMP  
dara-IV in combination with bortezomib, melphalan and dexamethasone
D-VRd 
daratumumab, bortezomib, lenalidomide, and dexamethasone
ECG  
electrocardiogram
ECOG  
Eastern Cooperative Oncology Group
eCRF  
electronic case report form
EORTC  
European Organization for Research and Treatment of Cancer
EORTC QLQ  
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire
EORTC 
QLQ-C30 
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core
3-item
EORTC 
QLQ-MY20 
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire
multiple myeloma 20-item
EOT  
end of treatment
EQ-5D-5L 
EuroQol Five Dimension Questionnaire
FDA  
Food and Drug Administration
FEV1 
Forced Expiratory Volume in 1 second
FFPE 
formalin-fixed, paraffin-embedded
FIRST  
Front-line Investigation of Revlimid and Dexamethasone versus Standard Thalidomide
FISH  
fluorescence in situ hybridization
FLC  
free light chain

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G-CSF  
granulocyte colony stimulating factor
HBsAg 
hepatitis B surface antigen
HBV  
hepatitis B virus
HCV  
hepatitis C virus
HIV  
human immunodeficiency virus
HR  
hazard ratio
HRQoL 
health-related quality of life
IB  
Investigator’s Brochure
ICF  
informed consent form
IDMC  
Independent Data Monitoring Committee
IEC  
Independent Ethics Committee
IFE 
Immunofixation electrophoresis
IFM  
Intergroupe Francophone du Myélome
Ig 
immunoglobulin
IHC  
immunohistochemistry
IMWG  
International Myeloma Working Group
IRB  
Institutional Review Board
IRR  
Injection-related reaction
ISS  
International Staging System
ITT  
intent-to-treat
IV  
intravenous
IWRS  
interactive web response system
MedDRA  
Medical Dictionary for Regulatory Activities
MM  
multiple myeloma
M-protein  
monoclonal protein
MPT  
melphalan-prednisone-thalidomide
MRD  
minimal residual disease
MRI 
magnetic resonance imaging
MRU  
medical resource utilization
NCI-CTCAE  
National Cancer Institute Common Terminology Criteria for Adverse Events
nCR  
near complete response
NGS  
next generation sequencing
ORR  
overall response rate
OS  
overall survival
PCR  
polymerase chain reaction
PD 
progressive disease
PET  
positron emission tomography
PFS  
progression-free survival
PFS2 
progression-free survival on the next line of therapy
PI 
proteasome inhibitor
PO 
orally
PK 
pharmacokinetic(s)
PR 
partial response
PRO  
patient-reported outcome
RBC  
red blood cell
Rd 
lenalidomide-dexamethasone
REMS  
Risk Evaluation and Mitigation Strategy
rHuPH20 
recombinant human hyaluronidase
SAC  
Safety Assessment Committee
SAE 
serious adverse event
SAP  
statistical analysis plan
SC 
subcutaneous
sCR  
stringent complete response
SCT  
stem cell transplantation
sIPPM  
site Investigator Product Procedures Manual

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SLiM  
S=≥Sixty-percent (≥60%) clonal BM plasma cells; Li=serum free Light chain ratio
involved:uninvolved ≥100; M=>1 focal lesion (≥5 mm each) detected by MRI studies
SmPC  
Summary of Product Characteristics
SOA  
Schedule of Activities
SOC  
standard of care
SPE 
serum protein electrophoresis
SPEP  
serum M-protein quantitation by electrophoresis
SVR  
sustained virologic response
SWOG  
Southwest Oncology Group
TEAE 
treatment-emergent adverse event
ULN  
upper limit of normal
UPEP  
24-hour urine M-protein quantitation by electrophoresis
USPI 
Unite States Product Information
US  
United States
VCd 
bortezomib + cyclophosphamide + dexamethasone
Vd 
bortezomib + dexamethasone
VGPR  
very good partial response
VMP  
bortezomib + melphalan + dexamethasone
VRd 
bortezomib + lenalidomide + dexamethasone
VTd 
Bortezomib + thalidomide + dexamethasone
Definition of Study Terms
Daratumumab = study drug
daratumumab+VRd = study treatment

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10.2. Appendix 2: Anticipated Events
Anticipated Event
An anticipated event is an AE (serious or non-serious) that commonly occurs as a consequence of
the underlying disease or condition under investigation (disease-related) or background regimen.
For the purposes of this study the following events will be considered anticipated events:
Bleeding
Bone diseases
Hypercalcemia
Hyperuricemia
Hyperviscosity syndrome
Infection
Renal failure or insufficiency
Reporting of Anticipated Events
All AEs will be recorded in the eCRF regardless of whether considered to be anticipated events
and will be reported to the sponsor as described in Section 10.4 (Appendix 4). Any anticipated
event that meets serious criteria will be reported to the sponsor as described in Section 8.3.2. Each
anticipated event will be assessed by the investigator at the individual case level and if considered
to be drug-related will undergo expedited reporting (if appropriate) as per applicable clinical trial
legislation to Health Authorities and IRB/ECs. If an anticipated event is considered disease-related
or not related to study drug the event will be exempt from expedited reporting.
To meet US regulatory clinical trial legislation, the sponsor will perform aggregate review of
anticipated events as outlined below, and if determined to be drug-related will implement
expedited reporting of these events to Health Authorities and IRBs/ECs. If an interim analysis of
trial results leads to an unblinded, aggregate review of safety data by the study team, the sponsor
may terminate the review of pre-specified anticipated events outlined above.
Safety Assessment Committee (SAC)
A Safety Assessment Committee (SAC) will be established to perform reviews of pre-specified
anticipated events at an aggregate level. The SAC is a safety committee within the sponsor's
organization that is independent of the sponsor's study team. The SAC will meet to aid in the
recommendation to the sponsor's study team as to whether there is a reasonable possibility that an
anticipated event is related to the study intervention based on a review of the aggregate data by
arm.

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Statistical Analysis
Details of statistical analysis of anticipated events, including the frequency of review and threshold
to trigger an aggregate analysis of anticipated events will be provided in a separate Anticipated
Events Safety Monitoring Plan.

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10.3. Appendix 3: Regulatory, Ethical, and Study Oversight Considerations
REGULATORY AND ETHICAL CONSIDERATIONS
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current International Conference on (ICH) guidelines on Good Clinical Practice (GCP),
and applicable regulatory and country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing,
conducting, recording, and reporting studies that involve the participation of human subjects.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study subjects are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by
the sponsor. All protocol amendments must be issued by the sponsor and signed and dated by the
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or
when the relevant competent authority has raised any grounds for non-acceptance, except when
necessary to eliminate immediate hazards to the subjects, in which case the amendment must be
promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable,
the investigator or other physician in attendance will contact the appropriate sponsor representative
listed in the Contact Information page(s), which will be provided as a separate document. Except
in emergency situations, this contact should be made before implementing any departure from the
protocol. In all cases, contact with the sponsor must be made as soon as possible to discuss the
situation and agree on an appropriate course of action. The data recorded in the CRF and source
documents will reflect any departure from the protocol, and the source documents will describe
this departure and the circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities
in each respective country, if applicable. A study may not be initiated until all local regulatory
requirements are met.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study drug to the
study site:

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Protocol and amendment(s), if any, signed and dated by the principal investigator
A copy of the dated and signed (or sealed, where appropriate per local regulations), written
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if
applicable, subject compensation programs. This approval must clearly identify the specific
protocol by title and number and must be signed (or sealed, where appropriate per local
regulations) by the chairman or authorized designee
Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their
function, with a statement that it is organized and operates according to GCP and the
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a
member of the study site personnel is a member of the IEC/IRB, documentation must be
obtained to state that this person did not participate in the deliberations or in the vote/opinion
of the study
Regulatory authority approval or notification, if applicable
Signed and dated statement of investigator (eg, Form FDA 1572), if applicable
Documentation of investigator qualifications (eg, curriculum vitae)
Completed investigator financial disclosure form from the principal investigator, where
required
Signed and dated Clinical Trial Agreement, which includes the financial agreement
Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first subject:
Completed investigator financial disclosure forms from all subinvestigators
Documentation of subinvestigator qualifications (eg, curriculum vitae)
Name and address of any local laboratory conducting tests for the study, and a dated copy of
current laboratory normal ranges for these tests, if applicable
Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB
with current and complete copies of the following documents (as required by local regulations):
Final protocol and, if applicable, amendments
Sponsor-approved ICF (and any other written materials to be provided to the subjects)
Investigator's Brochure (or equivalent information) and amendments/addenda
Sponsor-approved subject recruiting materials
Information on compensation for study-related injuries or payment to subjects for
participation in the study, if applicable

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Investigator's curriculum vitae or equivalent information (unless not required, as documented
by the IEC/IRB)
Information regarding funding, name of the sponsor, institutional affiliations, other potential
conflicts of interest, and incentives for subjects
Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final protocol,
amendments (if any, excluding the ones that are purely administrative, with no consequences for
subjects, data or study conduct, unless required locally), the ICF, applicable recruiting materials,
and subject compensation programs, and the sponsor has received a copy of this approval. This
approval letter must be dated and must clearly identify the IEC/IRB and the documents being
approved.
During the study the investigator (or sponsor where required) will send the following documents
and updates to the IEC/IRB for their review and approval, where appropriate:
Protocol amendments (excluding the ones that are purely administrative, with no
consequences for subjects, data or study conduct)
Revision(s) to ICF and any other written materials to be provided to subjects
If applicable, new or revised subject recruiting materials approved by the sponsor
Revisions to compensation for study-related injuries or payment to subjects for participation
in the study, if applicable
New edition(s) of the Investigator's Brochure and amendments/addenda
Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at
least annually)
Reports of AEs that are serious, unlisted/unexpected, and associated with the study drug
New information that may adversely affect the safety of the subjects or the conduct of the
study
Deviations from or changes to the protocol to eliminate immediate hazards to the subjects
Report of deaths of subjects under the investigator's care
Notification if a new investigator is responsible for the study at the site
Development Safety Update Report and Line Listings, where applicable
Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for subjects, data or study conduct), the amendment and applicable ICF revisions
must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.

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At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion (if applicable, the notification will be submitted through the head of
investigational institution).
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise help
ensure access to the developed product if the need for the product persists, unless explicitly
addressed as a specific ethical consideration in Section 4.2.1, Study-Specific Ethical Design
Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
FINANCIAL DISCLOSURE
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the course of
the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
INFORMED CONSENT PROCESS
Each subject (or a legally designated representative) must give written consent according to local
requirements after the nature of the study has been fully explained. The ICF(s) must be signed
before performance of any study-related activity. The ICF(s) that is/are used must be approved by
both the sponsor and by the reviewing IEC/IRB and be in a language that the subject can read and
understand. The informed consent should be in accordance with principles that originated in the
Declaration of Helsinki, current ICH and GCP guidelines, applicable regulatory requirements, and
sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study site personnel
must explain to potential subjects or their legally designated representatives the aims, methods,
reasonably anticipated benefits, and potential hazards of the study, and any discomfort
participation in the study may entail. Subjects will be informed that their participation is voluntary
and that they may withdraw consent to participate at any time. They will be informed that choosing
not to participate will not affect the care the subject will receive for the treatment of his or her
disease. Subjects will be told that alternative treatments are available if they refuse to take part and
that such refusal will not prejudice future treatment. Finally, they will be told that the investigator
will maintain a subject identification register for the purposes of long-term follow-up if needed
and that their records may be accessed by health authorities and authorized sponsor personnel
without violating the confidentiality of the subject, to the extent permitted by the applicable law(s)
or regulations. By signing the ICF the subject or legally designated representative is authorizing
such access, which includes permission to obtain information about his or her survival status. It

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also denotes that the subject agrees to allow his or her study physician to recontact the subject for
the purpose of obtaining consent for additional safety evaluations, and subsequent disease-related
treatments, if needed. The physician may also recontact the subject for the purpose of obtaining
consent to collect information about his or her survival status.
The subject or legally designated representative will be given sufficient time to read the ICF and
the opportunity to ask questions. After this explanation and before entry into the study, consent
should be appropriately recorded by means of either the subject's or his or her legally designated
representative's personally dated signature. After having obtained the consent, a copy of the ICF
must be given to the subject. Where local regulations require, a separate ICF may be used for the
required DNA component of the study.
Subjects who are rescreened are required to sign a new ICF.
If the subject or legally designated representative is unable to read or write, an impartial witness
should be present for the entire informed consent process (which includes reading and explaining
all written information) and should personally date and sign the ICF after the oral consent of the
subject or legally designated representative is obtained.
When prior consent of the subject is not possible, and the subject's legally designated
representative is not available, enrollment procedures should be described in the protocol with
documented approval/favorable opinion by the IEC/IRB to protect the rights, safety, and well-
being of the subject and to ensure compliance with applicable regulatory requirements. The subject
or legally designated representative must be informed about the study as soon as possible and give
consent to continue.
DATA PROTECTION
Privacy of Personal Data
The collection and processing of personal data from subjects enrolled in this study will be limited
to those data that are necessary to fulfill the objectives of the study. These data must be collected
and processed with adequate precautions to ensure confidentiality and compliance with applicable
data privacy protection laws and regulations. Appropriate technical and organizational measures
to protect the personal data against unauthorized disclosures or access, accidental or unlawful
destruction, or accidental loss or alteration must be put in place. Sponsor personnel whose
responsibilities require access to personal data agree to keep the identity of subjects confidential.
The informed consent obtained from the subject (or his or her legally designated representative)
includes explicit consent for the processing of personal data and for the investigator/institution to
allow direct access to his or her original medical records (source data/documents) for study-related
monitoring, audit, IEC/IRB review, and regulatory inspection. This consent also addresses the
transfer of the data to other entities and to other countries.
The subject has the right to request through the investigator access to his or her personal data and
the right to request rectification of any data that are not correct or complete. Reasonable steps will

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be taken to respond to such a request, taking into consideration the nature of the request, the
conditions of the study, and the applicable laws and regulations.
Exploratory PK and immunogenicity research is not conducted under standards appropriate for the
return of data to subjects. In addition, the sponsor cannot make decisions as to the significance of
any findings resulting from exploratory research. Therefore, exploratory research data will not be
returned to subjects or investigators, unless required by law or local regulations. Privacy and
confidentiality of data generated in the future on stored samples will be protected by the same
standards applicable to all other clinical data.
STORAGE, USE, TRANSFER, AND RETENTION OF DATA AND SAMPLES
Study samples will be coded or anonymized at all times in accordance with the informed consent
and will not be labeled with personal identifiers.
Investigator and study site will only store, use, transfer and retain data and study samples, including
optional study samples, in accordance with the informed consent and applicable law, and in
accordance with any separate written agreement with sponsor. Other than what is specified in a
separate written agreement with sponsor, study site and investigator shall not conduct or facilitate
any research by a third party not required by the protocol (i) on subjects if such research interferes
with the conduct of the study or (ii) on samples collected from study subjects during the study,
including optional samples, if the research relates to daratumumab or (iii) on data collected from
study subjects during the study if the research relates to daratumumab.
Sponsor may store, use, transfer or retain the data and study samples, including optional study
samples, for uses not specified by the protocol, including compatible research, in compliance with
the informed consent and applicable law.
COMMITTEES STRUCTURE
Independent Data Monitoring Committee
An IDMC will be established according to regulatory agency guidelines (Section 9.8). This
committee will consist of at least one medical expert in the relevant therapeutic area, 2 clinicians
and at least one statistician; committee membership responsibilities, authorities, and procedures
will be documented in its charter.
USE OF INFORMATION AND PUBLICATION
All information, including but not limited to information regarding daratumumab supplied by the
sponsor to the study site or investigator and not previously published, and any data analysis
generated as a result of this study, are considered confidential and remain the sole property of the
sponsor. Study site and investigator shall not use this information except in the performance of
this study and shall not disclose this information to anyone except to persons involved in the study
that need such information to assist in conducting the study, and then only on like terms of
confidentiality and non-use.

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Study site and investigator shall not publish study results except as required by law or as specified
in a separate, written agreement between the sponsor and the study site or investigator.
The Sponsor will register the study and publish the study results in compliance with applicable
law and may register the study or publish study results when not required.
Authorship of any peer-reviewed publications will be determined by mutual agreement in line with
International Committee of Medical Journal Editors authorship guidelines.
In accordance with standard editorial and ethical practice, the sponsor will generally support
publication of multicenter studies only in their entirety and not as individual site data. In this case,
a coordinating investigator will be designated by mutual agreement.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law.
The summary of the results from the primary MRD analysis, and the interim (approximately
98 events) and final (approximately 162 events) PFS analysis as described in Section 9.7, will be
submitted to the EU database within one year after unblinding the data.
The disclosure of the study results will be performed after the end of study.
DATA QUALITY ASSURANCE
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified
investigators and appropriate study sites, review of protocol procedures with the investigator and
study site personnel before the study, and periodic monitoring visits by the sponsor, and direct
transmission of clinical laboratory data from a central laboratory into the sponsor's data base.
Written instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for CRF completion will be provided and reviewed with study site personnel before
the start of the study. The sponsor will review CRF for accuracy and completeness during on-site
monitoring visits and after transmission to the sponsor; any discrepancies will be resolved with the
investigator or designee, as appropriate. After upload of the data into the study database they will
be verified for accuracy and consistency with the data sources.
ELECTRONIC CASE REPORT FORM COMPLETION
Electronic case report forms are prepared and provided by the sponsor for each subject in electronic
format. All data relating to the study must be recorded in CRF. All CRF entries, corrections, and
alterations must be made by the investigator or authorized study site personnel. The investigator
must verify that all data entries in the CRF are accurate and correct.

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The study data will be transcribed by study site personnel from the source documents onto an
electronic CRF, if applicable. Study-specific data will be transmitted in a secure manner to the
sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the CRF. Any
such worksheets will become part of the subject's source documents. Data must be entered into
CRF in English. The CRF must be completed as soon as possible after a subject visit and the forms
should be available for review at the next scheduled monitoring visit.
All participative measurements (eg, pain scale information or other questionnaires) will be
completed by the same individual who made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the eDC tool. If corrections to a CRF are needed after
the initial entry into the CRF, this can be done in either of the following ways:
Investigator and study site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
Sponsor or sponsor delegate can generate a query for resolution by the investigator and study
site personnel.
SOURCE DOCUMENTS
At a minimum, source documents consistent in the type and level of detail with that commonly
recorded at the study site as a basis for standard medical care must be available for the following:
subject identification, eligibility, and study identification; study discussion and date of signed
informed consent; dates of visits; results of safety and efficacy parameters as required by the
protocol; record of the assessment by the investigator of all AEs and follow-up of AEs;
concomitant medication; treatment receipt/dispensing/return records; study drug administration
information; and date of study completion and reason for early discontinuation of study drug or
withdrawal from the study, if applicable.
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be
reviewed with the investigator before the study and will be described in the monitoring guidelines
(or other equivalent document).
The following data will be recorded directly into the CRF and will be considered source data:
Race
Blood pressure and pulse/heart rate
Height and weight
Details of physical examination
Myeloma Frailty Score

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ECOG, PRO questionnaires, health economic data
The minimum source documentation requirements for Section 5.1, Inclusion Criteria and
Section 5.2, Exclusion Criteria that specify a need for documented medical history are as follows:
Referral letter from treating physician
Complete history of medical notes at the site
Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a
minimum by subject interview or other protocol required assessment (eg, physical examination,
laboratory assessment) and documented in the source documents.
An eSource system may be utilized, which contains data traditionally maintained in a hospital or
clinic record to document medical care (eg, electronic source documents) as well as the clinical
study-specific data fields as determined by the protocol. This data is electronically extracted for
use by the sponsor. If eSource is utilized, references made to the CRF in the protocol include the
eSource system, but information collected through eSource may not be limited to that found in the
CRF. Data in this system may be considered source documentation.
MONITORING
The sponsor will use a combination of monitoring techniques central, remote, or on-site monitoring
to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will
record dates of the visits in a study site visit log that will be kept at the study site. The first
post-initiation visit will be made as soon as possible after enrollment has begun. At these visits,
the monitor will compare data entered into the CRF with the source documents (eg,
hospital/clinic/physician’s office medical records); a sample may be reviewed. The nature and
location of all source documents will be identified to ensure that all sources of original data
required to complete the CRF are known to the sponsor and study site personnel and are accessible
for verification by the sponsor study site contact. If electronic records are maintained at the study
site, the method of verification must be discussed with the study site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review will
be discussed with the study site personnel. The sponsor expects that, during monitoring visits, the
relevant study site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.

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In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these
remote contacts, study site personnel will be available to provide an update on the progress of the
study at the site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
ON-SITE AUDITS
Representatives of the sponsor's clinical quality assurance department may visit the study site at
any time during or after completion of the study to conduct an audit of the study in compliance
with regulatory guidelines and company policy. These audits will require access to all study
records, including source documents, for inspection. Subject privacy must, however, be respected.
The investigator and study site personnel are responsible for being present and available for
consultation during routinely scheduled study site audit visits conducted by the sponsor or its
designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part
of a national GCP compliance program or to review the results of this study in support of a
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
RECORD RETENTION
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRF and
all source documents that support the data collected from each subject, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial, and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical
development of the investigational product. These documents will be retained for a longer period
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the
responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained. For trials performed under Regulation [EU] No. 536/2014, the sponsor
and the investigator shall archive the content of the clinical trial master file for at least 25 years
after the end of the clinical trial.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor must be notified in writing of the name and address of the new
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents
before having obtained written approval from the sponsor.

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If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
STUDY AND SITE CLOSURE
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A
study site is considered closed when all required documents and study supplies have been collected
and a study site closure visit has been performed.
The investigator may initiate study site closure at any time, provided there is reasonable cause and
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not
limited to:
Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local health authorities, the sponsor's procedures, or GCP guidelines
Inadequate recruitment of subjects by the investigator
Discontinuation of further study drug development

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10.4. Appendix 4: Adverse Events: Definitions and Procedures for Recording,
Evaluating, Follow-up, and Reporting
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS
Adverse Event
An AE is any untoward medical occurrence in a clinical study subject administered a medicinal
(investigational or non-investigational) product. An AE does not necessarily have a causal
relationship with the intervention. An AE can therefore be any unfavorable and unintended sign
(including an abnormal finding), symptom, or disease temporally associated with the use of a
medicinal (investigational or non-investigational) product, whether or not related to that medicinal
(investigational or non-investigational) product. (Definition per ICH)
This includes any occurrence that is new in onset or aggravated in severity or frequency from the
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Note: The sponsor collects AEs starting with the signing of the ICF (refer to All Adverse Events
under Section 8.4.1, Time Period and Frequency for Collecting Adverse Events and Serious
Adverse Events Information, for time of last AE recording).
Serious Adverse Event
A SAE based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human
Use is any untoward medical occurrence that at any dose:
Results in death
Is life-threatening
(The subject was at-risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe)
Requires inpatient hospitalization or prolongation of existing hospitalization
Results in persistent or significant disability/incapacity
Is a congenital anomaly/birth defect
Is a suspected transmission of any infectious agent via a medicinal product
Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life-threatening or result in death or hospitalization but may jeopardize the subject or may require
intervention to prevent one of the other outcomes listed in the definition above. These should
usually be considered serious.

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If a serious and unexpected AE occurs for which there is evidence suggesting a causal relationship
between the study drug and the event (eg, death from anaphylaxis), the event must be reported as
a serious and unexpected suspected adverse reaction even if it is a component of the study endpoint
(eg, all-cause mortality).
Expected progression of disease should not be considered an AE (or SAE). However, if determined
by the investigator to be more likely related to the study treatment than the underlying disease, the
clinical signs or symptoms of progression and the possibility that the study treatment is enhancing
disease progression, should be reported per the usual reporting requirements.
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable product
reference safety information. For daratumumab, the expectedness of an AE will be determined by
whether or not it is listed in the Investigator's Brochure. Anticipated events will be recorded and
reported as described in Appendix 2 (Section 10.2).
Adverse Event Associated with the Use of the Intervention
An AE is considered associated with the use of the intervention if the attribution is possible,
probable, or very likely by the definitions listed below (see Attribution Definitions).
ATTRIBUTION DEFINITIONS
Not Related
An AE that is not related to the use of the drug.
Related
An AE that is related to the use of the drug.
SEVERITY CRITERIA
The severity assessment for an AE or SAE should be completed using the NCI-CTCAE Version 5.
Any AE or SAE not listed in the NCI-CTCAE Version 5 will be graded according to investigator
clinical judgment by using the standard grades.
SPECIAL REPORTING SITUATIONS
Safety events of interest on a sponsor study drug in an interventional study that may require
expedited reporting or safety evaluation include, but are not limited to:
Overdose of a sponsor study drug. No MTD has been reached for daratumumab. However, if
the dose exceeds the maximum tested dose of 2000 mg, then it will be considered as an
overdose in this study
Suspected abuse/misuse of a sponsor study drug
Accidental or occupational exposure to a sponsor study drug

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Medication error involving a sponsor product (with or without subject exposure to the sponsor
study drug, eg, name confusion)
Exposure to a sponsor study drug from breastfeeding
Special reporting situations should be recorded in the CRF. Any special reporting situation that
meets the criteria of a SAE should be recorded on the SAE page of the CRF.
PROCEDURES
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from the
time a signed and dated ICF is obtained until 30 days after the last dose of any component of the
treatment regimen. The only exception is for subjects who have withdrawn informed consent for
study participation or for subjects who have received additional treatment with therapeutic intent
for MM within 30 days after the last dose of any component of the treatment regimen. For subjects
who have received additional treatment with therapeutic intent for MM during the AE reporting
period, only AEs that are considered to be related to the study drug or any part of the backbone
treatment regimen must be reported (unless the subject has been withdrawn from the study).
All AEs, regardless of seriousness, severity, or presumed relationship to study drug, must be
recorded using medical terminology in the source document and the CRF. Whenever possible,
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough,
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory
infection"). Investigators must record in the CRF their opinion concerning the relationship of the
AE to study therapy. All measures required for AE management must be recorded in the source
document and reported according to sponsor instructions.
Death should not be recorded as an AE or SAE, but as the outcome of an AE. The event that
resulted in the death should be reported as a SAE.
For all studies with an outpatient phase, including open-label studies, the subject must be provided
with a "wallet (study) card" and instructed to carry this card with them for the duration of the study
indicating the following:
Study number
Statement, in the local language(s), that the subject is participating in a clinical study
Investigator's name and 24-hour contact telephone number
Local sponsor's name and 24-hour contact telephone number (for medical staff only)
Site number
Subject number

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Serious Adverse Events
Serious adverse events, including those spontaneously reported to the investigator within 30 days
after last dose of last study drug, and those that are considered related to study drug within the
Follow-up Phase, must be reported using the Serious Adverse Event Form. The sponsor will
evaluate any safety information that is spontaneously reported by an investigator beyond the time
frame specified in the protocol.
All events that meet the definition of a SAE will be reported as SAEs, regardless of whether they
are protocol-specific assessments. Anticipated events will be recorded and reported as described
in Appendix 2 (Section 10.2). (Note: Some countries require reporting of all AEs to the health
authorities, eg, Japan will not identify anticipated events for the health authorities).
All SAEs occurring during the study must be reported to the appropriate sponsor contact person
by study site personnel immediately, but no later than 24 hours after their knowledge of the event.
Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event
Form, which must be completed and signed by a physician from the study site and transmitted to
the sponsor immediately, but no later than 24 hours after their knowledge of the event. The initial
and follow-up reports of a SAE should be transmitted electronically or by facsimile (fax). The
initial and follow-up reports of a SAE should be made by facsimile (fax).
All SAEs that have not resolved by the end of the study, or that have not resolved upon
discontinuation of the subject's participation in the study, must be followed until any of the
following occurs:
The event resolves
The event stabilizes
The event returns to baseline, if a baseline value/status is available
The event can be attributed to agents other than the study drug or to factors unrelated to study
conduct
It becomes unlikely that any additional information can be obtained (subject or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as a SAE.
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during the
course of a subject's participation in a study must be reported as a SAE, except hospitalizations for
the following:
If the subject has not experienced a significant medical event but is hospitalized overnight
only for observation following injection of study drug, then the hospitalization should not be
reported as a SAE.
Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as pending
placement in long-term care facility).

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Surgery or procedure planned before entry into the study (must be documented in the CRF).
Note: Hospitalizations that were planned before the signing of the ICF, and where the
underlying condition for which the hospitalization was planned has not worsened, will not be
considered SAEs. Any AE that results in a prolongation of the originally planned
hospitalization is to be reported as a new serious AE.
For convenience the investigator may choose to hospitalize the subject for the duration of the
intervention period.
Expected progression of disease should not be considered an AE (or SAE). However, if determined
by the investigator to be more likely related to the study treatment than the underlying disease, the
clinical signs or symptoms of progression and the possibility that the study treatment is enhancing
disease progression, should be reported per the usual reporting requirements.
CONTACTING SPONSOR REGARDING SAFETY
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues or questions regarding the study are listed in the Contact Information
page(s), which will be provided as a separate document.
PRODUCT QUALITY COMPLAINT HANDLING
A product quality complaint (PQC) is defined as any suspicion of a product defect related to
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality,
durability, or reliability of a product, including its labeling or package integrity. A PQC may have
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and
analysis of PQC information from studies are crucial for the protection of subjects, investigators,
and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor has established
procedures in conformity with regulatory requirements worldwide to ensure appropriate reporting
of PQC information; all studies conducted by the sponsor or its affiliates will be conducted in
accordance with those procedures.
Procedures
All initial PQCs must be reported to the sponsor by the study site personnel within 24 hours after
being made aware of the event.
If the defect is combined with a SAE, the study site personnel must report the PQC to the sponsor
according to the SAE reporting timelines (refer to Section 8.4.1, Time Period and Frequency for
Collecting Adverse Event and Serious Adverse Event Information). A sample of the suspected
product should be maintained for further investigation if requested by the sponsor.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding product quality issues are listed in the Contact Information page(s), which will be
provided as a separate document.

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10.5. Appendix 5: Contraceptive and Barrier Guidance and Collection of
Pregnancy Information
Subjects must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria.
Pregnancy information will be collected and reported as noted in Section 8.4.4, Pregnancy and
Appendix 4 (Section 10.4) Adverse Events: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting.
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless
permanently sterile (see below).
Woman Not of Childbearing Potential
premenarchal
A premenarchal state is one in which menarche has not yet occurred.
postmenopausal
A postmenopausal state is defined as no menses for 12 months without an alternative medical
cause. A high follicle stimulating hormone (FSH) level (>40 IU/L or mIU/mL) in the
postmenopausal range may be used to confirm a postmenopausal state in women not using
hormonal contraception or hormonal replacement therapy (HRT), however in the absence of
12 months 
of 
amenorrhea, 
a 
single 
FSH 
measurement 
is 
insufficient.
If there is a question about menopausal status in women on HRT, the woman will be required
to use one of the non-estrogen-containing hormonal highly effective contraceptive methods if
she wishes to continue HRT during the study.
permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral
oophorectomy.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually
active becomes active), a woman must begin a highly effective method of contraception, as
described throughout the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered.

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Examples of Contraceptives
EXAMPLES OF CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:
USER INDEPENDENT
Highly Effective Methods That Are User Independent Failure rate of ≤1% per year when used consistently and
correctly.
Implantable progestogen-only hormone contraception associated with inhibition of ovulationb
Intrauterine device
Intrauterine hormone-releasing system
Bilateral tubal occlusion
Vasectomized partner
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the sole sexual
partner of the woman of childbearing potential and the absence of sperm has been confirmed. If not,
additional highly effective method of contraception should be used. Spermatogenesis cycle is approximately
74 days.)
USER DEPENDENT
Highly Effective Methods That Are User Dependent Failure rate of <1% per year when used consistently and
correctly.
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of
ovulationb
oral
intravaginal
transdermal
injectable
Progestogen-only hormone contraception associated with inhibition of ovulationb
oral
injectable
Sexual abstinence
(Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual
intercourse during the entire period of risk associated with the study drug. The reliability of sexual
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle
of the subject.)
NOT ALLOWED AS SOLE METHOD OF CONTRACEPTION DURING THE STUDY(not considered to be
highly effective - failure rate of >1% per year)
Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary mode of
action.
Male or female condom with or without spermicidec
Cap, diaphragm, or sponge with spermicide
A combination of male condom with either cap, diaphragm, or sponge with spermicide (double-barrier
methods)c
Periodic abstinence (calendar, symptothermal, post-ovulation methods)
Withdrawal (coitus-interruptus)
Spermicides alone
Lactational amenorrhea method (LAM)
a) Typical use failure rates may differ from those when used consistently and correctly. Use should be
consistent with local regulations regarding the use of contraceptive methods for subjects in clinical studies.
b) Hormonal contraception may be susceptible to interaction with the study drug, which may reduce the efficacy
of the contraceptive method. In addition, consider if the hormonal contraception may interact with the study
drug.
c) Male condom and female condom should not be used together (due to risk of failure with friction).

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10.6. Appendix 6: IMWG Diagnostic Criteria
Multiple myeloma is defined as clonal bone marrow plasma cells 10% or biopsy proven bony or
extramedullary plasmacytomaa and any one or more of the following myeloma defining events:
Myeloma defining events:
o Evidence of end-organ damage that can be attributed to the underlying plasma cell
proliferative disorder, specifically:
Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the ULN or
>2.75 mmol/L (>11 mg/dL)
Renal insufficiency: creatinine clearance <40 mL per minb or serum creatinine >177
μmol/L (>2 mg/dL)
Anemia: hemoglobin value of >20 g/L below the lower limit of normal, or a
hemoglobin value <100 g/Lg
Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-
CTc,d
Any one or more of the following biomarkers of malignancy:
o Clonal bone marrow plasma cell percentagea 60%
o Involved: uninvolved serum FLC ratioe 100
o >1 focal lesions on MRI studiesf
a. 
Clonality should be established by showing κ/λ-light-chain restriction on flow cytometry,
immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be
estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the
highest value should be used.
b. 
Measured or estimated by validated equations.
c. 
If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish
from solitary plasmacytoma with minimal marrow involvement.
d. 
PET-CT=18F-fluorodeoxyglucose positron emission tomography with computed tomography.
e. 
These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The
involved FLC must be 100 mg/L.
f. 
Each focal lesion must be 5 mm or more in size.
g. 
Hemoglobin measurement performed as part of standard of care within 42 days before randomization is
acceptable for screening for CRAB criteria; but must be performed within 21 days before randomization for
other eligibility requirements.
Source: Rajkumar 201439

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10.7. Appendix 7: ECOG Performance Status Grade
Grade 
ECOG Performance Status
0 
Fully active, able to carry on all pre-disease performance without restriction
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a
light or sedentary nature (eg, light house work, office work)
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and
about more than 50% of waking hours
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5 
Dead
Source: Oken 198234

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10.8. Appendix 8: Calculated and Measured Creatinine Clearance
Cockcroft-Gault formula:
To calculate the subject’s creatinine clearance (CrCl), use the following Cockcroft-Gault
formula:
CrCl = (140 - age [in years]) x weight (kg) (x 0.85 for females)
(72 x serum creatinine [mg/dL])
If the serum creatinine is obtained using the International System of Units (SI) (ie, micromol/L),
use the following formula to convert SI units to conventional (mg/dL) units (Manual of
Laboratory and Diagnostic Tests, 2004):
• 
serum creatinine (micromol/L) divided by 88.4 = serum creatinine (mg/dL)
Formula to measure creatinine clearance:
CrCl = UCr x Uvol
PCr x Tmin
Corrected CrCl = CrCl x1.73
BSA
Notes: UCr, Urine creatinine concentration; Uvol, Urine volume from 24 hrs collection; PCr, plasma
creatinine concentration; Tmin, collection time in minutes (24 h x 60 min); BSA, body surface area.
If the BMI of a subject is >30kg/m2, lenalidomide dosing should be based on the CrCl calculated
with adjusted body weight.
Source: Cockcroft and Gault 19769

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10.9. Appendix 9: Modified Diet in Renal Disease Formula
For creatinine in mg/dL, the estimated glomerular filtration rate (e-GFR) for the modified diet in
renal disease (MDRD) formula is:
e-GFR (MDRD) mL/min per 1.73m2= 175 × [serum creatinine (mg/dL)]-1.154 × [age]-0.203 ×
[1.212 if black] × [0.742 if female]
For creatinine in µmol/L, the estimated glomerular filtration rate (e-GFR) for the modified diet
in renal disease (MDRD) formulas is:
e-GFR (MDRD) mL/min per 1.73m2= 175 x [serum creatinine (µmol/L)/88.4]-1.154 × [age]-
0.203 × [1.212 if black] × [0.742 if female]
Source: Levey 200622

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10.10. Appendix 10: Serum Calcium Corrected for Albumin
If calcium is expressed in mg/dL and albumin is expressed in g/dL:
Corrected calcium (mg/dL) =
serum calcium (mg/dL) + 0.8 × (4 - serum albumin [g/dL])
If calcium is expressed in mmol/L and albumin is expressed in g/L:
Corrected calcium (mmol/L) =
serum calcium (mmol/L) + 0.02 × (40 - serum albumin [g/L])
Source: Burtis 19985

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10.11. Appendix 11: Asthma Guidelines
Components of
Severity
Classification ofAsthmaSeverity
Intermittent
Persistent
Mild 
Moderate 
Severe
0-4 
yrs
5-11 yrs 
12 + yrs 
0-4yrs 
5-11 yrs 12 + yrs 
0-4yrs 
5-11 yrs 12 + yrs 
0-4yrs 
5-11 yrs 12 + yrs
Impairment 
Normal
FEV1/FVC :
8-19yr 85% 
20-39yr 80%
40-59yr 75% 
60-80yr 70% 
Symptoms 
≤2 days/week  
≥ 2 days/week but not daily  
Daily  
Throughout the day
Nighttime 
awakenings 
0 
≤2x/month  
1-2x/ 
month  
3-4x/month  
3-4x/ 
month  
> 1x/week but not 
nightly  
> 1x/
month  
Often 7x/week
SABA use for
symptom
control (not
prevention
of EIB)
≤2 days/week  
≤2 days/week but not 
daily
>2
days/
week  
but not
daily,
and
not
more
than 1x
on
any day
Daily  
Several time per day
Interference
with normal 
activity
None  
Minor limitation 
Some limitation  
Extremely limited
Lung function
FEV1 
FEV1/FVC  
N/A
Normal FEV1 
between 
exacerbations
>80% 
>85% 
Normal FEV1
between
exacerbations 
>80%
Normal 
N/A  
>80% 
>80% 
>80% 
Normal 
N/A  
60-80% 
75-80% 
60-80% 
Reduced 
5% 
N/A
<60% 
<75%
<60%
Reduced
5%
Risk  
Exacerbations 
requiring oral 
systemic 
corticosteroids 
0-1/year 
≥2 
exacerbations in  
6 months 
requiring oral 
steroids or >4 
wheezing 
episodes/1-year 
lasting >1 day  
and risk factors 
≥2/year 
Relative 
annual 
risk may
be 
related 
to 
FEV1. 
≥2/year 
Relative 
annual 
risk may  
be 
related 
to 
FEV1. 
≥ 2 
exacerbations 
in 6 months 
requiring oral 
steroids or >4 
wheezing 
episodes/1-year 
lasting >1 day  
and risk factors 
≥ 2/year 
Relative 
annual 
risk may  
be 
related 
to 
FEV1. 
≥ 2/year 
Relative 
annual 
risk may  
be 
related to 
FEV1. 
≥ 2 
exacerbations
in 
6 months 
requiring oral 
steroids or >4 
wheezing 
episodes/ 
1-year lasting
>1 day and
≥2/year 
Relative 
annual 
risk may  
be related 
to FEV1. 
≥2/year
Relative
annual
risk
may be
related
to FEV1.

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Components of
Severity
Classification ofAsthmaSeverity
Intermittent
Persistent
Mild 
Moderate 
Severe
0-4 
yrs
5-11 yrs 
12 + yrs 
0-4yrs 
5-11 yrs 12 + yrs 
0-4yrs 
5-11 yrs 12 + yrs 
0-4yrs 
5-11 yrs 12 + yrs
for persistent 
asthma 
for persistent 
asthma 
risk factors for
persistent
asthma
Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time for subjects in any severity category.
Recommended Step for
Initiating Treatment
Step 1 
Step 2 
Step 3and 
consider short 
course of oral 
steroids 
Step 3: 
medium  
dose 
ICS and 
consider
short 
course 
of oral 
steroids 
Step 3 
and 
consider 
short 
course of 
oral 
steroids 
Step 3and 
consider short 
course of oral 
steroids 
Step 3: 
medium 
dose ICS  
OR Step  
4 and 
consider 
short 
course of
oral
steroids
Step 4
or 5 and
consider
short
course
of oral
steroids
In 2-6 weeks, evaluate level of asthmacontrol that is achieved.
0-4years: If no clear benefit is observed in 4-6 weeks, stop treatment and consider alternate
diagnosis or adjusting therapy. 5-11 and 12+ years: adjust therapy accordingly.

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Components of
Control
Classification of Asthma Control
Well Controlled 
Not Well Controlled 
Very Poorly Controlled
0-4 yrs 
5-11 yrs 
12 + yrs 
0-4 yrs 
5-11 yrs 12 + yrs 
0-4 yrs 
5-11 yrs 
12 + yrs
Symptoms 
≤ 2 days/week but not 
more than once on  
each day  
≤ 2 days/ 
week  
> 2 days/week or
multiple times on 
≤2 days/week  
> 2 days/ 
week
Throughout the day
Impairment
Nighttime
awakenings 
≤ 1x/month  
≤ 2x/month  > 1x/month  ≥ 
2x/month
1-3x/week 
> 1x/week ≥ 2x/week ≥ 4x/week
Interference with
normal activity  
None  
Some limitation  
Extremely limited
SABA use for symptom
control (not prevention of
EIB) 
≤2 days/week  
> 2 days/week  
Several times per day
Lung function 
FEV1 or peak flow  
FEV1/FVC  
N/A  
> 80% 
> 80% 
> 80% 
N/A  
60-80% 
75-80% 
60-80% 
N/A
< 60% 
< 75%
< 60%
Validated questionnaires 
ATAQ  
ACQ
ACT
0 
≤ 0.75  
≥ 20 
1-2 
≥ 1.5  
16-19 
3-4
N/A
≤ 15
Risk
Exacerbations requiring 
oral systemic
corticosteroids 
0-1/year 
≥2/year
Consider severity and interval since last exacerbation
Reduction in lung growth/
Progressive loss of lung 
function
Evaluation requires long-term follow-up
• Maintain current step  
• Regular follow-up every 1- 
6 months 
Step up 1 
step  
Step up at 
least 1 
step  
• Step up 1 
step  
• Reevaluate 
• Consider short 
course of oral 
steroids 
• Step up 1-2 steps 
• Consider
short course
of oral
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Components of
Control
Classification of Asthma Control
Well Controlled 
Not Well Controlled 
Very Poorly Controlled
0-4 yrs 
5-11 yrs 
12 + yrs 
0-4 yrs 
5-11 yrs 12 + yrs 
0-4 yrs 
5-11 yrs 
12 + yrs
Recommended Action for
Treatment
• Consider step down if well 
controlled for at least 3 
months 
• Before step up: 
Review adherence to 
medication, inhaler 
technique, and 
environmental control. 
If alternative treatment 
was used, discontinue 
it and use preferred 
treatment for that step. 
• Reevaluate the 
level of asthma 
control in 2-6 weeks 
to achieve control. 
0-4 years: If no clear 
benefit is observed in  
4-6 weeks, consider 
alternative diagnoses 
or adjusting therapy. 
5-11 years: Adjust 
therapy accordingly. 
• For side effects, 
consider 
alternative 
treatment options. 
in 2-6 
weeks 
• For side 
effects, 
consider 
alternative 
treatment 
options 
• Before step up: 
Review adherence to 
medication, inhaler 
technique, and 
environmental control. 
If alternative treatment 
was used, discontinue 
it and use preferred 
treatment for that step. 
• Reevaluate the 
level of asthma
control in 2-6
weeks to achieve
control.
0-4 years: If no clear
benefit is observed in
4-6 weeks, consider
alternative diagnoses
or adjusting therapy.
5-11 years: Adjust
therapy accordingly.
• For side effects,
consider
alternative
treatment options.
• Step up 1-
2 steps
• Reevaluate
in 2 weeks
• For side
effects,
consider
alternative
treatment
options

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10.12. Appendix 12: Antihistamines That May Be Used Predose
The following antihistamines may be used predose, before Dara-SC injection (including, but not
limited to):
Diphenhydramine
Cetirizine
Fexofenadine
Loratadine
Clemastine
Dexchlorpheniramine
Promethazine*
* The IV use of promethazine should be avoided.

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10.13. Appendix 13: Conversion Table for Glucocorticosteroid Dose
Glucocorticoid  
Approximate Equivalent Dose (mg) 
Half-life (Biologic) hours
Intermediate-Acting
Methylprednisolone 
4 
18-36
Prednisolone 
5 
18-36
Prednisone 
5 
18-36
Triamcinolone 
4 
18-36
Long-Acting
Betamethasone 
0.6 –0.75 
36-54
Dexamethasone 
0.75 
36-54

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10.14. Appendix 14: Body Surface Area Calculation
BSA should be calculated using the Mosteller Formula (shown below); however, the DuBois Formula can
be used as an alternative.

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10.15. Appendix 15: EORTC QLQ-C30

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10.16. Appendix 16: EORTC QLQ-MY20
EORTC QLQ –MY20
Patients sometimes report that they have the following symptoms or problems. Please indicate the extent to which you
have experienced these symptoms or problems during the past week. Please answer by circling the number that best
applies to you.
During the past week: 
Not at 
A Quite 
Very
All 
Little 
a Bit 
Much
31. 
Have you had bone aches or pain? 
1 
2 
3 
4
32. 
Have you had pain in your back? 
1 
2 
3 
4
33. 
Have you had pain in your hip? 
1 
2 
3 
4
34. 
Have you had pain in your arm or shoulder? 
1 
2 
3 
4
35. 
Have you had pain in your chest? 
1 
2 
3 
4
36. 
If you had pain did it increase with activity? 
1 
2 
3 
4
37. 
Did you feel drowsy? 
1 
2 
3 
4
38. 
Did you feel thirsty? 
1 
2 
3 
4
39. 
Have you felt ill? 
1 
2 
3 
4
40. 
Have you had a dry mouth? 
1 
2 
3 
4
41. 
Have you lost any hair? 
1 
2 
3 
4
42. 
Answer this question only if you lost any hair:
Were you upset by the loss of your hair? 
1 
2 
3 
4
43. 
Did you have tingling hands or feet? 
1 
2 
3 
4
44. 
Did you feel restless or agitated? 
1 
2 
3 
4
45. 
Have you had acid indigestion or heartburn? 
1 
2 
3 
4
46. 
Have you had burning or sore eyes? 
1 
2 
3 
4
Please turn to next page

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During the past week: 
Not at 
A Quite 
Very
All 
Little 
a Bit 
Much
47. 
Have you felt physically less attractive as a result
of your disease or treatment? 
1 
2 
3 
4
48. 
Have you been thinking about your illness? 
1 
2 
3 
4
49. 
Have you been worried about dying? 
1 
2 
3 
4
50. 
Have you worried about your health in the future? 
1 
2 
3 
4

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10.18. Appendix 18: New York Heart Association (NYHA) Functional
Classification
NYHA Class Symptoms
Class I: Cardiac disease, but no symptoms and no limitation in ordinary physical activity (eg,
shortness of breath when walking or climbing stairs).
Class II: Mild symptoms (mild shortness of breath or angina) and slight limitation during ordinary
activity.
Class III: Marked limitation in activity due to symptoms, even during less-than-ordinary activity
(eg, walking short distances [20–100 m]). Comfortable only at rest.
Class IV: Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.

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10.19. Appendix 19: Individual and Myeloma-related Risk factors
Risk assessment model for the management of venous thromboembolism in multiple myeloma patents treated
with thalidomide or lenalidomide
Source: Palumbo 200838

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10.20. Appendix 20: Interpretation of The SEBIA Hydrashift 2/4 Daratumumab IFE
Interference test
Background: Clinical response assessment in myeloma relies on serum protein electrophoresis
(SPEP) and immunofixation electrophoresis (IFE). As daratumumab is a monoclonal IgG kappa
antibody, the SPEP and IFE can be positive for daratumumab at the serum levels anticipated during
this protocol.
Implementation: To mitigate this interference, the sponsor will use the SEBIA Hydrashift 2/4
Daratumumab IFE Interference test. During the period of central laboratory analysis, samples will
be sent automatically to the central laboratory if daratumumab interference is suspected.
Interpretation of results: The results will be available to the investigator via the central
laboratory interface and will be reported as follows:
DARA Hydra Impress1:  result defined as “DARA detected”, “DARA not detected”, OR
“DARA indeterminate”
DARA Hydra Impress2:  result defined as “M-protein not detected” OR the specific
protein detected (i.e. “IgG,k” or “IgA”)
DARA Hydra Impress3: result defined as “M-protein not detected” OR the specific
protein detected (i.e. “IgG,k” or “IgA”)
– If Impress1 result is “DARA detected” and Impress2 and 3 results are “M-protein not
detected”, the patient may be in complete response (CR) if the other criteria for CR (including
negative bone marrow aspirate/biopsy) are achieved.
– If Impress1 result is “DARA not detected” or “DARA indeterminate”, the patient is still
positive for underlying (endogenous) monoclonal protein and Impress2 and 3 can inform as
to the type of endogenous protein still present.  Therefore, this patient is not in a complete
response (CR), because the CR response criteria requires a negative SPEP and serum IFE.
– If Impress1 result is “DARA detected” but there is also protein present and reported by
Impress2 or 3, the patient is still positive for underlying (endogenous) monoclonal protein and
Impress2 and 3 can inform as to the type of endogenous protein still present.  Therefore, this
patient is not in a complete response (CR), because the CR response criteria requires a
negative SPEP and serum IFE.

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10.21. Appendix 21: General Guidance on Study Conduct During the COVID-19
Pandemic
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on
the conduct of this clinical study due to, for example, self-isolation/quarantine by subjects and
study-site personnel, travel restrictions/limited access to public places (including hospitals), and
study site personnel being reassigned to critical tasks.
In alignment with health authority guidance, the sponsor is providing options for study related
subject management in the event of disruption to the conduct of the study. This guidance does not
supersede local or government requirements or the clinical judgment of the investigator to protect
the health and well-being of subjects, his- or herself, and site staff. If, at any time, the investigator
assesses that the risk of treatment may outweigh the benefit, study procedure or treatment will be
interrupted, and study follow-up will be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each
contact, subjects will be interviewed to collect safety data. Key efficacy endpoint assessments
should be performed if required and as feasible. Subjects will also be questioned regarding general
health status to fulfill physical examination requirements. The PRO measures can be captured
using site-assisted interview mode where the site will record the subjects’ responses in the
electronic tablet.
Every effort should be made to adhere to protocol-specified assessments for subjects in the study,
including follow-up. Modifications to protocol-required assessments may be permitted after
consultation between the subject and the investigator, and with agreement of the sponsor. Missed
assessments/visits will be captured in the clinical trial management system for protocol deviations.
Dosing delays, discontinuation of study treatments, and withdrawal from the study due to the
coronavirus pandemic should be documented with the prefix “COVID-19-related” in the electronic
case report form (eCRF).
The sponsor will continue to monitor the conduct and progress of the clinical study, and any
changes will be communicated to the sites and to the health authorities according to local guidance.
GUIDANCE SPECIFIC TO THIS PROTOCOL:
Subject Dosing Visits
Evaluate the feasibility for each subject to return for scheduled dosing visits based on the
local situation.
Subjects who miss a scheduled dosing visit may be rescheduled to receive the missed dose
at the next appropriate opportunity. Evaluate the subject’s situation on a case by case basis.
Every effort should be made to keep subjects on treatment if it is in their best interest, and
to maintain phone contact with subjects who are unable to physically visit the hospital to
monitor their safety and medication usage.

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The use of local laboratories for safety evaluations is permitted if access to the treating
hospital is limited. All information should be collected regarding standard values for these
laboratories.
Subject Disease Evaluation Visits
Continue with central laboratory testing to the greatest extent possible. If central laboratory
tests cannot be performed, the use of a local laboratory will be allowed for efficacy
evaluations. Central laboratory testing should be resumed as soon as conditions permit, and
can occur via home health care options or satellite central laboratory locations if available
and approved by the sponsor.
Home Health Care and Tele-Health Visits
In some circumstances, home health care (with approval from sponsor) and tele-health
visits may be implemented per the clinical judgement of the investigator, where feasible
and permissible by local policy and regulations.
Subjects for whom there is no safety concern may have home health care and tele-health
(conducted via phone or video conference) visits.
See Section 8.3.1 for further details.
Exposure to COVID-19
In the event a subject requires treatment for a coronavirus infection, refer to the protocol
to determine any requirements for dose hold, dose modifications, or other prohibitions and
considerations. Report the COVID-19 infection as an adverse event (AE) and any
concomitant medications (CM) used to treat it to the sponsor following the usual CM and
AE reporting requirements. Ensure any AEs of COVID-19 include the exact term
“COVID-19” and any serious adverse events (SAE) document confirmed infection with
coronavirus.
It is important to follow local health authority guidance specific to your region of practice,
such as social distancing, masking in public places, and vaccinations, including boosters.
In the event a subject is diagnosed with a COVID-19 infection and requires treatment or is
eligible for prophylactic treatment after contact with an individual infected with
COVID-19, ensure that the subject receives all necessary treatments for COVID-19 that
are approved (including those available under Emergency Use Authorization) in the
country including, but not limited to antiviral drugs (eg. remdesivir, ritonavir, favipiravir,
molnupiravir, paxlovid), monoclonal antibodies (casirivimab and imdevimab,
bamlanivimab and etesevimab, sotrovimab), and dexamethasone.
On-site Monitoring Visits
In the event on-site monitoring visits are not possible, as per institution policies, the
sponsor’s site managers may contact the investigator to arrange remote monitoring visits.

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Additional on-site monitoring visits may be needed in the future to catch up on source data
review and verification.
Study Drug Supply
Since daratumumab must be administered in the clinic and closely monitored by
well-trained health care providers, shipment of daratumumab to patients for at-home
administration is not permitted.
A direct-to-patient delivery of oral, self-administered medication will be allowed within
countries where this is appropriate. This decision was made to allow study subjects access
to oral study treatments in the event they miss scheduled dosing visits due to the pandemic.
Therefore, iflocally permitted, alternative solutions to arrange direct-to-patient provision
of oral lenalidomide or dexamethasone that are part of the treatment regimen can be
discussed with the Medical Monitor.
A caregiver or family member may pick up oral study drug on behalf of the subject if first
discussed with and agreed by the subject. The conversation with the subject must be
documented in the subject's source records. The subject must name the individual who will
pick up study drug on the subject’s behalf. This is necessary for site staff to confirm the
study drug is provided to the appropriate individual, ensure proper chain of custody of
study drug, and to maintain subject privacy. Identification of who will pick up the study
drug must be confirmed and documented in the subject's source record.
Protocol Deviations
All deviations from the study protocol will be reported based on standard guidance. If
related to the coronavirus pandemic situation, these deviations will be recorded as
“COVID-19-related” prefix or category.

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10.22. Appendix 22: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).
Amendment 5 (24 March 2022)
Overall Rationale for the Amendment:  To mitigate the impact of Coronavirus Disease 2019
(COVID-19) pandemic. Changes applied to the relevant sections of the protocol are summarized below.
Section Number 
and Name
Description of Change 
Brief Rationale
6.8.2 Permitted 
Therapies 
Text was updated to include COVID-19 vaccine
permitted for study use. Verbiage clarified live,
attenuated vaccines or those with suspected
replication capabilities are not permitted.
To mitigate the impact of
COVID-19 pandemic on study
conduct/procedures.
8.1.1 Overview  
The text in strikethrough has been deleted:
‘During the treatment phase and prior to PD, the
PRO measures will be completed using an
electronic tablet (ePRO) by the subject, unless the
subject is unable to complete the visit in-person.’
Text has been removed to allow the
site coordinator or proxy to use the
electronic tablet to enter PRO
responses on the subject’s behalf.
10.21 Appendix 21: 
General Guidance 
on Study Conduct 
During the
COVID-19
Pandemic
Amendment includes recommendation for
vaccinations and therapies for COVID-19
infections.
To mitigate the impact of
COVID-19 pandemic on study
conduct/procedures.
Throughout the 
protocol 
Minor grammatical, formatting, or spelling
changes were made.
Minor errors were noted.
Amendment 4 (1 October 2020)
Overall Rationale for the Amendment: To update the timeframes and landmark analyses for primary
analysis of minimal residual disease (MRD) negativity rate. Primary endpoint of MRD negativity remains
unchanged, but primary analysis will now occur at approximately 18 months in order to maximize MRD
samples available for primary analysis, to ensure the maturity of MRD negativity at the primary analysis,
and to mitigate the impact of Coronavirus Disease 2019 (COVID-19) pandemic on MRD sample collection.
Section number 
and Name
Description of Change 
Brief Rationale
Synopsis: Statistical
methods; 4.1. Overall Study
Design; 4.2. Scientific
Rationale for Study Design,
Rationale for MRD as a
Primary Endpoint
Text was updated to clarify that primary
analysis of the overall MRD negativity rate
will be performed at approximately
18 months after the last subject is
administered his/her first dose of study
treatment instead of 1 year.
To maximize MRD samples
available for primary analysis due
to COVID-19 pandemic. This will
further ensure the maturity of the
MRD negativity at the primary
analysis, supported by the previous
daratumumab studies (MMY3007
and MMY3008) in which
accumulative MRD negativity rate
plateaued at 18 months.
3.1.1. Objectives,
Secondary objectives
Secondary objective “To evaluate
patient-reported outcomes (PROs)” was
included. This was previously indicated as
an exploratory endpoint.
Moved from exploratory to
secondary objective.
3.1.2. Endpoints, Secondary
Endpoints
Other secondary endpoint “Mean change
from baseline in the European Organization
for Research and Treatment of Cancer
Moved from exploratory endpoint
to secondary endpoint.

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Section number 
and Name
Description of Change 
Brief Rationale
Quality of Life Questionnaire (EORTC
QLQ) core 3-item (EORTC QLQ-C30) and
the multiple myeloma 20-item (EORTC
QLQ-MY20), and EuroQol Five Dimension
Questionnaire (EQ-5D-5L) scales” was
included.
The endpoint was moved from exploratory
to secondary objectives and further defined
as the mean change from baseline.
8.1.1. Overview  
Text was updated to include that the PRO 
measures will be completed using an 
electronic tablet (ePRO) by the subject or 
with site-assisted telephone administration,
per applicable interview-mode
questionnaire.
To accommodate the site-assisted
telephone option as part of the
COVID-19 mitigation strategy.
8.2.1. Response Categories 
Text was updated to clarify that the local 
laboratory results of blood and urine 
M-protein measurements may be used to 
determine disease response and progression. 
Local laboratories may be used to
determine response as well, in
exceptional circumstances, as a
part of the COVID-19 mitigation
strategy.
8.2.4. Bone Marrow 
Examination  
Text was updated to clarify that archived 
samples for MRD or cytogenetic evaluation 
may be requested to be sent to the central 
laboratory, if available, in cases in which 
there is difficulty in establishing baseline
clonality for MRD or if screening baseline
cytogenetics are not evaluable
To mitigate cases in which
baseline samples were not
evaluable for either cytogenetics or
a baseline clone for MRD.
8.3.1. Home Health Care 
and Tele-Health Visits 
A new section was included to describe 
home health care and tele-health visits with 
approval from the sponsor and per the 
clinical judgement of the investigator, where
feasible and permissible by local policy and
regulations.
To mitigate the impact of
COVID-19 pandemic on study
conduct/procedure.
8.3.6. Clinical Safety 
Laboratory Assessments 
Urea was deleted from Serum Chemistry 
Panel during Cycles 1 through 8. 
Blood urea nitrogen (BUN) was added in 
Serum Chemistry Panel during Cycle 9 and 
beyond.
To delete duplicate urea sampling
and to add BUN analysis in Cycles
1 through 8 and 9 and beyond by
allowing either BUN or urea.
10.21. Appendix 21: 
General Guidance on Study 
Conduct During the 
COVID-19 Pandemic
New appendix was added. 
To mitigate the impact of
COVID-19 pandemic on study
conduct/procedure.
Throughout the protocol 
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted
Amendment 3 (19 November 2019)
Overall Rationale for the Amendment:The overall reason for the amendment is to expand the scope of
efficacy review by Independent Data Monitoring Committee (IDMC) at different stages in the study.
Additionally, to ensure that the subjects continue to receive treatment with other components of study
treatment even if any one component is held, discontinued or reduced, to clarify that subsequent
anti-myeloma therapies should not be administered until disease progression and in subjects who
discontinue study treatment for reasons other than disease progression, should be monitored and subsequent
treatment should not be started until documented disease progression. To provide clarifications regarding

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the company which will conduct the Food and Drug Administration (FDA)-approved clonoSEQ minimal
residual disease (MRD) assay and which version will be used.
Section number 
and Name
Description of Change 
Brief Rationale
4.1. Overall Study 
Design; 4.2.1. 
Study-Specific Ethical 
Design 
Considerations; 9.8. 
Independent Data 
Monitoring
Committee
Updated text regarding IDMC review to add efficacy 
review along with safety review after each interim review 
at the primary MRD analysis and the interim analysis of 
progression-free survival (PFS) in order to make 
recommendations regarding unblinding and continuation
of the study.
To expand scope of IDMC
review to include efficacy
review at different stages
in the study.
6.6.2.2. 
Daratumumab-Related 
Toxicity Management 
Text was added to clarify that treatment with bortezomib, 
lenalidomide and dexamethasone may be continued if 
daratumumab is held or discontinued. 
To ensure that the subjects
continue to receive
treatment with other
components of study
treatment even if any one
component is held,
discontinued or reduced.
6.6.3. Lenalidomide 
Text was added to clarify that treatment with bortezomib, 
dexamethasone, and daratumumab (Arm B only) may be 
continued if lenalidomide is held or discontinued. 
6.6.4. Bortezomib  
Text was added to clarify that treatment with 
lenalidomide, dexamethasone, and daratumumab (Arm B
only) may be continued if bortezomib is held or
discontinued.
6.6.5. Dexamethasone 
Text was added to clarify that treatment with bortezomib,
lenalidomide, and daratumumab (Arm B only) may be
continued if dexamethasone dose is reduced or
interrupted.
6.8.4. Subsequent 
Therapies 
Text regarding non-permissibility of subsequent therapies 
until disease progression was further clarified. 
To clarify that subsequent
therapies should not be
administered until disease
progression is confirmed.
4.2. Scientific 
Rationale for Study 
Design  
The name of the company who will conduct the 
FDA-approved clonoSEQ v2.0 MRD assay was changed 
from “Adaptive Biotechnology” to “Adaptive 
Biotechnologies”. 
To specify that only
FDA-approved clonoSEQ
v2.0 will be used in this
study for MRD analysis
and correct the name of the
company who will conduct
this analysis.
8.8. Biomarkers 
Text regarding use of any other alternative method for 
MRD assessment was deleted and text regarding use of 
only FDA-approved clonoSEQ v2.0 conducted at 
Adaptive Biotechnologies was added.
9.4.4. Other Analyses 
Text regarding use of the FDA-approved clonoSEQ v2.0
MRD assay was added.
1.3. Schedule of 
Activities (SOA); 6.3. 
Bortezomib (Arms A 
and B) 
Text was edited to specify that ifa subject’s weight 
changes by more than 10% from baseline, the weight used 
for drug calculations should be adjusted and the dose of 
bortezomib will be re-calculated. 
Bortezomib dose will be
re-calculated ifa subject’s
weight changes by more
than 10% from baseline.
1.3. Schedule of 
Activities (SOA) 
Added a window of ±1 week for hepatitis B virus (HBV)- 
deoxyribonucleic acid (DNA) test which occurred every 6 
weeks on Day 1, 8 and 15 for Cycles 1 to 8 with the
exception of Cycle 1 Day 1.
Added a window of ±1 month for HBV-DNA test which
occurred every 12 weeks on Day 1, end of treatment
(EOT) and prior to progressive disease (PD) for Cycles 9
and beyond, EOT, prior to PD and post PD.
To allow a window period
for HBV-DNA testing.
2.1.5. Clinical Studies 
Updated the list of indications for which daratumumab is 
approved in the United States (US). 
To align with current
approvals for daratumumab
in the US.

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Section number 
and Name
Description of Change 
Brief Rationale
3.1.2. Endpoints 
The definition of MRD negative status was revised to 
clarify that subjects who achieve MRD negativity after 
the switch to subsequent antimyeloma therapy will not be 
considered MRD negative.
The reference to International Myeloma Working Group
(IMWG) PD criteria was added and reference to IMWG
diagnostic criteria was deleted.
To clarify definition of the
primary endpoint and
revise references.
4.2. Scientific 
Rationale for Study 
Design  
The text regarding enzyme recombinant human 
hyaluronidase (rHuPH20) was modified. 
To clarify the use of
rHuPH20 in the
daratumumab
subcutaneous (SC)
formulation.
5.1. Inclusion Criteria 
(Criterion 5) 
Added text to clarify use of adjusted body weight if body 
mass index (BMI) is >30 kg/m2 while calculating 
creatinine clearance using the Cockcroft-Gault formula. 
To clarify use of adjusted
body weight while
calculating creatinine
clearance during the
Screening Phase.
5.2. Exclusion Criteria 
(Criterion 2) 
The maximum limit of 4 days for prior therapy with 
dexamethasone was removed. 
To allow longer courses of
prior therapy with
dexamethasone.
5.2. Exclusion Criteria 
(Criterion 5) 
Patients with palliative focal radiotherapy for 
symptomatic pain management can participate in the 
study. 
To allow a greater number
of patients undergoing
radiotherapy to participate
in the study.
5.2. Exclusion Criteria 
(Criterion 10b) 
Modified the definition of subjects seropositive for 
hepatitis B. 
To ensure consistency with
the Centers for Disease
Control (CDC)
terminology for
hepatitis B.
5.3. Restrictions 
During Study 
Participation  
Additional text regarding the pregnancy prevention plan 
for lenalidomide was added. 
To further clarify the
measures to mitigate the
risk of embryo-fetotoxicity
associated with
lenalidomide.
1.3. Schedule of 
Activities (SOA) 
footnote e 
Text regarding requirement of pregnancy test for women 
with regular and irregular menstrual cycles after last dose 
of lenalidomide was added.
6.1.2. Daratumumab 
Administration  
The text regarding major protocol deviation criteria for 
daratumumab administration was modified. 
To ensure consistency with
the MPD criteria for
daratumumab
administration and add
clarification to allow
administration of
lenalidomide at night, as it
is the standard of care.
The text was added to allow for option to administer 
lenalidomide at night. 
6.3. Bortezomib 
(Arms A and B); 
6.6.4. Bortezomib  
The text regarding minimum time period “must be at least 
72 hours” between two doses of bortezomib was modified 
to “should be approximately 3 days”. 
To allow flexibility in the
time period between two
doses of bortezomib.
6.6.1. Cycle delay  
The text regarding cycle delay “from the planned start of 
new cycle” was deleted. 
To allow flexibility in the
counting the time period
from the last cycle when
none of the study
medications are given.
6.6.3.1. Renal 
Impairment 
Text was added to specify that lenalidomide doses can be 
re-escalated at the investigator’s discretion in the event of 
dose adjustment in subjects with changes in renal status
during treatment.
To clarify lenalidomide
dose re-escalation

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Section number 
and Name
Description of Change 
Brief Rationale
6.6.5. Dexamethasone 
(Table 8) 
Text was added to clarify that dexamethasone will be 
skipped on days when daratumumab is not given on 
Arm B, or corresponding days for Arm A..
To clarify dexamethasone
dose reduction guidelines.
6.6.6. Dose 
Modification 
Guidelines 
A note was added regarding importance of physician’s 
discretion and clinical judgement. 
Physician’s discretion and
clinical judgement should
prevail in dose
modification decisions.
6.8.1.2. 
Bisphosphonate 
Therapy and 
Denosumab
Text was added to describe addition of denosumab as an 
alternative to bisphosphonate therapy. 
To allow denosumab as an
alternative to
bisphosphonate therapy.
6.8.1.4. Prophylaxis 
for Bacterial 
Pneumonia and 
Pneumocystis Carinii 
Pneumonia 
Text regarding bacterial pneumonia was added. 
To include bacterial
pneumonia in the list of
diseases for which
prophylaxis is
recommended.
6.8.3. Prohibited 
Therapies 
Prednisone was deleted and dexamethasone was added, 
and maximum dose of dexamethasone was further 
described. 
To define prohibited
corticosteroid, use to be
consistent with doses that
have an anti-myeloma
effect.
7.2. Discontinuation 
of Study Treatment 
The word ‘one’ was deleted. 
To clarify the wording
regarding discontinuation
of any component of the
study treatment.
8.1.2. Screening Phase The wording “Cycle 1 Day 1” was deleted and 
“randomization” was added. 
To clarify that timing of
screening procedures will
be performed within 28
days before randomization.
8.2.4. Bone Marrow 
Examination  
The text regarding bone marrow examination was revised 
and details regarding which laboratories (central versus 
local laboratory) would perform bone marrow aspirate or 
bone marrow biopsy, or both were added.
To clarify the bone marrow
assessment laboratory
details.
8.2.6. Assessment of 
Lytic Disease 
Text regarding IMWG diagnostic criteria (SLiM criteria 
[S=≥Sixty-percent (≥60%) clonal BM plasma cells; 
Li=serum free Light chain ratio involved: uninvolved 
≥100; M=>1 focal lesion (≥5 mm each) detected by 
magnetic resonance imaging (MRI) studies]) and MRI
lesion was added.
To align with IMWG
diagnostic criteria (SLiM
criteria) for assessment of
lytic disease.
8.3.4. 
Electrocardiogram  
The text was revised to recommend that procedures will 
be performed in the following order: electrocardiogram 
(ECG), vital signs, and blood draw. 
To allow more flexibility
in the order of performing
the assessments.
8.3.5. Clinical Safety 
Laboratory 
Assessments 
Serum urea test was added during Cycles 1 to 8. 
To clarify the clinical
safety laboratory
assessments and allow
flexibility of conducting
the laboratory tests at the
local laboratory.
8.3.5. Clinical Safety 
Laboratory 
Assessments 
Text for assessment of calcium and albumin adjusted 
calcium test was revised to allow local laboratory 
assessments under exceptional circumstances if central 
laboratory is not evaluable.
8.4.1. Time Period 
and Frequency for 
Collecting Adverse
Event and Serious
Adverse Event
Information
The word ‘procedure’ was replaced with ‘treatment’. 
To clarify adverse event
(AE) reporting period.

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Section number 
and Name
Description of Change 
Brief Rationale
3.1.1. Objectives 
The patient-reported outcome (PRO) was moved from 
secondary to exploratory objective. 
To clarify that the PRO
endpoints will be for
exploratory purpose.
3.1.2. Endpoints 
The PRO endpoint was deleted from the list of secondary 
endpoints.
9.6. Patient-reported 
Outcomes Analyses 
The text regarding the PRO analyses was revised to
indicate that these analyses are now exploratory.
10.2. Appendix 2: 
Anticipated Events 
Anemia, neutropenia, and thrombocytopenia were deleted 
from the anticipated events list. The review and reporting 
requirements for anticipated events were clarified. 
Revised “Anticipated Event Review Committee” (ARC) 
to “Safety Assessment Committee” (SAC). 
Modified the list of
anticipated events to
remove any events that are
known ADRs of
daratumumab. Clarification
that after unblinding of
aggregate safety data by
the sponsor’s study team,
there is no need for
independent SAC review
of anticipated
events. Additional
clarification of the
reporting responsibilities
for anticipated events to
Health Authorities and
Institutional Review
Boards (IRB)/Independent
Ethics Committees (IEC).
Changed name of
committee to be in
alignment with company
procedures.
10.3. Appendix 3: 
Regulatory, Ethical, 
and Study Oversight 
Considerations 
The details regarding IDMC were added. 
To describe further that the
IDMC will be established
according to regulatory
guidelines.
10.4. Appendix 4: 
Adverse Events 
Definitions and 
Procedures for 
Recording,
Evaluating,
Follow-up, and
Reporting
Removed definitions of severity criteria as they are 
specified in the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI-CTCAE) 
v 5.
Clarification to correct
NCI-CTCAE version
inconsistency.
Throughout the 
protocol 
Minor grammatical, formatting, spelling or missed 
changes were made.
Minor errors were noted.
Amendment 2 (18 January 2019)
Overall Rationale for the Amendment:  The overall reason for the amendment is in response to
identification of a new important risk (hepatitis B virus [HBV] reactivation). Additionally, revisions and
clarifications were made to considerations for lenalidomide use, sequence of secondary endpoints, as well
as other measurement parameters throughout the Protocol.
Section number 
and Name
Description of Change 
Brief Rationale
Table 1 Schedule of
Activities
Added row for HBV serology, modified text for
HBV DNA test, and identified the timepoints at
The text for identification of
HBV reactivation, testing, and

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Section number
and Name
Description of Change 
Brief Rationale
5.2 Exclusion
Criteria (Criterion
10)
6.8.1.7 Management
of Hepatitis B Virus
Reactivation
8.1.1 Overview
8.3.7 HBV Serology
and DNA Tests
References
which HBV serology and HBV DNA test would be
conducted.
Clarified language to exclude subjects who are
seropositive for hepatitis B.
Added a new section providing information for the
management of hepatitis B virus reactivation.
Corrected the blood volume to be collected during
Screening to approximately 50 mL, thus accounting
for HBV serology.
Added and revised information detailing the conduct
of hepatitis B virus serology and DNA tests.
Removed reference: Drafting Committee for
Hepatitis Management Guidelines and the Japan
Society of Hepatology (JSH). Guidelines for the
Management of Hepatitis B Virus Infection. Hepatol
Res. 2014;44 Suppl S1:1-58.
Added reference: Tang DI, Geller NL. Closed testing
procedures for group sequential clinical trials with
multiple endpoints. Biometrics. 1999;55:1188-1192.
management of subjects with the
potential for HBV reactivation
was added or modified in
response to identification of a
new important risk (HBV
reactivation).
5.1 Inclusion
Criteria (Criterion 5)
Added “>” sign for hemoglobin >7.5 g/dL, absolute
neutrophil count (ANC) >1.0 x 109/L, and platelet
count >70 x 109/L
Clarifications were made to the
clinical laboratory value criteria
during the Screening Phase.
5.3 Restrictions
During Study
Participation
7.2 Discontinuation
of Study Treatment
Contraception must begin 4 weeks before initiating
treatment with daratumumab and lenalidomide, and
continue during the Treatment Phase, during dose
interruptions and continuing for 4 weeks after the
last dose of lenalidomide and 3 months following of
the last dose of daratumumab.
Added clarification to discontinuation of study
treatment if the subject becomes pregnant: unless the
subject (or the subject's legally acceptable
representative), investigator, and sponsor agree the
benefits outweigh the risks to the fetus and
continuation of study treatment, except for
lenalidomide, is in the best interests of the subject.
Clarification was provided
regarding the prohibition of
treatment with lenalidomide
during known pregnancy or
potential for pregnancy.
9.4.2 Efficacy
Analyses
Text indicating the sequence of secondary endpoints
was replaced: A hierarchical testing approach will be
used to control the family wise Type I error rate at a
2 sided level of 0.05 for key secondary efficacy
endpoints such as PFS, durable MRD negativity rate,
and rate of CR or better. Details of the procedure will
be specified in the SAP prior to any unblinded
analysis. If the primary endpoint of overall MRD
negativity rate is statistically significant, the key
secondary endpoints (ie, CR or better rate, PFS,
Clarification was made to the
analysis of secondary endpoints.

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Section number
and Name
Description of Change 
Brief Rationale
and durable MRD negativity rate) will be
sequentially tested, each with an overall two-sided
alpha of 0.05, by utilizing a hierarchical testing
approach as proposed by Tang and Geller (1999)
that strongly controls family wise Type I error
rate.
10.20 Appendix 20:
Interpretation of the
SEBIA Hydrashift
2/4 Daratumumab
IFE Interference
Test
The following text was modified: Implementation: 
To mitigate this interference, the sponsor will use the 
SEBIA Hydrashift 2/4 Daratumumab IFE 
Interference test. to distinguish a positive SPEP/IFE 
due to the presence of daratumumab versus the
presence of the underlying (endogenous) monoclonal
protein.  The SEBIA Hydrashift 2/4 Daratumumab
IFE Interference test Samples will be sent
automatically to the central laboratory if
daratumumab interference is suspected. a subject
with IgG kappa multiple myeloma has an SPEP at or
below 0.2 g/dL on 2 or more consecutive cycles. In
addition, the SEBIA Hydrashift 2/4 Daratumumab
IFE Interference test will be sent automatically to the
central laboratory if a subject has an SPEP of zero,
but persistently positive IFE for IgG kappa on 2 or
more occasions.
Clarification was made to the
implementation of the SEBIA
Hydrashift 2/4 Daratumumab IFE
Interference test.
Table 1 Schedule of
Activities
8.3.5 Clinical Safety
Laboratory
Assessments
10.6 Appendix 6:
IMWG Diagnostic
Criteria
Table 1 was updated to include instruction row for 
measurement of creatinine clearance. 
The notes for Bone marrow aspirate/biopsy were
clarified: For screening (collected within 42 days
before randomization) fresh aspirate required
(archived samples will not be accepted).
Modified creatinine measurement during Cycle 9 and
beyond: creatinine clearance (measured or
calculated).
Footnote g was added for the event of anemia:
Hemoglobin measurement performed as part of
standard of care within 42 days before
randomization is acceptable for screening for
CRAB criteria; but must be performed within 21
days before randomization for other eligibility
requirements.
Minor changes and clarifications
were made throughout.
Throughout the
protocol
Minor grammatical, formatting, or spelling changes
were made.
Minor errors were noted.
Amendment 1 (10 September 2018)
Overall Rationale for the Amendment:  To add language describing hepatitis testing, which is now
required across daratumumab studies for subjects who are positive for anti-HBc and/or anti-HBs.
Section number 
and Name
Description of Change 
Brief Rationale
Table 1: Schedule of Activities - 
Treatment and Follow-Up Phases 
Requirements for HBV-DNA monitoring 
at various timepoints during the study have 
Language regarding hepatitis
testing for subjects who are

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Section number
and Name
Description of Change 
Brief Rationale
Section 8.3.7: HBV-DNA Test
been added to the Time and Events 
Schedule. 
Clarification has been made to the
requirements for HBV-DNA testing.
positive for anti-HBc and/or
anti-HBs has been added.
Table 1: Schedule of Activities -
Treatment and Follow-Up Phases
Section 8.3.3: Vital Signs
Text added to specify that for Arm A, vital
signs are required only on Day 1 of every
cycle.
Details on the requirements for the
collection of vital signs has been added.
Clarification to vital sign
collection for subjects in Arm
A versus Arm B has been
made.
Table 2: Schedule of Activities -
Pharmacokinetic/Immunogenicity
Sample Collection Times –Arm
B ONLY
Posttreatment Week 4 collections have
been deleted.
Changes and clarifications
made to the timepoints for
collection of pharmacokinetic
and immunogenicity samples.
Section 8.1.1: Overview
Section 8.2.1: Response
Categories
New Appendix 20 (Section
10.20) Interpretation of The
SEBIA Hydrashift 2/4
Daratumumab IFE Interference
test
Table 11 added
Section 8.2.2: Myeloma Protein
Measurements in Serum and
Urine
Section 8.2.4: Bone Marrow
Examination
Section 8.8: Biomarkers
Section 9.4.4: Other Analyses -
Biomarker Analyses
Table 11 Bone Marrow Testing
To coincide with the revisions made to the
biomarker assessments and provide more
granularity in the breakdown of the blood
volumes for this study, the estimated total
blood volumes have been updated.
Added text to indicate that for subjects
with suspected daratumumab interference
on SPEP and immunofixation, a reflex
assay will be performed.
Included a description of the new SEBIA
Hydrashift 2/4 Daratumumab IFE
Interference test that will be used to
distinguish a positive SPEP/IFE.
Clarified the requirements for a fresh bone
marrow aspirate at screening and the MRD
assessment for cytogenetics evaluations.
 
Clarified the process for how the bone
marrow aspirate will be portioned out for
assessment. The title of the table was also
revised.
To update biomarker
assessments to require
mandatory a fresh bone
marrow aspirate for
cytogenetics and to remove the
option for archived sample for
MRD at screening. Also, the
description of the SEBIA
Hydrashift Interference Test
has been added to the protocol.
Appendix 4 (Section 10.4)
Attribution Definitions
Appendix 4 (Section 10.4)
Procedures
Revised the AE attribution definitions to
limit to:
Not Related: An adverse event that is not
related to the use of the drug
Related: An adverse event that might be
due to the use of the drug
To align with the revision to the AE
attribution definitions, revised text as
follows: “For subjects who have received
additional treatment with therapeutic intent
for multiple myeloma during the AE
reporting period, only AEs that are
considered to be possibly, probably, or
definitely related to the study drug or any
part of the backbone treatment regimen
To coincide with the causality
options presented on the
revised SAE reporting form,
the AE attribution definitions
have been revised.

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Section number
and Name
Description of Change 
Brief Rationale
must be reported (unless the subject has
been withdrawn from the study).”
Table 1: Schedule of Activities -
Treatment and Follow-Up Phases
Table 5 Dose Modification
Guidelines for Bortezomib,
Lenalidomide, and
Dexamethasone
Section 5.1 Inclusion Criteria
Criterion #6g
Section 5.2:
Exclusion criterion #2
Exclusion criterion #11
Section 6.8.1.1 Prevention of
Deep Vein Thrombosis and
Pulmonary Embolism
Section 8.2.3: Albumin and
Serum Calcium Corrected for
Albumin
Appendix 9 (Section 10.9)
Clarifications regarding hematology, 
serum chemistry, and HBV-DNA 
collection have been made. 
Revised footnote f to specify that
creatinine clearance is calculated by the
Cockcroft-Gault formula and adjusted for
body weight in subjects with a body mass 
index >30 kg/m
2
and that the eGFR
(MDRD) or CKD-epi formulas can also be
utilized to assess renal function.
Exclusion criterion #2 has been revised.
Exclusion criterion #11 has been revised.
Linked to the correct appendix
Revised text to specify that blood samples
for calculating serum calcium corrected for
albumin are to be analyzed by the central
laboratory rather than by local laboratories.
Modified Diet in Renal Disease Formula
has been added
Miscellaneous
edits/clarifications have been
made to the protocol.
Throughout the protocol 
Minor grammatical, formatting, or spelling
changes were made.
Minor errors were noted.

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11. 
REFERENCES
1. 
Ariza-Heredia EJ, Chemaly RF. Practical review of immunizations in adult patients with cancer. Hum Vaccin
Immunother. 2015;11(11):2606-2614.
2. 
Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with
transplantation for myeloma. N Engl J Med. 2017;376:1311-1320.
3. 
Avet-Loiseau H, Casneuf T, Chiu C, et al. Evaluation of minimal residual disease (MRD) in
relapsed/refractory multiple myeloma (RRMM) patients treated with daratumumab in combination with
lenalidomide plus dexamethasone or bortezomib plus dexamethasone. ASH Annual Meeting Abstracts. 2016;
Abstract 246. http: ash.confex.com/ash/2016/webprogram/Paper96569.html. Accessed 08 May 2017.
4. 
Benbouker L, Dimopoulos MA, Dispenzieri A et al. Lenalidomide and dexamethasone in transplant-ineligible
Patients with Myeloma. N Engl J Med. 2014;371:906-917.
5. 
Burtis CA, Ashwood ER. Tietz. Textbook of Clinical Chemistry, 3rd ed. Philadelphia; WB Saunders, 1998
6. 
Chapuy C, Nicholson R, Aguad MD, et al. Resolving the daratumumab interference with blood compatibility
testing. Transfusion. 2015;55:1545-1554.
7. 
Chapuy CI, Aguad MD, Nicholson RT, et. al, International validation of a dithiothreitol (DTT)-based method
to resolve the daratumumab interference with blood compatibility testing. Transfusion. 2016;56(12):2964-
2972.
8. 
Chari A, Arinsburg S, Jagannath S, et al. Blood Transfusion Management and Transfusion-Related Outcomes
in Daratumumab-Treated Patients With Relapsed or Refractory Multiple Myeloma. Clin Lymphoma Myeloma
Leuk. 2018;18(1):44-51.
9. 
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-
41.
10. Cocks K, Cohen D, Wisløff F, et al. An international field study of the reliability and validity of a disease-
specific questionnaire module (the QLQ-MY20) in assessing the quality of life of patients with multiple
myeloma. Eur. J. Cancer. 2007;43:1670-1678.
11. Dimopoulos MA, Oriol A, Nahi H et al. Daratumumab, lenalidomide, and dexamethasone for multiple
myeloma. [MMY3003] N Engl J Med 2016;375:1319-1331.
12. Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma.
Leukemia. 2006;20:1467–1473. Corrigenda/Erratum in: Leukemia. 2007;21:1134-1135.
13. Durie BG, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide
and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous
stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389(10068):519-
527.
14. Facon T, Dimopoulos MA, Dispenzieri A, et al. Initial Phase 3 Results Of The FIRST (Frontline Investigation
Of Lenalidomide + Dexamethasone Versus Standard Thalidomide) Trial (MM-020/IFM 07 01) In Newly
Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible For Stem Cell Transplantation (SCT). Blood.
October 21, 2013 vol. 122 no. 21 2. ASH 2013 Meeting Abstract.
http://bloodjournal.hematologylibrary.org/content/122/21/2.abstract?sid=06133b3d-094e-452b-aeb2-
f12d2a83ce53. Accessed 16 January 2014.
15. Facon T, Meletios A, Dimopoulos MA, Dispenzieri A et al. Final analysis of survival outcomes in the phase 3
first trial of up-front treatment for multiple myeloma. Blood. 2018;131:301-310.
16. Fayers PM, Palumbo A, Hulin C, et al. Thalidomide for previously untreated elderly patients with multiple
myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials.
Blood. 2011;118(5):1239-47.
17. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of
Medicine (2007). "/clinpharm/ddis/clinical-table/" Accessed 29 Mar 2018.
18. Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of
the EQ-5D (EQ-5D-5L). Qual Lif Res. 2011;20:1727-1736.

JNJ-54767414 (daratumumab)
Clinical Protocol 54767414MMY3019 Amendment 6
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Status: Approved, Date: 14 March 2024
19. Ladetto M, Brüggemann M, Monitillo L, et. al. Next-generation sequencing and real-time quantitative PCR for
minimal residual disease detection in B-cell disorders. Leukemia. 2014;(6):1299-307. doi:
10.1038/leu.2013.375. Epub 2013 Dec 17.
20. Lahuerta JJ, Mateos MV, Martinez-Lopez J, et al. Influence of pre- and post-transplantation responses on
outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete
response are associated with longer survival. J Clin Oncol 2008;26:5575-5782.
21. Landgren O, Giralt S. MRD-driven treatment paradigm for newly diagnosed transplant eligible multiple
myeloma patients. Bone Marrow Transplant. 2016;51(7):913-914.
22. Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in
renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145:247-254.
23. Lonial S, Weiss B, Usmani S, et al. Daratumumab monotherapy in patients with treatment-refractory multiple
myeloma (SIRIUS): an open-label, randomized, phase 2 trial. Lancet. 2016;387:1551-1560.
24. Martinez-Lopez J, Lahuerta JJ, Pepin F, et al. Prognostic value of deep sequencing method for minimal
residual disease detection in multiple myeloma. Blood. 2014. DOI 10.1182/blood-2014-01-550020.
25. McCudden, CR, Voorhees PM, Hainsworth SA, et al. Interference of monoclonal antibody therapies with serm
protein electrophoresis tests. Clin Chem 2010;56(12):1897-1899.
26. Moreau P, Mary J-Y, Attal, M. Bortezomib-thalidomide-dexamethasone versus bortezomib-
cyclophosphamide-dexamethasone as induction therapy prior to autologous stem cell transplantation in
multiple myeloma. British Journal of Haematology. 2015;168:604-614.
27. Moreau P, Miguel JS, Sonneveld P, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis,
treatment and follow-up. Annals of Oncol. 2017;0:1–11.
28. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in
patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol.
2011;12(5):431-440.
29. Moreau P, San Miguel J, Ludwig H, et al. Multiple Myeloma: ESMO Clinical Practice Guidelines for
Diagnosis, Treatment, and Follow-up. Ann Oncol. 2013; 1-5. Epub ahead of print:
doi:10.1093/annonc/mdt297.
30. Munshi NC, Avet-Loiseau H, Rawstron AC. Association of minimal residual disease with superior survival
outcomes in patients with multiple myeloma (a meta-analysis). JAMA Oncol. 2016; doi:10.1001/
jamaoncol.2016.3160.
31. Myeloma Frailty Score Calculator: http://www.myelomafrailtyscorecalculator.net/
32. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines®): Multiple Myeloma, version 2.2013.
33. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines®): Multiple Myeloma, version 3.2017.
34. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology
Group. Am J Clin Oncol. 1982;5(6):649-655.
35. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364:1046-1060.
36. Palumbo A, Bringhen S, Mateos MV, et al. Geriatric assessment predicts survival and toxicities in elderly
myeloma patients: an International Myeloma Working Group report. Blood. 2015;125(13):2068-2070.
37. Palumbo A, Chanan-Khan A, Weisel K, et al, Daratumumab, bortezomib, and dexamethasone for multiple
myeloma. N Engl J Med. 2016;375:754-766.
38. Palumbo A, Rajkumar S, Dimopoulos M, et al. Prevention ofthalidomide- and lenalidomide-associated
thrombosis in myeloma. Leukemia (2008); 22:414-423.
39. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for
the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538-e548.

JNJ-54767414 (daratumumab)
Clinical Protocol 54767414MMY3019 Amendment 6
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Status: Approved, Date: 14 March 2024
40. Rajkumar SV, Harousseau J-L, Durie B, et al. Consensus recommendations for the uniform reporting of
clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117:4691-4695.
41. REVLIMID  USPI. Lenalidomide United States Prescribing Information (December 2017), Celgene
Corporation. Available at http://www.revlimid.com; accessed 13 Apr 2018.
42. Richardson, PG, Weller, E, Lonial, S, et al. Lenalidomide, bortezomib, and dexamethasone combination
therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116:679-686.
43. San Miguel J, Schlag R, Khuageva NK et al. Bortezomib plus melphalan and prednisone for initial treatment of
multiple myeloma. N Engl J Med. 2008;359(9):906-917.
44. Tang DI, Geller NL. Closed testing procedures for group sequential clinical trials with multiple endpoints.
Biometrics. 1999;55:1188-1192.
45. Van der Veer M, de Weers M, van Kessel B. The therapeutic human CD38 antibody daratumumab improves the
anti-myeloma effect ofnewly emerging multi-drug therapies. Blood Cancer Journal. 2011b; 1 e41.
Doi:10.1038/bcj.2011.
46. Voorhees, PM, Costa LJ, Reeves B, et al. Interim Safety Analysis of a Phase 2 Randomized Study of
Daratumumab ﴾Dara﴿, Lenalidomide ﴾R﴿, Bortezomib ﴾V﴿, and Dexamethasone ﴾d; Dara-Rvd﴿ Vs. Rvd in
Patients ﴾Pts﴿ with Newly Diagnosed Multiple Myeloma ﴾MM﴿ Eligible for High-Dose Therapy ﴾HDT﴿ and
Autologous Stem Cell Transplantation ﴾ASCT﴿. 2017
https://ash.confex.com/ash/2017/webprogram/Paper99989.html
47. Wisloff F, Eika S, Hippe E, et al. Measurement of health-related quality of life in multiple myeloma. Nordic
Myeloma Study Group. Br J Haematol. 1996;92:604-613.
48. Wisloff F, Hjorth M. Health-related quality of life assessed before and during chemotherapy predicts for
survival in multiple myeloma. Nordic Myeloma Study Group. Br J Haematol. 1997;97:29-37.

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INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study intervention, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature: 
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature: 
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed): 
Institution: 
Janssen Research & Development
Signature: electronic signature appended at the end of the protocol 
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the study, written notification will be
provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD

Signature
User 
Date 
Reason
 
14-Mar-2024
20:21:12
(GMT)
Document Approval
PPD