Conditions: Multiple Myeloma
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 10
Healthy volunteers: no

Brief summary:
The main purpose of this study is to assess the safety of the combination of JNJ-63723283 and daratumumab (Part 1); to compare the overall response rate (ORR) in participants treated with JNJ-63723283 in combination with daratumumab versus daratumumab alone (Part 2); and to compare progression-free survival (PFS) in participants treated with JNJ-63723283 in combination with daratumumab versus daratumumab alone (Part 3).

Detailed description:
This is a multi-phase study of JNJ-63723283 in combination with daratumumab compared with daratumumab alone in participants with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or whose disease is double refractory to both a PI and an IMiD. The study consists of Screening Phase (procedures performed within 28 days before enrollment), Open-Label Treatment Phase (with End-of-Treatment Visit to occur 4 weeks after the last dose of study treatment) and Follow-up phase (8 weeks after the last dose of study treatment). Ongoing safety evaluation during Part 1 and Part 2 will be overseen by the Safety Evaluation Team (SET). In Part 3, ongoing safety and efficacy evaluation will be performed by the Independent Data Monitoring Committee (IDMC).

Arms:
arm 1: Participants in Safety Run-in cohort will receive daratumumab IV and JNJ-63723283 IV for 1 cycle (28 days). Participants will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met. Participants who were previously receiving JNJ-283 plus daratumumab have the opportunity to continue daratumumab therapy alone. arm 2: Participants in Treatment Arm A will receive daratumumab IV and in Treatment Arm B will receive daratumumab IV and JNJ-63723283 IV for cycles of 28 days each. All participants will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met. Participants who were previously receiving JNJ-283 plus daratumumab have the opportunity to continue daratumumab therapy alone.

Interventions: intervention 1: Daratumumab intervention 2: JNJ-63723283
Intervention descriptions: intervention 1: Participants will receive daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) once every week for 8 weeks (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards). intervention 2: Participants will receive JNJ-63723283 240 mg IV during Week 1 on Cycle 1 Day 2, Cycle 1 Day 15, then every 2 weeks thereafter.

Protocol document:
Prot_001.pdf: 
1
Status: Approved, Date: 20 June 2018
Janssen Research & Development *
Clinical Protocol
A Randomized, Open-label, Multicenter, Multiphase Study of JNJ-63723283, an Anti-PD-1 
Monoclonal Antibody, Administered in Combination with Daratumumab, Compared with 
Daratumumab Alone in Subjects with Relapsed or Refractory Multiple Myeloma
Protocol 54767414MMY2036
Phase 2 and 3
AMENDMENT 2
JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
*Janssen Research & Development is a global organization that operates through different legal entities in 
various countries. 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.
JNJ-63723283 is being investigated in a Phase 1 study.
Daratumumab is being investigated in Phase 2 and 3 clinical studies.
Daratumumab is approved for marketing in 4 indications.
This study will be conducted under US Food & Drug Administration IND regulations (21 CFR 
Part 312).
EudraCT NUMBER: 2017-002611-34
Status:
Approved
Date:
20 June 2018
Prepared by:
Janssen Research & Development, LLC
EDMS number: EDMS-ERI-141773787, 4.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed by 
them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or 
confidential.
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
2
Approved, Date: 20 June 2018
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 5
LIST OF IN-TEXT TABLES.......................................................................................................................... 5
PROTOCOL AMENDMENTS....................................................................................................................... 6
ABBREVIATIONS ........................................................................................................................................ 9
SYNOPSIS.................................................................................................................................................. 12
1.
INTRODUCTION................................................................................................................................ 19
1.1.
Background .................................................................................................................................... 19
1.2.
JNJ-63723283................................................................................................................................ 19
1.2.1.
Summary of Nonclinical Data ..................................................................................................... 19
1.2.2.
Summary of Clinical Data ........................................................................................................... 20
1.3.
Daratumumab ................................................................................................................................ 21
1.4.
Overall Study Rationale and Anticipated Benefits and Risks of Combination Therapy................. 22
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS........................................................................... 25
2.1.
Objectives and Endpoints .............................................................................................................. 25
2.2.
Hypothesis ..................................................................................................................................... 26
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 26
3.1.
Overview of Study Design.............................................................................................................. 26
3.2.
Safety Evaluation ........................................................................................................................... 30
3.3.
Study Design Rationale.................................................................................................................. 32
4.
SUBJECT POPULATION.................................................................................................................. 35
4.1.
Inclusion Criteria ............................................................................................................................ 35
4.2.
Exclusion Criteria ........................................................................................................................... 38
4.3.
Prohibitions and Restrictions ......................................................................................................... 40
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 41
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 41
6.1.
Daratumumab ................................................................................................................................ 41
6.1.1.
Daratumumab Treatment Schedule and Administration ............................................................ 41
6.1.2.
Preinfusion Medication ............................................................................................................... 42
6.1.3.
Postinfusion Medication.............................................................................................................. 43
6.1.4.
Monitoring During and After Daratumumab and JNJ-63723283 Administration ........................ 43
6.1.5.
Dose Delay ................................................................................................................................. 44
6.2.
JNJ-63723283................................................................................................................................ 45
6.2.1.
JNJ-63723283 Treatment Schedule and Administration............................................................ 46
6.2.2.
Dose Delay ................................................................................................................................. 46
6.2.3.
Toxicities Leading to Discontinuation of Study Treatment ......................................................... 47
6.2.4.
Guidelines for Management of Immune-Related Adverse Events and Adverse Events 
of Clinical Interest ....................................................................................................................... 47
6.2.4.1.
Gastrointestinal Adverse Events ............................................................................................. 48
6.2.4.2.
Hepatic Adverse Events .......................................................................................................... 48
6.2.4.3.
Endocrinopathies..................................................................................................................... 49
6.2.4.4.
Rash ........................................................................................................................................ 51
6.2.4.5.
Renal Adverse Events ............................................................................................................. 51
6.2.4.6.
Neurological Adverse Events .................................................................................................. 52
6.2.4.7.
Pulmonary Adverse Events ..................................................................................................... 52
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Approved, Date: 20 June 2018
6.2.4.8.
Uveitis and Visual Complaints................................................................................................. 53
6.2.4.9.
Lipase/Amylase Elevations...................................................................................................... 53
6.2.5.
Infection ...................................................................................................................................... 54
6.3.
Treatment of Infusion-related Reactions (IRRs) ............................................................................ 54
6.3.1.
Guidelines for Management of Daratumumab IRRs .................................................................. 54
6.3.2.
Guidelines for Management of JNJ-63723283 IRRs.................................................................. 54
7.
TREATMENT COMPLIANCE............................................................................................................ 60
8.
PRESTUDY AND CONCOMITANT THERAPY ................................................................................ 60
8.1.
Recommended Therapies.............................................................................................................. 60
8.1.1.
Bisphosphonate Therapy............................................................................................................ 60
8.1.2.
Therapy for Tumor Lysis Syndrome ........................................................................................... 61
8.1.3.
Therapy for Pneumocystis carinii/jirovecii .................................................................................. 61
8.1.4.
Prophylaxis for Herpes Zoster Reactivation ............................................................................... 61
8.2.
Permitted Therapies....................................................................................................................... 61
8.3.
Prohibited Therapies...................................................................................................................... 62
9.
STUDY EVALUATIONS .................................................................................................................... 63
9.1.
Study Procedures........................................................................................................................... 63
9.1.1.
Overview..................................................................................................................................... 63
9.1.2.
Screening Phase ........................................................................................................................ 63
9.1.3.
Open-Label Treatment Phase .................................................................................................... 64
9.1.4.
Follow-Up Phase ........................................................................................................................ 64
9.2.
Efficacy Evaluations....................................................................................................................... 65
9.2.1.
Disease Assessments ................................................................................................................ 65
9.2.2.
Myeloma Protein Measurements in Serum and Urine................................................................ 67
9.2.3.
Serum Calcium Corrected for Albumin....................................................................................... 68
9.2.4.
2-microglobulin and Albumin .................................................................................................... 69
9.2.5.
Bone Marrow Examination.......................................................................................................... 69
9.2.6.
Assessment of Lytic Bone Disease ............................................................................................ 69
9.2.7.
Documentation of Extramedullary Plasmacytomas.................................................................... 70
9.3.
Pharmacokinetics and Immunogenicity ......................................................................................... 70
9.3.1.
Evaluations ................................................................................................................................. 70
9.3.2.
Analytical Procedures................................................................................................................. 71
9.3.3.
Pharmacokinetic Parameters ..................................................................................................... 71
9.4.
Biomarker Assessments ................................................................................................................ 71
9.4.1.
Biomarker Assays in Blood Samples.......................................................................................... 72
9.4.2.
Minimal Residual Disease (MRD) Evaluation............................................................................. 72
9.4.3.
Biomarker Bone Marrow Aspirate Evaluations........................................................................... 72
9.4.4.
Stopping Analysis ....................................................................................................................... 72
9.4.5.
Additional Collections ................................................................................................................. 73
9.5.
Patient-reported Outcomes (Part 3)............................................................................................... 73
9.6.
Medical Resource Utilization (Part 3)............................................................................................. 73
9.7.
Safety Evaluations ......................................................................................................................... 74
9.8.
Sample Collection and Handling.................................................................................................... 77
10.
DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL FROM THE STUDY .................. 77
10.1.
Discontinuation of Study Treatment/Withdrawal from the Study ................................................... 77
10.2.
Study Termination for Safety Considerations ................................................................................ 79
10.3.
Withdrawal from the Use of Research Samples ............................................................................ 80
11.
STATISTICAL METHODS................................................................................................................. 80
11.1.
Subject Information ........................................................................................................................ 80
11.2.
Sample Size Determination ........................................................................................................... 81
11.3.
Efficacy Analyses ........................................................................................................................... 81
11.4.
Pharmacokinetic Analyses............................................................................................................. 82
11.5.
Immunogenicity Analyses .............................................................................................................. 82
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Approved, Date: 20 June 2018
11.6.
Biomarker Analyses ....................................................................................................................... 82
11.7.
Pharmacokinetic/Pharmacodynamic Analyses.............................................................................. 83
11.8.
Patient-reported Outcomes Analyses (Part 3) ............................................................................... 83
11.9.
Medical Resource Utilization Analyses (Part 3)............................................................................. 83
11.10.
Safety Analyses ............................................................................................................................. 83
11.11.
Interim Analyses for Part 3............................................................................................................. 84
12.
ADVERSE EVENT REPORTING ...................................................................................................... 85
12.1.
Definitions ...................................................................................................................................... 85
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 85
12.1.2.
Attribution Definitions.................................................................................................................. 86
12.1.3.
Severity Criteria .......................................................................................................................... 87
12.2.
Special Reporting Situations.......................................................................................................... 87
12.3.
Procedures..................................................................................................................................... 88
12.3.1.
All Adverse Events...................................................................................................................... 88
12.3.2.
Serious Adverse Events ............................................................................................................. 90
12.3.3.
Pregnancy................................................................................................................................... 91
12.4.
Contacting Sponsor Regarding Safety........................................................................................... 91
13.
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 91
13.1.
Procedures..................................................................................................................................... 91
13.2.
Contacting Sponsor Regarding Product Quality ............................................................................ 92
14.
STUDY DRUG INFORMATION......................................................................................................... 92
14.1.
Physical Description of Study Drug(s) ........................................................................................... 92
14.2.
Packaging ...................................................................................................................................... 92
14.3.
Labeling.......................................................................................................................................... 92
14.4.
Preparation, Handling, and Storage............................................................................................... 92
14.5.
Drug Accountability ........................................................................................................................ 93
15.
STUDY-SPECIFIC MATERIALS....................................................................................................... 93
16.
ETHICAL ASPECTS ......................................................................................................................... 94
16.1.
Study-Specific Design Considerations........................................................................................... 94
16.2.
Regulatory Ethics Compliance....................................................................................................... 95
16.2.1.
Investigator Responsibilities ....................................................................................................... 95
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................... 95
16.2.3.
Informed Consent ....................................................................................................................... 96
16.2.4.
Privacy of Personal Data ............................................................................................................ 97
16.2.5.
Long-Term Retention of Samples for Additional Future Research ............................................ 98
16.2.6.
Country Selection ....................................................................................................................... 98
17.
ADMINISTRATIVE REQUIREMENTS .............................................................................................. 98
17.1.
Protocol Amendments.................................................................................................................... 98
17.2.
Regulatory Documentation ............................................................................................................ 99
17.2.1.
Regulatory Approval/Notification ................................................................................................ 99
17.2.2.
Required Prestudy Documentation............................................................................................. 99
17.3.
Subject Identification, Enrollment, and Screening Logs .............................................................. 100
17.4.
Source Documentation................................................................................................................. 100
17.5.
Case Report Form Completion .................................................................................................... 101
17.6.
Data Quality Assurance/Quality Control ...................................................................................... 102
17.7.
Record Retention ......................................................................................................................... 102
17.8.
Monitoring .................................................................................................................................... 103
17.9.
Study Completion/Termination..................................................................................................... 104
17.9.1.
Study Completion/End of Study................................................................................................ 104
17.9.2.
Study Termination..................................................................................................................... 104
17.10.
On-Site Audits .............................................................................................................................. 104
17.11.
Use of Information and Publication.............................................................................................. 105
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JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
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Approved, Date: 20 June 2018
REFERENCES.......................................................................................................................................... 107
INVESTIGATOR AGREEMENT ............................................................................................................... 129
LIST OF ATTACHMENTS
Attachment 1:
PREINFUSION Antihistamine Medications (DARATUMUMAB) .............................. 109
Attachment 2:
Conversion Table for Glucocorticosteroid Dose....................................................... 110
Attachment 3:
Modified Diet in Renal Disease Formula.................................................................. 111
Attachment 4:
Serum Calcium Corrected for Albumin..................................................................... 112
Attachment 5:
ECOG Performance Status Scale ............................................................................ 113
Attachment 6:
Prior Lines of Therapy for Multiple Myeloma............................................................ 114
Attachment 7:
Interpretation of Daratumumab Interference Reflex Assay (DIRA).......................... 115
Attachment 8:
ASTHMA Guidelines................................................................................................. 116
Attachment 9:
Anticipated Events.................................................................................................... 119
Attachment 10:
Patient-Reported Outcomes Questionnaires............................................................ 121
Attachment 11:
Daratumumab Monotherapy Period For Subjects No Longer Receiving JNJ-
63723283 In  Combination With Daratumumab ....................................................... 126
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Time and Events Schedule – Parts 1, 2, and 3 ........................................................................ 14
Table 2:
Pharmacokinetics and Immunogenicity Sample Collection (Part 1, Part 2, and Part 3) .......... 18
Table 3:
Subject Randomization............................................................................................................. 28
Table 4:
Criteria for Dose- limiting Toxicity............................................................................................. 31
Table 5:
Daratumumab Administration ................................................................................................... 42
Table 6:
Infusion Duration and Monitoring After Infusion of Daratumumab and JNJ-63723283............ 44
Table 7:
Daratumumab-related Toxicity Management ........................................................................... 45
Table 8:
JNJ-63723283 Administration................................................................................................... 46
Table 9:
Management of Immune-Related Gastrointestinal Adverse Events......................................... 48
Table 10:
Management of Immune-Related Hepatic Adverse Events...................................................... 49
Table 11:
Management of Immune-Related Endocrinopathies ................................................................ 50
Table 12:
Management of Rash................................................................................................................ 51
Table 13:
Management of Renal Adverse Events .................................................................................... 51
Table 14:
Management of Neurological Adverse Events ......................................................................... 52
Table 15:
Management of Pulmonary Adverse Events ............................................................................ 53
Table 16:
Management of Uveitis and Visual Complaints ........................................................................ 53
Table 17:
Management Guidelines for Daratumumab Infusion-related Reactions................................... 54
Table 18:
Management of Infusion-Related Reactions for JNJ-63723283............................................... 55
Table 19:
Daratumumab Administration ................................................................................................... 56
Table 20:
Infusion Duration and Monitoring After Infusion of Daratumumab ........................................... 58
Table 21:
Daratumumab-related Toxicity Management ........................................................................... 59
Table 22:
International Uniform Response Criteria Consensus Recommendations ................................ 65
Table 23:
Bone Marrow Testing................................................................................................................ 69
Table 24:
Time and Events Schedule –Daratumumab Monotherapy Period for Subjects No 
Longer Receiving JNJ-63723283 in Combination with Daratumumab................................... 127
FIGURES
Figure 1:
Study Scheme........................................................................................................................... 27
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
6
Approved, Date: 20 June 2018
PROTOCOL AMENDMENTS
Protocol Version
Issue Date
Original Protocol
05 July 2017
Amendment 1
23 Aug 2017
Amendment 2
20 June 2018
Amendments below are listed beginning with the most recent amendment.
Amendment 2 (20 June 2018)
The overall reason for the amendment:
As of 25 May 2018, the Sponsor terminated further enrollment into this study, 54767414MMY2036 (TUCANA), 
based on safety and efficacy findings in the 54767414LUC2001 (CALLISTO) study, which combined daratumumab 
with atezolizumab in non-small cell lung cancer. At the third planned Data Monitoring Committee (DMC) review 
on 23 May 2018, the DMC reviewed the subject data (n=88, 44 per arm) for the CALLISTO Study. The DMC 
determined that there was no observed benefit within the combination treatment arm, daratumumab plus 
atezolizumab, over atezolizumab alone, and recommended stopping enrollment of the study. In addition, the DMC 
recommended discontinuation of daratumumab treatment to all active subjects receiving combination therapy 
(subjects randomized to the combination Arm B, as well as subjects randomized to Arm A who have crossed over 
into Arm B). Although no unexpected imbalances in on-treatment toxicities were observed, the DMC noted a clear 
early difference in the number of deaths between the atezolizumab monotherapy (n=13) and combination arm 
(n=18). The discrepancy was observed within the first 3 months from dosing, where the number of deaths are 4 for 
the atezolizumab arm and 10 for the combination arm, giving rise to 3-month survival rates of 90.7% for the 
atezolizumab arm and 76.2% for the combination arm. 
Since the benefit/risk ratio has changed for combination therapy in CALLISTO, the Sponsor has decided to suspend 
enrollment into other studies which combine daratumumab and a programmed death-1 (PD-1) or programmed 
death-ligand 1 (PD-L1) monoclonal antibody regardless of indication.  In addition to discontinuing enrollment into 
this study, treatment with the combination of daratumumab and JNJ-63723283 will be discontinued and ongoing 
subjects will be given the option to continue on daratumumab monotherapy until subject meets one or more of the 
treatment discontinuation criteria in Section 10.1.1.
Applicable Section(s)
Description of Change(s)
Rationale: The benefit/risk ratio has changed for combination therapy in CALLISTO which has led to the 
discontinuing enrollment and treatment of combination therapy in this study.
1.4 Overall Study Rationale and 
Anticipated Benefits and Risks of 
Combination Therapy;
New Attachment 11: Daratumumab 
Monotherapy Period for Subjects 
No Longer Receiving JNJ-
63723283 in Combination with 
Daratumumab; 4 Subject 
Population;
5 Treatment Allocation and 
Blinding
The rationale for stopping enrollment is discussed and it is clarified that 
subjects in Screening as of 25 May 2018 were deemed screen failures and 
were not randomized into the study.
Rationale: Ongoing subjects will be given the option to continue on daratumumab monotherapy. Assessments 
and data collection for the new Daratumumab Monotherapy Period are defined.
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JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
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Approved, Date: 20 June 2018
Applicable Section(s)
Description of Change(s)
3.1 Overview of Study Design; 6.4 
Dosage and Administration for 
Daratumumab Monotherapy 
Period; 9.1.1.1 Daratumumab 
Monotherapy period; 9.1.4 Follow-
Up Phase; 9.2.1.1 Disease 
Assessments in Daratumumab 
Monotherapy Period; 9.3 
Pharmacokinetics and 
Immumnogenicity; 9.4 Biomarker 
Assessments 9.7 Safety 
Evaluations; 10.1.1 Discontinuation 
of Study Treatment in 
Daratumumab Monotherapy 
Period; 11.12 Statistical Methods 
Effective Protocol Amendment 2; 
12.3.1.1 Daratumumab 
Monotherapy Period; 17.5 Case 
Report Form Completion; 17.8 
Monitoring; 17.9.1.1 Study 
Completion for the Daratumumab 
Monotherapy Period;
Attachment 11 Daratumumab 
Monotherapy Period For Subjects 
No Longer Receiving 
JNJ-63723283 In Combination 
With Daratumumab (Table 24)
A new Attachment and a new Time and Events Schedule are included for 
the Daratumumab Monotherapy Period. A new section for daratumumab 
monotherapy administration is included. Data collection will be limited 
(eg, no further pharmacokinetics or biomarker evaluations) and is 
described throughout the protocol. 
Data will no longer be recorded in the electronic case report form (eCRF)
once Protocol Amendment 2 is implemented. Data collection after the 
final database lock will be limited to serious adverse event (SAE)
reporting into the Sponsor’s global safety database.
Statistical analyses and reporting will also be limited for the Daratumumab 
Monotherapy Period.
Rationale: Added a window for the End-of-Treatment Visit.
9.1.3 Open-Label Treatment Phase, 
End-of-Treatment Visit subheading
Unless a subject withdraws consent for study participation or is lost to 
follow up, an End-of-Treatment Visit is to occur 4 weeks (+7 days) after 
the last dose of study treatment.
Amendment 1 (23 August 2017)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union.
The overall reason for the amendment: The overall reason for the amendment is to make changes based on the 
FDA IND review of the protocol, including revisions to the DLT criteria.
The rationale for and description of the changes are listed below, and representative revisions are sometimes 
provided; when revisions are provided verbatim, bold font denotes new text, and strikethrough denotes deleted 
text.
Applicable Section(s)
Description of Change(s)
Rationale: Revisions to DLT criteria
3.2 Safety Evaluation 
(Table 4)
AST or ALT: Grade ≥3 persisting 14 7 days after treatment with corticosteroids, Grade 4, 
or any case meeting Hy’s Law criteriab
Thrombocytopenia:  Grade 3 thrombocytopenia with clinically significant bleeding
and Grade 4 thrombocytopenia lasting more than 7 days despite BSCc
DLT criteria for both Non-hematologic and Hematologic Toxicitya:
Any Grade 5 non-hematologic or hematologic event
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
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Approved, Date: 20 June 2018
Applicable Section(s)
Description of Change(s)
Rationale: The eligibility criterion for recovery from toxicity from previous immunotherapy treatment is revised.
4.2 Exclusion Criteria
11. Unresolved Grade 3 2 or higher toxicity effects from previous treatment with 
immunotherapy not recovered to Grade 1 or baseline
Rationale: A criterion for dose delay because of non-immune-related AEs (irAEs) is added to the bulleted list.
6.2.2 Dose Delay
Grade 3 non-irAEs  (except for hematologic toxicities not attributed to 
JNJ-63723283)
Rationale: The split first dose of daratumumab is being replaced with the full daratumumab 16 mg/kg regimen 
(starting on Cycle 1 Day 1) to allow for additional safety monitoring after the first administration of JNJ-63723283.
Synopsis (Dosage and 
Administration);
Time and Events 
Schedule (Table 1);
Pharmacokinetics and 
Immunogenicity 
Sample Collection 
(Table 2);
Removed text regarding the split dose of daratumumab on Cycle 1 Day 1 and Cycle 1 
Day 2 throughout the protocol.
Vital signs – removed reference to C1D2 for daratumumab monitoring.
Study drug administration – removed row for the Run-in and Arm B because daratumumab 
will not be administered on C1D2 (same regimen is being used in all parts of the study).
For C1D2, the predose and end of infusion daratumumab PK samples were removed.
3.1 Overview of 
Study Design;
3.3 Study Design 
Rationale;
6.1.1 Daratumumab 
Treatment Schedule 
and Administration;
6.1.3 Postinfusion 
Medication;
6.1.4 Monitoring 
During and After 
Daratumumab and 
JNJ-63723283
Administration
Removed rationale related to the daratumumab split dose.
Table 5 was simplified, consistent with the approved labelling for daratumumab 
administration.
Text regarding corticosteroid administration after the second 8 mg/kg administration of 
daratumumab was removed.
A table was added to clarify infusion durations and monitoring after infusion of 
daratumumab and JNJ-63723283.
Rationale: To clarify that communication with health authorities will occur before proceeding to Part 3.
3.1 Overview of 
Study Design 
(Initiation of Part 3 
(Phase 3)
After all 80 randomized subjects in Part 2 (Phase 2) have been followed for approximately 
4 months or discontinued earlier, the Sponsor will determine whether the Part 2 primary 
efficacy endpoint was met and if the combination of the 2 drugs is safe. In addition, the 
secondary endpoint results, as well as all other available data, will be examined and taken 
into consideration. Based on the totality of the data, the Sponsor will decide whether Part 3 
(Phase 3) will be initiated. This decision will be made in consultation with health 
authorities and the final decision will be communicated in writing to sites and 
independent ethics committees (IECs)/institutional review boards (IRBs), as appropriate.
Rationale: To add a new section regarding study termination for safety considerations.
10.2 Study 
Termination for 
Safety Considerations
Added a new section regarding reasons for study termination because of safety issues. 
The final decision to terminate the study will be based on the totality of the benefit/risk 
assessment.
Rationale: To correct an error in criteria for subjects who may be replaced in Part 1.
3.2 Safety Evaluation
A subject who received 75% 25% of a planned dose without experiencing a DLT may be 
replaced.
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
9
Approved, Date: 20 June 2018
ABBREVIATIONS
ADA
anti-drug antibody
ADCC
antibody dependent cell-mediated cytotoxicity
ADCP
antibody-dependent cellular phagocytosis
AE
adverse event
ALC
absolute lymphocyte count
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
Breg
regulatory B cell
BSC
best supportive care
CBC
complete blood count
CDC
complement-dependent cytotoxicity
CI
confidence interval
CMV
cytomegalovirus
COPD
chronic obstructive pulmonary disease
CR, sCR
complete response; stringent complete response
CRF
case report form
CT
computed tomography
DCF
data clarification form
DILI
drug-induced-liver-injury
DLT
DMC
dose-limiting toxicity
Data Monitoring Committee
DoR
duration of response
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group Performance Status
EORTC QLQ-
C30
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 
30
EOI
end of infusion
EOT
end of treatment
EQ-5D-5L
European Quality of Life 5-Dimensions Questionnaire
FEV-1
forced expiratory volume; maximal amount of air forcefully exhaled in 1 sec.
FLC
Free light chain
GCP
Good Clinical Practice
GHS
global health status
GLP
Good Laboratory Practice
HBc
hepatitis B core antigen
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
IAT
indirect antiglobulin test
ICF
informed consent form
ICH
International Council on Harmonisation
IDMC
Independent Data Monitoring Committee
IEC
independent ethics committee
IF
immunofluorescence
IFE
Immunofixation electrophoresis
Ig
immunoglobulin
IHC
immunohistochemistry
IMiD
immunomodulatory agent
IMWG
International Myeloma Working Group
INR
International Normalized Ratio
IPPI
Investigational Product Preparation Instructions
irAE
immune-related adverse event
IRB
institutional review board
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
10
Approved, Date: 20 June 2018
IRR
infusion-related reaction
ISS
International Staging System
ITT
intent-to-treat
IWRS
interactive web response system
LDH
lactate dehydrogenase
LFT
liver function test
LLN
lower limit of normal
M-protein
monoclonal paraprotein
mAb
monoclonal antibody
MDSC
myeloid-derived suppressor cell
MedDRA
Medical Dictionary for Regulatory Activities
MLR
mixed lymphocyte reaction
MM
multiple myeloma
MR
minimal response
MRD
minimal residual disease
MRI
magnetic resonance imaging
MRU
medical resource utilization
MTD
maximum tolerated dose
NCI-CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
NFAT
nuclear factor of activated T cells
NGS
next-generation sequencing
NK
natural killer
NOAEL
no-observed-adverse-effect level
NSAIDs
nonsteroidal anti-inflammatory drugs
NSCLC
non-small cell lung cancer
ORR
overall response rate
OS
overall survival
PBMC
peripheral blood mononuclear cell
PC
plasma cell
PCR
polymerase chain reaction
PD
progressive disease
PD-1
programmed death-1
PD-L1
programmed death-ligand 1
PET
positron emission tomography
PFS
progression-free survival
PI
proteasome inhibitor
PK
pharmacokinetic(s)
PO
oral administration
PQC
product quality complaint
PR
partial response
PRO
patient-reported outcome
PT
prothrombin time
PTT
partial thromboplastin time
QIg
quantitative immunoglobulin
RO
receptor occupancy
RP2D
recommended Phase 2 dose
RRMM
relapsed or refractory multiple myeloma
SAE
serious adverse event
SCT
stem cell transplant
SD
stable disease
SET
safety evaluation team
SIPPM
Site Investigational Product Procedures Manual
SPEP
SPM
serum M-Protein quantification by electrophoresis
second primary malignancy
SUSAR
suspected unexpected serious adverse reaction
SVR
sustained virologic response
TDAR
T cell-dependent antibody responses
Treg
regulatory T cell
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
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Approved, Date: 20 June 2018
TSH
thyroid stimulating hormone
ULN
upper limit of normal
UPEP
urine M-protein quantitation by electrophoresis
VAS
visual analog scale
VGPR
very good partial response
β-hCG
β-human chorionic gonadotropin
Definition of Terms
AUC = area under the plasma drug concentration-time curve
Cmax = maximum observed concentration
Cmin = minimum observed concentration
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
12
Approved, Date: 20 June 2018
SYNOPSIS
A Randomized, Open-label, Multicenter, Multiphase Study of JNJ-63723283, an Anti-PD-1 Monoclonal 
Antibody, Administered in Combination with Daratumumab, Compared with Daratumumab Alone in 
Subjects with Relapsed or Refractory Multiple Myeloma
RATIONALE 
JNJ-63723283 is a human immunoglobulin (Ig) G4 kappa monoclonal antibody that binds to the cell 
surface signaling molecule programmed cell death receptor 1 (PD-1) with high affinity and specificity.
JNJ-63723283 blocks binding to both PD-1 ligands (PD-L1 and PD-L2), enhances pro-inflammatory 
cytokine production from ex vivo stimulated T cells, and reduces tumor volume in human PD-1 knock-in 
mice bearing MC38 murine colon carcinoma tumors. Daratumumab is a human IgG1ĸ monoclonal 
antibody (mAb) that binds with high affinity to a unique epitope on CD38, a transmembrane glycoprotein 
normally expressed on the surface of many immune cells, including CD4+, CD8+, B lymphocytes and 
natural killer (NK) cells, as well as on many tumor cells. Daratumumab is designed to attack tumor cells 
that overexpress CD38, such as in multiple myeloma.
Increased expression of PD-L1 in malignant plasma cells as well as upregulation of PD-1 on effector 
T cells and NK cells of multiple myeloma patients generates an immunosuppressive microenvironment 
that is associated with disease progression in multiple myeloma (Benson 2010; Rosenblatt 2017;
Yousef 2015). Daratumumab leads to the rapid and sustained elimination of highly immunosuppressive 
subsets of CD38+ regulatory T cells (Tregs), CD38+ myeloid derived suppressor cells (MDSCs), and
CD38+ regulatory B cells (Bregs) (Krejcik 2016). The elimination of these immunosuppressive cells and
modulation of CD38 enzymatic activity leads to the increased clonal expansion of CD8+ and CD4+
T cells. Therefore, modulation of multiple myeloma-host immune responses by targeting both PD-1 and 
CD38 with JNJ-63723283 in combination with daratumumab may be an effective therapeutic approach in 
treating relapsed or refractory multiple myeloma.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
PRIMARY OBJECTIVES
PRIMARY ENDPOINTS
Part 1 (Safety Run-in)

To assess the safety of the combination of JNJ-
63723283 and daratumumab

Incidence of adverse events, including dose-limiting 
toxicities (DLTs)
Part 2 (Phase 2)

To compare the overall response rate (ORR) in 
subjects treated with JNJ-63723283 in 
combination with daratumumab versus 
daratumumab alone

ORR, defined as the proportion of subjects with a 
best response of PR or better, as defined by IMWG 
response criteria
Part 3 (Phase 3)

To compare progression-free survival (PFS) in 
subjects treated with JNJ-63723283 in 
combination with daratumumab versus 
daratumumab alone

PFS, defined as the time from the date of 
randomization to the date of disease progression or 
death due to any cause, whichever occurs first
See Section 2 for the secondary and exploratory endpoints.
Hypotheses
Part 2: The primary hypothesis is that JNJ-63723283 in combination with daratumumab will significantly 
improve ORR compared to daratumumab alone in subjects with relapsed or refractory multiple myeloma.
Part 3: The primary hypothesis is that JNJ-63723283 in combination with daratumumab will significantly 
improve PFS compared to daratumumab alone in subjects with relapsed or refractory multiple myeloma.
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
13
Approved, Date: 20 June 2018
OVERVIEW OF STUDY DESIGN
This is a randomized, multicenter, multiphase study assessing the anti-tumor activity and safety of 
JNJ-63723283 administered in combination with daratumumab, compared with daratumumab alone in 
subjects with relapsed or refractory multiple myeloma. Subjects 18 years and older with multiple 
myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an 
immunomodulatory inhibitor (IMiD) or whose disease is double refractory to both a PI and an IMiD are 
eligible. Approximately 6 subjects will be enrolled in Part 1 (a safety run-in cohort) followed by 
80 subjects randomly assigned in a 1:1 ratio to the 2 treatment arms in Part 2 (Phase 2). After all subjects 
in Part 2 are followed-up for approximately 4 months or discontinue earlier, the Sponsor will review all 
available data and decide whether to initiate Part 3 (Phase 3) of this study, where an additional 
300 subjects will be randomly assigned in a 1:1 ratio to the 2 treatment arms. 
DOSAGE AND ADMINISTRATION
Treatment cycles will be 28 days in duration.
Treatment groups include a Safety Run-in 
(JNJ-63723283+daratumumab); and Arm A (daratumumab alone), and Arm B (JNJ-63723283+ 
daratumumab) in Parts 2 and 3. Starting on Cycle 1 Day 1, daratumumab 16 mg/kg IV will be 
administered once every week (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); 
thereafter once every 4 weeks (Week 25 onwards). JNJ-63723283 (Safety Run-in and Arm B) will be 
administered IV on Week 1 at a dose of 240 mg on Cycle 1 Day 2, Cycle 1 Day 15, and then every 
2 weeks thereafter. When both drugs are administered on the same day, daratumumab will be 
administered before JNJ-63723283. All subjects will continue to receive study treatment until confirmed 
disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met.
EFFICACY EVALUATIONS
Assessment of tumor response and disease progression will be performed in accordance with the IMWG 
response criteria. For subjects who discontinue study treatments before disease progression, disease 
assessments should continue to be performed as scheduled until disease progression is confirmed or until 
the start of subsequent anti-myeloma therapy. Survival status and subsequent anticancer treatment data 
will be collected.
SAFETY EVALUATIONS
Safety evaluations will include adverse event monitoring, clinical laboratory parameters (hematology and 
chemistry), ECGs, vital sign measurements, physical examination findings, and assessment of ECOG 
performance status score.
STATISTICAL METHODS
Efficacy data will be analyzed separately for each Part of this study; safety data from each Part may be 
combined as deemed appropriate.
Part 2: Assuming the ORR for daratumumab monotherapy is approximately 30% and the addition of 
JNJ-63723283 would improve ORR by 20%, approximately 80 subjects will be randomized in a 1:1 ratio 
to achieve at least 70% power with a 2-sided alpha of 0.20 to reject the null hypothesis that there is no 
difference in ORR between the 2 treatment arms.
Part 3: Assuming a median PFS of 4 months for the daratumumab monotherapy group and a 33% 
reduction in risk of disease progression or death for the combination group (hazard ratio=0.67; median 
PFS=6 months), 230 PFS events are needed to achieve a power of 85% using a log-rank test with a 
2-sided alpha of 0.05. With a 12-month accrual period and an additional 6-month follow-up, the sample 
size needed for the study is approximately 300 (150/treatment group) subjects.
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
14
Approved, Date: 20 June 2018
Table 1:
Time and Events Schedule – Parts 1, 2, and 3
Assessments
Screening 
Phase
Treatment Phase
(28-day Cycles)
Follow-up 
Phase
Cycle 1
Cycle 2
Cycle 
3-6
Cycle 
7+
EOT
FUP
Survival
Study Day
-28 to -1
1
2
8
15
22
1
8
15
22
1
15
1
15
Post 
Treat-
ment
Wk 4 
(±7 d) 
Post 
Treat-
ment
Wk 8
Every 
12
Wks
Procedures: Study procedures may occur within 3 days prior to Day 1
Informed consent
Subjects must sign the informed consent form before any study-specific procedures are performed.
Eligibility criteria
X
Spirometry test - subjects with known or suspected COPD
X
Demography/height/medical history
X
Physical examination
X
Only a symptom-directed physical examination is required
Weight - only on Day 1 of each daratumumab cycle
X
X
X
X
X
X
Vital signs (pulse, blood pressure, and temperature)
Daratumumab: C1D1 - immediately before start of 
infusion; 0.5, 1, 1.5, 2, and 3.5 hr after start of 
infusion; end of infusion; and 0.5, and 1 hr after 
end of infusion. For all other daratumumab and 
JNJ-63723283 infusions: immediately before start 
of infusion and at the end of infusion.
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECOG performance status 
X
X
X
X
X
X
Electrocardiogram 12-lead
After ~5 minutes of rest, prior to any blood draw
X
As clinically indicated
X
Laboratory Assessments - local laboratory analysis
-14 to -1
Up to 3 days prior to dosing. Laboratory test results must be reviewed by the investigator or qualified 
designee and found to be acceptable prior to administration of each dose of study drug.
Biochemistry
X
X
X
X
X
X
X
X 
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
X 
Blood group, type, and indirect antiglobulin (IAT).  
A study identification wallet card, including subject 
blood group, type and IAT [ABO, Rh, IAT] will be 
provided
X
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
15
Approved, Date: 20 June 2018
Table 1:
Time and Events Schedule – Parts 1, 2, and 3
Assessments
Screening 
Phase
Treatment Phase
(28-day Cycles)
Follow-up 
Phase
Cycle 1
Cycle 2
Cycle 
3-6
Cycle 
7+
EOT
FUP
Survival
Study Day
-28 to -1
1
2
8
15
22
1
8
15
22
1
15
1
15
Post 
Treat-
ment
Wk 4 
(±7 d) 
Post 
Treat-
ment
Wk 8
Every 
12
Wks
Urine or serum pregnancy test 
- women of childbearing potential only
-14 to 
C1D1 
dosing
As clinically indicated
Coagulation; HBV/HCV Serology
X
Thyroid function 
X
X
X
Every 3rd cycle, D1
Study Drug Administration
See Section 6 and the IPPI for drug administration details, and Section 8 for preinfusion and postinfusion medications for daratumumab.
Daratumumab
Run-in, Arm A, Arm B
X
X
X
X
X
X
X
X
X
X
X
JNJ-63723283
Run-in (Part 1) and
Arm B (Parts 2 and 3)
X
X
X
X
X
X
X
X
For Pharmacokinetics and Immunogenicity Samples: See Table 2.
Biomarkers and Pharmacodynamics  
All samples must be taken prior to dosing unless otherwise specified. If a dose delay occurs, then biomarker samples should be taken on the actual day of drug 
administration, not on the originally scheduled administration day.
Bone marrow aspirate, biopsy
See Disease Evaluations (Other)
Diagnostic archival tissue
X
Whole blood for immunophenotyping
X
X
X
X
X
C4 D1
At progression
Whole blood for PBMC (peripheral blood 
mononuclear cell), serum, and plasma biomarker 
assessments
X
X
X
X
X
C4 D1
At progression
Cytokines
X
Unscheduled
A blood sample should be drawn within 6 hr of suspected cytokine-release syndrome, and the prepared 
serum sample should be sent to the central laboratory. 
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
16
Approved, Date: 20 June 2018
Table 1:
Time and Events Schedule – Parts 1, 2, and 3
Assessments
Screening 
Phase
Treatment Phase
(28-day Cycles)
Follow-up 
Phase
Cycle 1
Cycle 2
Cycle 
3-6
Cycle 
7+
EOT
FUP
Survival
Study Day
-28 to -1
1
2
8
15
22
1
8
15
22
1
15
1
15
Post 
Treat-
ment
Wk 4 
(±7 d) 
Post 
Treat-
ment
Wk 8
Every 
12
Wks
Disease Evaluations (Blood/Urine; central laboratory analysis) If collected within 14 days before Cycle 1 Day 1, not mandatory to collect again at the Cycle 1 Day 1 visit unless 
central lab results are not available for screening for any reason. If the 24-h urine collection (UPEP) began before informed consent was obtained as part of routine patient care, the sample 
may be used in this study as long as it is sent to the central lab for analysis after the informed consent is obtained. Unless otherwise stated, all blood and urine samples must be obtained 
before administration of study drug, within 3 days prior to the scheduled assessment day. All responses (including PD based on biochemical investigations) require 2 consecutive 
assessments by central lab for confirmation.
Serum 2-microglobulin
X
QIgs (IgG, IgA, IgM, IgD, IgE)
X
Every 3 months (±1 month) during treatment. Testing for IgD and IgE will 
only be performed for subjects with IgD and IgE-type myeloma
SPEP
X
X
X
X
X
X
X
UPEP (24-hr urine sample)
X
X
X
X
X
X
X
Serum calcium corrected for albumin
X
X
X
X
X
X
X
Serum FLC & serum/urine immunofixation
X 
All subjects: performed when CR is suspected or maintained. For light chain only disease, serum 
FLC performed on Day 1 of every cycle (±3 days), at EOT, and at follow-up until PD
Disease Evaluations (Other)
-28 to -1;
if per SOC:
-42 to -1
Bone marrow aspirate/biopsy
Performed locally at Screening (morphology, 
cytogenetics [by conventional karyotype and/or 
fluorescence in-situ hybridization], and at least 1 of the 
following to determine clonality of plasma cells: 
immunohistochemistry, immunofluorescence, or flow 
cytometry). MRD and molecular subtyping: a portion of 
bone marrow aspirates collected at Screening will be sent 
to a central laboratory. For Screening, fresh aspirate is 
preferred. If not performed because a sample is available 
within 42 days before first study drug administration or 
randomization, non-decalcified aspirate slides (smears or 
clots) should be provided.
X
if fresh, 
send portion 
to central 
lab for 
biomarker 
assessments
To confirm CR, sCR, and if feasible, at the time of disease progression.
A portion of bone marrow aspirates will be sent to a central laboratory for evaluation of MRD and 
biomarker assessments
(sampling for MRD at suspected CR or CR and sCR and every 6 months for those with maintained 
CR and sCR)
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
17
Approved, Date: 20 June 2018
Table 1:
Time and Events Schedule – Parts 1, 2, and 3
Assessments
Screening 
Phase
Treatment Phase
(28-day Cycles)
Follow-up 
Phase
Cycle 1
Cycle 2
Cycle 
3-6
Cycle 
7+
EOT
FUP
Survival
Study Day
-28 to -1
1
2
8
15
22
1
8
15
22
1
15
1
15
Post 
Treat-
ment
Wk 4 
(±7 d) 
Post 
Treat-
ment
Wk 8
Every 
12
Wks
Imaging for lytic bone disease
Low-dose whole body CT is preferred. Skeletal survey, 
including the cranium at Screening. Additional imaging 
(X-ray or MRI): perform as clinically indicated (eg, to 
document response or progression)
X
As clinically indicated for imaging (X-ray, CT, or MRI). 
Same methodology used at Screening should be used throughout the study for comparison 
purposes.
Imaging for extramedullary plasmacytomas
At screening, by clinical exam or radiologic imaging 
(PET-CT or MRI). Use consistent methodology 
throughout study. 
X
For subjects with a history of plasmacytomas or as clinically indicated for others.
Measurable sites every 4 weeks ±3 days (if applicable) by physical examination 
and every 12 weeks ±14 days by imaging. Irradiated or excised lesions will not be 
considered measurable, and will be monitored for PD only.
To confirm MR, PR, VGPR, CR, or sCR; at suspected PD; and as clinically indicated.
X
Patient-reported outcomes (Part 3)
EORTC-QLQ-C30, EQ-5D-5L.  Both questionnaires must 
be administered and completed prior to any other study 
procedures/assessments for that study visit.
X
Part 3 only
Part 3 only
D1 of every 3rd cycle (eg, Cycles 3, 6, 9, 12) until PD
X
X
Medical resource utilization (Part 3)
(see Section 9.6)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Ongoing Subject Review
Adverse event monitoring
Continuous from ICF until 30 days after last study treatment dose, regardless of when EOT 
assessment occurs. For subjects that have received subsequent treatment for multiple myeloma, only 
adverse events that are considered to be possibly, probably, or definitely related to JNJ-63723283 or 
daratumumab need to be reported.
Drug-related SAEs, 
only
Prior and Concomitant medication recording
Continuous from ICF until 30 days after last study treatment dose
Subsequent anti-cancer therapy and Survival
Continuous from first dose of study drug until end of study
X
Abbreviations: C=Cycle; COPD=chronic obstructive pulmonary disease; CR=complete response; CT=computed tomography; D=Day; ECOG=Eastern Cooperative Oncology Group; 
EOT=End-of-Treatment; FLC=free light chain; FUP=Follow-up Phase; HBV=hepatitis B virus; HCV=hepatitis C virus; IAT= indirect antiglobulin; ICF=informed consent form; 
IPPI=Investigational Product Preparation Instructions; MR=minimal response; MRD=minimal residual disease; MRI=magnetic resonance imaging; PBMC (peripheral blood mononuclear 
cell); PET=positron emission tomography; PD=progressive disease; PR=partial response; QIgs= quantitative immunoglobulins; SAE=serious adverse event; sCR=stringent CR;
SOC=standard of care; SPEP=Serum M-protein quantitation by electrophoresis; UPEP=urine M-protein quantitation by electrophoresis; VGPR=very good partial response
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
18
Approved, Date: 20 June 2018
Table 2:
Pharmacokinetics and Immunogenicity Sample Collection (Part 1, Part 2, and Part 3)
Visit/Timepoint
Daratumumab
(Safety Run-in, Arm A, Arm B)
JNJ-63723283
(Safety Run-in, Arm B)
PK
Samplea
Immunogenicity
(taken from PK 
sample)a
PK 
Samplea
Immunogenicity
(taken from PK 
sample)a
Cycle 1 Day 1  
predosea
X
X
X
X
dara EOI
X
Cycle 1 Day 2
283 EOI
X
Cycle 2 Day 1 
Cycle 3 Day 1
predose
X
X
X
X
dara EOI
X
283 EOI 
X
Cycle 5 Day 1
predose
X
X
dara EOI
X
283 EOI 
X
Cycle 7 Day 1 
Cycle 12 Day 1
predose
X
X
X
X
dara EOI
X
283 EOI 
X
Cycle 16 Day 1
predose
X
dara EOI
283 EOI
X
Cycle 24 Day 1; 
every 12 cycles 
thereafter 
(C36D1, C48D1, 
etc) until EOT
predose
X
X
X
X
dara EOI
X
283 EOI
X
EOT (Week 4 ±1 week)
X
X
X
X
Follow-up (Week 8 ±1 week)
X
X
X
X
C=cycle; D=day; dara=daratumumab; EOI=end of infusion; EOT=end of treatment; PK=pharmacokinetics; 283=JNJ-63723283
a.
Separate samples are taken for daratumumab and JNJ-63723283. JNJ-63723283 should be administered after daratumumab. 
In subjects receiving both agents on the same day, predose PK and immunogenicity samples for daratumumab and 
JNJ-63723283 should be obtained up to 2 hours before the start of the daratumumab infusion. End of infusion samples are to 
be taken within 2 hours after the end of the infusion of the respective drug. If a dose delay occurs, then samples should be 
taken on the actual day of drug administration, not on the originally scheduled administration day.
NCT03357952


JNJ-63723283; JNJ-54767414 (DARZALEX®, daratumumab)
Clinical Protocol 54767414MMY2036 Amendment 2
19
Approved, Date: 20 June 2018
1.
INTRODUCTION
JNJ-63723283 is a human immunoglobulin (Ig) G4 kappa (IgG4k) monoclonal antibody (mAb) 
containing the hinge-stabilizing S228P mutation. JNJ-63723283 binds to programmed death-1 
(PD-1) receptor with high affinity and specificity, blocks binding to the programmed death 
ligands 1 and 2 (PD-L1 and PD-L2), enhances pro-inflammatory cytokine production from 
ex vivo stimulated T cells, and reduces tumor volume in human PD-1 knock-in (hPD-1KI) mice 
bearing MC38 murine colon carcinoma tumors. Several anti-PD-l and PD-L1 therapeutic 
antibodies (eg, nivolumab, pembrolizumab, atezolizumab) have been approved to treat various
cancers.
Daratumumab is a human immunoglobulin G1 kappa (IgG1ĸ) monoclonal antibody (mAb) that 
binds CD38-expressing cells with high affinity. CD38 is a transmembrane glycoprotein normally 
expressed on the surface of many immune cells, including CD4+, CD8+, B lymphocytes, and 
natural killer cells. Daratumumab is designed to attack tumor cells that overexpress CD38, such 
as in multiple myeloma (see Section 1.3 for information on the clinical experience with 
daratumumab in the patient population for this study).
For the most comprehensive nonclinical and clinical information regarding JNJ-63723283 and 
daratumumab, refer to the latest versions of the respective Investigator's Brochures. The term 
"Sponsor" used throughout this document refers to the entities listed in the Contact Information 
page, which will be provided as a separate document.
1.1.
Background
Treatment options for multiple myeloma and vary depending on the aggressiveness of the 
disease, underlying prognostic factors, physical condition of the patient, and existing co-
morbidities. Currently approved treatments for patients with relapsed/refractory multiple 
myeloma
include PIs
(eg, bortezomib, carfilzomib, ixazomib), IMiDs (thalidomide, 
lenalidomide, or pomalidomide), histone deacetylase inhibitors, and monoclonal antibodies 
(daratumumab, elotuzumab). Although recent advances in the development of targeted 
therapeutics and stem cell transplantation have improved overall and event-free survival, the 
great majority of patients with myeloma will relapse and experience disease progression, and 
there continues to be a significant unmet clinical need in this patient population. This study is 
designed to evaluate if JNJ-63723283 in combination with daratumumab will improve clinical 
responses in relapsed or refractory multiple myeloma by enhancing the anti-tumor and 
immunomodulatory effects of daratumumab through PD-1 blockade.
1.2.
JNJ-63723283
1.2.1.
Summary of Nonclinical Data
In vitro assays with JNJ-63723283 showed enhanced T cell function and reversed PD-1
mediated suppression of T cell receptor signaling by promoting nuclear factor of activated 
T cells (NFAT)-reporter transcriptional activity. These findings with JNJ-63723283 were
comparable to the observed activities for 2 anti-PD-1 mAb analogues for nivolumab and
pembrolizumab. In vivo, JNJ-63723283 inhibited tumor growth in human PD-1 knock-in mice 
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bearing MC38 murine colon carcinoma tumors and showed comparable antitumor efficacy to a
nivolumab analogue.
Toxicology studies in cynomolgus monkeys indicate JNJ-63723283 was well tolerated and the 
pivotal Good Laboratory Practice (GLP) 5-week study demonstrated T-dependent antigen 
responses (TDAR). No JNJ-63723283-related effects were noted in the cardiovascular,
respiratory, or central nervous system during the 5-week study. Primary JNJ-63723283-related 
findings noted in 4- and 5-week monkey studies at 10 mg/kg/wk included slight increases in 
blood monocyte counts and prothrombin times, and minor/transient decreases in absolute counts 
for blood CD3+ T, CD3+/CD4+ T-helper, and CD3+/CD8+ T-cytotoxic lymphocytes, increases 
in the IgM and IgG secondary TDAR response to keyhole limpet hemocyanin (KLH) antigen 
challenge, and minimally reduced thymic cellularity (decreased lymphocytes) that were 
considered not to be toxicologically significant. None of these findings were considered adverse 
and are anticipated to present low to no clinical risk in humans (eg, reduced thymic cellularity 
that was minimal in nature and was not associated with a correlative decrease in thymus weight 
or in thymus-to-body and thymus-to-brain ratios). In the 5-week study, the no-observed-adverse-
effect level (NOAEL) was 100 mg/kg/wk (mean Cmax 3,055.75 g/mL and AUCDay29-36 
12,658.15 g day/mL following the dose on Day 29). Additionally, JNJ-63723283 did not induce
hemolysis in whole human blood and was compatible with human serum at in vitro 
concentrations between 0.010 to 10 mg/mL, and the JNJ-63723283 cytokine response in vitro in 
human blood was similar to other immune-modulatory compounds that have a low risk of 
cytokine release syndrome.
1.2.2.
Summary of Clinical Data
JNJ-63723283 is being evaluated as a monotherapy in an ongoing Phase 1/2, first-in-human 
study (63723283LUC1001). As of 18 May 2017, preliminary data are available for 17 subjects 
with solid tumors who have been treated with JNJ-63723283 at 3 dose levels (80 mg, 240 mg, 
and 460 mg) with a once every 2-week dosing schedule. Eight of the 17 subjects have been 
treated with 240 mg every 2 weeks and 2 of these subjects had a partial response (PR) at the first 
disease assessment. This study continues to enroll and 240 mg every 2 weeks is being explored 
as the recommended Phase 2 dose (RP2D) regimen. Refer to the JNJ-63723283 Investigator’s 
Brochure for the most current information.
To date, the safety profile of JNJ-63723283 is similar to the safety profile of other anti-PD-1 
mAbs with expected immune-related adverse events (irAEs) observed including rash and 
pneumonitis. The most common treatment-emergent AEs (in 3 or more subjects) reported in 
63723283LUC1001 were dyspnea, hyponatremia, sinus tachycardia
(5
subjects
each);
hypertension and nausea (4 subjects each); and anemia, alanine aminotransferase (ALT) 
increased, aspartate aminotransferase (AST) increased, C-reactive protein increased, decreased 
appetite, headache, hypocalcemia, pleural effusion, vomiting (3 subjects each). Ten serious 
adverse events (SAEs) were reported in 7 subjects across the 3 dose levels: abdominal 
distension, abdominal pain, AST increased, bile duct obstruction, dysesthesia, dyspnea, pyrexia, 
pleural effusion, and pneumonitis. Each of the SAEs occurred in 1 subject each, except for 
pyrexia in 2 subjects, and all SAEs were Grade 3 except for dysesthesia (Grade 2) and 1 SAE of 
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pyrexia (Grade 1). One DLT was reported to date in this study: pleural effusion (Grade 3) in a 
subject with non-small cell lung cancer (NSCLC) who presented with Grade 1 pleural effusion at 
study entry. This subject continued study treatment and had stable disease at the first disease 
assessment.
Preliminary serum pharmacokinetics (PK) of JNJ-63723283 and PD-1 receptor occupancy (RO) 
were evaluated in 16 subjects in Study 63723283LUC1001 following every 2 week IV
administration (n=4 at 80 mg, n=8 at 240 mg, n=4 at 460 mg; as of May 2017). JNJ-63723283 
serum concentration data following the first dose showed that JNJ-63723283 exhibited 
approximately linear PK. Following the first dose, Cmax, Cmin1, and AUCtau all increased in an 
approximately dose- proportional manner. Interpatient variability was generally consistent with 
monoclonal antibody therapeutics (see the Investigator’s Brochure for further details).
Evaluation of preliminary PD-1 RO on circulating CD3+ T cells indicated saturation at Dose 2 
predose for all dose levels tested. The presence of anti-drug antibodies (ADAs) to JNJ-63723283 
is currently under evaluation in Study 63723283LUC1001.
1.3.
Daratumumab
Regulatory Approvals and Relevant Clinical Studies
In November 2015, daratumumab (DARZALEX®) was approved by the US FDA for the 
treatment of patients with MM who have received at least 3 prior lines of therapy, including a PI 
and an IMiD, or who are double-refractory to a PI and an IMiD agent. In May 2016, the
European Commission granted approval of daratumumab as monotherapy for the treatment of 
adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a 
proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease 
progression on the last therapy. Daratumumab in combination with lenalidomide and 
dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple 
myeloma who have received at least 1 prior therapy has also been approved in the US 
(Nov 2016) and EU (Apr 2017). In June 2017, the FDA approved daratumumab in combination 
with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who 
have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. Refer 
to the daratumumab Investigator’s Brochure for details on the clinical experience in patients 
treated with daratumumab.
Study MMY2002 (SIRIUS) enrolled patients with relapsed or refractory multiple myeloma
(RRMM) who received at least 3 prior lines of therapy or were double refractory, the same target 
population as proposed in this study. Note that 95% of subjects in the study were double 
refractory to a PI and IMiD and subjects had received a median of 5 prior lines of therapy. 
Treatment with single-agent daratumumab resulted in an overall response rate (ORR) of 29.2% 
(95% confidence interval [CI]: 20.8, 38.9). Median duration of response was 7.4 months (95% 
CI: 5.5, not estimable [NE]). Stringent complete response (sCR) was reported in 2.8% of 
subjects, very good partial response (VGPR) in 9.4% of subjects, and partial response (PR) in 
17 % of subjects. The most common AEs, which occurred in more than 20% percent of subjects, 
were fatigue, anemia, nausea, thrombocytopenia, back pain, neutropenia, and cough 
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(Lonial 2016).22 While 4.7% of subjects discontinued treatment due to adverse events (AEs), 
none of which were considered drug-related, no subjects discontinued treatment due to infusion-
related reactions (IRRs). 
These results were supported by the Phase 1/2 GEN501 study, which enrolled a similar patient 
population and confirmed that daratumumab is an effective single-agent treatment option for
patients with relapsed and refractory myeloma, especially for those who are resistant to other
treatments or with unacceptable side effects from other treatments. In GEN501, daratumumab 
demonstrated a 36% ORR in subjects treated with a 16 mg/kg dose, with responses
improving (or “deepening”) over time (Lokhorst 2015).2121 The safety profile was acceptable in 
this study.
1.4.
Overall Study Rationale and Anticipated Benefits and Risks of 
Combination Therapy
Significant progress has been made in the management of multiple myeloma with the 
development of targeted immunotherapies and stem cell transplantation. However, it remains an 
incurable malignancy with significant unmet clinical need, particularly in the relapsed or 
refractory patient population. Novel approaches, particularly combination therapies, are required 
to improve treatment options for these patients. 
Daratumumab is a human IgG kappa mAb that binds with high affinity to CD38, a 
transmembrane glycoprotein expressed by tumor cells, and induces tumor cell death through 
multiple mechanisms of action. These MoAs include several immune-mediated activities, 
including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity 
(ADCC), and antibody-dependent cellular phagocytosis (ADCP), and direct cytotoxicity by 
induction of apoptosis by Fc gamma receptor mediated crosslinking of tumor-bound monoclonal 
antibodies (de Weers 2011; Overdijk 2015; Phipps 2015; Jansen 2012).9,28,31,15 In addition to its 
direct anti-tumor mechanisms, daratumumab leads to the rapid and sustained elimination of
highly immunosuppressive subsets of CD38+ regulatory T cells (Tregs), CD38+ myeloid derived 
suppressor cells (MDSCs), and CD38+ regulatory B cells (Bregs) (Krejcik 2016).17 It has also 
been shown that daratumumab may modulate the enzymatic activity of CD38 and may lead to a 
reduction in immunosuppressive adenosine levels (Horenstein 2013).13 The elimination of these 
immunosuppressive cells and modulation of CD38 enzymatic activity leads to the increased 
clonal expansion of CD8+ and CD4+ T cells.
There is a compelling rationale for targeting PD-1 signaling in multiple myeloma. Increased 
expression of PD-L1 in malignant plasma cells as well as upregulation of PD-1 on effector T and 
natural killer (NK) cells of multiple myeloma patients generates an immunosuppressive 
microenvironment that is associated with disease progression (Benson 2010; Rosenblatt 2017;
Yousef 2015).4,35,41 Blockade of the PD-1/PD-L1 signaling was also associated with increased 
CD8+ cytotoxic T-lymphocyte activity and NK-mediated cell lysis in multiple myeloma
preclinical models (Ray 2015).34 Additionally, expression of PD-1 has been shown to correlate 
with resistance to myeloma therapies (Tamura 2013).37
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However, PD-1 blockade alone may not be an optimal therapeutic approach in multiple 
myeloma, as indicated in a Phase 1 study of single-agent nivolumab, which failed to demonstrate
objective responses (Lesokhin 2016).19 Combination studies with anti-PD-1 agents in multiple 
myeloma have shown more favorable results (Jung 2017).16 A Phase 2 single-arm study of 
pembrolizumab, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma 
showed an ORR of 60% with 6% sCR, 2% CR 9% VGPR, and 33% PR (Badros 2015).2
Additionally, a study of pembrolizumab, lenalidomide, and dexamethasone showed an ORR of 
76% (24% VGPR and 53% PR) (San Miguel 2015).36
Therefore, JNJ-63723283 in combination of with daratumumab may lead to significant 
improvement in clinical responses through multiple mechanisms of action in treating relapsed or 
refractory multiple myeloma. By targeting CD38, daratumumab exhibits not only conventional 
anti-tumor effects of CDC, ADCC, ADCP and apoptosis, but also immunomodulatory effects. 
By targeting PD-1, treatment with JNJ-63723283 should reactivate antitumor immune responses.
By jointly targeting different epitopes on multiple myeloma cells, effector T and NK cells, as 
well as the bone marrow microenvironment through discrete and complementary mechanisms of 
action, this combination may be an effective therapeutic approach in treating relapsed or 
refractory multiple myeloma. This shift away from an immunosuppressive environment may lead 
to the generation of protective immune responses, which may be further potentiated by PD-1 
blockade with JNJ-63723283, potentially leading to improved clinical responses.
Overlapping toxicities of JNJ-63723283 and daratumumab are not expected based on nonclinical 
and clinical data generated to date with each compound. While infusion-related reactions (IRRs) 
are observed in approximately half of patients treated with daratumumab, IRRs occur in only 
approximately 3/17 (18%) subjects treated with JNJ-63723283. Given the mechanism of action 
of JNJ-63723283, events associated with immune-mediated adverse events will also be 
considered as anticipated events. Because this is the first study of JNJ-63723283 in combination 
with daratumumab, other unforeseen toxicities or adverse events cannot be anticipated. The 
potential risks of this drug combination will be mitigated by comprehensive and careful medical 
monitoring and pre- and postinfusion medications to reduce mAb-associated IRRs during the 
conduct of the study. The protocol is designed with a safety run-in phase and the safety will be 
closely monitored by an SET. In addition, the protocol and the Investigator’s Brochures also 
provide appropriate preventative measures and guidelines for managing potential toxicities.
Immune-related risks have been identified with other anti-PD-1 antibodies, including 
gastrointestinal AEs such as colitis and diarrhea, pneumonitis, renal AEs such as nephritis and 
acute renal failure, hepatic AEs such as hepatitis and liver enzyme elevations, endocrinopathies 
such as hypothyroidism and adrenal insufficiency, and rash. A series of precautions has been put 
into place to manage the potential risks that could rise in response to JNJ-63723283 
administration. In addition, safety of all participating subjects will be closely monitored via 
collaboration between the investigator and the Sponsor. Symptom monitoring and management 
guidelines are provided in the protocol. 
The potential effect of coadministration of JNJ-63723283 and daratumumab on the incidence of 
anti-drug antibodies to either drug is unknown. Serum drug concentrations, anti-drug antibodies, 
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and safety will be monitored throughout the study. Pharmacokinetic-based drug-drug interactions 
resulting in clinically significant changes to exposure are not anticipated based on the nature of 
metabolism for protein therapeutics.
In summary, the favorable benefit-risk profile of daratumumab in multiple myeloma, the 
available safety and efficacy data in JNJ-63723283, and the potential to improve clinical 
responses in multiple myeloma by further enhancing the anti-tumor and immunomodulatory 
effects of daratumumab through PD-1 blockade supports further investigation and evaluation of
JNJ-63723283 and daratumumab in multiple myeloma.
As of 25 May 2018, the Sponsor terminated
further enrollment into this study, 
54767414MMY2036
(TUCANA), 
based 
on 
safety 
and 
efficacy 
findings 
in 
the 
54767414LUC2001 (CALLISTO) study, which combined daratumumab with atezolizumab in 
non-small cell lung cancer.  
At the third planned Data Monitoring Committee (DMC) review on 23 May 2018, the DMC 
reviewed the subject data (n=88, 44 per arm) for the CALLISTO Study. The DMC determined 
that there was no observed benefit within the combination treatment arm, daratumumab plus 
atezolizumab, over atezolizumab alone, and recommended stopping enrollment of the study. In 
addition, the DMC recommended discontinuation of daratumumab treatment to all active 
subjects receiving combination therapy (subjects randomized to the combination Arm B, as well 
as subjects randomized to Arm A who have crossed over into Arm B). Although no unexpected 
imbalances in on-treatment toxicities were observed, the DMC noted a clear early difference in 
the number of deaths between the atezolizumab monotherapy (n=13) and combination arm 
(n=18). The discrepancy was observed within the first 3 months from dosing, where the number 
of deaths are 4 for the atezolizumab arm and 10 for the combination arm, giving rise to 3-month 
survival rates of 90.7% for the atezolizumab arm and 76.2% for the combination arm.
Since the benefit/risk ratio has changed for combination therapy in CALLISTO, the Sponsor has 
decided to suspend enrollment into other studies which combine daratumumab and a PD-1 or 
PD-L1 monoclonal antibody regardless of indication.  In addition to discontinuing enrollment 
into this study, treatment with the combination of daratumumab and JNJ-63723283 will be 
discontinued and ongoing subjects will be given the option to continue on daratumumab 
monotherapy until subject meets one or more of the treatment discontinuation criteria in Section 
10.1.1 (see Attachment 11).
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2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
2.1.
Objectives and Endpoints
OBJECTIVES
ENDPOINTS
Part 1 (Safety Run-in)
Primary

To assess the safety of the combination of 
JNJ-63723283 and daratumumab

Incidence of adverse events, including dose-
limiting toxicities (DLTs)
Part 2 (Phase 2)
Primary

To compare the overall response rate (ORR) in subjects 
treated with JNJ-63723283 in combination with 
daratumumab versus daratumumab alone

ORR, defined as the proportion of subjects with 
a best response of PR or better, as defined by 
IMWG response criteria
Secondary 

To assess the safety of the combination of 
JNJ-63723283 and daratumumab

To compare the complete response (CR) or better rate 
and very good partial response (VGPR) or better rate of 
JNJ-63723283 in combination with daratumumab versus 
daratumumab alone

To compare the duration of response and time to 
response of JNJ-63723283 in combination with 
daratumumab versus daratumumab alone

To compare the progression-free survival (PFS) and 
overall survival (OS) of JNJ-63723283 in combination 
with daratumumab versus daratumumab alone

To compare the minimal residual disease (MRD)-
negative rate of JNJ-63723283 in combination with 
daratumumab versus daratumumab alone

To evaluate the pharmacokinetic and immunogenicity 
profile of JNJ-63723283 when given in combination 
with daratumumab

To evaluate the pharmacokinetic and immunogenicity 
profile of daratumumab when given alone or in 
combination with JNJ-63723283

Incidence of adverse events, including immune-
related AEs and infusion-related reactions

CR or better rate, VGPR or better rate, defined 
as the proportion of subjects with a best 
response of at least CR or at least VGPR, as 
defined by the IMWG response criteria

Duration of response, defined as the time from 
onset of first response until date of disease 
progression or death

Time to response, defined as the time between 
the date of randomization and the onset of first 
response

PFS, defined as the time from the date of 
randomization to the date of disease 
progression or death due to any cause, 
whichever occurs first

Overall survival (OS), defined as the time from 
the date of randomization to the date of death

MRD-negative rate, defined as the proportion 
of MRD- negative subjects

Serum JNJ-63723283 pharmacokinetic 
parameters including but not limited to Cmin and 
Cmax, and incidence of anti-JNJ-63723283 
antibodies 

Serum daratumumab pharmacokinetic 
parameters including but not limited to Cmin and 
Cmax, and incidence of anti-daratumumab 
antibodies
Part 3 (Phase 3)
Primary

To compare progression-free survival (PFS) in subjects 
treated with JNJ-63723283 in combination with 
daratumumab versus daratumumab alone

PFS, defined as the time from the date of 
randomization to the date of disease 
progression or death due to any cause, 
whichever occurs first
Secondary 

To evaluate the overall response rate (ORR) and overall 
survival (OS)

To compare the duration of response and time to 
response of JNJ-63723283 in combination with 
daratumumab versus daratumumab alone

To compare the complete response (CR) or better rate 

ORR, defined as the proportion of subjects with 
a best response of PR or better, as defined by 
the IMWG response criteria 

Overall survival (OS), defined as the time from 
the date of randomization to the date of death

Duration of response, defined as the time from 
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OBJECTIVES
ENDPOINTS
and very good partial response (VGPR) or better rate of 
JNJ-63723283 in combination with daratumumab versus 
daratumumab alone

To compare the MRD-negative rate of JNJ-63723283 in 
combination with daratumumab versus daratumumab 
alone

To assess the safety of the combination of JNJ-
63723283 and daratumumab

To evaluate the pharmacokinetic and immunogenicity 
profile of JNJ-63723283 when given in combination 
with daratumumab

To evaluate the pharmacokinetic and immunogenicity 
profile of daratumumab when given alone or in 
combination with JNJ-63723283

To compare the effect of JNJ-63723283 in combination 
with daratumumab versus daratumumab alone on 
disease-related symptoms, functioning, quality of life, 
and health status using the following patient reported 
outcomes (PROs) measures:
-
European Organization for Research and Treatment 
of Cancer Quality of Life Questionnaire-Core 30 
(EORTC-QLQ-C30)
-
European Quality of Life 5 Dimensions 
Questionnaire (EQ-5D-5L)
onset of first response until date of disease 
progression or death

Time to response, defined as the time between 
the date of randomization and the onset of first 
response

CR or better rate, VGPR or better rate, defined 
as the proportion of subjects with a best 
response of at least CR or at least VGPR, as per
the IMWG response criteria

MRD-negative rate, defined as the proportion 
of MRD-negative subjects 

Incidence of adverse events, including immune-
related AEs and infusion-related reactions

Serum JNJ-63723283 concentration (Cmin, 
Cmax) and incidence of anti-JNJ-63723283 
antibodies

Serum daratumumab concentration (Cmin, Cmax) 
and incidence of anti-daratumumab antibodies

Change from baseline in disease-related 
symptom scales, functioning scales, and Global 
Health Status (GHS) scale of the EORTC 
QLQ-C30, and the utility scale and visual 
analog scale (VAS) of the EQ-5D-5L.
Exploratory Objectives

To explore biomarkers predictive of response or resistance to therapy

To evaluate potential pharmacodynamic biomarkers in response to therapy

To explore the relationships between pharmacokinetics, pharmacodynamics, AE profiles, and clinical activity of 
JNJ-63723283 given in combination with daratumumab

To compare the health economic/resource utilization of JNJ-63723283 in combination with daratumumab 
versus daratumumab alone (Part 3 only)
2.2.
Hypothesis
Part 2: The primary hypothesis is that treatment with JNJ-63723283 in combination with 
daratumumab will improve ORR compared to daratumumab alone in subjects with relapsed or 
refractory multiple myeloma.
Part 3: The primary hypothesis is that treatment with JNJ-63723283 in combination with 
daratumumab will improve PFS compared to treatment with daratumumab alone in subjects with 
relapsed or refractory multiple myeloma.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a randomized, open-label, multicenter, multiphase study assessing the efficacy and safety 
of JNJ-63723283 (an anti-PD-1 monoclonal antibody) in combination with daratumumab 
compared with daratumumab alone in subjects with multiple myeloma who have received at
least 3 prior lines of therapy including a PI and an IMiD or whose disease is double refractory to 
both a PI and an IMiD. 
A diagram of the study design is provided in Figure 1.
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Figure 1:
Study Scheme
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Part 1: Safety Run-in Phase
A 6-subject Safety Run-in cohort will be evaluated by the Safety Evaluation Team (SET; see 
Section 3.2) to determine the safety and tolerability of JNJ-63723283 in combination with 
daratumumab before the start of the randomized phase of Part 2 of the study. The DLT 
evaluation period for the Safety Run-in cohort will be 1 cycle (28-days).

Study drug administration:

Daratumumab: Daratumumab 16 mg/kg IV will be administered once every week
(Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once 
every 4 weeks (Week 25 onwards).

JNJ-63723283: 240 mg IV (fixed dose) will be administered during Week 1 on Cycle 1 
Day 2, Cycle 1 Day 15, then every 2 weeks thereafter.

Daratumumab will be administered prior to administration of JNJ-63723283. Subjects 
will continue to receive study treatment until confirmed disease progression, 
unacceptable toxicity, or any other treatment discontinuation criteria are met.

If <2 of the first 6 DLT evaluable subjects experience a dose-limiting toxicity (DLT; see 
Section 3.2) during the first treatment cycle (ie, 28 days), the selected doses and dose 
regimens for JNJ-63723283+daratumumab
combination therapy will be considered 
tolerable, and the study will proceed to the Part 2 randomized phase after the SET provides 
approval.

If 2 subjects experience a DLT during the first treatment cycle (ie, 28 days), new subject 
enrollment into the Safety Run-in cohort will stop until after the SET convenes to review 
DLT data from those subjects and makes recommendations regarding the conduct of the 
study. The SET may consider the exploration of alternate doses and dose regimens, in an 
additional safety run-in cohort.

Subjects in the Safety Run-in cohort may continue to receive additional cycles of 
JNJ-63723283+daratumumab while enrollment into the Safety Run-in cohort is ongoing and 
after the study has proceeded to the randomized phase until they meet protocol-specified 
discontinuation criteria. Subjects who experience unacceptable toxicity directly attributable 
to JNJ-63723283 may be eligible to receive daratumumab alone, after consultation with the 
Sponsor.
Part 2 (Phase 2) and Part 3 (Phase 3)
Subjects will be assigned randomly in a 1:1 ratio into 2 treatment arms as indicated in Table 3.
Table 3:
Subject Randomization
Planned Number of Subjects 
Study Arm 
Part 2
Part 3
Arm A: daratumumab 
40
150
Arm B: JNJ-63723283 + daratumumab
40
150 
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Treatment (Part 2 and Part 3)
Treatment cycles will be 28 days in duration. 

Daratumumab: Daratumumab 16 mg/kg will be administered IV once every week
(Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 
4 weeks (Week 25 onwards).

JNJ-63723283: For Arm B, JNJ-63723283 240 mg IV (fixed dose) will be administered 
during Week 1 on Cycle 1 Day 2, Cycle 1 Day 15, then every 2 weeks thereafter. 
Daratumumab will be administered prior to administration of JNJ-63723283, when they are 
administered on the same dosing days.
Subjects 
will 
continue 
receiving
the 
assigned 
study 
treatment 
(daratumumab
or 
JNJ-63723283+daratumumab) until treatment discontinuation due to disease progression, 
unacceptable toxicity, or other protocol-defined treatment discontinuation criteria are met
(see Section 10). Subjects in Arm B, who experience unacceptable toxicity directly attributable 
to JNJ-63723283 and who are experiencing clinical benefit (ie, stable disease or better) may stay 
on daratumumab until treatment discontinuation criteria are met, after discussion with the 
Sponsor. After disease progression is documented, survival status, subsequent anticancer 
treatment, and response to subsequent anticancer treatment will be recorded for all subjects until 
study end. The end of the study is defined in Section 17.9.1. Study evaluations (eg, disease 
assessments) are described in Section 9. The timing of study assessments is provided in the Time 
and Events Schedules (Table 1 and Table 2).
Initiation of Part 3 (Phase 3)
After all 80 randomized subjects in Part 2 (Phase 2) have been followed for approximately 
4 months or discontinued earlier, the Sponsor will determine whether the Part 2 primary efficacy 
endpoint was met and if the combination of the 2 drugs is safe. In addition, the secondary 
endpoint results, as well as all other available data, will be examined and taken into 
consideration. Based on the totality of the data, the Sponsor will decide whether Part 3 (Phase 3) 
will be initiated. This decision will be made in consultation with health authorities and the final 
decision will be communicated in writing to sites and independent ethics committees 
(IECs)/institutional review boards (IRBs), as appropriate.
If Part 3 is initiated, after the primary efficacy analysis, subjects remaining in the study will 
continue to be followed up until 205 deaths have occurred in this part.
Overall Design for Daratumumab Monotherapy Period
As of 25 May 2018, the Sponsor
terminated
further enrollment into this study, 
54767414MMY2036. In addition to discontinuing enrollment into this study, treatment with the 
combination of daratumumab and JNJ-63723283 will be discontinued and ongoing subjects will 
be given the option to continue on daratumumab monotherapy.
In the Daratumumab Monotherapy Period, each cycle is 28 days, and administration of 
daratumumab is to occur weekly for Cycles 1 and 2, every other week for Cycles 3 to 6, and 
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every 4 weeks for Cycles 7 and onwards until disease progression, pregnancy, unacceptable 
toxicity, loss of follow-up, withdrawal of consent, or death. Scheduled assessments to be 
performed during the daratumumab monotherapy period for subjects no longer receiving JNJ-
63723283 in combination with daratumumab are outlined in the Time and Events Schedule 
in Attachment 11 / Table 24.
3.2.
Safety Evaluation
Dose-Limiting Toxicity (DLT) Evaluation - Safety Run-in
Toxicities will be graded for severity according to the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03. During the 6-subject 
Safety Run-in phase, the DLT evaluation period is 28 days starting from the day of the first dose 
of study drug. Only toxicities that occur during the DLT evaluation period will be considered for 
DLT assessment. A subject who received 75% of a planned dose without experiencing a DLT 
may be replaced.
Dose-limiting toxicity is defined as any of the events listed in Table 4. Toxicities with a clear 
alternative explanation (eg, due to disease progression) or transient toxicities (72 hours) and 
abnormal laboratory values without associated clinically significant signs or symptoms based on 
investigator determination can be deemed a non-DLT.
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Table 4:
Criteria for Dose- limiting Toxicity
DLT criteria for Non-hematologic Toxicitya
AST or ALT
Grade 3 persisting 7 days after treatment with corticosteroids, Grade 4, or 
any case meeting Hy’s Law criteriab
Laboratory abnormality
Grade 3 persisting 7 days despite BSCc or Grade 4
Any other
Grade 3 persisting 7 days despite BSCc or Grade 4; except Grade 3 
asymptomatic or mildly symptomatic rash that can be adequately managed 
with supportive care or resolves to become asymptomatic or Grade 2 within 
7 days of supportive therapy.
Infusion-related reaction
Grade 4 infusion-related reaction that occurs during or within 24 hours after 
the infusion of JNJ-63723283 or daratumumab.
DLT criteria for Hematologic Toxicitya
Neutropenia
Grade 4 neutropenia lasting more than 7 days despite BSCc, or Grade 3 febrile 
neutropenia (ANC <1000 cells/mm3 and a single temperature >38.3C or a 
sustained temperature 38C for >1 hour), or sepsis
Thrombocytopenia
Grade 3 thrombocytopenia with clinically significant bleeding and Grade 4 
thrombocytopenia lasting more than 7 days despite BSCc
Anemia
Grade 4 for more than 7 days despite BSCc
DLT criteria for both Non-hematologic and Hematologic Toxicitya
Any Grade 5 non-hematologic or hematologic event
ALT=alanine aminotransferase, AST=aspartate aminotransferase, ALP=alkaline phosphatase; BSC=best supportive 
care
a.
Toxicity graded according to the NCI-CTCAE, Version 4.03.
b.
Hy’s Law criteria, defined as ALT or AST value 3 x upper limit of normal (ULN), total bilirubin 2 x ULN, and ALP 2 x 
ULN; with no alternative etiology.
c.
Best supportive care (BSC) if available, according to institutional standards.
Safety Evaluation Team (SET)
Ongoing safety evaluation during Part 1 and Part 2 will be overseen by the SET. The SET 
established by the Sponsor will monitor all available treatment-emergent adverse events on an 
ongoing basis. The SET will also be responsible for reviewing the safety data during the safety 
run-in phase and making a recommendation on whether the study will proceed to the 80-subject
randomized phase (Part 2) based on the DLT rules set forth above.
The SET will be chaired by the Sponsor’s Study Responsible Physician. Membership will 
include a Sponsor clinical scientist, safety physician, statistician, clinical pharmacologist, along 
with additional Sponsor staff, as appropriate. Additionally, the investigators who have enrolled 
the subjects in Part 1 and 2 will be members. The team will meet during the safety run-in phase 
and as necessary during the remainder of Part 1 and Part 2. Decisions with the potential to affect
subject safety (eg, unfavorable change in benefit/risk assessment) will be promptly 
communicated to investigators and regulatory authorities as appropriate. Additional details will 
be specified in a separate SET charter.
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Independent Data Monitoring Committee (IDMC) – Part 3 (Phase 3)
In Part 3, ongoing safety evaluation will be performed by the IDMC. In addition, a formal safety 
review will be performed after 50 subjects have been treated for at least 8 weeks or discontinued 
the study treatment. The purpose of this safety review is to have a comprehensive evaluation of 
safety for the new drug product for JNJ-63723283 (see Section 14.1) in combination with 
daratumumab.
The IDMC, consisting of 2 clinicians and 1 statistician, will be established by the Sponsor to 
review efficacy and safety results at the pre-planned analyses. After the interim reviews, they 
will make recommendations regarding the continuation of the study. The details will be provided 
in a separate IDMC charter.
3.3.
Study Design Rationale
Rationale for Study Design
Adequate steps have been taken to ensure the validity of data in an open-label study design. This 
includes performing tumor assessments at the same frequency in both arms, adhering to protocol-
defined schedules, and determining the strategy for the final analysis of the primary endpoint 
prior to study start, including predefined methods for handling missing data and censoring rules.
Randomization will be used to minimize bias in the assignment of subjects to treatment groups. 
To further minimize imbalance across treatment arms and to allow for balanced enrollment in 
important subgroup analyses, subjects will be stratified based on ISS staging and number of prior 
lines of therapy (3 prior lines vs. >3 prior lines). 
Rationale for Daratumumab Dose Selection
The daratumumab dose regimen used in this study (16 mg/kg) is approved in many regions as 
monotherapy and in combination with other therapies for the treatment of subjects with relapsed
and refractory multiple myeloma. This dose regimen was selected based on an acceptable safety 
profile, maximal clinical activity, and pharmacokinetics consistent with saturation of the target.
This dose and similar schedules have been shown to be tolerable in several combination studies.
Rationale for JNJ-63723283 Monotherapy Dose Selection
As of May 2017, 17 subjects have been dosed with JNJ-63723283 monotherapy and completed 
DLT evaluation in the first-in-human study in patients with advanced solid tumors 
(Study 63723283LUC1001). This study continues to enroll subjects with various advanced solid 
tumor types and has expanded to Part 2, where subjects with selected tumor types are dosed at a 
recommended Phase 2 dose (RP2D) regimen of 240 mg every 2 weeks. The maximum dose 
regimen of JNJ-63723283 in the first-in-human study to date is 460 mg every 2 weeks; no 
maximum tolerated dose has been identified. To date, the safety profile of JNJ-63723283 is 
similar to the safety profile of other anti-PD-1 mAbs. Adverse events have been broadly
consistent across tumor types following monotherapy and have not demonstrated a clear dose-
response relationship (see Section 1.2.2 and the Investigator’s Brochure for additional details).
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The clinically efficacious dosing regimen for JNJ-63723283 is anticipated to be in the same 
range as similar anti-PD-1 mAbs. The approved dose regimens for these drugs include 
nivolumab 3 mg/kg or 240 mg every 2 weeks and pembrolizumab 2 mg/kg or 200 mg every 
3 weeks (the body weights across nivolumab and pembrolizumab clinical studies have been 
reported as 79 kg [mean] and 77 kg [median], respectively, (Bajaj 2017; Freshwater 2017)3,11. 
The RP2D regimen for JNJ-63723283 is 240 mg every 2 weeks in all tumor types based on the 
following:

JNJ-63723283 demonstrated similar in vitro binding affinity to human PD-1 as 
pembrolizumab and nivolumab analogues (within 3-fold), similar potency in ex vivo mixed 
lymphocyte reaction and cytomegalovirus (CMV) assays as pembrolizumab and nivolumab 
analogues, and similar tumor growth inhibition in a MC38 mouse syngeneic model as a 
nivolumab analogue (see the Investigator’s Brochure for additional details).   

Pharmacokinetic simulations based on preliminary modeling of observed clinical PK data 
through May 2017 (n=14, median body weight 75 kg) showed that following 240 mg IV 
JNJ-63723283 every 2 weeks, the predicted steady-state trough concentration, or Cmin,ss of 
JNJ-63723283 (47 µg/mL) is expected to be similar to reported nivolumab Cmin,ss at 3 mg/kg 
every 2 weeks (57 µg/mL) (CDER 2014)6 and approximately double the reported 
pembrolizumab Cmin,ss at 2 mg/kg every 3 weeks (23 µg/mL) (CDER 2014)7.  

Preliminary PD-1 RO assessment on circulating CD3+ T cells following JNJ-63723283 
dosing suggests dose-independent saturation from 80 to 460 mg, similar to the dose-
independent clinical RO observed for nivolumab from 1 to 10 mg/kg (Topalian 2012)38.

A semi-mechanistic translational PK/pharmacodynamics (PD) model was developed using 
PK, RO, and tumor growth inhibition data from MC38 syngeneic mouse studies as well as 
PK and RO data from healthy cynomolgus monkey studies. This translational PK/PD model 
suggested that IV doses 240 mg every 2 weeks in humans (corresponding to a predicted 
serum Cmin,ss of 42 µg/mL) would lead to maximum tumor killing effect in patients with 
non-small cell lung cancer (NSCLC). This prediction is consistent with the established 
clinically efficacious doses for nivolumab and pembrolizumab. 

Preliminary PK modeling of observed JNJ-63723283 clinical PK data through May 2017 
projected a serum Cmin,ss of 47 µg/mL following 240 mg every 2 week dosing, providing 
further evidence that the targeted JNJ-63723283 trough concentrations can be achieved at 
this dosing regimen. 

No clinically relevant impact of tumor type on drug exposure or clearance has been 
observed for nivolumab or pembrolizumab (Bajaj 2017; Ahamadi 2017)3,1.
Rationale for JNJ-63723283 Dose Selection in Combination with Daratumumab 
The JNJ-63723283 monotherapy RP2D regimen selection, was based on an acceptable safety 
profile, similarity to other anti-PD-1 mAbs, and preliminary evidence that target concentrations 
are achieved (see Rationale for JNJ-63723283 Monotherapy Dose Selection). JNJ-63723283 has 
not been clinically evaluated in combination with other agents. In patients with advanced 
hematologic malignancies including multiple myeloma, nivolumab has demonstrated a similar 
safety profile as in patients with solid tumors and Hodgkin lymphoma at a dose of 3 mg/kg every 
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2 weeks (Lesokhin 2016)19. JNJ-63723283 at 240 mg every 2 weeks (equivalent to 3 mg/kg 
based on a body weight of 80 kg) is expected to have a similar safety profile as nivolumab. In 
combination cohorts, JNJ-63723283 will be administered following completion of daratumumab 
infusions (on Cycle 1 Day 2 and on Day 1 for all other doses) in order to better manage 
daratumumab-associated IRRs.
Rationale for Pharmacokinetics and Immunogenicity Assessments
The coadministration of JNJ-63723283 and daratumumab in relapsed or refractory multiple 
myeloma is not expected to substantially alter the pharmacokinetics of either agent but may 
impact the incidence of immunogenicity. Minimum and maximum observed concentrations (Cmin
and Cmax) will be assessed for all parts of the study and will contribute to the characterization of 
study drug pharmacokinetic profiles. The JNJ-63723283 concentration results after combination 
dosing may be compared with available data from other JNJ-63723283 clinical studies to assess 
if there is any alteration in JNJ-63723283 pharmacokinetics when co-administered with
daratumumab in this study population and to correlate any clinical activity and safety events. The 
daratumumab concentration results after monotherapy and combination dosing will be evaluated 
(and may be compared with available data from other daratumumab clinical studies) to assess if 
there is
any alteration in daratumumab pharmacokinetics when co-administered with
JNJ-63723283 and to correlate any clinical activity and safety events. Data may also be used for 
a population pharmacokinetic analysis to estimate additional pharmacokinetic parameters and 
provide information about the determinants of inter-subject variability in this population. The 
presence of antibodies to JNJ-63723283 and daratumumab (immunogenicity) will be assessed to 
evaluate impact of anti-drug antibodies on pharmacokinetics.
Rationale for Biomarker Evaluations
Published results suggest that PD-1 is highly expressed on multiple myeloma malignant plasma 
cells (Yousef 2015).41 Engagement of PD-1 on T-cells by PD-L1 expressed on malignant plasma 
cells and other immune cells may be one mechanism of tumor immune evasion. Another 
mechanism of tumor immune evasion includes accumulation of immunosuppressive cells such as 
MDSCs, Tregs, and Bregs. Previous studies have demonstrated that treatment with daratumumab 
leads to a reduction in CD38+ immunosuppressive MDSCs, Tregs, and Bregs in addition to an 
increase in the absolute T-cell count, T-cell clonality, and T-cell functionality (Krejcik 2016)17. 
Therefore, the combination of JNJ- 63723283 with daratumumab may enhance the magnitude 
and duration of response by targeting different mechanisms of immunosuppression allowing for 
a more robust anti-myeloma T-cell response. Based on data from single-agent studies, blood and 
bone marrow samples will be collected to explore biomarkers predictive of response or 
resistance and evaluate potential pharmacodynamic biomarkers in response to JNJ-63723283 
given in combination with daratumumab.
Rationale for Patient-reported Outcomes Assessments
The EORTC QLQ-C30 and the EQ-5D-5L instruments will assess the effect of the study drugs 
on subject functional status, well-being, and symptoms to support market access and requests 
from payers (see Attachment 10). The EORTC QLQ-C30 has been widely used among cancer 
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patients and in prior multiple myeloma clinical trials. The EQ-5D-5L is a standardized 
preference instrument for use as a measure of health status and to calculate utility values.
4.
SUBJECT POPULATION
Screening for eligible subjects will be performed within 28 days before enrollment in either the 
safety run-in or randomized phases. The inclusion and exclusion criteria for enrolling subjects in 
this study are described in the following 2 subsections. Enrollment/randomization will occur 
after the Sponsor reviews and approves subject eligibility (inclusion and exclusion criteria).
Waivers are not allowed.
As of 25 May 2018, this study is closed to further enrollment.
4.1.
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study. 
1.
At least 18 years of age.
2.
Have received at least 3 prior lines of therapy (refer to Attachment 6) including a PI and an 
IMiD in any order during the course of treatment for multiple myeloma.
or
Have disease that is refractory to both a PI and an IMiD. (For subjects who have received 
more than 1 type of PI, their disease must be refractory to the most recent one. Similarly, for 
those who have received more than 1 type of IMiD, their disease must be refractory to the 
most recent one.)
3.
Evidence of a response (PR or better based on investigator’s determination of response by 
IMWG criteria) to at least 1 prior treatment regimen.
4.
Documented measurable disease for multiple myeloma at screening as defined by the 
criteria below:

IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level 1.0 g/dL or 
urine M-protein level 200 mg/24 hours; or

IgA, IgM, IgD, or IgE multiple myeloma: serum M-protein level 0.5 g/dL or urine 
M-protein level 200 mg/24 hours; or

Light chain multiple myeloma without measurable disease in the serum or urine: Serum 
immunoglobulin free light chain 10 mg/dL and abnormal serum immunoglobulin 
kappa lambda free light chain ratio.
5.
Have relapsed or refractory disease at time of enrollment as defined below:

Relapsed disease is defined as an initial response to previous treatment, followed by PD by 
IMWG criteria >60 days after cessation of treatment.

Refractory disease is defined as <25% reduction in M-protein or PD by IMWG criteria 
during previous treatment or 60 days after cessation of treatment.
6.
ECOG performance status score of 0, 1, or 2 (refer to Attachment 5).
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7.
Laboratory criteria:

Adequate bone marrow function:
a) hemoglobin 7.5 g/dL (5 mmol/L; it is not permissible to transfuse a subject to reach 
this level)
b) absolute neutrophil count (ANC) 1.0 x 109/L (granulocyte colony stimulating factor 
[GCSF] use is permitted);
c) platelet count 75 × 109/L in subjects in whom <50% of bone marrow nucleated cells 
are plasma cells and platelet count 50 x 109/L in subjects in whom 50% of bone 
marrow nucleated cells are plasma cells (it is not permissible to transfuse a subject to 
reach this level)

Adequate liver function:
a) aspartate aminotransferase (AST) 2.5 x upper limit of normal (ULN);
b) alanine aminotransferase (ALT) 2.5 x ULN;
c) total bilirubin 2.0 x ULN, except in subjects with congenital bilirubinemia, such as 
Gilbert syndrome (direct bilirubin 2.0 x ULN)

Adequate renal function:
a) estimated creatinine clearance 30 mL/min (refer to Attachment 3)

Corrected serum calcium 14 mg/dL (3.5 mmol/L); or free ionized calcium 6.5 mg/dL 
(1.6 mmol/L) (Attachment 4)
8.
A woman of childbearing potential must have a negative serum or urine pregnancy test 
within 14 days prior to study drug administration.
9.
Contraceptive use by men or women should be consistent with local regulations regarding 
the use of contraceptive methods for subject participating in clinical studies.
Before enrollment, a woman must be either:

Not of childbearing potential defined as: 
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, however in the absence of 12 months of amenorrhea, a single 
FSH measurement is insufficient.
permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, 
bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy.
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
Of childbearing potential and practicing 2 methods of reliable birth control 
simultaneously: 1 highly effective method of contraception (failure rate of <1% per 
year when used consistently and correctly) and 1 additional effective method.
Examples of highly effective contraceptives include:

user-independent methods:
implantable progestogen-only hormone contraception associated with inhibition of 
ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); 
vasectomized partner; 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.)

user-dependent methods:
combined (estrogen-
and progestogen-containing) 
hormonal contraception 
associated with inhibition of ovulation: oral, intravaginal, and transdermal; 
progestogen-only hormone contraception associated with inhibition of ovulation: 
oral and injectable
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 participating in clinical studies. Hormonal contraception may be 
susceptible to interaction with the study drug, which may reduce the efficacy of the 
contraceptive method.
Examples of additional effective contraceptive methods include:

male latex or synthetic condom, diaphragm, or cervical cap

agrees to remain on the 2 contraception methods (1 highly effective and 1 additional 
reliable method) throughout the study and for at least 3 months after last dose of 
daratumumab or 5 months after the last dose of JNJ-63723283. In addition, during 
the study and for 3 months after receiving the last dose of daratumumab or 
5 months after the last dose of JNJ-63723283, a woman must agree not to donate 
eggs (ova, oocytes) for the purposes of assisted reproduction.
Note: If the childbearing potential changes after start of the study 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 and 1 additional reliable 
method, as described throughout the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered. 
10. During the study and for a minimum of approximately 3 months after the last dose of 
daratumumab or 5 months after the last dose of JNJ-63723283, in addition to the highly 
effective method of contraception, a man
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
who is sexually active with a woman of childbearing potential must agree to use a 
barrier 
method 
of 
contraception 
(eg, 
condom 
with 
spermicidal 
foam/gel/film/cream/suppository)

who is sexually active with a woman who is pregnant must use a condom

must agree not to donate sperm.
11. Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
12. Must sign an informed consent form (ICF) indicating that he or she understands the purpose 
of, and procedures required for, the study and is willing to participate in the study. 
4.2.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study:
1.
Received any of the following prescribed medications or therapies in the past: 

Anti-CD38 antibody, including daratumumab

Anti-PD-1 and anti-PD-L1 antibodies
2.
Received any of the following prescribed medications or therapies within the specified 
period:

Antimyeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the 
treatment, whichever is longer, prior to first administration of study drug. The only 
exception is emergency use of a short course of corticosteroids (equivalent of 
dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment prior to 
first administration of study drug.

An allogenic stem cell transplant (SCT) at any time; or autologous SCT within 
12 weeks prior to first administration of study drug.

Other investigational agent (including investigational vaccines), participation in another 
clinical study with therapeutic intent, or used an invasive investigational medical device
within 28 days or 5 pharmacokinetic half-lives of the investigational agent (whichever 
is longer) prior to first administration of study drug.

Systemic radiotherapy within 14 days prior to first administration of study drug.
3.
Plans to undergo a stem cell transplant prior to progression of disease on this study (these 
subjects should not be enrolled to reduce disease burden prior to transplant).
4.
History of malignancy (other than multiple myeloma) within 2 years prior to first 
administration of study drug (exceptions are squamous and basal cell carcinomas of the skin 
and carcinoma in situ of the cervix, or malignancy 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).
5.
Clinical signs of meningeal involvement of multiple myeloma.
6.
Either of the following:
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
Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume 
in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for 
subjects suspected of having COPD and subjects must be excluded if FEV1 is <50% of 
predicted normal. 

Known moderate or severe persistent asthma within the past 2 years (see Attachment 8), 
or uncontrolled asthma of any classification. Note that subjects who currently have 
controlled intermittent asthma or controlled mild persistent asthma are allowed to 
participate in the study.
7.
Any of the following:

Known to be seropositive for human immunodeficiency virus (HIV).

Known to be seropositive for hepatitis B (defined by a positive test for hepatitis B 
surface antigen [HBsAg]) or with known prior hepatitis B infection without evidence of 
immunity (ie patients who are positive for antibodies to hepatitis B core antigen 
(anti-HBc) but negative for antibodies to hepatitis B surface antigen (anti-Hbs)

Known to be seropositive for hepatitis C (except in the setting of a sustained virologic 
response (SVR), defined as aviremia at least 12 weeks after completion of antiviral 
therapy).
8.
Clinically significant cardiac disease, including:

Myocardial infarction within 6 months (except for those with normal cardiac function, 
eg, normal LVEF) before first administration of study drug, 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)

Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] 
Grade 3 or higher) or clinically significant electrocardiogram (ECG) abnormalities.

Screening 12-lead ECG showing a baseline corrected QT interval (QTc) >470 msec.
9.
Known allergies, hypersensitivity, or intolerance to mannitol or corticosteroids, monoclonal 
antibodies or human proteins, or their excipients (refer to Investigator's Brochures), or 
known sensitivity to mammalian-derived products.
10. Prior diagnoses of autoimmune disease including but not limited to uncontrolled 
autoimmune thyroid disease or Type 1 diabetes, systemic lupus erythematosus, Sjögren’s 
syndrome, glomerulonephritis, multiple sclerosis, rheumatoid arthritis, vasculitis, idiopathic 
pulmonary fibrosis (IPF, including bronchiolitis obliterans organizing pneumonia), and 
inflammatory bowel disease, will be excluded from study participation, with the exception 
of subjects: 

with autoimmune thyroid disease or type 1 diabetes that is well controlled on a stable 
medication regimen

with vitiligo, alopecia, or resolved childhood asthma/atopy

with psoriasis not requiring systemic therapy

with transient autoimmune manifestations of an acute infectious disease that resolved 
upon treatment of the infectious agent (eg, acute Lyme arthritis)
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11. Criterion modified per Amendment 1
11.1 Unresolved Grade 2 or higher toxicity effects from previous treatment with 
immunotherapy not recovered to Grade 1 or baseline
12. Vaccination with live attenuated vaccines within 4 weeks prior to first study agent 
administration
13. Women who are pregnant, lactating, or intending to become pregnant during the study or 
within at least 3 months after last dose of daratumumab or 5 months after the last dose of 
JNJ-63723283; men who intend to father a child during the study or within at least 3 months 
after the last dose of daratumumab or 5 months after the last dose of JNJ-63723283.
14. Concurrent medical or psychiatric condition or disease (eg, active systemic infection, 
uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere 
with the study procedures or results, or that in the opinion of the investigator, would 
constitute a hazard for participating in this study.
15. Major surgery within 2 weeks prior to first study drug administration, or will not have fully 
recovered from surgery, or has surgery planned during the time the subject is expected to 
participate in the study or within 2 weeks after the last dose of study treatment. 
Note: subjects with planned surgical procedures to be conducted under local anesthesia may 
participate. Kyphoplasty or vertebroplasty are not considered major surgery.
16. Plasmapheresis within 28 days prior to first study drug administration
17. Known or suspected of not being able to comply with the study protocol (eg, because of 
alcoholism, drug dependency, or psychological disorder). Subject has any condition for 
which, in the opinion of the investigator, participation would not be in the best interest of the 
subject (eg, compromise the well-being) or that could prevent, limit, or confound the 
protocol-specified assessments. Subject is taking any prohibited medications as per 
Section 8.3.
4.3.
Prohibitions and Restrictions
Potential subjects must be willing and able to adhere to the following prohibitions and 
restrictions during the course of the study to be eligible for participation:
1.
Refer to Section 8 Concomitant Therapy for details regarding prohibited and restricted 
therapy during the study.
2.
Agree to follow the contraceptive requirements as noted in the inclusion criteria.
3.
Typically, IV contrast is NOT used in computed tomography (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.
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5.
TREATMENT ALLOCATION AND BLINDING
Following the safety run-in, central randomization will be implemented in this open-label study.
Randomization for Part 2 and Part 3 will be performed separately. Subjects enrolled in Part 2 
will not be eligible for Part 3.
For each Part, subjects will be assigned randomly to 1 of the 2 treatment groups based on a 
computer-generated randomization schedule prepared before the study by or under the 
supervision of the Sponsor. The randomization will be balanced by using randomly permuted 
blocks and will be stratified by International Staging System (ISS; I, II, or III) and number of 
prior lines of therapy (3 prior lines vs. >3 prior lines). The interactive web response system 
(IWRS) will assign a unique treatment code, which will dictate the treatment assignment and 
matching study drug kit for the subject. The requestor must use his or her own user identification 
and personal identification number when contacting the IWRS, and will then give the relevant 
subject details to uniquely identify the subject.
As of 25 May 2018, subjects in Screening were deemed Screen Failures and were not 
randomized into the study.
6.
DOSAGE AND ADMINISTRATION
6.1.
Daratumumab
Daratumumab will be administered to subjects as described in the Time and Events Schedule
Table 1. Daratumumab should always be administered prior to JNJ-63723283, when they are 
administered on the same dosing day. Subjects will continue to receive daratumumab until 
disease progression, unacceptable toxicity, or other reasons as listed in Section 10. Refer to the 
Investigational Product Preparation Instructions (IPPI) and the Site Investigational Product and 
Procedures Manual (SIPPM) for detailed descriptions for preparation and administration of 
daratumumab.
6.1.1.
Daratumumab Treatment Schedule and Administration
Each cycle is 28 days. The daratumumab administration dose and schedule is summarized below:

Daratumumab 16 mg/kg IV will be administered once every week (Weeks 1 to 8); then once 
every other week for 16 weeks (Weeks 9 to 24); thereafter once every 4 weeks (Week 25 
onwards).
Each subject’s dose will be calculated based on the subject’s weight at Cycle 1 Day 1 rounded to 
the nearest kilogram. The dose of daratumumab does not need to be recalculated for weight 
changes <10% from baseline. Subjects will receive preinfusion medications and postinfusion 
medications as outlined in Sections 6.1.2 and 6.3.1.
The dilution volumes, initial infusion rates, and increment of infusion rates for the first, second, 
and subsequent doses in the absence of an infusion-related reaction >Grade 1 are provided in
Table 5. 
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Table 5:
Daratumumab Administration
Dilution 
Volume
Initial Infusion 
Rate (first hour)
Incremental 
Increases in Infusion 
Ratea
Maximum Infusion 
Rate
Week 1 infusion
(Cycle 1 Day 1)
1000 mL
50 mL/hour
50 mL/every hour
200 mL/hour
Week 2 infusionb
500 mL
50 mL/hour
50 mL/hour
every hour
200 mL/hour
Subsequent infusionsc
500 mL
100 mL/hour
50 mL/hour
every hour
200 mL/hour
a.
Consider titration of the infusion rate only in the absence of infusion-related reactions.
b.
Dilution volume of 500 mL should be used only if there were no Grade 1 (mild) or greater infusion-related reactions during 
the first 3 hours of the first infusion. Otherwise, continue to use a dilution volume of 1000 mL.
c.
Use a modified initial rate for subsequent infusions (ie, third infusion onwards) only if there were no Grade 1 (mild) or 
greater infusion-related reactions during a final infusion rate of 100 mL/h in the first two infusions. Otherwise, continue to 
use instructions for the second infusion.
As noted in Table 1 (Time and Events Schedule), vital signs for subjects in the Safety Run-in and 
Arm B cohorts should be monitored frequently on Cycle 1 Day 1 before, during, and after the 
first infusion of daratumumab. For all subsequent infusions, vital signs should be measured 
before the start of infusion and at the end of the infusion. If a 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 serious 
adverse event.
6.1.2.
Preinfusion Medication
Preinfusion medications for subjects receiving daratumumab will be administered on all
daratumumab infusion days (see the Time and Events Schedule; Table 1). On daratumumab 
infusion days, subjects will receive the following medications approximately 1 hour prior to 
daratumumab infusion; premedication up to 3 hours before the dose of daratumumab is 
permitted:

An antipyretic: paracetamol (acetaminophen) 650 to 1000 mg IV or orally (PO).

An antihistamine: diphenhydramine 25 to 50 mg IV or PO, or equivalent). Avoid the use of 
IV promethazine (see Attachment 1 for a list of antihistamines that may be used). 

A corticosteroid: methylprednisolone 100 mg IV or PO or equivalent for the first 2 doses 
and 60 mg for all subsequent doses (in the absence of IRR adverse events in the first 
2 doses). Substitutions for methylprednisolone are allowed (refer to Attachment 2).
In addition, a leukotriene inhibitor (optional; montelukast 10 mg PO) may be administered up to 
24 hours before infusion as per investigator discretion.
If necessary, all PO preinfusion medications may be administered outside of the clinic on the day 
of the infusion, provided they are taken 1 to 3 hours before the infusion.
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6.1.3.
Postinfusion Medication
Postinfusion medication should be administered to reduce the risk of delayed infusion-related 
reactions in all subjects:

Oral corticosteroid (20 mg methylprednisolone PO or equivalent) in accordance with local 
standards) on the 2 days following each daratumumab administration (beginning the day 
after study drug administration). In the absence of IRR adverse events after the first 3 doses, 
postinfusion corticosteroids should be administered per investigator discretion.
For subjects with a higher risk of respiratory complications (eg, subjects with COPD who have 
an FEV1 <80% or subjects with asthma), the following postinfusion medications should be 
considered:

antihistamine (diphenhydramine or equivalent) on the first and second days after each 
infusion;

short-acting 2 adrenergic receptor agonist such as salbutamol aerosol; and

control medications for lung disease (eg, inhaled corticosteroids long-acting 2 adrenergic 
receptor agonists for subjects with asthma; long-acting bronchodilators such as tiotropium or 
salmeterol inhaled corticosteroids for subjects with COPD).
In addition, these at-risk subjects may be hospitalized for monitoring for up to 2 nights after 
study drug administration. If these at-risk subjects are hospitalized, then their FEV1 should be 
measured and managed per local standards 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 each study drug administration. 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 serious adverse event. Investigators may prescribe bronchodilators, 
antihistamines, and corticosteroids that are deemed necessary to provide adequate supportive 
care in the event a bronchospasm occurs after subjects are released from the hospital/clinic. If an 
at-risk subject experiences no major IRRs, then these postdose medications may be waived after 
4 doses at the investigator's discretion.
6.1.4.
Monitoring During and After Daratumumab and JNJ-63723283
Administration
Subjects should be observed carefully during study agent infusions. Trained study staff at the 
clinic should be prepared to intervene in case of any IRRs occurring, and resources necessary for 
resuscitation (eg, agents such as epinephrine and aerosolized bronchodilator, also medical 
equipment such as oxygen tanks, tracheostomy equipment, and a defibrillator) must be available 
at the bedside. If an IRR develops, then the infusion should be paused. Guidelines outlined in 
Section 6.3 must be followed to manage IRRs.
Subjects should be monitored for at least 2 hours after the completion of the first infusion and 
may be discharged if considered clinically stable and all other study procedures have been 
completed (see Table 6 below). The investigator will determine the duration of safety monitoring 
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for subsequent administrations. In addition, subjects should be monitored for symptoms of tumor 
lysis syndrome, see Section 8.1.2.
Table 6:
Infusion Duration and Monitoring After Infusion of Daratumumab and JNJ-63723283
Cycle 1 Day 1
Daratumumab – First infusion
Daratumumab is administered over a 6 to 8 hour infusion period followed by a 2-hour 
observation period. The subject may be discharged if considered clinically stable and all 
other study procedures have been completed
Cycle 1 Day 2
JNJ-63723283 – First Infusion
1-hour infusion followed by a 4-hour observation period. The subject may be 
discharged if considered clinically stable and all other study procedures have been 
completed
Cycle 1 Day 8
Daratumumab – Second infusion
If the first daratumumab infusion is well tolerated (defined as no Grade 1 or higher 
IRRs), then the second daratumumab infusion should administered over 3 to 4 hours, 
followed by a 2-hour observation period. However, if the first daratumumab infusion is 
not well tolerated, then the second daratumumab infusion will follow the C1D1 
daratumumab infusion schedule, as described above and in Table 5.
Cycle 1 Day 15
Daratumumab and JNJ-63723283
Daratumumab is administered over a 3 to 4 hour infusion period, followed by a 
30-minute JNJ-63723283 infusion (approximately 30 min. if no IRRs with the initial 
1-hour infusion of JNJ-63723283; see also Section 6.2.1). A 2-hour observation period 
will be conducted after the completion of the JNJ-63723283 infusion.
Cycle 1 Day 22
Daratumumab
Daratumumab is administered over a 3 to 4 hour infusion period and then followed by a 
2-hour observation period.
Cycle 2 Day 1 and 
subsequent infusions
Daratumumab and JNJ-63723283
If all the infusions in Cycle 1 are well tolerated, then starting on C2D1, the observation 
period can be 1-hour after sequential combination dosing of daratumumab and 
JNJ-63723283. If not well tolerated (ie, Grade 1 or higher infusion-related reactions), 
then follow the C1D15 procedures.
6.1.5.
Dose Delay
Dose modification of daratumumab is not permitted. Dose delay is the primary method for 
managing daratumumab-related toxicities.
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 4.03. Dose 
delays will be made based on the toxicity experienced during the previous infusion or newly 
encountered on Day 1 of a new cycle. 
The study treatment must be held if any of the following criteria below are met, to allow for 
recovery from toxicity, regardless of relationship to daratumumab.
The criteria for a dose delay are:

Grade 4 hematologic toxicity, except for Grade 4 lymphopenia

Grade 3 or higher thrombocytopenia with bleeding

Febrile neutropenia
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
Neutropenia with infection, of any grade

For all other adverse events, daratumumab should be withheld for Grade 3 or higher 
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 that was present at baseline or that lasts for <7 days after the last 
administration of daratumumab

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 1 or 
baseline, with the exception of Grade 2 laryngeal edema, Grade 2 bronchospasm or febrile 
neutropenia, which must be fully recovered. If daratumumab administration does not commence 
within the prespecified window (Table 7) of the scheduled administration date, then the dose will 
be considered a missed dose. Administration may resume at the next planned dosing date. A 
missed dose will not be made up. A delay in daratumumab dosing will result in a subsequent 
delay in JNJ-63723283 dosing. In the case of daratumumab missed dose(s), JNJ-63723283
should continue to be administered per schedule and not delayed or alternatively, dosing 
decisions should be discussed with the Sponsor.
Table 7:
Daratumumab-related Toxicity Management
Cycles
Frequency
Dose Held
Dosing Restart
1 and 2
Weekly (q1wk)
>3 days
Next planned weekly dosing date
3 to 6
Biweekly (q2wks)
>7 days
Next planned biweekly dosing date
7+
Every 4 weeks (q4wks)
>14 days
Next planned every 4 weeks dosing date
If 2 consecutive planned doses of daratumumab are missed due to any adverse event, then 
consultation with the Sponsor is required before dosing may be continued. 
For subjects whose dose is held for more than 28 days for any drug related adverse event or who 
miss 3 or more consecutive planned doses of daratumumab due to any adverse event, then the 
treatment should be permanently discontinued. Dose holds of more than 28 days for other 
reasons should be discussed with the Sponsor. If daratumumab is permanently discontinued, then 
JNJ-63723283 should be permanently discontinued.
If a dose delay occurs, then pharmacokinetic and biomarker assessments should be performed on 
the actual daratumumab administration day, not on the originally scheduled administration day.
6.2.
JNJ-63723283
JNJ-63723283 will be administered to subjects as described in the Time and Events Schedule
Table 1. JNJ-63723283 will be administered after daratumumab, when they are administered on 
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the same dosing day. Subjects will continue to receive JNJ-63723283 until disease progression, 
unacceptable toxicity, or other reasons as listed in Section 10. The IPPI and SIPPM provide
detailed descriptions for preparation and administration of JNJ-63723283. The manufacturing 
processes for the drug substance and drug product for JNJ-63723283 will be changed during this 
study, see Section 14.1 for more information.
6.2.1.
JNJ-63723283 Treatment Schedule and Administration
A summary of JNJ-63723283 administration details are provided in Table 8. Additional dose 
levels and schedules will be considered based on the emerging JNJ-63723283 safety, 
pharmacokinetics, pharmacodynamics, and any other available data.
Table 8:
JNJ-63723283 Administration
Study Drug
JNJ-63723283
Dose/schedule
240 mg (fixed dose) every 2 weeks
Route/Regimen
Administered IV, initially over a 50-70 minute infusion. In the absence of infusion-related 
reactions, subsequent infusions may be administered IV over 25-40 minutes. Study drug is 
to be administered under the supervision of site staff.
See Section 6.1.4 for information on monitoring during and after infusion.
6.2.2.
Dose Delay
Dose delay is the primary method for managing JNJ-63723283-related toxicities. In the event of 
a toxicity that meets the criteria below or is otherwise considered to be clinically significant by 
the treating physician, treatment will be held and supportive therapy administered as clinically 
indicated. If clinically significant drug-related toxicity is present, treatment should be delayed 
until the toxicity resolves (with or without supportive therapy) to baseline or Grade 1 except for 
alopecia, hyperthyroidism and rash for which resolution to Grade 2 is required for subsequent 
treatment. If the toxicity does not resolve to Grade 1 or baseline within 12 weeks of 
identification of the toxicity, withdrawal from the study is recommended unless otherwise agreed 
to by the Sponsor medical monitor and the investigator based on evidence of clinical benefit. 
Dose delays will be required if:

Grade 2 pneumonitis (recurrent Grade 2 pneumonitis, study drug must be permanently 
discontinued)

Grade 2 or 3 diarrhea or colitis

Grade 2 nephritis with creatinine >1.5 to 3.0 x upper limit of normal (ULN)

Grade 2 or 3 creatinine elevation

Grade 2 elevation in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 
(3-5 x ULN) except for subjects with tumor involvement in the liver at baseline, or total 
bilirubin (1.5-3 x ULN) except in subjects with congenital bilirubinemia, such as Gilbert 
syndrome (direct bilirubin 3 x ULN)

Symptomatic endocrinopathies (including hypothyroidism, hyperthyroidism, hypophysitis, 
adrenal insufficiency, and diabetes)
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
Grade 3 rash

Grade 3 non-irAEs (except for hematologic toxicities not attributed to JNJ-63723283)
The criteria for discontinuation of study treatment are described in Section 6.2.3 and Section 10.
6.2.3.
Toxicities Leading to Discontinuation of Study Treatment
A subject must discontinue study treatment if:

Grade 2 or 3 irAEs that persist despite treatment modifications or corticosteroid dosing 
cannot be reduced to 10 mg prednisone or equivalent per day within 12 weeks

A treatment-related AE does not resolve to Grade 1 within 12 weeks of the last dose of 
study drug unless otherwise agreed to by the Sponsor medical monitor and the investigator 
based on evidence of clinical benefit

Any non-hematologic treatment-related event occurs a second time at Grade 3 severity

Grade 3 (or recurrent Grade 2) pneumonitis

Grade 3 nephritis with creatinine 3xULN

Grade 3 elevation of AST or ALT >5xULN or total bilirubin >3xULN 

Grade 4 infusion-related reactions (IRRs) due to JNJ-63723283

Immune-mediated encephalitis
If a subject's study treatment is discontinued, this will not result in automatic withdrawal of the 
subject from the study. Following treatment discontinuation, the subject should complete the 
End-of-Treatment Visit as described in Table 1. Once a subject discontinues treatment with 
JNJ-63723283, the subject may not be retreated with the study drug. If JNJ-63723283 is 
permanently discontinued, then treatment with daratumumab may be continued with discussion 
with the Sponsor.
If a dose delay occurs, then pharmacokinetic and biomarker assessments should be performed on 
the actual daratumumab administration day, not on the originally scheduled administration day.
6.2.4.
Guidelines for Management of Immune-Related Adverse Events and 
Adverse Events of Clinical Interest 
Therapy with immuno-oncology agents such as JNJ-63723283 may lead to specific irAEs that 
differ in nature, severity and duration as compared to AEs caused by agents with a different 
mode of action. Early recognition and management of these irAEs may mitigate more 
severe/subsequent toxicity. However, differential diagnoses including non-inflammatory 
etiologies as well as the impact of the underlying malignant disease and/or concomitant 
medication should be evaluated according to standard medical practice. 
Management algorithms have been developed to assist investigators in assessing and managing 
specific irAEs following administration of nivolumab (SmPC; PI)25,26 and pembrolizumab
(SmPC; PI).29,30 These guidelines are presented below and should be followed for JNJ-63723283. 
In addition to the management algorithms provided in following sections, it is recommended that 
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irAEs are managed according to the general treatment guidelines outlined for ipilimumab (PI).14
These guidelines recommend the following:
1.
Subjects should be evaluated to identify any alternative etiology.
2.
In the absence of a clear alternative etiology, all events of an inflammatory nature should be 
considered immune related.
3.
Symptomatic and topical therapy should be considered for low-grade events.
4.
Systemic corticosteroids should be considered for a persistent low-grade event or for a 
severe event.
5.
More potent immunosuppressives should be considered for events not responding to 
systemic corticosteroids (eg, anti-TNF agents or mycophenolate).
If delaying the dose is necessary to ameliorate toxicity, follow the guidance in Section 6.2.2.
6.2.4.1.
Gastrointestinal Adverse Events
Diarrhea and colitis have been observed in subjects receiving anti-PD-1 therapies. Early 
recognition and treatment of diarrhea and colitis are critical to their management (see Table 9). 
Subjects should be advised to seek immediate medical evaluation if they develop new-onset 
diarrhea, blood in stool, or severe abdominal pain or if they have worsening of baseline diarrhea. 
In subjects with pre-existing diverticulosis or diverticulitis receiving concomitant medication 
with corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioid analgesics 
together with anti-PD-1 therapies, diverticular perforation has been observed.
Table 9:
Management of Immune-Related Gastrointestinal Adverse Events
Guidelines for dose delay can be found in Section 6.2.2.
Grade 1
Symptomatic treatment according to institutional standards
Close monitoring; instruct subject to report worsening immediately and treat as Grade 2
Grade 2
5 days: Symptomatic treatment according to institutional standards
>5 days or recurrence: 0.5–1.0 mg/kg/d methylprednisolone; consider prophylactic antibiotics; 
Persistence or worsening despite steroids >3 days: treat as Grade 3/4
Improvement to Grade 1: taper steroids over at least 4 weeks, consider prophylactic antibiotics 
for opportunistic infections, resume study therapy per protocol
Grade 3-4
Immediately: 1.0–2.0 mg/kg/d methylprednisolone IV; consider prophylactic antibiotics and 
lower endoscopy
Persistence >3 days or recurrence: add infliximab 5 mg/kg (if no contraindication such as 
perforation or sepsis)
Improvement to Grade 2 within 3 days: taper steroids over at least 4 weeks
General
The oral corticosteroid equivalent of the recommended IV dose may be considered for 
ambulatory patients; the lower bioavailability of oral corticosteroids needs to be considered.
Clinical caution should be exercised, for subjects receiving concomitant medications of 
corticosteroids, NSAID, or opioid analgesics. In addition, monitor for signs and symptoms of 
potential perforation, especially in subjects with known diverticular disease. Narcotics should be 
used with caution as pain medicines may mask the signs of colonic perforation. 
6.2.4.2.
Hepatic Adverse Events
Hepatic 
AEs, 
including 
elevated 
liver 
function 
tests 
(LFTs) 
and, 
infrequently, 
drug-induced-liver-injuries (DILI) have been observed following treatment with anti-PD-1 
therapies. Early recognition and treatment of elevated LFTs and DILI are critical to their 
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management (see Table 10). Subjects should be advised to seek medical evaluation if they notice 
jaundice (yellow appearance of skin or sclera) or if they develop bruising, bleeding, or right-
sided abdominal pain. LFTs should be monitored prior to treatment.
Table 10:
Management of Immune-Related Hepatic Adverse Events
Guidelines for dose delay can be found in Section 6.2.2.
Grade 1
Monitor LFTs as outlined in the protocol; 
Worsening: treat as Grade 2
Grade 2
Monitor every 3 days;
Returning to baseline: resume per protocol monitoring
LFT elevation >5 days or worsening: 0.5-1.0 mg/kg/d methylprednisolone IV or oral equivalent; 
consider prophylactic antibiotics
LFT return to Grade 1 or baseline: taper steroids over at least 4 weeks; resume routine 
monitoring and resume study treatment per protocol
Grade 3-4
Monitor every 2 days;
Immediately: 1.0-2.0 mg/kg/d methylprednisolone IV or IV equivalent; start prophylactic 
antibiotics; consult gastroenterologist
Persistence >3 days or recurrence: add mycophenolate mofetil 1g bid; if no response within 
5 days consider other immunosuppressants per local guidelines
LFT return to Grade 2: stop immunosuppressants
LFT return to Grade 1: taper steroids over at least 4 weeks
6.2.4.3.
Endocrinopathies
Endocrinopathies have been observed following treatment with anti-PD-1 therapies. The events 
have typically been identified through either routine periodic monitoring of specific laboratory 
tests (eg, TSH) or as part of a work-up for associated symptoms (eg, fatigue) (see Table 11). 
Events may occur within weeks of beginning treatment, but also have been noted to occur after 
many months (while still on treatment). More than 1 endocrine organ may be involved 
(eg, hypophysitis [pituitary inflammation] may need to be evaluated at the time adrenal 
insufficiency or thyroid disorder is suspected). Subjects should be advised to seek medical 
evaluation if they notice new-onset fatigue, lightheadedness, or difficulty with vision or if 
baseline fatigue worsens.
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Table 11:
Management of Immune-Related Endocrinopathies
Guidelines for dose delay can be found in Section 6.2.2.
Asymptomatic TSH 
elevation
TSH <0.5xLLN or TSH >2xULN or TSH >ULN in 2 subsequent measurements: include 
free T4 assessment prior/after subsequent cycles of study treatment; consider 
endocrinology consultation
Symptomatic 
endocrinopathy
Assess endocrine function with appropriate laboratory testing; consider pituitary 
magnetic resonance imaging (MRI) scan.
With abnormal lab and pituitary scan: 1.0–2.0 mg/kg/d methylprednisolone IV or oral 
equivalent; initiate appropriate hormone therapy; consider prophylactic antibiotics

In hyperthyroidism, non-selective beta-blockers (eg, propranolol) are suggested 
as initial therapy.

In hypothyroidism, thyroid hormone replacement therapy, with levothyroxine or 
liothyronine, is indicated per standard of care.
Clinical and laboratory improvement: taper steroids over at least 4 weeks; patients with 
adrenal insufficiency may need to continue steroids with mineralocorticoid component
Without abnormal lab and pituitary scan but symptoms persist: repeat laboratory 
assessments in 3 weeks and MRI in 4 weeks
Suspicion of adrenal 
crisis (eg, severe 
dehydration, 
hypotension, shock out 
of proportion to current 
illness) 
Rule out sepsis
Immediately: initiate/stress dose of IV steroids with mineralocorticoid activity; fluids 
IV; consult endocrinologist
Adrenal crisis ruled out: treat as symptomatic endocrinopathy
Type 1 diabetes mellitus 
(if new onset, including 
diabetic ketoacidosis 
[DKA]) or Grade 3 
Hyperglycemia, if 
associated with ketosis 
(ketonuria) or metabolic 
acidosis (DKA)
For T1DM or Grade 3-4 hyperglycemia: Insulin replacement therapy is recommended 
for Type I diabetes mellitus and for Grade 3-4 hyperglycemia associated with metabolic 
acidosis or ketonuria. 
Evaluate patients with serum glucose and a metabolic panel, urine ketones, glycosylated 
hemoglobin, and C-peptide.
General
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids 
(eg, prednisone) at start of tapering or earlier, once sustained clinical improvement is 
observed. The lower bioavailability of oral corticosteroids need to be considered.
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6.2.4.4.
Rash
Rash and pruritus are the most common skin irAEs observed following treatment with anti-PD-1 
therapies. Typically, it is a focal rash with a maculopapular appearance. It is usually distributed
on the trunk, back, or extremities. Most cases have been of low or moderate grade. In some 
cases, rash and pruritus resolved without intervention. Subjects should be advised to seek 
medical evaluation if they notice new-onset rash (see Table 12 regarding action to be taken). A 
case of toxic epidermal necrolysis occurred in a subject receiving concomitant prophylaxis with 
trimethoprim/sulfamethoxazole, and it is possible that the initial rash was due to a sulfa-
hypersensitivity reaction that was eventually augmented by anti-PD-1 therapy. This case 
highlights the potential importance of discontinuing other suspected drugs in the management of 
rash.
Table 12:
Management of Rash
Guidelines for dose delay can be found in Section 6.2.2.
Grade 1-2
Immediately: Symptomatic therapy (eg, antihistamines, topical steroids)
Persistence 2 weeks or recurrence: consider skin biopsy; consider 0.5-1.0 mg/kg/d 
methylprednisolone IV or oral equivalent; consider prophylactic antibiotics
Improvement to Grade 1: taper steroids over at least 4 weeks
Worsening to >Grade 2: treat as Grade 3-4
Grade 3-4
Immediately: consult dermatologist; consider skin biopsy; start 1.0-2.0 mg/kg/d 
methylprednisolone IV or IV equivalent; add prophylactic antibiotics
Improvement to Grade 1: taper steroids over at least 4 weeks
General
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids 
(eg, prednisone) at start of tapering or earlier, once sustained clinical improvement is observed. 
The lower bioavailability of oral corticosteroids need to be considered
6.2.4.5.
Renal Adverse Events
Elevated creatinine and biopsy-confirmed tubulointerstitial nephritis and allergic nephritis have 
been infrequently observed following treatment with anti-PD-1 therapies. Creatinine should be 
monitored regularly (see Table 13). 
Table 13:
Management of Renal Adverse Events
Guidelines for dose delay can be found in Section 6.2.2.
Grade 1
Monitor creatinine weekly
Creatinine returns to baseline: continue monitoring per protocol
Creatinine increases: treat as Grade 2
Grade 2-3
Monitor creatinine every 3 days
Immediately: start 0.5-1.0 mg/kg/d methylprednisolone IV or oral equivalent; consider 
prophylactic antibiotics; consider renal biopsy
Improvement to Grade 1: taper steroids over at least 4 weeks
Persistence >7 days or worsening: treat as Grade 4
Grade 4
Monitor creatinine daily
Immediately: consult nephrologist; consider renal biopsy; start 1.0-2.0 mg/kg/d 
methylprednisolone IV or IV equivalent; add prophylactic antibiotics
Improvement to Grade 1: taper steroids over at least 4 weeks
General
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids 
(eg, prednisone) at start of tapering or earlier, once sustained clinical improvement is observed. 
The lower bioavailability of oral corticosteroids need to be considered
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6.2.4.6.
Neurological Adverse Events
Neurological AEs have been observed uncommonly following treatment with anti-PD-1 
therapies. Neurological AEs may manifest as central abnormalities (eg, aseptic meningitis or 
encephalitis) or peripheral sensory/motor neuropathies (eg, Guillain-Barre Syndrome). The onset 
has been observed as early as after a single treatment. Early recognition and treatment of 
neurologic AEs is critical to their management (see Table 14). Subjects should be advised to seek 
medical evaluation if they notice impairment in motor function (eg, weakness), changes in 
sensation (eg, numbness), or symptoms suggestive of possible central nervous system 
abnormalities such as new headache or mental status changes.
Table 14:
Management of Neurological Adverse Events
Guidelines for dose delay can be found in Section 6.2.2.
Grade 1
Monitor per protocol
Worsening: treat as Grade 2
Grade 2
Immediately: treat symptoms according to institutional standards; consider 0.5-1.0 mg/kg/d 
methylprednisolone IV or oral equivalent
Worsening: treat as Grade 3-4
Grade 3-4
Immediately: consult neurologist; treat symptoms according to institutional standards; start 
1.0-2.0 mg/kg/d methylprednisolone IV or IV equivalent; prophylactic antibiotics
Worsening or atypical presentation: consider immunoglobulins IV (IVIG) or other 
immunosuppressive therapies according to institutional standards
Improvement to Grade 2: taper steroids over at least 4 weeks
General
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids 
(eg, prednisone) at start of tapering or earlier, once sustained clinical improvement is observed. 
The lower bioavailability of oral corticosteroids need to be considered
6.2.4.7.
Pulmonary Adverse Events
Pulmonary AEs including radiographic changes (eg, focal ground glass opacities and patchy 
infiltrates) indicative of drug-related pneumonitis have been observed in subjects receiving 
anti-PD-1 therapies. These pulmonary AEs were either asymptomatic or associated with 
symptoms such as dyspnea, cough, or fever. The initial occurrence of pulmonary AEs may be as 
early as after a single dose of anti-PD-1 therapies or delayed after prolonged therapy. Early 
recognition and treatment of pneumonitis is critical to its management (see Table 15). Subjects 
should be advised to seek medical evaluation promptly if they develop new-onset dyspnea, 
cough, or fever or if they have worsening of these baseline symptoms.
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Table 15:
Management of Pulmonary Adverse Events
Guidelines for dose delay can be found in Section 6.2.2.
Grade 1
Monitor for symptoms every 2-3 days; consider pulmonary and infectious-disease consult; 
re-image every 3 weeks
Worsening: treat as Grade 2
Grade 2
Monitor symptoms daily; re-image every 1-3 days; pulmonary and infectious-disease consultation; 
consider bronchoscopy and lung biopsy; consider hospitalization
Immediately: start 1.0 mg/kg/d methylprednisolone IV or oral equivalent; prophylactic antibiotics
Persistence for 2 weeks or worsening: treat as Grade 3-4
Improvement to Grade 1 or baseline: taper steroids over at least 4 weeks
Grade 3-4
Hospitalize; pulmonary and infectious-disease consult; consider bronchoscopy and lung biopsy
Immediately: 2-4 mg/kg/d methylprednisolone or IV equivalent; add prophylactic antibiotics;
Persistence for 2 days or worsening: add immunosuppression (eg, infliximab, cyclophosphamide, 
IVIG, or mycophenolate mofetil)
Improvement to Grade 2: taper steroids over at least 6 weeks
General
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids 
(eg, prednisone) at start of tapering or earlier, once sustained clinical improvement is observed. 
The lower bioavailability of oral corticosteroids need to be considered
6.2.4.8.
Uveitis and Visual Complaints
Immune therapies have been uncommonly associated with visual complaints. Inflammation of 
components within the eye (eg, uveitis) is an uncommon, but clinically important, event. An 
ophthalmologist should evaluate visual complaints with examination of the conjunctiva, anterior 
and posterior chambers, and retina (see Table 16). If the subject has double vision, prompt 
medical evaluation should occur. In addition to ocular inflammatory events, a work-up should 
also consider pituitary inflammation as a cause.
Table 16:
Management of Uveitis and Visual Complaints
Guidelines for dose delay can be found in Section 6.2.2.
Grade 1
Thorough eye examination 
Topical corticosteroids should be considered
Persisting despite topical steroids, treat as Grade 3-4
Grade 2
Grade 3-4
Thorough eye examination
Systemic corticosteroids
6.2.4.9.
Lipase/Amylase Elevations
Asymptomatic elevations in lipase and amylase have been reported in anti-PD-1 therapy studies 
in which systemic monitoring was used. Very few subjects reported associated symptoms 
(eg, abdominal pain) or radiographic findings (eg, stranding) consistent with pancreatitis. Thus, 
there does not seem to be clinical significance to the elevated laboratory values. The 
recommended management of anti-PD-1 therapy-related elevated lipase/amylase values centers 
around close observation. Physicians should ensure that subjects have no associated symptoms 
consistent with pancreatitis, such as abdominal pain. Corticosteroids do not seem to alter the 
natural history of lipase/amylase elevations. Laboratory values tend to fluctuate on a day-to-day 
basis and eventually return to baseline or low-grade levels over the course of weeks, whether or 
not subjects receive corticosteroids. Asymptomatic elevations should be monitored 
approximately weekly. 
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6.2.5.
Infection
Subjects with a documented infectious complication should receive oral or IV antibiotics or other 
anti-infective agents as considered appropriate by the treating investigator for a given infectious 
condition, according to standard institutional practice.
6.3.
Treatment of Infusion-related Reactions (IRRs)
6.3.1.
Guidelines for Management of Daratumumab IRRs
For infusion reactions of any grade/severity, immediately interrupt the daratumumab infusion 
and manage symptoms. Management of infusion reactions may require reduction in the rate of 
infusion, or discontinuation of daratumumab (see Table 17).
Table 17:
Management Guidelines for Daratumumab Infusion-related Reactions
Guidelines for dose delay can be found in Section 6.1.5.
Severity of IRR
Management
Grade 1-2 
(mild to moderate)
Once IRR symptoms resolve and the subject's condition is stable, the infusion may be 
restarted at the investigator's discretion.  Resume the infusion at no more than half the rate 
at which the IRR occurred. If the subject does not experience any further IRR symptoms, 
infusion rate escalation may resume at increments and intervals as clinically appropriate up 
to the maximum rate of 200 mL/hr (see Table 5).
Grade 2 or higher 
laryngeal edema, or 
bronchospasm
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 permanently discontinue 
daratumumab treatment.
Grade 3 
(severe)
Once reaction symptoms resolve, consider restarting the infusion at no more than half the 
rate at which the IRR occurred. If the subject does not experience additional symptoms, 
then resume infusion rate escalation at increments and intervals as outlined in Table 5. 
Repeat the procedure above in the event of recurrence of Grade 3 symptoms or discontinue 
the subject from treatment. At the subsequent infusion, permanently discontinue 
daratumumab if the subject experiences a Grade 3 IRR for a third time.
Grade 4 
(life threatening)
Permanently discontinue daratumumab treatment.
IRRinfusion-related reaction.
6.3.2.
Guidelines for Management of JNJ-63723283 IRRs
For infusion reactions of any grade/severity, immediately interrupt the JNJ-63723283 infusion 
and manage symptoms. Management of infusion reactions may require reduction in the rate of 
infusion, or discontinuation of JNJ-63723283 (see Table 18).
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Table 18:
Management of Infusion-Related Reactions for JNJ-63723283
Guidelines for dose delay can be found in Section 6.2.2.
Severity of IRR
Management
Grade 1
No intervention indicated; remain at bedside and monitor subject until recovery from 
symptoms, Consider diphenhydramine 50 mg (or equivalent) and or paracetamol 325 to 
1000 mg (acetaminophen) at least 30 minutes before additional study drug administration
Grade 2
Stop infusion; start IV saline infusion; give diphenhydramine 50 mg (or equivalent) IV and/or 
paracetamol 325 to 1000 mg (acetaminophen); consider corticosteroids and bronchodilator 
therapy; remain at bedside and monitor subject until recovery from symptoms
Restart infusion at 50% of initial rate: if no further complications ensue after 30 minutes, the 
rate may be increased to 100% of the original infusion rate; monitor subject closely. 
Symptoms recur: stop and discontinue further treatment at that visit; administer 
diphenhydramine 50 mg IV, and remain at bedside and monitor the subject until resolution of 
symptoms. The amount of study drug infused must be recorded on the CRF.
Grade 3-4
Stop infusion; start IV saline infusion; recommend bronchodilators, epinephrine 0.2 to 1 mg 
of a 1:1,000 solution for subcutaneous administration or 0.1 to 0.25 mg of a 1:10,000 solution 
injected slowly for IV administration, and/or diphenhydramine 50 mg IV with 
methylprednisolone 100 mg IV (or equivalent), as needed.
Subject should be monitored until the investigator is comfortable that the symptoms will not 
recur. Study drug will be permanently discontinued. Investigators should follow their 
institutional guidelines for the treatment of anaphylaxis. Remain at bedside and monitor 
subject until recovery from symptoms. In the case of late-occurring hypersensitivity 
symptoms (eg, appearance of a localized or generalized pruritis within 1 week after 
treatment), symptomatic treatment may be given (eg, oral antihistamine, or corticosteroids).
General
Prophylactic medications (after initial event): diphenhydramine 50 mg (or equivalent) and/or 
paracetamol 325 to 1000 mg (acetaminophen) at least 30 minutes before additional study 
drug administrations; if necessary, corticosteroids (recommended dose: up to 80 mg of IV 
methylprednisolone or equivalent) may be used
Appropriate resuscitation equipment should be available in the room and a physician readily 
available during the infusion of study drug.
6.4.
Dosage and Administration for Daratumumab Monotherapy Period
The start of each cycle (i.e., Day 1) may occur within ±3 days of the scheduled day in order to 
accommodate the schedule of the site or subject.  If the start of a cycle is delayed, Day 1 of the 
subsequent cycle should be adjusted accordingly to maintain the 28-day cycle duration.  The 
weekly or bi-weekly study treatment administrations (i.e., Day 8, 15, and 22 dosing dates) may 
occur within ±1 day of the scheduled day to accommodate the schedule of the site or subject.  
Changes to within-cycle dosing should not impact Day 1 of the next cycle.
6.4.1.
Daratumumab Monotherapy
Daratumumab will be administered to subjects as described in the Time and Events Schedule 
Table 24.  Subjects will continue to receive daratumumab until disease progression, unacceptable 
toxicity, or other reasons as listed in Section 10. Refer to the Investigational Product Preparation 
Instructions (IPPI) and the Site Investigational Product and Procedures Manual (SIPPM) for 
detailed descriptions for preparation and administration of daratumumab. 
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6.4.1.1.
Daratumumab Treatment Schedule and Administration
Each cycle is 28 days. The daratumumab administration dose and schedule is summarized below: 

Daratumumab 16 mg/kg IV will be administered once every week (Weeks 1 to 8); then once 
every other week for 16 weeks (Weeks 9 to 24); thereafter once every 4 weeks (Week 25 
onwards).
Each subject’s dose will be calculated based on the subject’s weight at Cycle 1 Day 1 rounded to 
the nearest kilogram. The dose of daratumumab does not need to be recalculated for weight 
changes <10% from baseline. Subjects will receive preinfusion medications and postinfusion 
medications as outlined in Sections 6.4.1.2 and 6.4.1.3. 
The dilution volumes, initial infusion rates, and increment of infusion rates for the first, second, 
and subsequent doses in the absence of an infusion-related reaction >Grade 1 are provided in
Table 19.
Table 19:
Daratumumab Administration
Dilution 
Volume
Initial Infusion 
Rate (first hour)
Incremental 
Increases in Infusion 
Ratea
Maximum Infusion 
Rate
Week 1 infusion 
(Cycle 1 Day 1)
1000 mL
50 mL/hour
50 mL/every hour
200 mL/hour
Week 2 infusionb
500 mL
50 mL/hour
50 mL/hour
every hour
200 mL/hour
Subsequent infusionsc
500 mL
100 mL/hour
50 mL/hour
every hour
200 mL/hour
a.
Consider titration of the infusion rate only in the absence of infusion-related reactions.
b.
Dilution volume of 500 mL should be used only if there were no Grade 1 (mild) or greater infusion-related reactions during 
the first 3 hours of the first infusion. Otherwise, continue to use a dilution volume of 1000 mL.
c.
Use a modified initial rate for subsequent infusions (ie, third infusion onwards) only if there were no Grade 1 (mild) or 
greater infusion-related reactions during a final infusion rate of 100 mL/h in the first two infusions. Otherwise, continue to 
use instructions for the second infusion.
Vital signs should be measured before the start of each daratumumab infusion and at the end of 
each daratumumab infusion. If a 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 serious adverse event.
6.4.1.2.
Preinfusion Medication
In an effort to prevent infusion related reactions, all subjects will receive the following 
medications 1 to 3 hours prior to the start of each daratumumab infusion (see the Time and 
Events Schedule; Table 24):
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
An antipyretic: paracetamol (acetaminophen) 650 to 1000 mg IV or orally (PO).

An antihistamine: diphenhydramine 25 to 50 mg IV or PO, or equivalent). Avoid the use of 
IV promethazine (see Attachment 1 for a list of antihistamines that may be used). 

A corticosteroid: methylprednisolone 100 mg IV or PO or equivalent for the first 2 doses 
and 60 mg for all subsequent doses (after 2 consecutive daratumumab infusions are 
completed with no IRR adverse events). Substitutions for methylprednisolone are allowed 
(refer to Attachment 2).
In addition, a leukotriene inhibitor (optional; montelukast 10 mg PO) may be administered up to 
24 hours before infusion as per investigator discretion. 
If necessary, all PO preinfusion medications may be administered outside of the clinic on the day 
of the infusion, provided they are taken 1 to 3 hours before the infusion.
6.4.1.3.
Postinfusion Medication
Postinfusion medication should be administered to reduce the risk of delayed infusion-related 
reactions in all subjects:

Oral corticosteroid (20 mg methylprednisolone PO or equivalent in accordance with local 
standards) on the 2 days following each daratumumab administration (beginning the day 
after study drug administration). After 3 consecutive daratumumab infusions with no IRR 
adverse events, postinfusion corticosteroids should be administered per investigator 
discretion.
For subjects with a higher risk of respiratory complications (eg, subjects with COPD who have 
an FEV1 <80% or subjects with asthma), the following postinfusion medications should be 
considered:

antihistamine (diphenhydramine or equivalent) on the first and second days after each 
infusion;

short-acting 2 adrenergic receptor agonist such as salbutamol aerosol; and

control medications for lung disease (eg, inhaled corticosteroids long-acting 2 adrenergic 
receptor agonists for subjects with asthma; long-acting bronchodilators such as tiotropium or 
salmeterol inhaled corticosteroids for subjects with COPD).
In addition, these at-risk subjects may be hospitalized for monitoring for up to 2 nights after 
study drug administration. If these at-risk subjects are hospitalized, then their FEV1 should be 
measured and managed per local standards 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 each daratumumab administration. 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 serious adverse event. Investigators may prescribe bronchodilators, 
antihistamines, and corticosteroids that are deemed necessary to provide adequate supportive 
care in the event a bronchospasm occurs after subjects are released from the hospital/clinic. If an 
at-risk subject experiences no major IRRs, then these postdose medications may be waived after 
4 doses at the investigator's discretion.
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6.4.1.4.
Monitoring During and After Daratumumab Administration
Subjects should be observed carefully during study agent infusions. Trained study staff at the 
clinic should be prepared to intervene in case of any IRRs occurring, and resources necessary for 
resuscitation (eg, agents such as epinephrine and aerosolized bronchodilator, also medical 
equipment such as oxygen tanks, tracheostomy equipment, and a defibrillator) must be available 
at the bedside. If an IRR develops, then the infusion should be paused. Guidelines outlined in 
Section 6.3 must be followed to manage IRRs. 
Subjects should be monitored for at least 2 hours after the completion of the first infusion and 
may be discharged if considered clinically stable and all other study procedures have been 
completed (see Table 20 below). The investigator will determine the duration of safety 
monitoring for subsequent administrations. In addition, subjects should be monitored for 
symptoms of tumor lysis syndrome, see Section 8.1.2.
Table 20:
Infusion Duration and Monitoring After Infusion of Daratumumab
Cycle 1 Day 1
Daratumumab – First infusion
Daratumumab is administered over a 6 to 8 hour infusion period followed by a 2-hour 
observation period. The subject may be discharged if considered clinically stable and all 
other study procedures have been completed
Cycle 1 Day 8
Daratumumab – Second infusion
If the first daratumumab infusion is well tolerated (defined as no Grade 1 or higher 
IRRs), then the second daratumumab infusion should administered over 3 to 4 hours, 
followed by a 2-hour observation period. However, if the first daratumumab infusion is 
not well tolerated, then the second daratumumab infusion will follow the C1D1 
daratumumab infusion schedule, as described above and in Table 5.
Cycle 1 Day 15
Daratumumab 
Daratumumab is administered over a 3 to 4 hour infusion period, followed by a 2-hour 
observation period.
Cycle 1 Day 22
Daratumumab
Daratumumab is administered over a 3 to 4 hour infusion period, followed by a 2-hour 
observation period.
Cycle 2 Day 1 and 
subsequent infusions
Daratumumab 
If all the infusions in Cycle 1 are well tolerated, then starting on C2D1, the observation 
period can be 1-hour after dosing of daratumumab. If not well tolerated (ie, Grade 1 or 
higher infusion-related reactions), then follow the C1D15 procedures.
6.4.1.5.
Dose Delay
Dose modification of daratumumab is not permitted. Dose delay is the primary method for 
managing daratumumab-related toxicities.
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 4.03. Dose 
delays will be made based on the toxicity experienced during the previous infusion or newly 
encountered on Day 1 of a new cycle. 
The study treatment must be held if any of the following criteria below are met, to allow for 
recovery from toxicity, regardless of relationship to daratumumab.
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The criteria for a dose delay are:

Grade 4 hematologic toxicity, except for Grade 4 lymphopenia

Grade 3 thrombocytopenia with bleeding

Febrile neutropenia

Neutropenia with infection, of any grade

For all other adverse events, daratumumab should be withheld for Grade 3 or higher 
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 that was present at baseline or that lasts for <7 days after the last 
administration of daratumumab

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 of Grade 2 laryngeal edema, Grade 2 bronchospasm or febrile 
neutropenia, which must be fully recovered. If daratumumab administration does not commence 
within the prespecified window (Table 21) of the scheduled administration date, then the dose 
will be considered a missed dose. Administration may resume at the next planned dosing date. A 
missed dose will not be made up. Alternatively, dosing delays can be discussed with the Sponsor.
Table 21:
Daratumumab-related Toxicity Management
Cycles
Frequency
Dose Held
Dosing Restart
1 and 2
Weekly (q1wk)
>3 days
Next planned weekly dosing date
3 to 6
Biweekly (q2wks)
>7 days
Next planned biweekly dosing date
7+
Every 4 weeks (q4wks)
>14 days
Next planned every 4 weeks dosing date
The start (ie, Day 1) of a cycle may be delayed up to 4 weeks.  Day 1 of a cycle should never be 
skipped.  If the start of a cycle is delayed, Day 1 of subsequent cycles should be adjusted 
accordingly to maintain the 28-day cycle duration.  However, if a within-cycle dose (i.e., Day 8, 
Day 15, or Day 22) is delayed, then the dates of the subsequent within-cycle doses should not be 
adjusted. 
If 2 consecutive planned doses of daratumumab are missed due to any adverse event, then 
consultation with the Sponsor is required before dosing may be continued.
For subjects whose dose is held for more than 28 days for any drug related adverse event or who 
miss 3 or more consecutive planned doses of daratumumab due to any adverse event, then the 
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treatment should be permanently discontinued. Dose holds of more than 28 days for other 
reasons should be discussed with the Sponsor.
7.
TREATMENT COMPLIANCE
Study drugs (JNJ-63723283 and daratumumab) will be administered by qualified site staff, and 
the details of each administration will be recorded in the case report form (CRF). Additional 
details are provided in the SIPPM. A patient diary card may be used to record drugs taken at 
home to prevent IRR (eg, pre-infusion medication).
8.
PRESTUDY AND CONCOMITANT THERAPY
All prior treatments for malignancies, including those since diagnosis, must be recorded at 
Screening. Throughout the study, investigators may prescribe any concomitant medications or 
treatments deemed necessary to provide adequate supportive care except for those listed in 
Section 8.3. The Sponsor must be notified in advance (or as soon as possible thereafter) of any 
instances in which prohibited therapies are administered.
Routine systemic use of the following concomitant medications will be collected in the CRF and 
recorded in the source documents beginning with signing of the ICF to PD or until the start of 
subsequent anticancer treatment, if earlier: growth factors, transfusions, anti-infectives 
(antibacterials, antivirals, and antimycotics), corticosteroids, anti-arrhythmics and other cardiac 
supportive therapy, anti-epileptics, centrally acting psychiatric medication, anti-histamines and 
other medications targeting postinfusion systemic reactions, bisphosphonates, and any anticancer 
therapy (including radiation).
The use of concomitant medications used to treat adverse events or any infusion-related reactions 
will be collected in the CRF and recorded in the source documents beginning with the signing of 
the ICF until PD.
Prestudy therapies administered up to 30 days before first dose of study drug must be recorded at 
Screening. Concomitant therapies described above must be recorded throughout the study 
beginning with start of the first dose of study drug until the end of treatment assessment. 
Concomitant therapies should be recorded beyond 30 days after the last dose of study drug only 
in conjunction with serious adverse events that meet the criteria outlined in Section 12.3.2,
Serious Adverse Events.
8.1.
Recommended Therapies
8.1.1.
Bisphosphonate Therapy
Bisphosphonate therapy is strongly recommended for all subjects with evidence of lytic 
destruction of bone or with osteopenia. Bisphosphonate therapy is recommended to be continued 
per treatment guidelines (Moreau 2017; NCCN 2017).23,24 Commercially available IV 
bisphosphonates (pamidronate and zoledronic acid) are preferred when available, and should be 
used according to the manufacturer's recommendations, as described in the prescribing 
information, for subjects with osteolytic or osteopenic myelomatous bone disease. Oral 
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bisphosphonates may be used as alternatives if IV bisphosphonates are not available at the study 
site. Investigators should use the same route of bisphosphonate therapy for all subjects at their 
sites. Subjects with evidence of lytic destruction of bone or with osteopenia who are not using a 
bisphosphonate prior to first study drug administration should start a bisphosphonate as soon as 
possible during Cycle 1 or 2 of treatment. Investigators should not start bisphosphonate therapy 
during the study, unless it has been agreed with the Sponsor that there is no sign of disease 
progression.
8.1.2.
Therapy for Tumor Lysis Syndrome
Subjects should be monitored for symptoms of tumor lysis syndrome. Management of tumor 
lysis syndrome, including hydration for abnormal laboratory test results such as hyperkalemia, 
hyperuricemia, and hypocalcemia, is highly recommended. High-risk subjects (ie, those with a 
high tumor burden) should be treated prophylactically in accordance with local standards 
(eg, rehydration, diuretics, allopurinol 300 mg daily, and medication to increase urate excretion). 
Subjects are to be provided prophylactic therapy to manage IRRs as described in Section 6.1.2
for daratumumab. 
8.1.3.
Therapy for Pneumocystis carinii/jirovecii
Pneumocystis carinii/jirovecii pneumonia (PCP) prophylaxis should be considered, as per 
institutional guidelines.
8.1.4.
Prophylaxis for Herpes Zoster Reactivation
Antiviral prophylaxis should be considered for the prevention of herpes zoster virus reactivation.
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:

Antivirals 

Granulocyte colony stimulating factors, erythropoietin, and transfusion of platelets and red 
cells is allowed, except as prophylaxis during Cycle 1

Prevention of constipation (eg, adequate hydration, high-fiber diet, and stool softeners if 
needed)

Prophylactic antiemetics, with the exception of corticosteroids

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.

Adequate hydration is recommended for prevention of myeloma-related kidney disease.
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
Oral contraceptives

Hormone-replacement therapy
Other symptoms may be managed according to institutional guidelines provided prohibited 
therapies are not administered (see Section 8.3).
In general, investigators should manage subject care with supportive therapies as clinically
indicated per local standards.
8.3.
Prohibited Therapies
Use of the treatments listed below is prohibited during the study:

Other agents that target CD38, PD-1 or its ligand, PD-L1.

Concomitant administration of any other antineoplastic therapy for the intention of treating 
multiple myeloma is prohibited, including medications used for other indications that have 
anti-myeloma properties (eg, interferon and clarithromycin). Continuation of study treatment 
(during or after emergency orthopedic surgery or radiotherapy because subject benefit) may 
only occur in the absence of disease progression and after consultation with and approval by 
the Sponsor. 

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 
local 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.

Concomitant administration of approved or investigational agents with activity against or 
under investigation for multiple myeloma is prohibited (including but not limited to 
conventional chemotherapies, IMiDs, or proteasome inhibitors). Systemic corticosteroids 
(>10 mg prednisone per day or equivalent for over 5 days) other than those given for IRRs, 
as described in Section 6.2.2 should be avoided. Nonsteroidal anti-inflammatory agents 
should be avoided to prevent myeloma-related kidney disease. 

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.

Any live, attenuated vaccine within 4 weeks prior to administration of study drug or during
treatment or within 5 months following the last JNJ-63723283 dose.
The Sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.
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9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
The Time and Events Schedules (Table 1 and Table 2) summarizes the frequency and timing of 
efficacy, safety, biomarker, PK, and immunogenicity measurements applicable to this study. 
Additional serum or urine 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. Repeat or unscheduled samples may be taken for 
safety reasons or for technical issues with the samples.
9.1.1.1.
Daratumumab Monotherapy Period
Subjects continuing with daratumumab monotherapy will follow the procedures as outlined in
Attachment 11, Table 24.
9.1.2.
Screening Phase
The signed ICF must be obtained before any study-specific procedures are performed. The 
Screening Phase begins when the first protocol specified Screening Phase assessment is 
performed (typically signing of the ICF). During the Screening Phase, eligibility criteria will be 
reviewed and a complete clinical evaluation will be performed as specified in the Time and 
Events Schedule (Table 1). Subjects will be stratified by International Staging System (ISS; I, II, 
or III), and number of prior lines of therapy (3 prior lines vs. >3 prior lines). Screening 
procedures will be performed within 28 days before enrollment. Subjects may be retested for 
laboratory values that do not meet eligibility criteria within the 28-day Screening Phase.
If a subject does not meet all inclusion and exclusion criteria (is a screen failure) but at some 
point in the future is expected to meet the subject eligibility criteria, the subject may be 
rescreened on 1 occasion. Subjects who are rescreened will be assigned a new subject number, 
undergo the informed consent process, and then restart a new Screening Phase.
Screening procedures will be performed within 28 days before Cycle 1, Day 1, with the 
exceptions of disease evaluations, laboratory tests, and pregnancy tests. Serum and urine baseline 
disease evaluations are to be performed by the central laboratory within 14 days before Cycle 1, 
Day 1. It is not mandatory to collect these samples again at the Cycle 1, Day 1 visit. Results from 
skeletal survey and radiologic plasmacytoma assessments performed as routine follow up for 
subject's disease within 42 days before Cycle 1, Day 1 and bone marrow aspirate/biopsy within a 
maximum of 42 days before Cycle 1, Day 1 may be used without these tests being repeated. If 
the 24-hour collection of urine M-protein quantitation by electrophoresis (UPEP) began before 
informed consent was obtained as part of routine patient care, the sample can be used in this 
study as long as it was sent to the central lab for analysis after the informed consent was 
obtained. During Screening, a pregnancy test must be performed within 14 days prior to dosing. 
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Prior to enrollment/randomization, the Sponsor will review key eligibility criteria for all subjects. 
Eligibility information will be provided to the Sponsor for review prior to approval for 
enrollment/randomization being granted by the Sponsor. If the Sponsor agrees that the eligibility 
criteria have been met, then the investigator will receive confirmation that the subject may be 
enrolled/randomized into the study. If the Sponsor considers that the eligibility criteria have not 
been met, then the Sponsor will contact the investigator to discuss the subject.
All evaluations will be done in all parts of the study, unless otherwise noted.
9.1.3.
Open-Label Treatment Phase
Details of the procedures performed during the Treatment Phase are outlined in the Time and 
Events Schedule. Subjects should start study treatment within 72 hours after assignment to 
treatment. Subjects will be closely monitored for adverse events, laboratory abnormalities, and 
clinical response. Clinical evaluations and laboratory studies may be repeated more frequently, if 
clinically indicated. If disease progression is confirmed, then the subject will discontinue study 
treatment, complete the End-of-Treatment Visit, and enter the Follow-up Phase.
End-of-Treatment Visit
Unless a subject withdraws consent for study participation or is lost to follow up, an End-of-
Treatment Visit is to occur 4 weeks (±7 days) after the last dose of study treatment. Every effort 
should be made to conduct the End-of-Treatment Visit before the subject starts subsequent 
treatment. If a subject is unable to return to the site for the End-of-Treatment Visit, then the 
subject should be contacted to collect information on adverse events and concomitant 
medications used to treat adverse events as specified in Section 12.3.1. If the End-of-Treatment 
visit occurs before 30 days, then the subject should be contacted after 30 days so that all adverse 
events that occurred within the 30-day period are recorded. Additional information on reporting 
of adverse events is presented in Section 12.
9.1.4.
Follow-Up Phase 
Each subject is to have a follow-up visit 8 weeks after the last dose of study treatment. Beyond 
the Week 4 End-of-Treatment Visit, information on serious adverse events considered related to 
study treatment will continue to be collected. For a subject who discontinues study treatment 
before disease progression, disease evaluations should continue to be performed as specified in 
the Time and Events Schedule. After disease progression is documented, subsequent anticancer 
treatment, response to subsequent treatment, and date of progression will be recorded and 
survival status will be obtained. If the information is obtained via telephone contact, then 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 on the 
eCRF.
During the Daratumumab Monotherapy Period, SAEs (including SPMs) must be reported 
continuously from time of ICF until EOT Visit or until the subject withdraws consent for study 
participation or until the subject starts subsequent anticancer therapy whichever occurs first. 
Beyond the EOT Visit reporting period after the last dose of study medication, information on 
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SAEs, including SPMs, considered possibly, probably or definitely related to study drug will 
continue to be collected.
9.2.
Efficacy Evaluations
9.2.1.
Disease Assessments
Disease evaluations must be performed every 28 days (3 days), regardless of any changes to the 
dosing regimen, until disease progression. Disease evaluations will be performed by a central 
laboratory (unless otherwise specified). This study will use the IMWG consensus 
recommendations for multiple myeloma treatment response criteria (Durie 2006; Kumar 2016;
Rajkumar 2011)10,18,32 presented in Table 22 For quantitative Ig (QIg), M-protein, and 
immunofixation measurements in serum and 24-hour urine, the investigator will use results 
provided by the central laboratory. For subjects with light chain multiple myeloma, only serum 
free light chain assay will be performed routinely. Otherwise, serum free light chain assay test 
results will be analyzed by the central laboratory only for the assessment of sCR. For subjects 
with suspected daratumumab interference on serum M-protein quantitation by electrophoresis 
(SPEP) and immunofixation, a reflex assay will be performed (Attachment 7). Subjects with 
confirmed daratumumab interference who meet all other clinical criteria for CR or sCR will be 
considered CR/sCR. An assessment of MRD may be conducted centrally on bone marrow 
samples (see Section 9.4.2).
Table 22:
International Uniform Response Criteria Consensus Recommendations
Response 
Response Criteria
Stringent complete
Response (sCR)
1.
CR as defined below, plus
2.
Normal FLC ratio, and
3.
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.
Minimal response

25% but 49% reduction of serum M-protein, and

Reduction in 24-h urine M-protein by 50–89%

In addition to the above criteria, if present at baseline, a 25% to 49% reduction in the size of soft 
tissue plasmacytomas also is required
Stable disease 
(SD)

Not meeting criteria for CR, VGPR, PR, MR, or progressive disease
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Response 
Response Criteria
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 percentage must be 10%)

Bone marrow plasma cell percentage: the absolute percentage 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
FLC=free light chain; PC=plasma cell
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.
Clinical Relapse
Clinical relapse is defined using the definition of clinical relapse in IMWG criteria (Durie 2006; Kumar 2016;
Rajkumar 2011).10,18,32 In IMWG criteria, clinical relapse is defined as requiring one or more of the following direct indicators of 
increasing disease or end-organ dysfunction that are considered related to the underlying plasma cell proliferative disorder:
1.
Development of new soft tissue plasmacytomas or bone lesions on skeletal survey, magnetic resonance imaging, or other 
imaging
2.
Definite increase in the size of existing plasmacytomas or bone lesions. A definite increase is defined as a 50% (and at least 
1 cm) increase as measured serially by the sum of the products of the cross-diameters of the measurable lesion
3.
Hypercalcemia (>11.5 mg/dL; >2.875 mM/L)
4.
Decrease in hemoglobin of more than 2 g/dL (1.25 mM) or to less than 10 g/dL
5.
Rise in serum creatinine by more than or equal to 2 mg/dL (177 mM/L)
6.
Hyperviscosity
In some subjects, bone pain may be the initial symptom of relapse in the absence of any of the above features. However, bone 
pain without imaging confirmation is not adequate to meet these criteria in studies.
M-protein levels need to meet the definition of disease progression (see Table 22) for subjects to 
have disease progression. Disease evaluations will continue beyond relapse from CR until 
disease progression is confirmed.
Disease progression must be consistently documented across clinical study sites using the criteria 
in Table 22. It is important that instances of disease progression be reported to the Sponsor as 
soon as possible. Diagnosis and documentation of disease progression will be reported to the 
Sponsor within 24 hours of suspected disease progression. The medical monitor will review the 
information to confirm that the IMWG criteria for disease progression have been met. If the 
medical monitor agrees that disease progression has occurred, then a confirmation will be 
returned to the investigator, and the subject will be withdrawn from study treatment. If the 
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medical monitor considers that the IMWG criteria for disease progression have not been met, 
then the medical monitor will contact the investigator to discuss the subject.
For continuation of treatment, the IMWG response will be determined on an ongoing basis by 
the investigator. For data analysis and reporting, 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 IMWG criteria.
For subjects who discontinue study treatment before disease progression, disease evaluations 
should continue to be performed as described in the Time and Events Schedule, until confirmed 
disease progression, death, start of a new treatment for multiple myeloma, withdrawal of consent 
for study participation, or the end of the study, whichever occurs first. Blood and urine for 
disease evaluations scheduled for treatment days should be collected before study treatment is 
administered.
9.2.1.1.
Disease Assessments In Daratumumab Monotherapy Period
During the Daratumumab Monotherapy Period, disease evaluations will be conducted at the local 
site, including laboratory tests. Assessment of response to treatment will be determined by the 
investigator using local laboratory data. Disease assessments SPEP, UPEP, and serum calcium 
corrected for albumin should be collected at an interval consistent with the investigator’s 
standard of care. The Sponsor recommends, but does not require, disease assessments to be 
performed every cycle for the first 18 months of this daratumumab monotherapy period and 
every-other-month thereafter.
Daratumumab interference testing will not be performed in the Daratumumab Monotherapy 
Period.
9.2.2.
Myeloma Protein Measurements in Serum and Urine
Blood and 24-hour urine samples will be collected as specified in the Time and Events Schedule 
until the development of confirmed disease progression. Samples for M-protein measurements 
will be sent to and analyzed by a central laboratory. Only 1 serum and one 24-hour urine sample 
per time point are required by the central laboratory to perform the following tests:

Serum quantitative immunoglobulins (QIgs)

All subjects will be evaluated for IgG, IgA, IgM, IgD, and IgE at Screening. Every 3 months 
during treatment and at the EOT visit, subjects with IgD or IgE disease will be evaluated for 
IgG, IgA, IgM, IgD, and IgE and subjects with IgG, IgA, or IgM disease will be evaluated 
for IgG, IgA, and IgM.

Serum M-Protein quantification by electrophoresis (SPEP)

Serum immunofixation at Screening and thereafter when a CR is suspected. If daratumumab 
interference is suspected based on SPEP and immunofixation electrophoresis (IFE) results, 
additional reflex IFE testing may be performed.

Serum free light chain assay
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
24-hour UPEP

Urine immunofixation at Screening and thereafter when a CR is suspected
Disease progression based on 1 of the laboratory tests alone must be confirmed by at least 1 
repeat investigation. Disease evaluations will continue beyond relapse from CR until disease 
progression is confirmed. 
Subjects with measurable disease by UPEP at Screening will provide UPEP on the same 
schedule as SPEP. Subjects can stop post-baseline UPEP measurement if they have no 
measurable disease by UPEP at Screening, or if they have measurable disease by UPEP at 
Screening and then no measurable disease by UPEP at 2 consecutive post-baseline 
measurements. A urine sample to measure UPEP should be obtained at suspected disease 
progression and to confirm PD.
Serum and urine immunofixation test and serum free light chain assay will be performed at 
Screening and thereafter when a CR is suspected (when serum or 24-hour urine M-protein 
electrophoresis [by SPEP or UPEP] are 0 or nonquantifiable). For subjects with suspected 
daratumumab interference on serum immunofixation, another reflex assay using the anti-idiotype 
monoclonal antibody will be used to confirm daratumumab migration on immunofixation.
Subjects that meet all other IMWG criteria for CR, and whose positive immunofixation is 
confirmed to be daratumumab, will be considered complete responders. However, for subjects 
with light chain multiple myeloma, serum free light chain assay will be performed routinely. 
Serum immunofixation assay samples will be split into 2 aliquots, with 1 reserved for potential 
follow-on testing if daratumumab interference with immunofixation is suspected. As 
daratumumab is a monoclonal IgG antibody, additional serum samples may be utilized to 
monitor for potential daratumumab interference with immunofixation.
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.
9.2.3.
Serum Calcium Corrected for Albumin
Blood samples for calculating serum calcium corrected for albumin will be collected as specified 
in the Time and Events Schedule and analyzed centrally 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 19). 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 Attachment 4. When blood is analyzed at a local laboratory, measurement of free ionized 
calcium is an acceptable alternative to corrected serum calcium to determine hypercalcemia. Free 
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ionized calcium levels greater than the ULN (local laboratory reference ranges) are considered to 
be hypercalcemic for this study.
9.2.4.
2-microglobulin and Albumin
Blood samples for 2 microglobulin and albumin are to be collected at Screening, and will be 
analyzed by the central laboratory and used for the assessment of International Staging System 
staging at study entry. The central laboratory will also measure albumin at any time during the 
study that a serum calcium sample is taken.
9.2.5.
Bone Marrow Examination
Bone marrow assessments to be performed locally and centrally are summarized in Table 23.
Table 23:
Bone Marrow Testing
Local Testing
Central Testing
Screening
Bone marrow 
aspirate/biopsy
Disease characterization (morphology 
and either immunohistochemistry, 
immunofluorescence, or flow cytometry). 
Cytogenetics by FISH.
MRD and molecular subtyping: a portion of bone 
marrow aspirates collected at Screening will be sent to 
a central laboratory for evaluation of 
immunophenotype by flow cytometry and baseline 
assessment of MRD.
For Screening, fresh aspirate is preferred. If not 
performed because a sample is available within 
42 days prior to first study drug administration or 
randomization, non-decalcified aspirate slides (smears 
or clots) should be provided.
CR, sCR
Bone marrow aspirate or 
biopsy (or both)
For morphology examination and either 
flow cytometry, immunohistochemistry, 
or immunofluorescence to confirm CR or 
sCR. 
For sCR: 2- to 4-color flow cytometry, or 
immunohistochemistry, or 
immunofluorescence (requires to record 
kappa/lambda ratio from analysis of 
100 cells)
A portion of bone marrow aspirate will be sent to a 
central laboratory for evaluation of immunophenotype 
by flow cytometry and to assess MRD (at suspected 
CR or sCR, or post-CR every 6 months for those who 
maintain CR).
Disease Progression
Bone marrow aspirate or 
biopsy (or both)
Not applicable
If feasible, a bone marrow aspirate may be collected 
from subjects at disease progression to evaluate
mechanisms of daratumumab resistance.
CR=complete response; FISH=fluorescence in situ hybridization; MRD=minimal residual disease; sCR=stringent complete 
response
9.2.6.
Assessment of Lytic Bone 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 laboratory by roentgenography (low-dose CT is preferred) 
during the Screening Phase. 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, x-rays should be performed to document response or progression whenever clinically 
indicated based on symptoms. Magnetic resonance imaging (MRI) or low-dose CT are 
acceptable methods for evaluation of bone disease and may be included at the discretion of the 
investigator (see the disease response criteria in Table 19). If a radionuclide bone scan was used 
at Screening in addition to the complete skeletal survey, then both methods must be used to 
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document disease status. These tests must be performed at the same time. However, a 
radionuclide bone scan does not replace a complete skeletal survey.
Subjects present with disease progression manifested by symptoms of pain due to bone changes. 
In these cases, disease progression may be documented by skeletal survey or other radiographs, 
depending on the symptoms that the subject experiences. If the diagnosis of disease progression 
is obvious by radiographic investigations, then repeat confirmatory x-rays are not necessary. In 
instances where changes may be subtle, a repeat x-ray may be needed in 1 to 3 weeks and then 
disease progression is assessed per IMWG criteria.
9.2.7.
Documentation of Extramedullary Plasmacytomas
Sites of known extramedullary plasmacytomas must be documented during the Screening Phase. 
Clinical examination or MRI may be used to document extramedullary sites of disease. 
Computed tomography (CT) scan and positron emission tomography (PET)-CT scan evaluations 
are an acceptable alternative if there is no contraindication to the use of intravenous contrast. 
PET scan alone or ultrasound tests are not acceptable to document the size of extramedullary 
plasmacytomas. The diameters of long axis and short axis must be documented for identified 
extramedullary plasmacytomas.
For subjects with a history of plasmacytomas, extramedullary plasmacytomas should be assessed 
at Screening by clinical examination or radiologic imaging. They should also be assessed to 
confirm response, disease progression, or as clinically indicated. 
To qualify for PR or better, 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 19). To qualify for CR or 
better, all extramedullary plasmacytomas must have resolved. 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 of the perpendicular diameters of the reported plasmacytomas have 
increased by at least 50%, this will also qualify as disease progression.
9.3.
Pharmacokinetics and Immunogenicity
See Table 2 for pharmacokinetics and immunogenicity sample collection.
During the Daratumumab Monotherapy Period, pharmacokinetic and
immunogenicity 
evaluations will not be performed.
9.3.1.
Evaluations
Samples will be collected for measurement of serum concentrations of JNJ-63723283 and 
daratumumab and the assessment of anti-JNJ-63723283 and anti-daratumumab antibodies
(immunogenicity) according to the Time and Events Schedule for Pharmacokinetic and 
Immunogenicity Assessments (Table 2). Serum samples should be collected at the final visit 
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from subjects who are discontinued from treatment or withdrawn from the study. Subjects who 
discontinue treatment will also be asked to return for immunogenicity evaluation during the 
Follow-up Phase. These samples will be tested by the Sponsor or Sponsor's designee.
The exact dates and times of blood sampling must be recorded. Refer to the Laboratory Manual 
for sample collection requirements. Collected samples must be stored under the specified and 
controlled conditions for the temperatures indicated in the Laboratory Manual. Additional 
information about the collection, handling, and shipment of biological samples can be found in 
the Laboratory Manual.
9.3.2.
Analytical Procedures
Serum samples will be analyzed to determine concentrations of daratumumab, concentrations of 
JNJ-63723283, and the generation of antibodies to JNJ-63723283 or daratumumab using
validated immunoassay methods. All samples collected for detection of anti-JNJ-63723283 and 
daratumumab antibodies will also be evaluated for serum concentration to enable interpretation 
of the antibody data. In separate immunogenicity assessments, serum samples will be screened 
for antibodies binding to JNJ-63723283 or 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.
9.3.3.
Pharmacokinetic Parameters
The PK parameters are defined as:
Cmax = Maximum observed concentration
Cmin = Minimum observed concentration
For both JNJ-63723283 and daratumumab, the PK evaluations include Cmin and Cmax. If 
sufficient data are available, other PK parameters may be calculated. The Cmin and Cmax will be 
summarized by descriptive statistical methods for the Safety Run-in, Arm A, and Arm B. If there 
are sufficient data, then a population PK analysis of serum concentration-time data of 
daratumumab and JNJ-63723283 may be performed and may include data from other clinical 
studies. If performed, details will be provided in a population-PK analysis plan and the results of 
the analysis will be presented in a separate report.
9.4.
Biomarker Assessments
Bone marrow and blood samples will be taken from all study subjects as outlined in the Time 
and Events Schedule for Biomarkers (Table 1). Bone marrow aspirate samples may be used to 
evaluate immune status and plasma cell expression of PD-L1 and CD38 in addition to depth of 
response through evaluation of MRD.
During the Daratumumab Monotherapy Period, no bone marrow and blood samples will be 
collected for central testing.
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9.4.1.
Biomarker Assays in Blood Samples
Blood samples will be obtained for biomarker evaluation from all eligible subjects. Whole blood 
immune profiling will be performed to explore immune markers associated with response or 
resistance to JNJ-63723283 and daratumumab. Samples will be processed to obtain plasma and 
serum for the determination of changes in blood-based biomarkers. Whole blood samples may be 
processed to obtain their derivatives (eg, RNA and DNA) and evaluated for immune-related, 
tumor typerelated, and other exploratory biomarkers (eg, alterations in gene expression or 
clonal T-cell expansion). Currently, cytokine release syndrome has not been recognized as a 
known risk for PD-1 inhibitors or daratumumab. However, an unscheduled serum sample will be 
analyzed for selected cytokines (including but not limited to IFN gamma, TNF alpha, and IL-6) 
in the event of a suspected cytokine release syndrome. Also, based on emerging scientific 
evidence, the Sponsor may request additional blood samples for biomarker evaluation. In this 
case, such analyses will be limited to research related to the study drug(s) or diseases being 
investigated.
9.4.2.
Minimal Residual Disease (MRD) Evaluation
Bone marrow aspirates will be collected to monitor MRD in those subjects who attain a CR/sCR. 
Minimal residual disease negativity is being evaluated as a potential surrogate for PFS and OS. 
Minimal residual disease will be monitored in subjects who achieve a CR/sCR using next 
generation sequencing (NGS) on bone marrow aspirate DNA. If this methodology is unavailable, 
or determined to be scientifically inferior, then alternative methods for MRD assessment may be 
utilized. Baseline bone marrow aspirates will be used to define the myeloma clones, and post-
treatment samples collected as specified in the Time and Events Schedule will evaluate the MRD 
negativity. In cases where daratumumab is suspected of interfering with IFE and preventing 
clinical CR response calls, subjects with VGPR may also be evaluated for MRD. In the event 
fresh bone marrow aspirate will not be collected at Screening, non-decalcified diagnostic tissue 
(aspirate slides – smear or clot) should be collected to use as a baseline MRD sample. 
9.4.3.
Biomarker Bone Marrow Aspirate Evaluations
A portion of the bone marrow aspirate samples collected as specified in the Time and Events 
Schedule will be used to examine multiple myeloma cell expression of specific proteins 
presumed to be associated with immune-mediated ADCC/CDC/ADCP or other mechanisms of 
action of or resistance to JNJ-63723283 and daratumumab. Additionally, DNA or RNA may be 
extracted to determine whether specific mutations or molecular subgroups are responsive to the 
combination of JNJ-63723283 and daratumumab.
9.4.4.
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.
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9.4.5.
Additional Collections
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.
9.5.
Patient-reported Outcomes (Part 3)
The EORTC QLQ-C30 has been widely used among cancer patients and in prior multiple 
myeloma clinical trials. 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 scale, 3 symptom scales (fatigue, nausea and vomiting, and 
pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial 
difficulties). Reliability, validity, and clinically meaningful change have been demonstrated in 
multiple myeloma patients (Wisloff 1996; Wisloff 1997).39,40 The focus of the PRO assessment 
will be the global health scale which is designated as a secondary endpoint. The remaining 
domains are included as exploratory endpoints.
The EQ-5D-5L is a standardized instrument for use as a measure of health status and utility. 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” (Herdman 2011).12
Both questionnaires will be completed at the timepoints outlined in the Time and Events 
Schedule, for Part 3 only (see Attachment 10). All visit-specific PRO assessments should be 
conducted before any tests, procedures, or other consultations for that visit to prevent influencing 
subject perceptions.
9.6.
Medical Resource Utilization (Part 3)
Medical resource utilization data will be collected to determine the medical cost impact of the 
two treatment arms that may be used to support the value story and cost-effectiveness modeling 
for market access. Medical resource utilization data associated with medical encounters, 
primarily hospitalizations, outpatient visits, and emergency department visits, 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. The data collected in Part 3
will include:

Duration of hospitalization (total length of stay, including duration by each hospital unit)

Number and character of diagnostic and therapeutic tests and procedures 

Outpatient medical encounters (including physician, nurse practitioner or emergency 
department visits, tests and procedures)
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9.7.
Safety Evaluations
Safety will be assessed by the incidence and severity of adverse events, laboratory test results, 
ECGs, vital sign measurements, physical examination findings, ECOG performance status score,
and other evaluations, as described in the Time and Events Schedule (Table 1). Toxicities will be 
graded according to the NCI-CTCAE Version 4.03. Any clinically relevant changes occurring 
during the study must be recorded on the Adverse Event section of the CRF. Any 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.
Based on the previous human experience with daratumumab, in vitro studies, and animal 
toxicological 
findings, 
infusion-related 
reactions/allergic 
reactions, 
hemolysis, 
and 
thrombocytopenia will be closely monitored. Immune-related risks have been identified with 
other anti-PD-1 antibodies and this will be closely monitored. As JNJ-63723283 and 
daratumumab are both biologic agents, immunogenicity also will be monitored. Any of the 
safety monitoring assessments may be performed more frequently, and adverse events should be 
evaluated by the investigator according to the standard practice, if clinically indicated.
Adverse Events
Adverse events will be reported by the subject (or, when appropriate, by a caregiver, surrogate, 
or the subject's legally acceptable representative) for the duration of the study. Adverse events 
will be followed by the investigator as specified in Section 12, Adverse Event Reporting.
Clinical Laboratory Tests 
Blood samples for clinical laboratory evaluation will be collected. The investigator must review 
the laboratory results, document this review, and record any clinically relevant changes occurring 
during the study in the adverse event section of the CRF. The laboratory reports must be filed 
with the source documents.
The following tests will be performed by the local laboratory, unless otherwise specified:
Hematology
Hemoglobin
White blood cell (WBC)
Absolute neutrophil count (ANC)
Absolute lymphocyte count (ALC)
Platelet count
Coagulation
Prothrombin time/International Normalized 
Ratio
Activated partial thromboplastin time
Chemistry
Sodium
Total bilirubinb
Potassium
Alkaline phosphatase
Creatinine
Calcium
Aspartate aminotransferase (AST)
Amylase, lipase
Alanine aminotransferase (ALT)
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Other Tests
Thyroid panela
Thyroid stimulating hormone (TSH)
Triiodothyronine (free T3; total)
Free thyroxine (free T4)
Serology (hepatitis B, hepatitis C) and HCV Viral Load: 
Hepatitis B: HBsAg, anti-HBc
Hepatitis C: anti-HCV; HCV RNA PCR, if necessary
Pregnancy Test (for women of childbearing potential 
only)
serum (<5 IU/mL) -hCG at Screening; 
serum or urine thereafter as clinically 
indicated
a. At baseline. If normal, then only TSH thereafter.
b. Direct bilirubin if Gilbert’s disease.
During the Daratumumab Monotherapy Period, limited laboratory tests will be required as per 
the Time & Events Schedule (Table 24), but reporting in the eCRF is not required.
The following clinical laboratory tests will be performed by the local laboratory during treatment 
in the Daratumumab Monotherapy Period:
Hematology
Hemoglobin
White blood cell (WBC)
Absolute neutrophil count (ANC)
Absolute lymphocyte count (ALC)
Platelet count
Chemistry
Sodium
Total bilirubinb
Potassium
Alkaline phosphatase
Creatinine
Calcium
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Indirect Antiglobulin Test (IAT) results
Blood group, type, and indirect antiglobulin test (IAT) should be assessed before the first dose of 
daratumumab. Subject red blood cell (RBC) phenotyping (standard or extended) is an alternative 
option to the IAT test, if locally required. Either must be completed prior to first daratumumab 
infusion.
Daratumumab interferes with the IAT, which is a routine pre-transfusion test performed to 
identify a subject’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 (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 or phenotyping) determined before the first infusion of daratumumab 
along with information on the IAT interference for healthcare providers/blood banks. Subjects 
are to carry this card throughout the treatment period and for at least 6 months after treatment 
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ends. Blood banks can eliminate the daratumumab interference with IAT by treating reagent 
RBCs with dithiothreitol (DTT) (Chapuy 2015).8
Possible methods for blood banks to provide safe RBCs for transfusion to subjects receiving 
daratumumab include:
a.
Providing ABO/RhD compatible, phenotypically (standard or extended phenotyping) or 
genotypically matched units
b.
Providing ABO/RhD compatible, K-negative units after ruling out or identifying 
alloantibodies using DTT-treated reagent RBCs
Uncrossmatched, 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 Investigator’s Brochure.
Pulmonary Function Test
Subjects with known or suspected COPD must have a FEV1 test during Screening. Refer to 
Section 6.2.4.7 of the protocol for details on subjects with higher risk of respiratory 
complications.
Electrocardiogram: 
A 12-lead ECG will be performed at Screening and at End-of-Treatment; and as clinically 
indicated. 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 timepoint as ECG recording, 
the procedures should be performed in the following order: ECG(s), vital signs, blood draw.
Clinically significant abnormalities will be recorded as adverse events in the appropriate CRF.
Vital Signs
Temperature, pulse, and blood pressure will be performed as specified in the Time and Events 
Schedule (Table 1). Clinically significant abnormalities will be recorded as adverse events in the 
appropriate CRF. Blood pressure and pulse measurements should be preceded by at least 
5 minutes of rest in a quiet setting without distractions (eg, television, cell phones).
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Physical Examination and ECOG performance status
A complete physical examination should be performed during the Screening Phase. Thereafter, 
only a symptom directed physical examination is required. Height will be measured at Screening
only; weight will be measured at Screening and as specified in Time and Events schedule. 
Abnormalities will be recorded in the appropriate section of the CRF. ECOG performance status 
will be used to evaluate the effect of the disease status on the activities of daily living
(Attachment 5). When scheduled, ECOG assessments should be obtained prior to any other study 
procedures planned for the same day.
9.8.
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 Time and Events Schedules 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. Collection, handling, storage, and shipment of samples must be under the 
specified, and where applicable, controlled temperature conditions as indicated in the Laboratory 
Manual.
10.
DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL FROM THE 
STUDY
10.1.
Discontinuation of Study Treatment/Withdrawal from the Study
Discontinuation of Study Treatment
A subject will not be automatically withdrawn from the study if he or she has to discontinue 
treatment. The End-of-Treatment Visit and Follow-up visit assessments should continue as 
specified in the Time and Events Schedules.
A subject's study treatment must be discontinued if:

The investigator believes that for safety reasons or tolerability reasons (eg, adverse event) it 
is in the best interest of the subject to discontinue study treatment

The subject becomes pregnant

The subject withdraws consent for administration of study treatment

The subject experiences unacceptable toxicity, including IRRs described in Section 6.3

The subject missed more than 3 consecutive planned daratumumab doses with a delay up to 
4 weeks at Cycles 1 to 6 and up to 6 weeks beyond Cycle 6, due to daratumumab-related 
AEs

The subject missed more than 12 weeks of planned does of JNJ-63723283 due to 
JNJ-63723283-related AEs
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
For subjects whose JNJ-63723283 treatment is discontinued, they may continue to receive 
daratumumab alone. For subjects whose daratumumab is discontinued, JNJ-63723283 
treatment should also be discontinued.

The subject experiences confirmed disease progression per IMWG. However, subjects in 
either Arm A or Arm B may continue treatment in the setting of clinical benefit with 
Sponsor approval.

A subject who experiences a second primary malignancy that cannot be treated by surgery 
alone must be withdrawn from the study. However, a subject who develops a malignancy 
that may 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 CRF.
Withdrawal from the Study
A subject will be withdrawn from the study for any of the following reasons:

Lost to follow-up

Withdrawal of consent to study participation

Pregnancy

Second primary malignancy (see Discontinuation of Study Treatment for additional details)

Death

The study investigator, for any reason, stops the subject's participation in the study

Sponsor terminated the study
Before a subject is lost to follow-up, every reasonable effort must be made by the study-site 
personnel to contact the subject and determine the reason for discontinuation/withdrawal. The 
measures taken to follow up must be documented.
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. Subjects who withdraw will not be replaced. If a 
subject discontinues from treatment, end-of-treatment assessments should be obtained.
10.1.1.
Discontinuation of Study Treatment in Daratumumab Monotherapy 
Period
A subject's study treatment must be discontinued if:

The investigator believes that for safety reasons or tolerability reasons (eg, adverse event) it 
is in the best interest of the subject to discontinue study treatment

The subject becomes pregnant

The subject withdraws consent for administration of study treatment

The subject experiences unacceptable toxicity, including IRRs described in Section 6.3
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
The subject missed more than 3 consecutive planned daratumumab doses with a delay up to 
4 weeks at Cycles 1 to 6 and up to 6 weeks beyond Cycle 6, due to daratumumab-related 
AEs

The subject experiences disease progression. 

A subject who experiences a second primary malignancy that cannot be treated by surgery 
alone must be withdrawn from the study. However, a subject who develops a malignancy 
that may be cured surgically may continue to receive the assigned study treatment and 
should continue to be followed for subsequent progression of multiple myeloma. 
The End-of-Treatment Visit assessments should continue as specified in the Time and Events 
Schedule (Table 24).
End of Study
Subjects will discontinue the study upon completion of the End of Treatment Visit.
Withdrawal from the Study
Prior to the End of Treatment Visit, a subject will be withdrawn from the study for any of the 
following reasons:

Lost to follow-up

Withdrawal of consent to study participation

Pregnancy

Second primary malignancy (see Discontinuation of Study Treatment for additional details)

Death

The study investigator, for any reason, stops the subject's participation in the study

Sponsor terminated the study
Before a subject is lost to follow-up, every reasonable effort must be made by the study-site 
personnel to contact the subject and determine the reason for discontinuation/withdrawal. The 
measures taken to follow up must be documented.
10.2.
Study Termination for Safety Considerations
As described in Section 17.9.2, the Sponsor reserves the right to terminate the study at any time. 
Reasons for terminating the study because of safety issues and not proceeding to Part 3, may 
include, but are not limited to the following:

The incidence or severity of adverse events indicates a potential health hazard to subjects, 
including a higher incidence of Grade 3 irAEs and Grade 4 or 5 drug-related adverse 
events compared with marketed anti-PD-1 products as well as in the ongoing single-agent 
Phase 1 study (637232283LUC1001).
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The final decision to terminate the study will be based on the totality of the benefit/risk 
assessment. Procedures for managing toxicities, including irAEs, are described in Section 6.
10.3.
Withdrawal from the Use of Research Samples
A subject who withdraws from the study will have the following options regarding the optional
research samples:

The collected samples will be retained and used in accordance with the subject's original 
informed consent for optional research samples.

The subject may withdraw consent for optional research samples, in which case the samples
will be destroyed and no further testing will take place. To initiate the sample destruction 
process, the investigator must notify the Sponsor study site contact of withdrawal of consent 
for the optional research samples and to request sample destruction. The Sponsor study site 
contact will, in turn, contact the biomarker representative to execute sample destruction. If 
requested, the investigator will receive written confirmation from the Sponsor that the 
samples have been destroyed.
Withdrawal from the Use of Samples in Future Research
The subject may withdraw consent for use of samples for research (refer to Section 16.2.5, Long-
Term Retention of Samples for Additional Future Research). In such a case, samples will be 
destroyed after they are no longer needed for the clinical study. Details of the sample retention
for research are presented in the main ICF and in the separate ICF for optional research samples.
11.
STATISTICAL METHODS
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.
11.1.
Subject Information
Safety will be evaluated for all subjects who have received at least 1 dose of study drug 
(JNJ-63723283 or daratumumab) in any part of the study. The subjects in the Safety Run-in 
cohort may be included in the efficacy analyses and listed separately. The pharmacokinetic 
analyses will be performed on the population described in Section 11.4.
Part 2:
The primary analysis population for the efficacy endpoints will be the intent-to-treat (ITT) 
population, which will include all randomized subjects in Part 2.
Part 3:
The primary analysis population for the efficacy endpoints will be the ITT population, which 
will include all randomized subjects in Part 3. 
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11.2.
Sample Size Determination
Part 2:
Assuming the ORR for daratumumab monotherapy is approximately 30% and the addition of 
JNJ-63723283 improves ORR by 20%, approximately 80 subjects will be randomized in a 
1:1 ratio to achieve at least 70% power with a 2-sided alpha of 0.20 to reject the null hypothesis 
that there is no difference in ORR between the 2 treatment arms.
Part 3:
Assuming a median PFS of 4 months for the daratumumab monotherapy group (Lokhorst 2015;
Lonial 2016)21,22 and a 33% reduction in risk of disease progression or death for the combination
group (hazard ratio=0.67; median PFS=6 months), 230 PFS events are needed to achieve a 
power of 85% using a log-rank test with a 2-sided alpha of 0.05. With a 12-month accrual period 
and an additional 6-month follow-up, the sample size needed for the study is approximately 
300 (150/treatment group) subjects.
Long-term survival follow-up will continue until 205 deaths have been observed. Therefore, 
Part 3 of this study will achieve approximately 80% power to detect a 33% reduction in the risk 
of death (hazard ratio=0.67) with a log-rank test (2-sided alpha=0.05).
11.3.
Efficacy Analyses
Response to study treatment and progressive disease will be evaluated by a validated computer 
algorithm. Efficacy analyses will be performed separately for Part 2 and Part 3 of this study.
Part 2:
The primary endpoint, ORR, will be tabulated, and its two-sided 95% exact confidence interval 
will also be presented. For the calculation of ORR, those subjects who are not evaluable for 
response will be considered as non-responders In addition, the number and percentage of 
subjects in each response category will also be tabulated.
For time-to-event endpoints (PFS, OS, and duration of response), Kaplan-Meier estimates of the 
survival functions will be presented. For PFS and OS, treatment comparison will be made via a 
log-rank test. Cox’s regression will be performed to obtain the hazard ratio estimate and the 
corresponding 95% CI, which will be used as a measure for treatment effect. Additional Cox’s 
regression may be performed to include appropriate baseline prognostic variables. 
Part 3:
For the primary endpoint of PFS, the primary analysis will consist of a stratified log-rank test for 
the comparison of the PFS distribution between the 2 treatment groups. The Kaplan-Meier 
method will be used to estimate the distribution of overall PFS for each treatment. The treatment 
effect (hazard ratio) and its two-sided 95% confidence intervals are to be estimated using a 
stratified Cox regression model with treatment as the sole explanatory variable. 
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Duration of response will be provided descriptively using the Kaplan-Meier method without 
formal statistical comparison. Other time-to-event efficacy endpoints will be analyzed similarly. 
Comparison between the 2 treatment groups for ORR and other binary endpoints will be 
conducted using the stratified Cochran-Mantel-Haenszel test. The Mantel-Haenszel odds ratio 
will be provided along with its two-sided 95% confidence interval.
A multiplicity adjustment strategy will be implemented to control the overall family wise type I 
error rate for the Phase 3 part of this study. Additional details will be provided in the Statistical 
Analysis Plan.
11.4.
Pharmacokinetic Analyses
Pharmacokinetic analyses will be performed on the PK-evaluable population, defined as subjects 
who have received at least 1 dose of daratumumab or JNJ-63723283 and have at least 
1 postinfusion sample.
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. The number of subjects and samples excluded 
from the analysis will be clearly documented in the Clinical Study Report.
Descriptive statistics will be used to summarize daratumumab and JNJ-63723283 serum 
concentrations at each sampling time point. Cmin is defined as the minimal concentration 
observed immediately before infusion and Cmax is defined as the maximum concentration 
observed at the end of infusion, as presented in the summary of serum concentration by sampling 
time point. Other PK parameters, if available, may also be summarized. 
If sufficient data are available, population-PK analysis of serum concentration-time data of 
daratumumab or JNJ-63723283 may be performed and may be combined with data from other 
studies. If the population-PK analysis is conducted, details will be given in a population-PK 
analysis plan and the results of the analysis will be presented in a separate report.
11.5.
Immunogenicity Analyses
The incidence of anti-JNJ-63723283 and anti-daratumumab antibodies will be summarized for 
all subjects who receive at least 1 dose of JNJ-63723283 and daratumumab and have appropriate 
serum samples for detection of antibodies to JNJ-63723283 and daratumumab (ie, subjects with 
at least 1 sample obtained after their first dose). In addition, subjects who are positive for 
antibodies to JNJ-63723283 or daratumumab will be listed.
Other immunogenicity analyses may be performed to further characterize the immune responses 
that are generated.
11.6.
Biomarker Analyses
Biomarker analyses will be stratified by clinical covariates or molecular subgroups using the 
appropriate statistical methods (eg, parametric or non-parametric, univariate or multivariate, 
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analysis of variance, or survival analysis, depending on the endpoint). Correlation of baseline 
expression levels or changes in expression levels with response to time-to-event endpoints will 
identify responsive (or resistant) subgroups in addition to genes and pathways attenuated 
following treatment with daratumumab.
Any pharmacodynamic measures will be listed, tabulated, and where appropriate, plotted. 
Subjects may be grouped by cohort, dose schedule, or clinical response. Results of biomarker 
and pharmacodynamic analyses may be presented in a separate report. Planned analyses are 
based on the availability of clinically valid assays and may be deferred if emerging study data 
show no likelihood of providing useful scientific information.
11.7.
Pharmacokinetic/Pharmacodynamic Analyses
If sufficient data are available, then other pharmacokinetic/pharmacodynamic modeling may be 
performed, including exploring the relationship between serum concentrations of daratumumab 
and/or JNJ-63723283 and endpoints of clinical efficacy and safety. If performed, details and 
results of the analysis will be presented in a separate report.
11.8.
Patient-reported Outcomes Analyses (Part 3)
The EORTC-QLQ-C30 scale scores, EQ-5D-5L utility value, and EQ-5D-5L VAS will be 
summarized at each timepoint, by treatment arm. Within-group and between-group treatment 
effect on the PRO endpoints will be assessed by change from baseline using mixed models for 
repeated measures.
11.9.
Medical Resource Utilization Analyses (Part 3)
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.
11.10. Safety Analyses
Safety data from each part of this study may be combined as deemed appropriate.
Adverse Events
The verbatim terms used in the CRF by investigators to identify adverse events will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA). Treatment-emergent adverse 
events are adverse events with onset during the treatment phase or that are a consequence of a 
pre-existing condition that has worsened since baseline. All reported adverse events will be 
included in the analysis. For each adverse event, 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 treatment due to an adverse event, or who experience a severe 
or a serious adverse event.
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Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Reference ranges and markedly 
abnormal results (specified in the Statistical Analysis Plan) 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 timepoint. 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.
Parameters with predefined NCI-CTCAE toxicity grades will be summarized. Change from 
baseline to the worst adverse event grade experienced by the subject during the study will be 
provided as shift tables.
Electrocardiogram
Electrocardiogram data will be summarized based on categories of normal, abnormal either 
clinically significant or not clinically significant and listed.
Vital Signs
Descriptive statistics of temperature, pulse/heart rate, and blood pressure (systolic and diastolic)
values and changes from baseline will be summarized at each scheduled timepoint. The 
percentage of subjects with values beyond clinically important limits will be summarized.
11.11. Interim Analyses for Part 3
For PFS, one interim analysis is planned. The interim analysis will be performed when 138 PFS 
events, which is 60% of the total planned PFS events, have been accumulated. The purpose of 
this interim analysis is to evaluate interim efficacy data. The significance level at this interim 
analysis will be calculated based on the observed number of PFS events at the interim analysis, 
using the O’Brien-Fleming boundaries as implemented by the Lan-DeMets alpha spending 
method. Assuming 138 (60%) PFS events are observed, the alpha to be spent in this interim 
analysis will be 0.00762 2-sided). If the observed PFS hazard ratio is greater than 1, favoring the
daratumumab group, the study may be terminated for futility.
For OS, 2 interim analyses are planned. The timing of these analyses corresponds to that of PFS 
interim and final analyses, respectively; the final OS analysis will occur after 205 deaths have 
been observed. At the first interim analysis, an alpha of 0.0001 will be spent. For the second 
interim analysis and final analysis, the alpha to be spent will be determined by a linear alpha 
spending function based on the observed number of deaths at that time, ie, the cumulative alpha 
to be spent will be the total alpha (0.05) multiplied by the proportion of the observed number of 
deaths out of the total planned number of deaths (205). It is noted that, even if the significance of 
PFS has already been established, testing of OS may continue as planned until a definitive 
conclusion on OS is reached.
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11.12. Statistical Methods Effective Protocol Amendment 2
As of 25 May 2018, the Sponsor terminated further enrollment into this study and subjects 
continuing study will receive daratumumab monotherapy. Since the total number of subjects 
treated in this study is small, no formal statistical hypothesis testing will be performed. A 
descriptive data summary will be provided only for all subjects who received study medication. 
Subject information will be summarized or listed for all treated subjects. Subject narratives may 
be provided, as appropriate. Safety assessment data (AEs, Laboratory values, vital signs etc.) will 
be listed for each subject.
12.
ADVERSE EVENT REPORTING
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.
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting adverse events or serious adverse events. 
Open-ended and nonleading verbal questioning of the subject is the preferred method to inquire 
about adverse event occurrence.
12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study subject administered a 
medicinal (investigational or non-investigational) product. An adverse event does not necessarily 
have a causal relationship with the treatment. An adverse event 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 
International Council on Harmonisation [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 adverse events starting with the signing of the ICF (refer to 
Section 12.3.1, All Adverse Events, for time of last adverse event recording).
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Serious Adverse Event
A serious adverse event 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.
If a serious and unexpected adverse event 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).
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the 
applicable product reference safety information. For JNJ-63723283 and daratumumab, the 
expectedness of an adverse event will be determined by whether or not it is listed within the 
Reference Safety Information in the Investigator's Brochures.
Adverse Event Associated With the Use of the Drug
An adverse event is considered associated with the use of the drug if the attribution is possible, 
probable, or very likely by the definitions listed in Section 12.1.2, Attribution Definitions.
12.1.2.
Attribution Definitions
Not Related
An adverse event that is not related to the use of the drug.
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Doubtful
An adverse event for which an alternative explanation is more likely, eg, concomitant drug(s), 
concomitant disease(s), or the relationship in time suggests that a causal relationship is unlikely.
Possible
An adverse event that might be due to the use of the drug. An alternative explanation, 
eg, concomitant drug(s), concomitant disease(s), is inconclusive. The relationship in time is 
reasonable; therefore, the causal relationship cannot be excluded.
Probable
An adverse event that might be due to the use of the drug. The relationship in time is suggestive 
(eg, confirmed by dechallenge). An alternative explanation is less likely, eg, concomitant 
drug(s), concomitant disease(s).
Very Likely
An adverse event that is listed as a possible adverse reaction and cannot be reasonably explained 
by an alternative explanation, eg, concomitant drug(s), concomitant disease(s). The relationship 
in time is very suggestive (eg, it is confirmed by dechallenge and rechallenge).
12.1.3.
Severity Criteria
The severity assessment for an adverse event or serious adverse event should be completed using
the NCI-CTCAE Version 4.03 Any adverse event or serious adverse event not listed in the 
NCI-CTCAE Version 4.03 will be graded according to investigator clinical judgment by using 
the standard grades as follows:
Grade 1 (Mild): Awareness of symptoms that are easily tolerated, causing minimal discomfort 
and not interfering with everyday activities
Grade 2 (Moderate): Sufficient discomfort is present to cause interference with normal activity
Grade 3 (Severe): Extreme distress, causing significant impairment of functioning or 
incapacitation. Prevents normal everyday activities
Grade 4: Life-threatening or disabling adverse event
Grade 5: Death related to the adverse event
The investigator should use clinical judgment in assessing the severity of events not directly 
experienced by the subject (eg, laboratory abnormalities).
12.2.
Special Reporting Situations
Safety events of interest on a Sponsor study drug that may require expedited reporting or safety 
evaluation include, but are not limited to:
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
Overdose of a Sponsor study drug

Suspected abuse/misuse of a Sponsor study drug

Accidental or occupational exposure to a Sponsor study drug

Medication error involving a Sponsor product (with or without subject/patient 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 serious adverse event should be recorded on the serious adverse event page 
of the CRF.
12.3.
Procedures
12.3.1.
All Adverse Events
All adverse events and special reporting situations will be reported from the time a signed and 
dated ICF is obtained until 30 days after the last dose of study drug, or until start of subsequent 
anticancer therapy or the subject withdraws consent for study participation, if earlier, which may 
include contact for follow-up of safety. For subjects who have received subsequent treatment 
with therapeutic intent for multiple myeloma during the adverse event reporting period, only 
adverse events that are considered to be possibly, probably, or definitely related to 
JNJ-63723283 or daratumumab need to be reported. Serious adverse events, including those 
spontaneously reported to the investigator, must be reported using the Serious Adverse Event 
Form. Serious adverse events considered by the investigator to be related to JNJ-63723283 or 
daratumumab should continue to be reported during the follow-up period. The Sponsor will 
evaluate any safety information that is spontaneously reported by an investigator beyond the time 
frame specified in the protocol.
Disease progression should not be recorded as an adverse event or serious adverse event term; 
instead, clinical sequelae resulting from disease progression/lack of efficacy will be reported if 
they fulfill the serious adverse event definition (refer to Section 12.1.1). Death should not be 
recorded as an adverse event or serious adverse event, but as the outcome of an adverse event. 
The adverse event that resulted in the death should be reported as a serious adverse event. All 
events that meet the definition of a serious adverse event will be reported as serious adverse 
events, regardless of whether they are protocol-specific assessments. Anticipated events will be 
recorded and reported as described in Attachment 9.
All adverse events, 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 adverse event to study therapy. All measures required for adverse event 
management must be recorded in the source document and reported according to Sponsor
instructions.
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The Sponsor assumes responsibility for appropriate reporting of adverse events to the regulatory 
authorities. 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 serious adverse events 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 drug caused a serious 
anticipated event, they will submit a safety report in narrative format to the investigators (and the 
head of the institute).
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.
Subjects (or their designees, if appropriate) will 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

Blood type and IAT (as described in Section 9.7)
12.3.1.1.
Daratumumab Monotherapy Period  
Non-serious adverse events will not be reported during the daratumumab monotherapy period.  
However, SAEs (including SPMs) must be reported continuously from time of ICF until EOT 
Visit or until the subject withdraws consent for study participation or until the subject starts 
subsequent anticancer therapy whichever occurs first. Beyond the EOT Visit reporting period 
after the last dose of study medication, information on SAEs, including SPMs, considered 
possibly, probably or definitely related to study drug will continue to be collected.
Serious Adverse Event reporting after the final database lock, established once Protocol 
Amendment 2 is implemented at all sites, will be limited to SAE reporting into the Sponsor’s 
global safety database, using SAE Form (paper form) faxed to Sponsor’s Local Operational 
Company/Local Safety Officer.
SAEs (see Section 12.3.2) should include information on study agent administration and 
concomitant medications associated with an SAE.
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12.3.2.
Serious Adverse Events
All serious adverse events occurring during the study must be reported to the appropriate 
Sponsor contact person by study-site personnel within 24 hours of their knowledge of the event.
Information regarding serious adverse events 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 within 24 hours. The initial and follow-up reports of a serious 
adverse event should be made by facsimile (fax).
All serious adverse events 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 
serious adverse event. 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 serious 
adverse event, except hospitalizations for the following:

If the subject has not experienced a significant medical event but is hospitalized overnight 
only for observation following infusion of JNJ-63723283 or daratumumab, then the 
hospitalization should not be reported as a serious adverse event. A standard procedure for 
protocol therapy administration will not be reported as a serious adverse event. In addition, 
hospitalization due to a longer than anticipated infusion time. Hospitalization or prolonged 
hospitalization for a complication of therapy administration will be reported as a serious 
adverse event.

Hospitalizations not intended to treat an acute illness or adverse event (eg, social reasons 
such as pending placement in long-term care facility)

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 serious adverse events. Any adverse event that results in a prolongation of the 
originally planned hospitalization is to be reported as a new serious adverse event.

The administration of blood or platelet transfusions. Hospitalization or prolonged 
hospitalization for a complication of such transfusion remains a reportable serious adverse 
event.
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
A procedure for protocol-related investigations (eg, surgery, scans, endoscopy, sampling for 
laboratory tests, bone marrow sampling, pharmacokinetic, or biomarker blood sampling). 
Hospitalization or prolonged hospitalization for a complication of such procedures remains a 
reportable serious adverse event.
12.3.3.
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 serious 
adverse events and must be reported using the Serious Adverse Event Form. Any subject who 
becomes pregnant during the study must be promptly withdrawn from the study and discontinue 
further study treatment.
Pregnancies in partners of male subjects included in the study will be reported as noted above,
because the effect of the study drugs on sperm is unknown.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
12.4.
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.
13.
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.
13.1.
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 serious adverse event, the study-site personnel must report the 
PQC to the Sponsor according to the serious adverse event reporting timelines (refer to 
Section 12.3.2, Serious Adverse Events). A sample of the suspected product should be 
maintained for further investigation if requested by the Sponsor.
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13.2.
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.
14.
STUDY DRUG INFORMATION
14.1.
Physical Description of Study Drug(s)
The daratumumab supplied for this study is a colorless to yellow liquid and sterile concentrate of 
20 mg/mL in a vial for IV administration. It will be manufactured and provided under the 
responsibility of the Sponsor. JNJ-63723283 is a colorless to yellow frozen liquid and sterile 
concentrate of 10 mg/mL in a vial for IV administration. Refer to the respective Investigator's 
Brochures for a list of excipients.
Manufacturing changes to the JNJ-63723283 drug substance and drug product used in this study 
are being proposed to support ongoing clinical development. During this study the drug product 
(DP-1) will be changed from a frozen liquid in vial, to a lyophilized drug product (DP-2). 
Additionally, a new cell line for the drug substance for DP-2 was developed to remove an 
unprocessed signal peptide variant; however, the host cell line and the core amino acid sequence 
of the JNJ-63723283 monoclonal antibody remains unchanged. Comprehensive nonclinical 
comparability studies will be performed to assess the biochemical, biophysical, and biological 
characteristics of DP-2 to ensure that there is no impact on subject safety and product quality. 
The drug substance and drug product manufacturing changes along with the results of the 
comparability studies will be submitted to the Health Authorities prior to the introduction of 
DP-2 into the clinical program. Part 1 of this study will start with DP-1. Once the comparability 
amendment is approved by the Health Authorities, DP-2 will be incorporated into the study, 
which is anticipated to be prior to initiating Part 3.
14.2.
Packaging
JNJ-63723283 is supplied in glass vials containing JNJ-63723283 at a concentration of 
10 mg/mL. Daratumumab is supplied in glass vials containing daratumumab at a concentration 
of 20 mg/mL.
14.3.
Labeling
Study drug labels will contain information to meet the applicable regulatory requirements. Each 
vial will contain a study-specific label with a unique identification number.
14.4.
Preparation, Handling, and Storage
JNJ-63723283 must be stored frozen -40C and protected from light. Daratumumab must be stored 
in the original carton in a refrigerator at controlled temperatures ranging from 2°C to 8°C,
protected from light and must not be frozen.
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Study drug must not be utilized after the expiry date printed on the label. JNJ-63723283 and 
daratumumab do not contain preservatives; therefore, any unused portion remaining in the vial 
must be discarded. 
Refer to the SIPPM and IPPI for additional guidance on study drug preparation, handling, and 
storage.
14.5.
Drug Accountability
The investigator is responsible for ensuring that all study drug received at the site is inventoried 
and accounted for throughout the study. The study drug administered to the subject must be 
documented on the drug accountability form. All study drug will be stored and disposed of 
according to the Sponsor's instructions. Study-site personnel must not combine contents of the 
study drug containers.
Study drug must be handled in strict accordance with the protocol and the container label, and 
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate 
environmental conditions. Unused study drug must be available for verification by the Sponsor's 
study site monitor during on-site monitoring visits. The return to the Sponsor of unused study 
drug will be documented on the drug return form. When the study site is an authorized 
destruction unit and study drug supplies are destroyed on-site, this must also be documented on 
the drug return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for drug accountability purposes.
Study drug should be dispensed under the supervision of the investigator or a qualified member 
of the study-site personnel, or by a hospital/clinic pharmacist. Study drug will be administered
only to subjects participating in the study. Returned study drug must not be dispensed again, 
even to the same subject. Study drug may not be relabeled or reassigned for use by other 
subjects. The investigator agrees neither to dispense the study drug from, nor store it at, any site 
other than the study sites agreed upon with the Sponsor.
15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Investigator’s Brochures for JNJ-63723283 and daratumumab

Site Investigational Product Procedures Manual (SIPPM)

Investigational Product Preparation Instructions (IPPI)

Laboratory manual

IWRS manual

eCRF completion guidelines
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
Sample ICF

Subject identification wallet card, including space for blood group/type and IAT result

Subject diaries may be used for recording predose and postdose medications administered at 
home for the prevention of IRRs

PRO questionnaires

Other manuals and guidance documents as needed
16.
ETHICAL ASPECTS
16.1.
Study-Specific Design Considerations
This is the first clinical evaluation of JNJ-63723283 in combination with daratumumab in 
multiple myeloma subjects; hence, the benefits and risks of the combination in this population 
are unknown. However, as described in Section 1, subjects in clinical studies of JNJ-63723283
and daratumumab, as single agents, have shown safety issues including irAEs and IRRs, which
will be monitored and managed with rapid intervention. Subjects will be closely monitored 
throughout the study, as discussed throughout this protocol, for both safety and clinical benefit. 
Subjects in both arms will receive daratumumab, which is approved for this study population in 
many regions (see Section 1.3 for an overview of the efficacy and safety results). As discussed in 
Section 1.4, based on the known data and the mechanism of action of both study drugs, there is 
adequate justification, including significant unmet clinical need, for evaluating these drugs in 
combination for the treatment of multiple myeloma in subjects who are eligible for this study.
Daratumumab leads to the elimination of highly immunosuppressive subsets of CD38+ Tregs, 
CD38+ MDSCs, and CD38+ Bregs and induces clonal T cell expansion (Krejcik 2016).17 This 
shift away from an immunosuppressive environment may lead to the generation of protective 
immune responses, which may be further potentiated by PD-1 blockade with JNJ-63723283, 
potentially leading to improved clinical responses.
Additionally, all subjects will undergo periodic disease assessments to monitor the underlying 
disease. The frequency of evaluations is similar to standard practice for patients outside of 
clinical trials and the overall risk is low. Subjects will have pre- and posttreatment bone marrow 
aspirations. In general, these procedures are routinely performed during a subject’s diagnostic 
workup and follow-up care. Although bone marrow aspirate collection is associated with risk,
the complication rate for these procedures is low. The data obtained from this procedure will 
generate valuable scientific data on the pharmacodynamic effect of the combination of these 
study drugs in multiple myeloma subjects.
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 informed 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 adverse events of the study, and provide their consent voluntarily will be 
enrolled.
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The blood volume collection for a subject is estimated at approximately 35 mL/month. This blood 
volume is not burdensome and falls within the normal range of a single blood donation.
16.2.
Regulatory Ethics Compliance
16.2.1.
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current 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.
16.2.2.
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

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.
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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 Brochures and amendments/addenda

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB
(at least annually)

Reports of adverse events 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.
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).
16.2.3.
Informed Consent
Each subject or a legally acceptable 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 
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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 acceptable 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 acceptable 
representative is authorizing such access, which includes permission to obtain information about 
his or her survival status. It 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 subject or legally acceptable 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 acceptable 
representative's personally dated signature. After having obtained the consent, a copy of the ICF
must be given to the subject.
If the subject or legally acceptable 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 acceptable representative is obtained.
When prior consent of the subject is not possible and the subject's legally acceptable 
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 acceptable representative must be informed about the study as soon as possible 
and give consent to continue.
16.2.4.
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 
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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 acceptable 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 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 biomarker 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.
16.2.5.
Long-Term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years (or according to local 
regulations) for additional research. Samples will only be used to understand daratumumab and 
JNJ-63723283, to understand multiple myeloma, to understand differential drug responders, and 
to develop tests/assays related daratumumab and JNJ-63723283, and multiple myeloma. The 
research may begin at any time during the study or the post-study storage period.
Stored samples will be coded throughout the sample storage and analysis process and will not be
labeled with personal identifiers. Subjects may withdraw their consent for their samples to be 
stored for research (refer to Section 10.2, Withdrawal from the Use of Samples in Future 
Research).
16.2.6.
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
16.1, Study-Specific Design 
Considerations.
17.
ADMINISTRATIVE REQUIREMENTS
17.1.
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 
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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) involves 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.
17.2.
Regulatory Documentation
17.2.1.
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.
17.2.2.
Required Prestudy Documentation
The following documents must be provided to the Sponsor before shipment of study drug to the 
study site:

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
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
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
17.3.
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 date of birth. In cases where the subject is not enrolled or randomized into the study, the date 
seen and date of birth will be used.
The investigator must also complete a subject screening log, which reports on all subjects who 
were seen to determine eligibility for inclusion in the study.
17.4.
Source Documentation
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 all adverse events and follow-up of adverse events; concomitant medication; 
drug 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.
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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 minimum source documentation requirements for Section 4.1, Inclusion Criteria and 
Section 4.2, Exclusion Criteria that specify a need for documented medical history are as 
follows:

Referral letter from treating physician or

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 electronic source 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 the electronic source system is utilized, references made to 
the CRF in the protocol include the electronic source system but information collected through 
the electronic source system may not be limited to that found in the CRF. Data in this system 
may be considered source documentation.
17.5.
Case Report Form Completion
Electronic Data Capture (eDC) will be used for this study. Case report forms (CRF) are provided 
for each subject in electronic format. Study site personnel must log in eDC via a secure manner -
personal password. The individual password must keep confidential for personal use. 
The study data will be transcribed by study-site personnel from the source documents onto an 
CRF according to CRF completion guideline provided by the Sponsor. Data must be entered into
CRFs 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. 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 documentation. 
All subjective measurements (eg, pain scale information or other questionnaires) shall be 
completed by the same individual who made the initial baseline determinations whenever 
possible. The investigator must verify that all data entries in the CRFs are accurate and correct.
All CRF entries, corrections, and alterations must be made by the investigator or other authorized 
study-site personnel. If necessary, queries will be generated in the eDC tool. The investigator or 
study-site personnel must address the queries and update the CRF if applicable.
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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.
Daratumumab Monotherapy Period:
Data collection will be limited to SAE reporting into the Sponsor’s global safety database.
No data will be entered in eCRF once Protocol Amendment 2 is implemented at a site. Once 
Protocol Amendment 2 is implemented at all sites, clinical database can be locked.
17.6.
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.
17.7.
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.
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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.
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.
17.8.
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 the data entered into the CRF
with the source documents
(eg, hospital/clinic/physician’s office medical records). 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.
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.
Daratumumab Monotherapy Period:
Monitoring will be limited to on-site monitoring visits and remote contacts for the verification 
and follow-up of SAEs reported to the Sponsor.
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17.9.
Study Completion/Termination
17.9.1.
Study Completion/End of Study
The end of the study in Part 1 and Part 2 is anticipated to be approximately 6 to 12 months after 
the last patient has been enrolled (last patient in) and the study may be extended to allow for 
follow-up of subjects. The end of the study in Part 3 will occur when 205 deaths have been 
documented. 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.
17.9.1.1.
Study Completion for the Daratumumab Monotherapy Period
Study completion in Part 1 and Part 2 will occur when the last patient has discontinued from 
study treatment and completed the End of Treatment Visit. Part 3 is no longer applicable for this 
study.  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.
17.9.2.
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
17.10. 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.
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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.
17.11. Use of Information and Publication
All information, including but not limited to information regarding JNJ-63723283 and 
daratumumab or the Sponsor's operations (eg, patent application, formulas, manufacturing 
processes, basic scientific data, prior clinical data, formulation information) supplied by the 
Sponsor to the investigator and not previously published, and any data, including exploratory
biomarker research data, generated as a result of this study, are considered confidential and 
remain the sole property of the Sponsor. The investigator agrees to maintain this information in 
confidence and use this information only to accomplish this study, and will not use it for other 
purposes without the Sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the 
Sponsor in connection with the continued development of JNJ-63723283 and daratumumab, and 
thus may be disclosed as required to other clinical investigators or regulatory agencies. To permit 
the information derived from the clinical studies to be used, the investigator is obligated to 
provide the Sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the Sponsor and 
will contain data from all study sites that participated in the study as per protocol. Recruitment 
performance or specific expertise related to the nature and the key assessment parameters of the 
study will be used to determine a coordinating investigator. Results of exploratory biomarker
analyses performed after the Clinical Study Report has been issued will be reported in a separate 
report and will not require a revision of the Clinical Study Report. Study subject identifiers will 
not be used in publication of results. Any work created in connection with performance of the 
study and contained in the data that can benefit from copyright protection (except any 
publication by the investigator as provided for below) shall be the property of the Sponsor as
author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors guidelines, the Sponsor shall have the right to publish such primary (multicenter) data 
and information without approval from the investigator. The investigator has the right to publish 
study site-specific data after the primary data are published. If an investigator wishes to publish 
information from the study, a copy of the manuscript must be provided to the Sponsor for review 
at least 60 days before submission for publication or presentation. Expedited reviews will be 
arranged for abstracts, poster presentations, or other materials. If requested by the Sponsor in 
writing, the investigator will withhold such publication for up to an additional 60 days to allow 
for filing of a patent application. In the event that issues arise regarding scientific integrity or 
regulatory compliance, the Sponsor will review these issues with the investigator. The Sponsor
will not mandate modifications to scientific content and does not have the right to suppress 
information. For multicenter study designs and substudy approaches, secondary results generally 
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should not be published before the primary endpoints of a study have been published. Similarly, 
investigators will recognize the integrity of a multicenter study by not submitting for publication 
data derived from the individual study site until the combined results from the completed study
have been submitted for publication, within 12 months of the availability of the final data (tables, 
listings, graphs), or the Sponsor confirms there will be no multicenter study publication. 
Authorship of publications resulting from this study will be based on the guidelines on 
authorship, such as those described in the Uniform Requirements for Manuscripts Submitted to 
Biomedical Journals, which state that the named authors must have made a significant 
contribution to the design of the study or analysis and interpretation of the data, provided critical 
review of the paper, and given final approval of the final version.
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.
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Badros AZ, Kocoglu MH, Ma N, et al. A Phase II study of anti PD-1 antibody pembrolizumab, pomalidomide 
and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Blood. 2015;126:520-31.
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Bajaj, G et al. Model-Based Population Pharmacokinetic Analysis of Nivolumab in Patients With Solid 
Tumors.” CPT: Pharmacometrics & Systems Pharmacology 6.1 (2017): 58–66. PMC. Web. 21 June 2017.
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Benson DM Jr, Bakan CE, Mishra A et al. The PD-1/PD-L1 axis modulates the natural killer cell versus 
multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood. 
2010;116(13):2286-2294.
5.
Burtis C, Ashwood E, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 3rd Edition. 
Philadelphia, PA: WB Saunders, 1999; p.1400.
6.
Center for Drug Evaluation and Research, FDA. Clinical Pharmacology and Biopharmaceutics Review 125554 
for Opdivo (nivolumab), 2014. 
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/125554Orig1s000ClinPharmR.pdf. Accessed 
12 July 2016.
7.
Center for Drug Evaluation and Research, FDA. Clinical Pharmacology and Biopharmaceutics Review 125514 
for Keytruda (pembrolizumab), 2014. 
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/125514Orig1s000ClinPharmR.pdf. Accessed 
12 July 2016.
8.
Chapuy CI, Nicholoson RT, Aguad MD et al. Resolving the daratumumab interference with blood 
compatibility testing. Transfusion. 2015;55:1545-1554.
9.
de Weers M, Tai YT, van der Veer MS, et al. Daratumumab, a novel therapeutic human CD38 monoclonal 
antibody, induces killing of multiple myeloma and other hematological tumors. J Immunology. 
2011;186(3):1840-1848.
10.
Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. 
Leukemia. 2006;20(9):1467-1473.
11.
Freshwater, Tomoko et al. Evaluation of Dosing Strategy for Pembrolizumab for Oncology Indications. J 
Immun C. 2017:43. PMC. Web. 22 June 2017.
12.
Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of 
EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727-1736.
13.
Horenstein, AL, Chillemi A, Zaccarello G, et al. A CD38/CD203a/CD73 ectoenzymatic pathway independent 
of CD39 drives a novel adenosinergic loop in human T lymphocytes. Oncoimmunology. 2013;2:e26246.
14.
Ipilimumab US Package Insert. Princeton, NJ: Bristol-Myers Squibb. October 2015.
15.
Jansen JM, Boross P, Overdijk MB, et al. Daratumumab, a human CD38 antibody induces apoptosis of 
myeloma tumor cells via fc receptor-mediated crosslinking. Blood. 2012;120:2974.
16.
Jung S-H, Lee H-J, Vo M-C, et al. Immunotherapy for the treatment of multiple myeloma. Crit Rev Onc/Hem. 
2017;111:87-93.
17.
Krejcik J, Casneuf T, Nijhof I, et al. Daratumumab depletes CD38+ immune-regulatory cells, promotes T-cell 
expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016;128(3):384-394.
18.
Kumar S, Paiva B, Anderson KC et al. International Myeloma Working Group consensus criteria for response 
and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328-46. 
19.
Lesokhin AM, Ansell SM, Armand P, et al. Nivolumab in patients with relapsed or refractory hematologic 
malignancy: Preliminary results of a Phase Ib study. J Clin Oncol. 2016;34(23):2698-2704.
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20.
Levey AS, Coresh J, Greene T, Stevens LA, Zhang Y. Using Standardized Serum Creatinine Values in the 
Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate. Ann Int Med. 
2006;145:247-55.
21.
Lokhorst HM, Plesner T, Laubach JP et al. Targeting CD38 with daratumumab monotherapy in multiple 
myeloma. N Engl J Med. 2015;373(13):1207-1219.
22.
Lonial S, Weiss BM, Usmani SZ et al. Daratumumab monotherapy in patients with treatment-refractory 
multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016;387(10027):1551-1560.
23.
Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for 
diagnosis, treatment, and follow-up. Ann Oncol. 2017;1-11
24.
NCCN Guidelines. Multiple myeloma. Version 3.2017. Available at: 
https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 15 May 2017.
25.
Nivolumab Summary of Product Characteristics. Uxbridge, United Kingdom: Bristol-Myers Squibb Pharma 
EEIG.
26.
Nivolumab US Package Insert. Princeton, NJ: Bristol-Myers Squibb Company; May 2016.
27.
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.
28.
Overdijk MB, Verploegen S, Bögels M, et al. Antibody-mediated phagocytosis contributes to the anti-tumor 
activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 
2015;7(2):311-321.
29.
Pembrolizumab Summary of Product Characteristics. Hertfordshire, United Kingdom: Merck Sharp & Dohme 
Limited.
30.
Pembrolizumab US Package Insert. Whitehouse Station, NJ: Merck Sharp & Dohme Corp., a subsidiary of 
Merck & Co., Inc.; December 2015.
31.
Phipps C, Chen Y, Gopalakrishnan S, Tan D. Daratumumab and its potential in the treatment of multiple 
myeloma:  overview of  the preclinical and clinical development. Ther Adv Hematol. 2015;6(3): 120–127.
32.
Rajkumar SV, Harousseau JL, Durie B, et al. Consensus recommendations for the uniform reporting of clinical 
trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117(18):4691-4695.
33.
Rajkumar SV, Richardson P, San Miguel JF. Guidelines for determination of the number of prior lines of 
therapy in multiple myeloma. Blood. 2015;126(7):921-922.
34.
Ray A, Das DS, Song Y, et al. Targeting PD1-PDL1 immune checkpoint in plasmacytoid dendritic cell 
interaction with T cells, natural killer cells and multiple myeloma cells. Leukemia. 2015;29(6):1441-1444.
35.
Rosenblatt J, Avigan D. Targeting the PD-1/PD-L1 axis in multiple myeloma: a dream or a reality? Blood. 
2017;129(3):275-279.
36.
San Miguel J, Mateos M-V, Shah JJ, et al. Pembrolizumab in combination with lenalidomide and low-dose 
dexamethasone for relapsed/refractory multiple myeloma (RRMM): Keynote-023. Blood. 2015;126:505-518.
37.
Tamura H, Ishibashi M, Yamashita T, Tanosaki S, Okuyama N, Kondo A, et al. Marrow stromal cells induce 
B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma. Leukemia. 
2013;27(2):464–472.
38.
Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of antiPD-1 antibody in 
cancer. N Engl J Med. 2012;366:24432454.
39.
Wisloff F, Hjorth M, Westin J. Measurement of health-related quality of life in multiple myeloma. The Nordic 
Myeloma Study Group. Br J Haematol. 1996;92(3):604-613.
40.
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(1):29-37.
41.
Yousef S, Marvin J, Steinbach M et al. Immunomodulatory molecule PD-L1 is expressed on malignant plasma 
cells and myeloma-propagating pre-plasma cells in the bone marrow of multiple myeloma patients. Blood 
Cancer J. 2015;5:e285. 
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Attachment 1: PREINFUSION Antihistamine Medications (DARATUMUMAB)
The following antihistamines may be used predose, before daratumumab IV infusion (including, but not 
limited to):

Diphenhydramine

Cetirizine

Fexofenadine

Loratadine

Clemastine

Dexchlorpheniramine

Promethazine*
       * The IV use of promethazine should be avoided.
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Attachment 2: 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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Attachment 3: Modified Diet in Renal Disease Formula
NOTE:

These formulas estimate GFR in mL/min/1.73 m2. No additional correction for body surface area 
is necessary.

The unit for age is years.

Different formulas are listed depending on the unit of standardized serum creatinine used.
For standardized serum creatinine (SCr) in mg/dL, the estimated glomerular filtration rate (eGFR) is: 
eGFR = 175 x [standardized SCr (mg⁄dL)]-1.154 x age-0.203 x 1.212if black x 0.742if female
Creatinine levels in µmol/L can be converted to mg/dL by dividing them by 88.4.
creatinine (mg⁄dL) =
creatinine (µmol)⁄L
88.4
Alternatively, for standardized serum creatinine (SCr) in µmol/L, the estimated glomerular filtration rate 
(eGFR) is:
eGFR = 30,849 x [standardized SCr (µmol)/L)]-1.154) x age -0.203 x 1.212if black x 0.742if female
Source: Levey 200620
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Attachment 4: 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 19995
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Attachment 5: ECOG Performance Status Scale
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 selfcare but unable to carry out any work 
activities. Up and about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of 
waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or 
chair
5
Dead
Source: Oken 198227
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Attachment 6: Prior Lines of Therapy for Multiple Myeloma
A line of therapy is defined as one or more cycles of a planned treatment program. This may consist of 
one or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of 
treatments administered in a planned manner. For example, a planned treatment approach of induction 
therapy followed by autologous stem cell transplantation, followed by maintenance is considered one line 
of therapy. A new line of therapy starts when a planned course of therapy is modified to include other 
treatment agents (alone or in combination) as a result of disease progression, relapse, or toxicity. A new 
line of therapy also starts when a planned period of observation off therapy is interrupted by a need for 
additional treatment for the disease. 
Source: Rajkumar 201533
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Attachment 7: Interpretation of Daratumumab Interference Reflex Assay (DIRA)
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 for 
subjects who are randomly assigned to the daratumumab, lenalidomide, and dexamethasone group. 
Implementation: To mitigate this interference, the Sponsor has developed the Daratumumab Interference 
Reflex Assay (DIRA) to distinguish a positive SPEP/IFE due to the presence of daratumumab versus the 
presence of the underlying (endogenous) monoclonal protein.a The DIRA test will be sent automatically 
to the central laboratory if 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 DIRA 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.
Interpretation of results:
The results will be available to the investigator via the central laboratory interface and will be reported as 
either “POSITIVE” or “NEGATIVE”.
POSITIVE: indicates that the sample is still positive for underlying (endogenous) monoclonal 
myeloma protein. Therefore, this patient is not in a complete response (CR), because the CR 
response criteria require a negative SPEP and serum IFE.
NEGATIVE: indicates that the sample is negative for underlying (endogenous) monoclonal 
myeloma protein. This subject may be in a CR if the other criteria for CR (including negative bone 
marrow aspiration/biopsy) are achieved.
                                                
a McCudden C, Axel A, Slaets D, et al. Assessing clinical response in multiple myeloma (MM) patients treated with 
monoclonal antibodies (mAbs): Validation of a daratumumab IFE reflex assay (DIRA) to distinguish malignant 
M-protein from therapeutic antibody. J Clin Oncol. 2015 (suppl; abstr 8590).
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Attachment 8: ASTHMA Guidelines
Components of Severity
Classification of Asthma Severity
Intermittent
Persistent
Mild
Moderate
Severe
0-4
yrs
5-11 yrs
12 + yrs
0-4 yrs
5-11 yrs 12 + yrs
0-4 yrs
5-11 yrs 12 + yrs
0-4 yrs
5-11 yrs 12 + yrs
Impairment
Normal 
FEV1/FVC :
8-19 yr 85%
20-39 yr 80%
40-59 yr 75%
60-80 yr 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
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
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
for persistent asthma
≥ 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
for persistent asthma
≥ 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 
for persistent asthma
≥ 2/year
Relative 
annual risk 
may be 
related to 
FEV1.
≥ 2/year
Relative 
annual risk
may be
related
to FEV1.
Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time for patients in any severity category.
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Recommended Step
for
Initiating Treatment
Step 1
Step 2
Step 3 and 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 3 and 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 asthma control that is achieved.
0-4 years: 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.
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
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Recommended Action for
Treatment
• Maintain current step
• Regular follow-up every 
1-6 months
• Consider step down if well 
controlled for at least 3 
months
Step up 1 
step
Step up at 
least 1 step
• Step up 1 
step
• Reevaluate
in 2-6 
weeks
• For side 
effects, 
consider 
alternative 
treatment 
options
• Consider short course
of oral steroids
• Step up 1-2 steps
• Consider 
short course 
of oral 
steroids
• Step up 1-2 
steps
• Reevaluate 
in 2 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.
• 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.
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Attachment 9: Anticipated Events
Anticipated Event
An anticipated event is an adverse event (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: 

Anaemia

Bleeding

Bone diseases

Hypercalcaemia

Hyperuricemia

Hyperviscosity syndrome

Infection

Neutropenia

Renal failure or insufficiency

Thrombocytopenia
Given the mechanism of action of JNJ-63723283, events associated with immune-mediated adverse 
events will also be considered as anticipated events, including:

Pneumonitis

Colitis

Endocrinopathies (diabetes mellitus, pancreatitis, adrenal insufficiency, or hyperthyroidism)

Hepatitis 

Transaminitis Grade 2 (AST or ALT > 3xULN and bilirubin > 2xULN, or AST/ALT 
> 10xULN) 

Systemic lupus erythematosus

Neurologic: 
Guillain-Barré 
syndrome, 
myasthenia 
gravis/myasthenic 
syndrome, 
meningoencephalitis 

Nephritis

Events suggestive of hypersensitivity, cytokine release, influenza-like illness, systemic 
inflammatory response syndrome, systemic immune activation, infusion-related reactions
syndrome
Because this is the first study of the combination of JNJ-63723283 and daratumumab, other adverse 
events cannot be anticipated.
Reporting of Anticipated Events
All adverse events will be recorded in the CRF regardless of whether considered to be anticipated events
and will be reported to the Sponsor as described in Section 12.3.1, All Adverse Events. Any anticipated
event that meets serious adverse event criteria will be reported to the Sponsor as described in 
Section 12.3.2, Serious Adverse Events. These anticipated events are exempt from expedited reporting as 
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individual single cases to Health Authorities. However, if based on an aggregate review, it is determined 
that an anticipated event is possibly related to study drug, the Sponsor will report these events in an 
expedited manner.
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 (ASMP).
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Attachment 10:
Patient-Reported Outcomes Questionnaires
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 
30 (EORTC-QLQ-C30)
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European Quality of Life 5 Dimensions Questionnaire (EQ-5D-5L)
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Attachment 11:
Daratumumab Monotherapy Period For Subjects No Longer Receiving JNJ-
63723283 In 
Combination With Daratumumab
Overall Design for Daratumumab Monotherapy Period
Each cycle is 28 days, and administration of daratumumab is to occur weekly for Cycles 1 and 2, 
every other week for Cycles 3 to 6, and every 4 weeks for Cycles 7 and onwards until disease 
progression, pregnancy, unacceptable toxicity, loss of follow-up, withdrawal of consent, or 
death. Scheduled assessments to be performed during the Daratumumab Monotherapy Period for 
Subjects No Longer Receiving JNJ-63723283 in Combination with Daratumumab are outlined in 
the Time and Events Schedule in Table 24.
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Table 24:
Time and Events Schedule –Daratumumab Monotherapy Period for Subjects No Longer Receiving JNJ-63723283 in Combination with 
Daratumumab
Treatment Phase
(28 day cycles)
Cycles 1 and 2
Cycles 3 to 6
Cycles 7+
EOT a
Study Day  
1 
8 
15
22 
1
15
1
Post-Treatment Week 4 
(±7 days)
Procedures/Assessments Study procedures may occur within 3 days of Day 1
Informed consent
Subjects must sign the informed consent form before any study-specific procedures are performed.
Physical Examination
Symptom-directed physical examination only
Dosing
Daratumumab 16 mg/kg dosing (IV)
X 
X 
X 
X 
X 
X 
X 
Preinfusion and postinfusion medicationsb
X 
X 
X 
X 
X 
X 
X 
Weight
X
X
X
X
Vital Signs (immediately before start and 
at end of each daratumumab infusion)
X 
X 
X 
X 
X 
X 
X 
X
Laboratory Assessmentsc
Urine or serum pregnancy test (women of 
childbearing potential only)
Only if clinically indicated. 
Biochemistry
X
X
X
X
Hematology
X 
X
X
X
X
X
X
X
Investigator assessment of responsec
   SPEP and 24-hour UPEPd, Serum 
calcium corrected for albumind, Serum 
FLC & serum/urine immunofixationd, 
Bone marrow aspirate/bone marrow biopsy 
Local assessments of disease response as per standard of care until PD
  Skeletal survey/Assessment of lytic bone 
disease
As clinically indicated and per the local standard of care for imaging (X-ray, CT, or MRI may be used).
  Assess extramedullary plasmacytomas
As per local standard of care
Ongoing Subject Review
SAEs, including SPMs 
Continuous from time of ICF until EOT Visit or until the subject withdraws consent for study participation 
or until the subject starts subsequent anticancer therapye whichever occurs first. Beyond the EOT Visit
reporting period after the last dose of study medication, information on SAEs, including SPMs, considered 
possibly, probably or definitely related to study drug will continue to be collected.
Abbreviations: EOT=End-of-Treatment; FLC=free light chain; ICF=informed consent form; MRI=magnetic resonance imaging; SAE=serious adverse event; SPEP=Serum 
M-protein quantitation by electrophoresis; UPEP=urine M-protein quantitation by electrophoresis;
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a) To occur 4 weeks (±7 days) after the last dose of study drug or as soon as possible before the start of subsequent therapy.
b) Refer to Section 6.4.1.2 and Section 6.4.1.3 for additional information.  
c) Evaluations will be conducted at the local laboratory and responses will be interpreted by the investigator.
d) Disease assessments SPEP, UPEP, and serum calcium corrected for albumin should be collected at an interval consistent with the investigator’s standard of care. For 
guidance, the Sponsor recommends (but does not require) local laboratory assessments to be conducted every cycle for the first 18 months after initiating 
daratumumab monotherapy, and every other month thereafter. 
e) For subjects who have received additional treatment with therapeutic intent for multiple myeloma during the SAE reporting period, only SAEs that are considered to 
be possibly, probably, or definitely related to daratumumab must be reported (unless the subject has been withdrawn from the study).
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INVESTIGATOR AGREEMENT
NCT03357952

SAP_000.pdf: 
1
Approved, Date: 25 September 2018
Janssen Research & Development
Biostatistics and Programming
Statistical Analysis Plan/Data Presentation Specifications for Clinical Study Report
A Randomized, Open-label, Multicenter, Multiphase Study of JNJ-63723283, an Anti-PD-1
Monoclonal Antibody, Administered in Combination with Daratumumab, Compared with
Daratumumab Alone in Subjects with Relapsed or Refractory Multiple Myeloma
Protocol 54767414MMY2036; Phase 2/3
JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Date:
25 September 2018
Status:
Approved
Date:
25 September 2018
Prepared by:
Janssen Research & Development, LLC 
Document No.: EDMS-ERI-167849379:2.0
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed 
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
2
Approved, Date: 25 September 2018
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 2
AMENDMENT HISTORY.............................................................................................................................. 3
1.
ANALYSIS DETAILS .......................................................................................................................... 4
1.1.
Overview of Study Design................................................................................................................ 4
1.2.
Analysis Sets.................................................................................................................................... 5
1.3.
Treatment Groups............................................................................................................................ 5
1.4.
End of Follow-up and Duration of Follow-up.................................................................................... 5
1.5.
Subject information .......................................................................................................................... 5
1.6.
Efficacy............................................................................................................................................. 7
1.7.
Safety ............................................................................................................................................... 8
1.8.
Pharmacokinetics/Immunogenicity .................................................................................................. 8
1.9.
Biomarker......................................................................................................................................... 9
2.
LIST OF PLANNED OUTPUT........................................................................................................... 10
3.
COLUMN LAYOUTS FOR TABLES................................................................................................. 15
4.
MOCK LAYOUTS.............................................................................................................................. 16
5.
NARRATIVE CRITERION ................................................................................................................. 49
6.
PROGRAMMING CODE FOR STATISTICAL PROCEDURES (IF REQUIRED)............................. 49
7.
LIST OF POST HOC OUTPUT (IF REQUIRED)............................................................................... 49
8.
ADDITIONAL ANALYSIS/DEVIATION RULES................................................................................ 49
REFERENCES............................................................................................................................................ 50
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: Demographic Variables................................................................................................................... 6
Table 2: Baseline Disease Characteristics ................................................................................................... 6
FIGURES
Figure 1:
Study Scheme............................................................................................................................. 4
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JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
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Approved, Date: 25 September 2018
AMENDMENT HISTORY
The statistical analysis plan (SAP) has been revised and description of the changes and the 
section affected are provided below.
Amendment -1 (07Sep2018)
Summary of change:
1. Included biomarker analysis 
Applicable Section
Description of Change
1.9 Biomarker
Since biomarker analysis would be included in the final CSR, 
this new section for biomarker analysis was added in this SAP.
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Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
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Approved, Date: 25 September 2018
1.
ANALYSIS DETAILS
This document contains definitions of analysis sets, derived variables and planned data 
presentation specifications
which will be used in
clinical study report of study 
54767414MMY2036. The analysis will be performed after final data base lock when protocol 
54767414MMY2036, Amendment 2 is approved and implemented at all sites.
1.1.
Overview of Study Design
This is a randomized, open-label, multicenter, multiphase study assessing the efficacy and safety 
of JNJ-63723283 (an anti-PD-1 monoclonal antibody) in combination with daratumumab 
compared with daratumumab alone in subjects with multiple myeloma who have received at
least 3 prior lines of therapy including a PI and an IMiD or whose disease is double refractory to 
both a PI and an IMiD. A diagram of the study design is provided in Figure 1.
Figure 1:
Study Scheme
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JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
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Approved, Date: 25 September 2018
As of 25 May 2018, the Sponsor terminated further enrollment into this study and subjects in 
Screening were deemed Screen Failures and were not further randomized into the study. Subjects 
continuing on study will receive daratumumab monotherapy starting 25 May 2018. Part 3 is no 
longer applicable for this study.  
1.2.
Analysis Sets
Safety analysis set: includes all subjects who have received at least 1 dose of study agent 
(JNJ-63723283 or daratumumab, partial or complete) in either Safety Run-in Part 1 or Part 2
of the study. This analysis set will be used for below analyses.
Pharmacokinetics (PK)-evaluable analysis set: includes all subjects who have received at 
least 1 dose of daratumumab or JNJ-63723283 and have at least 1 post-infusion sample in 
Safety Run-in Part 1 of the study.
Immunogenicity analysis set: include all subjects who have received at least 1 dose of 
JNJ-63723283 or daratumumab and have appropriate serum samples for detection of 
antibodies to JNJ-63723283 or daratumumab (i.e., subjects with at least 1 sample obtained 
after their first dose of JNJ-63723283 or daratumumab) in Safety Run-in Part 1 of the study.
1.3.
Treatment Groups
The treatment groups are Safety Run-in (JNJ-63723283+daratumumab); and Arm A 
(daratumumab alone) and Arm B (JNJ-63723283+ daratumumab) for Part 2.
1.4.
End of Follow-up and Duration of Follow-up
The end of follow-up is the date of death for subjects who died. For those who are still alive, the 
end of follow-up  is  defined  as  the  maximum  date  of  the  following  study  evaluations:  labs  
(hematology, chemistry, serology, coagulation, thyroid function ), adverse events, vital signs, 
ECOG performance status, study drug administration, 12-lead ECG, pre-infusion medications, 
post-infusion medications, concomitant medications, subsequent anti-cancer treatment, tumor 
assessment, clinical events/disease response per investigator and date of last known to be alive.
Duration of follow-up (in months) equals the end of follow-up minus the first dosing date plus 1 
for Part 1 and equals the end of follow-up minus the randomization date plus 1 for Part 2, 
divided by 365.25/12.
Study duration of follow-up will be summarized by treatment group and overall for safety 
Analysis Set.
1.5.
Subject information
The distribution of subjects by region and country will be presented for safety analysis set by 
treatment group and overall.
Demographics and baseline characteristics: Demographics and baseline characteristics will 
be summarized for safety analysis set by treatment group and overall. A listing of subject 
demographic and baseline characteristics will be provided as well. Table 1 and Table 2
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Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
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respectively present a list of the demographic variables and baseline disease characteristics 
that will be summarized by treatment group and overall.
Table 1: Demographic Variables
Continuous Variables:
Summary Type
Age (years)
Descriptive statistics (N, mean, 
standard deviation [STD], median 
and range [minimum and 
maximum]).
Weight (kg)
Height (cm)
Categorical Variables
Age (<65 years, ≥65 years and <75 years, ≥75 years)
N, frequency distribution with the 
number and percentage of 
subjects in each category.
Weight (≤65kg, >65kg and ≤85kg, >85kg)
Sex (male, female)
Race (American Indian or Alaska Native, Asian, Black or African 
American, Native Hawaiian or other Pacific Islander, White, 
Multiple a, not reported)
Ethnicity (Hispanic or Latino, not Hispanic or Latino, not reported)
Baseline ECOG (0, 1, 2)
                   a If multiple race categories are indicated, the Race is recorded as 'Multiple'
Table 2: Baseline Disease Characteristics
Continuous Variables:
Summary Type
Time since MM diagnosis (years)
Descriptive statistics (N, mean, 
standard deviation [STD], median 
and range [minimum and 
maximum]).
Categorical Variables
Type of multiple myeloma (IgG, IgA, IgM, IgD, IgE, light 
chain only [kappa and lambda], biclonal, negative 
immunofixation, not detected)
N, frequency distribution with the 
number and percentage of subjects 
in each category.
Type of measurable disease (serum measurable only [IgG, IgA 
and Other], both serum and urine measurable, urine measurable 
only, serum FLC measurable)
ISS staging at screening by central laboratory assessment (I, II,
III)
Number of lytic bone lesions (None, 1-3, 4-10, more than
10)
Presence of diffuse myeloma-related osteopenia (Yes, No)
Number of extramedullary plasmacytomas (0, ≥1)
Bone marrow % plasma cells (<10, 10 – 30, >30)
Status of cytogenetic abnormality (standard-risk, high-risk 
[Del17p, T(4;14), T(14;16)] ),
ECG overall conclusion (normal, abnormal [clinically 
significant, not clinically significant, not evaluable)

Subject Disposition: The number of subjects in the following disposition categories will be 
summarized throughout the study for safety population by treatment group and overall: 
subjects who discontinued study treatment, reasons for discontinuation of study treatment, 
subjects who terminated study prematurely, and reasons for termination of study. Listings of 
subjects will be provided for the following categories: subjects who discontinued study 
treatment, and subjects who terminated study prematurely.
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Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
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
Medical history: Medical history collected at baseline or screening visit will be
summarized by system-organ class and preferred term for each treatment group and overall.

Prior and concomitant medication: Summaries of concomitant medications will be 
presented by therapeutic class, pharmacologic class and preferred term by treatment group 
and overall for safety population. A summary of prior therapies (systemic therapy, 
radiotherapy, or cancer-related surgery/ procedure) will be provided by treatment group. 
Specifically, the number of prior lines of therapy will be calculated according to IWMG 
consensus guidelines (Durie 2006; Kumar 2016; Rajkumar 2011) 1,2,3 and summarized by the 
following categories: ≤ 3 and > 3 through frequency and descriptive statistics. Subjects with 
prior cancer-related surgery/procedure and with prior radiotherapy will be listed for safety 
population.

Pre-infusion and post-infusion medication: Pre-infusion and post-infusion medication will 
be summarized by therapeutic class, pharmacologic class and preferred term by treatment 
group and overall for safety population. A listing will be provided for pre-infusion 
medication and post-infusion medication, respectively.

Exposure: Summary of treatment exposure will be provided for safety population. The total 
number of treatment cycles received for each subject will be summarized by frequency and 
descriptive statistics (N, mean [SD], median, range [minimum, maximum]) by treatment 
group. Descriptive statistics for duration of study treatment, defined as (date of last dose of 
study treatment – date of first dose of study treatment) +1, will be presented by treatment 
group. Subject-month of exposure are calculated as days of duration/365.25*12. Total 
number of daratumumab and JNJ-63723283 infusions will be calculated. respectively. 
Exposure will be listed for safety population. 
The number and percentage of subjects with treatment cycle delay will be calculated by 
treatment group. The frequencies of actions planned prior to infusion start (infusion delayed, 
infusion skipped or study drug permanently discontinued) and taken during infusion 
(infusion interrupted, infusion rate decrease, infusion aborted) will be summarized, together 
with reasons reported (adverse events or other) accordingly.
Descriptive statistics will be presented for the following parameters: dose and relative dose 
intensity of daratumumab, dose and relative dose intensity of JNJ-63723283. 

Protocol deviation: A listing of subjects with major protocol deviations including treatment 
group, subject ID, type of deviation, and reasons for deviation will be provided.
1.6.
Efficacy
A listing of subjects’ best response, and disease progressions based on investigator’s assessment, 
and overall survival will be provided for the safety analysis set, including treatment group, 
subject ID, and baseline measurable disease type. For subjects who had progression disease 
(PD), the PD reasons based on investigator’s assessment will be listed.
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JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
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1.7.
Safety
Adverse events: 
An overview of treatment-emergent adverse events (TEAEs) will be summarized for safety 
population by treatment group and overall.
Incidence of TEAEs will be summarized by MedDRA SOC, and preferred term.
List of subjects with any TEAEs, serious TEAEs, toxicity grade 3 or 4 TEAEs, treatment-
emergent Infusion Related Reactions (IRRs), and immune-mediated TEAEs will be 
provided for safety population.
List of subjects with any TEAEs leading to all treatment discontinuation, TEAEs leading 
to any treatment discontinuation, TEAEs with outcome death, TEAEs leading to cycle 
delay or dose modifications, and TEAEs leading to infusion interrupted, infusion rate 
decreased or infusion aborted will be provided for safety population.
Subjects who died during the study, and had new malignancies will also be listed, 
respectively.
Laboratory values: Laboratory values will be listed at each time points for safety analysis 
set.
– The hematology parameters include: hemoglobin, lymphocytes, neutrophils, platelet, and 
white blood cell (WBC). 
– The chemistry parameters include: alanine aminotransferase (ALT), alkaline phosphatase, 
aspartate aminotransferase (AST), amylase, calcium, creatinine, creatinine clearance, 
potassium, sodium, total bilirubin, and total lipase,
– The thyroid function parameters include: free thyroxine, free triiodothyronine, thyroid 
stimulating hormone, and total triiodothyronine. 
Electrocardiograms (ECG): ECG values will be reported at each time points for safety
analysis set in listings.
Vital signs: Vital signs will be listed at each time points for safety analysis set. The variables 
include: weight, blood pressure (systolic and diastolic).
1.8.
Pharmacokinetics/Immunogenicity
Pharmacokinetics: PK analyses will be performed on the PK-evaluable population. The 
pharmacokinetic parameters are defined as

Minimum observed concentration (Cmin) - the concentration observed immediately before 
infusion. 

Maximum observed concentration (Cmax) – the concentration observed after the end of 
infusion 
For both JNJ-63723283 and daratumumab, the PK evaluations include Cmin and Cmax. All 
serum concentrations below the lowest quantifiable concentration or missing data will be 
labeled as such in the concentration data presentation. Concentrations below the lowest 
quantifiable concentration will be treated as zero in the summary statistics. 
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JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
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The Cmin and Cmax will be summarized at each sampling time point by descriptive statistics 
(N, mean, STD, median, range, coefficient variation and geometric mean) for JNJ-63723283 
and daratumumab, respectively, by treatment group. Line plot of mean (±STD) daratumumab 
and JNJ-63723283 serum peak and trough concentrations over time will be provided.
Immunogenicity: Immunogenicity analyses will be performed on the immunogenicity 
analysis set. The incidence of anti-daratumumab and anti-JNJ-63723283 antibodies will be 
summarized for all subjects who receive a dose of daratumumab or JNJ-63723283 and have 
appropriate samples for detection of antibodies to daratumumab or JNJ-63723283 by 
treatment group. In addition, subjects who are positive for antibodies to daratumumab or JNJ-
63723283 will also be listed. 
1.9.
Biomarker
Descriptive statistics for values and changes from baseline at each scheduled visit for absolute 
counts (cells/µl) and percentage of total NK cells, CD8+ T cells, and B cells in peripheral blood
will be provided by treatment group. Similar analysis for total and CD38+ myeloid derived 
suppressor cells (MDSCs), and total and CD38+ regulatory T cells (Tregs) will be performed.
Plots for these biomarkers over time will be provided. In additional, percent of activated CD8+ T 
cells will be summarized and plotted.
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JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
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Approved, Date: 25 September 2018
2.
LIST OF PLANNED OUTPUT 
Output 
Identifier
Output Title
Analysis Set
Use for 
What Effort 
(TLR, IA, 
INTXT, 
DMC)
Reference 
Mock
Column 
Layout
Subject and Treatment Information (SI)
Subject Disposition and Study Completion/Withdrawal Information
TSIDS01
Subjects Disposition 
Safety
INTXT
TSIDS-ST02
1
LSIDS01
Listing of Subjects 
Disposition
Safety
LSIDS-ST01
TSIFU01
Summary of Study Duration 
of Follow-up
Safety
INTXT
TSIFU01
1
Demographics and Baseline Characteristics
TSIPOP01
Subject Populations for 
Evaluation
Safety
INTXT
TSIDEM-ST03
1
TSIENR01
Subject Enrollment by Region 
and Country
Safety
TSIDEM-ST04
1
TSIDEM01
Summary of Demographics 
and Baseline Characteristics
Safety
INTXT
TSIDEM-ST01
1
TSIDEM02
Summary of Baseline Disease 
Characteristics;
Safety
INTXT
TSIDEM02
1
LSIDEM01
Listing of Demographics and 
Baseline Characteristics 
Safety
LSIDEM-ST01
TSIMH01
Summary of Medical History 
by MedDRA System Organ 
Class and Preferred Term
Safety
TSIMH01
1
Prior and Concomitant Therapies
TSIPM01
Summary of Prior Systemic 
Therapy
Safety
INTXT
TSIPM01
1
TSICM01
Summary of Concomitant 
Medications
Safety
TSICM-ST01
1
TSICM02
Summary of Pre-infusion 
Medications
Safety
TSICM-ST01
1
TSICM03
Summary of Post-infusion 
Medications
Safety
TSICM-ST01
1
LSICM01
Listing of Pre-infusion 
Medications
Safety
LSICM01
LSICM02
Listing of Post-infusion 
Medications
Safety
LSICM02
LSIPM01
Listing of Subjects with Prior 
Cancer-related 
Surgery/Procedure
Safety
LSIPM01
LSIPM02
Listing of Subjects with Prior 
Radiotherapy
Safety
LSIPM02
Protocol Deviations
LSIDEV01
Listing of Subjects with Major 
Protocol Deviations
Safety
LSIDEV-ST01
Extent of Exposure
TSIEXP01
Summary of Treatment 
Cycles, Duration of Study 
Treatment and Dose Intensity
Safety
INTXT
TSIEX-ST01
2
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JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
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Approved, Date: 25 September 2018
Output 
Identifier
Output Title
Analysis Set
Use for 
What Effort 
(TLR, IA, 
INTXT, 
DMC)
Reference 
Mock
Column 
Layout
TSIEXP02
Summary of Treatment Cycle 
Delays, Incidences of and 
Reasons for Study Treatment 
Dose Modifications
Safety
TSIEXP02
2
TSIEXP03
Summary of Action Taken 
During the Infusion
Safety
TSIEXP03
2
LSIEX01
Listing of Treatment Exposure
Safety 
LSIEX-ST01
Efficacy Results (EF)
LEFRSP01
Listing of Efficacy Variables 
Based on Investigator 
Assessment
Safety
LEFRSP01
Safety Results (SF)
Adverse Events
TSFAE01
Overview of Treatment-
emergent Adverse Events
Safety
INTXT
TSFAE-ST01
1
TSFAE02
Treatment-emergent Adverse 
Events by System Organ 
Class and Preferred Term
Safety
INTXT
TSFAE-ST02
1
LSFAE01 
Listing of Treatment-emergent
Adverse Events 
Safety
LSFAE01
LSFAE02
Listing of Treatment-emergent
Serious Adverse Events 
Safety
LSFAE01
LSFAE03
Listing of Treatment-emergent
Grade 3 or 4 Adverse Events
Safety
LSFAE01
LSFAE04
Listing of Subjects who 
Discontinued All Study 
Treatment Because of 1 or 
More Treatment-emergent
Adverse Events;
Safety
LSFAE01
LSFAE05
Listing of Subjects Who 
Discontinued Any of Study 
Drugs Because of 1 or More 
Treatment-emergent Adverse 
Events 
Safety
LSFAE01
LSFAE06
Listing of Treatment-emergent 
Infusion Related Reactions
Safety
LSFAE01
LSFAE07
Listing of Immune-mediated 
Treatment-emergent Adverse 
Event
Safety
LSFAE01
LSFAE08
Listing of Treatment-emergent
Adverse Events Leading to 
Cycle Delay or Dose 
Modifications
Safety
LSFAE01
LSFAE09
Listing of Treatment-emergent
Adverse Events Leading to 
Infusion Interrupted, Infusion 
Rate Decreased or Infusion 
Aborted
Safety
LSFAE01
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Approved, Date: 25 September 2018
Output 
Identifier
Output Title
Analysis Set
Use for 
What Effort 
(TLR, IA, 
INTXT, 
DMC)
Reference 
Mock
Column 
Layout
LSFAE10
Listing of Subjects Who Had 
New Malignancies
Safety
LSFAE10
LSFDTH01
Listing of Subjects Who Died 
During the Study
Safety
LSFDTH-ST01
Clinical Laboratory Evaluation
TSFLAB01
Shift Table of Baseline versus 
Worst Toxicity Grade during 
Treatment in Hematological 
Test
Safety
TSFLAB-ST07
2
TSFLAB02
Shift Table of Baseline versus 
Worst Toxicity Grade during 
Treatment in Biochemistry 
Test;
Safety
TSFLAB-ST07
2
LSFLAB01
Listing of Other Laboratory 
Values
Safety
LSFLAB-ST01
Electrocardiograms
LSFECG01
Listing of ECG Results
Safety
LSFECG-ST01
Vital Signs
LSFVS01
Listing of Vital Signs Values
Safety
LSFLAB-ST01
Pharmacokinetics/Immunogenicity (PK/IR) 
TPKCONC01
Summary of Daratumumab 
Concentration (ug/mL)
PK-evaluable
INTXT
TPK-ST07
3
TPKCONC02
Summary of JNJ-63723283 
Concentration (ug/mL)
PK-evaluable
INTXT
TPK-ST07
3
GPKCONC01
Mean (SD) Daratumumab 
Serum Peak and Trough 
Concentrations (ug/mL)
PK-evaluable
GPK-ST05
GPKCONC02
Mean (SD) JNJ-63723283 
Serum Peak and Trough 
Concentrations (ug/mL)
PK-evaluable
GPK-ST05
TPKIR01
Summary of Anti-
daratumumab Antibodies 
Status
Immunogenicity
INTXT
TPKIR-ST01
4
TPKIR02
Summary of Anti-JNJ-
63723283 Antibodies Status
Immunogenicity
INTXT
TPKIR-ST01
4
LPKCONC01
List of Subjects Positive for
Anti-daratumumab Antibodies 
Status 
Immunogenicity
LPKIR-ST01
LPKCONC02
List of Subjects Positive for
Anti-JNJ-63723283 
Antibodies Status
Immunogenicity
LPKIR-ST01
Biomarkers
Natural Killer (NK) Cells
TBMKNK01
Summary of Percent of Total 
Natural Killer Cells in Blood 
Over Time
Safety
TBMK01
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JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
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Approved, Date: 25 September 2018
Output 
Identifier
Output Title
Analysis Set
Use for 
What Effort 
(TLR, IA, 
INTXT, 
DMC)
Reference 
Mock
Column 
Layout
TBMKNK02
Summary of Total Natural 
Killer Cells (Absolute Count) 
in Blood Over Time  
Safety
TBMK01
GBMKNK01
Plot of Percent of Total 
Natural Killer cells in Blood 
over time
Safety
GBMK01
GBMKNK02
Plot of Total Natural Killer 
Cells (Absolute Count) in 
Blood Over Time
Safety
GBMK01
T Cells
TBMKTC01
Summary of Percent of CD8+ 
T Cells in Blood Over Time
Safety
TBMK01
TBMKTC02
Summary of CD8+ T Cells 
(Absolute Count) in Blood 
Over Time
Safety
TBMK01
GBMKTC01
Plot of Percent of CD8+ T 
Cells in Blood Over Time
Safety
GBMK01
GBMKTC02
Plot of CD8+ T Cells 
(Absolute Count) in Blood 
Over Time
Safety
GBMK01
TBMKTC03
Summary of Percent of 
Activated CD8+T Cells in 
Blood Over Time
Safety
TBMK01
GBMKTC03
Plot of Percent of Activated 
CD8+ T cells in Blood Over 
Time
Safety
GBMK01
B Cells
TBMKBC01
Summary of Percent of B 
Cells in Blood Over Time
Safety
TBMK01
TBMKBC02
Summary of B Cells 
(Absolute Count) in Blood 
Over Time
Safety
TBMK01
GBMKBC02
Plot of B Cells (Absolute 
Count) in Blood Over Time
Safety
GBMK01
GBMKBC01
Plot of Percent of B Cells in 
Blood Over Time
Safety
GBMK01
CD38+ MDSCs
TBMKMDSC
01
Summary of Percent of Total 
monocytic MDSCs in Blood 
Over Time
Safety
TBMK01
TBMKMDSC
02
Summary of Percent of 
CD38+ monocytic MDSCs in 
Blood Over Time
Safety
TBMK01
GBMKMDSC
01
Plot of Percent of Total 
monocytic MDSCs in Blood 
over time
Safety
GBMK01
GBMKMDSC
02
Plot of Percent of CD38+ 
monocytic MDSCs in Blood 
Over Time
Safety
GBMK01
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
14
Approved, Date: 25 September 2018
Output 
Identifier
Output Title
Analysis Set
Use for 
What Effort 
(TLR, IA, 
INTXT, 
DMC)
Reference 
Mock
Column 
Layout
TBMKMDSC
03
Summary of Total Monocytic 
MDSCs (Absolute Count) in 
Blood Over Time 
Safety
TBMK01
GBMKMDSC
03
Plot of Total monocytic 
MDSCs (Absolute Count) in 
Blood Over Time 
Safety
GBMK01
CD38+ Tregs
TBMKTR01
Summary of Percent of Total 
Tregs in Blood Over Time
Safety
TBMK01
TBMKTR02
Summary of Percent of 
CD38+ Tregs in Blood Over 
Time
Safety
TBMK01
TBMKTR03
Summary of Total Tregs 
(Absolute Count) in Blood 
Over Time
Safety
TBMK01
TBMKTR04
Summary of CD38+ Tregs 
(Absolute Count) in Blood 
Over Time
Safety
TBMK01
GBMKTR01
Plot of Percent of Total Tregs 
in Blood Over Time
Safety
GBMK01
GBMKTR02
Plot of Percent CD38+ Tregs 
in Blood Over Time
Safety
GBMK01
GBMKTR03
Plot of Total Tregs (Absolute 
Count) in Blood Over time
Safety
GBMK01
GBMKTR04
Plot of CD38+ Tregs 
(Absolute Count) in Blood 
Over Time
Safety
GBMK01
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
15
Approved, Date: 25 September 2018
3.
COLUMN LAYOUTS FOR TABLES
All tables listed in Section 2 are to be presented with the following columns layout, unless 
specified otherwise.  
Layout 1: To be used in demographics, baseline disease characteristics, prior systemic therapies, 
medical history, TEAE overview, safety.
Safety Run-in
Phase 2
Arm A
Total
Layout 2: To be used in exposure tables.
Safety Run-in
Phase 2
Arm A
Layout 3: To be used in PK tables
Safety Run-in
Pre-dose
Post-dose
Layout 4: To be used in immunogenicity tables
Safety Run-in
Programming notes: 
1.
Footnotes that correspond to the naming of the treatment groups are specified as below:
Key: Arm A = daratumumab alone; 
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
16
Approved, Date: 25 September 2018
4.
MOCK LAYOUTS
TSIDS-ST02:
Subjects Disposition; Safety Analysis Set (Study 54767414MMY2036)
Analysis set: Safety
###
###
###
###
###
Subjects who discontinued treatment
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Reason for discontinuation
Adverse Event
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Death
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Non-compliance with study drug
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Physician decision 
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Pregnancy
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Progressive disease
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Study terminated by sponsor
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Subject refused further study 
treatment
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
        Other
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
## (xx.x%)
Subjects who discontinued study
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
     Reason for discontinuation
Death
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Lost to follow-up
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Physician desicion
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Pregnancy
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Screen failure
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Study terminated by sponsor
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Withdrawal by subject
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Other
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Note: Percentages calculated with the number of subjects in each group as denominator.
Display Specifications 
Output Identifier
TSIDS01
Programming Notes:
1.
Reasons for discontinuation should be presented in descending frequency in the overall total column.
2.
Remove the specific reason for discontinuation if there is no subject belongs to that. 
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
17
Approved, Date: 25 September 2018
LSIDS-ST01:
Listing of Subjects Disposition; Safety Analysis Set (Study 54767414MMY2036)
Treatment Group
Site ID
Subject
ID
Disposition 
Event
Study Daya of Last 
Study Agent 
Administered
Total Dose for 
Dara/JNJ283 
(mg/kg or mg)b
Discontinuation 
Date
(Study Daya)
Primary Reason for
Discontinuation
a Study day is relative to the date of first dose of study agent.
b Total dose is defined as a cumulative sum of all study agent administered. Dara=daratumumab; JNJ283=JNJ-63723283. 
Display Specifications 
Output Identifier
LSIDS01
Programming Notes:
1.
Sort listing based on treatment group (Safety run-in, Arm A, Arm B), site ID, and subject ID.
2.
Study day of last study agent administered is the study day that the subject received their last non-zero dose of 
study agent.
3.
If the reason for discontinuation is Adverse event or Other, specify the AE preferred term or other reason in 
parentheses. 
TSIFU01: Summary of Study Duration of Follow-up; Safety Analysis Set (Study 54767414MMY2036)
Analysis set: Safety
##
##
##
Duration of follow-up (months)
N
##
##
##
Mean (SD)
##.# (##.##)
##.# (##.##)
##.# (##.##)
Mediana
##
##
##
Range
(##; ##)
(##; ##)
(##; ##)
a Based on Kaplan-Meier product limit estimate.
Note: Duration of follow-up is relative to the date of first dose.
Programming Notes:
1. Mark ‘+” for the range values if come from the subjects who died, and the following footnote is needed: “+ 
Denotes subjects who died”.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
18
Approved, Date: 25 September 2018
TSIDEM-ST04:
Subject Enrollment by Region and Country; Safety Analysis Set (Study 
54767414MMY2036)
Analysis set: Safety
### 
###
###
###
###
Region/Country
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Region 1
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Country 1
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Country 2
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Country 3
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Note: Percentages are calculated with the number of subjects in each group as denominator.
Programming Notes:
1.
Region and Country are presented in alphabetical order
TSIDEM-ST03: Subject Populations for Evaluation; Safety Analysis Set (Study 54767414MMY2036)
Safety analysis set a
### 
### 
### 
### 
### 
Pharmacokinetic-evaluable analysis 
set b
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Immunogenicity analysis set c
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
a Safety analysis set includes all subjects who have received at least 1 dose of study agent (JNJ-63723283 or
daratumumab, partial or complete) in either safety run-in or Part 2 of the study.
b Pharmacokinetic-evaluable analysis set includes all subjects who have received at least 1 dose of daratumumab or 
JNJ-63723283 and have at least 1 postinfusion sample in either safety run-in or Part 2 of the study.
c Immunogenicity analysis set include all subjects who have received at least 1 dose of JNJ-63723283 or
daratumumab and have appropriate serum samples for detection of antibodies to JNJ-63723283 or daratumumab
(i.e., subjects with at least 1 sample obtained after their first dose of JNJ-63723283 or daratumumab) in either safety 
run-in or Part 2 of the study
Note: Percentages are calculated with the number of subjects in each group as denominator.
Display Specifications 
Output Identifier
TSIPOP01
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
19
Approved, Date: 25 September 2018
TSIDEM-ST01: Summary of Demographics and Baseline Characteristics; Safety Analysis Set (Study 
54767414MMY2036)
Analysis set: Safety 
###
###
###
###
###
Age, (years)
N
###
###
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
(xx;xx)
(xx;xx)
Category, n(%)
    < 65
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
   65-<75
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
            ≥ 75
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Sex, n(%)
N
###
###
###
###
###
Female
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Male
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Race, n(%)
N
###
###
###
###
###
American Indian or Alaska 
Native
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Asian
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Black or African American
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Native Hawaiian or Other Pacific 
Islander
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
White
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Multiplea
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Not reported
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Ethnicity, n(%) 
N
###
###
###
###
###
Hispanic or Latino
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Not Hispanic or Latino
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Not reported
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Weight, kg
N
###
###
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
(xx;xx)
(xx;xx)
Category, n(%)
    ≤ 65
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
   >65-85
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
   >85
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Height, cm
N
###
###
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
(xx;xx)
(xx;xx)
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
20
Approved, Date: 25 September 2018
TSIDEM-ST01: Summary of Demographics and Baseline Characteristics; Safety Analysis Set (Study 
54767414MMY2036)
Baseline ECOG score, n(%)
N
###
###
###
###
###
   0
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
   1
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
   2
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Key: ECOG=Eastern Cooperative Oncology Group.
a If multiple race categories are indicated, the subject’s race is include in ‘Multiple’.
Note: Percentages are calculated with the number of subjects in each group with available data as denominator.
Programming Notes:
1.
For sex, race, and ethnicity, categories are presented in alphabetical order.
2.
For race, each subject must appear in only one category.  
3.
For ordered categories (eg, age (years): <65, >=60), all category levels will be displayed regardless of whether 
there are zero counts within a level; for categories with no inherent order (eg, race), only category levels with 
counts >0 will be displayed. 
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
21
Approved, Date: 25 September 2018
TSIDEM02: Summary of Baseline Disease Characteristics; Safety Analysis Set (Study 54767414MMY2036)
Analysis set: Safety
##
##
##
Type of myeloma by immunofixation or serum FLC assay, n (%)
N
##
##
##
IgG
### (xx.x%)
### (xx.x%)
### (xx.x%)
IgA
### (xx.x%)
### (xx.x%)
### (xx.x%)
IgM
### (xx.x%)
### (xx.x%)
### (xx.x%)
IgD
### (xx.x%)
### (xx.x%)
### (xx.x%)
IgE
### (xx.x%)
### (xx.x%)
### (xx.x%)
Light chain
### (xx.x%)
### (xx.x%)
### (xx.x%)
Kappa
### (xx.x%)
### (xx.x%)
### (xx.x%)
Lambda
### (xx.x%)
### (xx.x%)
### (xx.x%)
Biclonal
### (xx.x%)
### (xx.x%)
### (xx.x%)
       Negative Immunofixation
### (xx.x%)
### (xx.x%)
### (xx.x%)
       Not detected
### (xx.x%)
### (xx.x%)
### (xx.x%)
Type of measurable disease a, n(%)
N
##
##
##
Serum only
IgG
### (xx.x%)
### (xx.x%)
### (xx.x%)
IgA
### (xx.x%)
### (xx.x%)
### (xx.x%)
Other b
### (xx.x%)
### (xx.x%)
### (xx.x%)
    Serum and urine
### (xx.x%)
### (xx.x%)
### (xx.x%)
    Urine only
### (xx.x%)
### (xx.x%)
### (xx.x%)
    Serum FLC only
### (xx.x%)
### (xx.x%)
### (xx.x%)
    NE
### (xx.x%)
### (xx.x%)
### (xx.x%)
ISS staging c, n(%)
N
##
##
##
I
### (xx.x%)
### (xx.x%)
### (xx.x%)
II
### (xx.x%)
### (xx.x%)
### (xx.x%)
III
### (xx.x%)
### (xx.x%)
### (xx.x%)
Number of lines of prior therapy d
    N
##
##
##
Mean (SD)
##.# (##.##)
##.# (##.##)
##.# (##.##)
Median
##
##
##
Range
(##; ##)
(##; ##)
(##; ##)
Category, n (%)
≤ 3
#(XX.X%)
#(XX.X%)
#(XX.X%)
> 3
#(XX.X%)
#(XX.X%)
#(XX.X%)
Time from MM diagnosis to first dosing date(years)
    N
##
##
##
    Mean (SD)
##.##(##.###)
##.##(##.###)
##.##(##.###)
    Median
##.##
##.##
##.##
    Range
(##.#; ##.#)
(##.#; ##.#)
(##.#; ##.#)
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
22
Approved, Date: 25 September 2018
TSIDEM02: Summary of Baseline Disease Characteristics; Safety Analysis Set (Study 54767414MMY2036)
Number of lytic bone lesions, n (%)
  N
##
##
##
    None
### (xx.x%)
### (xx.x%)
### (xx.x%)
    1-3
### (xx.x%)
### (xx.x%)
### (xx.x%)
    4-10
### (xx.x%)
### (xx.x%)
### (xx.x%)
    More than 10
### (xx.x%)
### (xx.x%)
### (xx.x%)
Presence of diffuse myeloma-related osteopenia, n (%)
  N
##
##
##
Yes
### (xx.x%)
### (xx.x%)
### (xx.x%)
No
### (xx.x%)
### (xx.x%)
### (xx.x%)
Number of extramedullary plasmacytomas, n (%)
   N
##
##
##
0
### (xx.x%)
### (xx.x%)
### (xx.x%)
≥ 1
### (xx.x%)
### (xx.x%)
### (xx.x%)
Presence of evaluable bone marrow assessment, n (%)
   N
##
##
##
Yes
### (xx.x%)
### (xx.x%)
### (xx.x%)
No
### (xx.x%)
### (xx.x%)
### (xx.x%)
% Plasma cells, bone marrow biopsy/aspirate, n (%)
    N
##
##
##
<10
### (xx.x%)
### (xx.x%)
### (xx.x%)
10-30
### (xx.x%)
### (xx.x%)
### (xx.x%)
>30
### (xx.x%)
### (xx.x%)
### (xx.x%)
Cytogenetic risk e, n (%)
    N
##
##
##
Standard Risk
### (xx.x%)
### (xx.x%)
### (xx.x%)
High Risk f
### (xx.x%)
### (xx.x%)
### (xx.x%)
    Del(17p)
### (xx.x%)
### (xx.x%)
### (xx.x%)
    T(4;14)
### (xx.x%)
### (xx.x%)
### (xx.x%)
    T(14;16)
### (xx.x%)
### (xx.x%)
### (xx.x%)
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
23
Approved, Date: 25 September 2018
TSIDEM02: Summary of Baseline Disease Characteristics; Safety Analysis Set (Study 54767414MMY2036)
Baseline ECG 
     N
##
##
##
Normal
### (xx.x%)
### (xx.x%)
### (xx.x%)
Abnormal, not clinically significant
### (xx.x%)
### (xx.x%)
### (xx.x%)
Abnormal, clinically significant
### (xx.x%)
### (xx.x%)
### (xx.x%)
Key: ECG = electrocardiogram; FLC = serum free light chain; ISS = International Staging System; MM = multiple myeloma; 
NE=not evaluable.
a Includes subjects without measurable disease in serum and urine.  
b Includes subjects with IgD, IgM, IgE and biclonal. 
c ISS staging is derived based on the combination of serum β2-microglobulin and albumin. 
d Based on data recorded on prior systemic therapy eCRF page.
e Cytogenetic risk is based on FISH or karyotype testing. 
f Subject may have more than one high-risk abnormality [del17p, t(4;14) or t(14;16)].
Note: Percentages calculated with the number of subjects in each group with available data as denominator.
Display Specifications 
Output Identifier
TSIDEM02
Programming Notes: 
1.
No need to show “Not detected” or “NE” categories if no such subjects exist 
LSIDEM-ST01:
Listing of Demographics and Baseline Characteristics; Safety Analysis set (Study 
54767414MMY2036)
Baseline
Treatment 
Group
Site 
ID
Subject ID
Informed 
Consent Date
Age (years)/
Sex/Race
Ethnicity
Weight 
(kg)
Height (cm)
ECOG 
Performance 
Score
30/M/
Key: ECOG=Eastern Cooperative Oncology Group.
Display Specifications
Output Identifier
LSIDEM01
Programming Notes:
1.
Sort listing based on treatment group (Safety run-in, Arm A, Arm B), site ID, and subject ID.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
24
Approved, Date: 25 September 2018
TSIMH01: Summary of Medical History by MedDRA System Organ Class and Preferred term; Safety Analysis Set 
(Study 54767414MMY2036)
Analysis set: Safety
##
##
##
Total number of subjects with 1 or more medical history
#(X.X%)
#(X.X%)
#(X.X%)
MedDRA system organ class / Preferred term
#(X.X%)
#(X.X%)
#(X.X%)
System organ class
#(X.X%)
#(X.X%)
#(X.X%)
Preferred term
#(X.X%)
#(X.X%)
#(X.X%)
Note: Percentages calculated with the number of subjects in each treatment group as denominator. Medical history is coded using 
MedDRA version 20.X.
TSIPM01: Summary of Prior Systemic Therapies; Safety Analysis Set (Study 54767414MMY2036)
Analysis set: Safety
##
##
##
Total number of subjects with any prior therapies for multiple 
myeloma, n (%)
#(XX.X%)
#(XX.X%)
#(XX.X%)
Prior systemic therapy
#(XX.X%)
#(XX.X%)
# (XX.X%)
Prior autologous stem cell transplant (ASCT)
#(XX.X%)
#(XX.X%)
#(XX.X%)
Prior radiotherapy
#(XX.X%)
#(XX.X%)
# (XX.X%)
Prior cancer-related surgery
#(XX.X%)
#(XX.X%)
#(XX.X%)
Prior PI, n (%)
Bortezomib
#(XX.X%)
#(XX.X%)
#(XX.X%)
Carfilzomib
#(XX.X%)
#(XX.X%)
#(XX.X%)
Ixazomib
#(XX.X%)
#(XX.X%)
#(XX.X%)
Prior IMiD, n (%)
Lenalidomide
#(XX.X%)
#(XX.X%)
#(XX.X%)
Pomalidomide
#(XX.X%)
#(XX.X%)
#(XX.X%)
Thalidomide
#(XX.X%)
#(XX.X%)
#(XX.X%)
Prior PI+IMiD, n (%)
Prior corticosteroids, n (%)
Dexamethasone
#(XX.X%)
#(XX.X%)
#(XX.X%)
Prednisone
#(XX.X%)
#(XX.X%)
#(XX.X%)
Prior alkylating agents, n (%)
#(XX.X%)
#(XX.X%)
#(XX.X%)
Prior anthracyclines, n (%)
#(XX.X%)
#(XX.X%)
# (XX.X%)
Note: Percentages calculated with the number of subjects in each group as denominator
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
25
Approved, Date: 25 September 2018
TSICM-ST01:
Summary of Concomitant Medications; Safety Analysis Set (Study 54767414MMY2036)
Analysis set: Safety
###
###
###
###
###
Subjects with one or more 
concomitant medications
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
ATC Level 2
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
ATC Level 3 
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Standardized medication name
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Note: Percentages calculated with the number of subjects in each group as denominator.
Display Specifications 
Output Identifier
TSICM01
Programming Notes:
1.
Order by decreasing incidence of ATC level and decreasing incidence of standardized medication name based 
on the overall total column. 
Display Specifications 
Output Identifier
TSICM02
Programming note:
1.
Change the ‘concomitant’ to ‘pre-infusion’ in the title and table.
2.
Order by decreasing incidence of ATC level and decreasing incidence of standardized medication name 
based on the overall total column. 
Display Specifications 
Output Identifier
TSICM03
Programming note:
1.
Change the ‘concomitant’ to ‘post-infusion’ in the title and table.
2.
Order by decreasing incidence of ATC level and decreasing incidence of standardized medication name 
based on the overall total column. 
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
26
Approved, Date: 25 September 2018
LSICM01: Listing of Pre-infusion Medications; Safety Analysis Set (Study 54767414MMY2036)
Treatment Group
Site ID
Subject
ID 
Visit 
Start Date/Time
(Study Day) 
Medication
Coded Term [Verbatim Term] 
Dose
(unit) 
Route
Safety run-in
XXX
XXXXXXXX
CYCLE 1 DAY 1
2017-11-01T09:00 (1)
CLEMASTINE FUMARATE [TAVEGYL]
2 (mg)
INTRAVENOUS
CYCLE 1 DAY 8
2017-11-08T09:00 (8)
CLEMASTINE FUMARATE [TAVEGYL]
2 (mg)
INTRAVENOUS
XXXXXXXX
CYCLE 1 DAY 1
2017-11-01T09:00 (1)
CLEMASTINE FUMARATE [TAVEGYL]
2 (mg)
INTRAVENOUS
Programming note: please sort data by Treatment group (Safety run-in, Arm A, Arm B), site ID, subject ID, start Date/Time
LSICM02: Listing of Post-infusion Medications; Safety Analysis Set (Study 54767414MMY2036)
Treatment 
Group
Site ID
Subject
ID 
Visit 
Start Date
(Study Day) 
End Date
(Study Day) 
Medication
Coded Term [Verbatim Term] 
Dose
(unit) 
Route
Frequency
Safety run-in
XXX
XXXXXXXX
CYCLE 1 DAY 
1
2017-11-01 (1)
2017-11-02 (2)
METHYLPREDNISOLONE [MEDROL]
20 (mg)
ORAL
Twice Daily
CYCLE 1 DAY 
8
2017-11-08 (8)
2017-11-08 (9)
METHYLPREDNISOLONE [MEDROL]
20 (mg)
ORAL
Twice Daily
XXXXXXXX
CYCLE 1 DAY 
1
2017-11-01 (1)
2017-11-02 (2)
METHYLPREDNISOLONE [MEDROL]
20 (mg)
ORAL
Twice Daily
XXXXXXXX
CYCLE 1 DAY 
1
2017-11-01 (1)
2017-11-02 (2)
METHYLPREDNISOLONE [MEDROL]
20 (mg)
ORAL
Twice Daily
Programming note: please sort data by Treatment group (Safety run-in, Arm A, Arm B), site ID, subject ID, Start date.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
27
Approved, Date: 25 September 2018
LSIPM01: List of Subjects with Prior Cancer-Related Surgery/Procedure; Safety Analysis Set (Study 54767414MMY2036)
Treatment Group 
Site 
ID 
Subject  ID 
Description of Surgery or Procedure
Start Date 
End Date 
Indication 
Programming Notes:
1.
Listing is sorted by treatment (Safety run-in, Arm A and Arm B), site ID, subject ID, start date of procedure.
LSIPM02: List of Prior Radiotherapy; Safety Analysis Set (Study 54767414MMY2036)
Treatment 
Group
Site 
ID
Subject ID
Start Date
End Date
Location
Indication
Total Dose (Gy)
Programming Notes:
1.
Listing is sorted by treatment (Safety run-in, Arm A and Arm B), site ID, subject ID, start date of procedure.
2.
If indication/location is “Other” and there is a specific description of the indication/location, then the specific description should be displayed
LSIDEV-ST01: Listing of Subjects with Major Protocol Deviations; Safety Analysis Set (Study 54767414MMY2036)
Treatment Group
Site ID
Subject ID
Type of Protocol Deviation
Protocol Deviation Verbatim Term
Programming Notes:
1.
The sort order is Treatment Group (Safety run-in, Arm A and Arm B), Site ID, Subject ID, and Study Day of Deviation.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
28
Approved, Date: 25 September 2018
TSIEX-ST01:
Summary of Treatment Cycles, Duration of Study Treatment and Dose Intensity; Safety
Analysis Set (Study 54767414MMY2036)
Analysis set: Safety
###
###
###
Duration of treatment (months)
N
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
Number of treatment cycles
N
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
≥ 1 cycle
## (XX.X%)
## (XX.X%)
## (XX.X%)
≥ 2 cycles
## (XX.X%)
## (XX.X%)
## (XX.X%)
≥ 3 cycles
## (XX.X%)
## (XX.X%)
## (XX.X%)
≥ 4 cycles
## (XX.X%)
## (XX.X%)
## (XX.X%)
≥ 5 cycles
## (XX.X%)
## (XX.X%)
## (XX.X%)
Total number of daratumumab infusions
N
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
Total dose of daratumumab (mg/kg)
N
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
Dose intensity for daratumumab (mg/kg/cycle) a
N
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
Relative dose intensity for daratumumab (%)
    N
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
Total number of JNJ-63723283 infusions
N
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
Total dose of JNJ-63723283 (mg)
N
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
29
Approved, Date: 25 September 2018
TSIEX-ST01:
Summary of Treatment Cycles, Duration of Study Treatment and Dose Intensity; Safety
Analysis Set (Study 54767414MMY2036)
Dose intensity for JNJ-63723283 (mg/cycle) b
N
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
Relative dose intensity for JNJ-63723283 (%)
N
###
###
###
Mean (SD)
xx.x (xx.xx)
xx.x (xx.xx)
xx.x (xx.xx)
Median
xx.x
xx.x
xx.x
Range
(xx;xx)
(xx;xx)
(xx;xx)
a Dose intensity (mg/kg/cycle) is calculated as the sum of total doses (mg/kg) received in all cycles divided by the number of 
treatment cycles on daratumumab. 
b Dose intensity (mg/cycle) is calculated as the sum of total doses (mg) received in all cycles divided by the number of treatment 
cycles on JNJ-63723283.
Note: The relative dose intensity (%) is the ratio of total actually received dose and total planned dose.
TSIEXP02: Summary of Treatment Cycle Delays, Incidences of and Reasons for Study Treatment 
Dose Modifications; Safety Analysis Set (Study 54767414MMY2036)
Analysis set: Safety
##
##
Subjects with cycle delays
## (XX.X%)
## (XX.X%)
Reason for cycle delays
Adverse event
## (XX.X%)
## (XX.X%)
Other
## (XX.X%)
## (XX.X%)
Subjects with dose delays
Daratumumab
## (XX.X%)
## (XX.X%)
Reason for delays
Adverse event
## (XX.X%)
## (XX.X%)
Other
## (XX.X%)
## (XX.X%)
JNJ-63723283
## (XX.X%)
## (XX.X%)
Reason for delays
Adverse event
## (XX.X%)
## (XX.X%)
Other
## (XX.X%)
## (XX.X%)
Subjects with dose skipped
Daratumumab
## (XX.X%)
## (XX.X%)
Reason for skipping
Adverse event
## (XX.X%)
## (XX.X%)
Other
## (XX.X%)
## (XX.X%)
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
30
Approved, Date: 25 September 2018
TSIEXP02: Summary of Treatment Cycle Delays, Incidences of and Reasons for Study Treatment 
Dose Modifications; Safety Analysis Set (Study 54767414MMY2036)
JNJ-63723283
## (XX.X%)
## (XX.X%)
Reason for skipping
Adverse event
## (XX.X%)
## (XX.X%)
Other
## (XX.X%)
## (XX.X%)
Note: Percentages calculated with the number of subjects in each group as denominator.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
31
Approved, Date: 25 September 2018
TSIEXP03: Summary of Action Taken During the Infusion; Safety Analysis Set (Study 
54767414MMY2036)
Analysis set: Safety
##
##
Subjects with infusion interrupted
Daratumumab
## (XX.X%)
## (XX.X%)
Reason for infusion interrupted
Adverse event
## (XX.X%)
## (XX.X%)
Other
## (XX.X%)
## (XX.X%)
JNJ-63723283
## (XX.X%)
## (XX.X%)
Reason for infusion interrupted
Adverse event
## (XX.X%)
## (XX.X%)
Other
## (XX.X%)
## (XX.X%)
Subjects with infusion rate decreased
Daratumumab
## (XX.X%)
## (XX.X%)
Reason for infusion rate decreased
Adverse event
## (XX.X%)
## (XX.X%)
Other
## (XX.X%)
## (XX.X%)
JNJ-63723283
## (XX.X%)
## (XX.X%)
Reason for infusion rate decreased
Adverse event
## (XX.X%)
## (XX.X%)
Other
## (XX.X%)
## (XX.X%)
Subjects with infusion aborted
       Daratumumab
## (XX.X%)
## (XX.X%)
             Reason for infusion aborted 
Adverse event
## (XX.X%)
## (XX.X%)
Other
## (XX.X%)
## (XX.X%)
        JNJ-63723283
## (XX.X%)
## (XX.X%)
             Reason for infusion aborted 
Adverse event
## (XX.X%)
## (XX.X%)
Other
## (XX.X%)
## (XX.X%)
Note: Percentages calculated with the number of subjects in each group as denominator.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
32
Approved, Date: 25 September 2018
LSIEX-ST01:
Listing of Treatment Exposure; Safety Analysis Set (Study 54767414MMY2036)
Treatment 
Group
Site 
ID
Subject 
ID
Study 
Drug
Visit
Infusion 
Date
(Study 
Day)
Total 
Dose
(mg)
Start/End 
Time
Action Planned 
Prior to Infusion 
Start
Reason for 
Action Planned 
Prior to 
Infusion Start
Action Taken 
During 
Infusioin
Reason for 
Action 
Taken 
During 
Infusion
If ‘INFUSION 
INTERRUPTED’, Interruption 
Start/End Time
Programming Notes:
The sort order is Treatment Group (Safety run-in, Arm A, Arm B), Site ID, Subject ID, Study Drug and Infusion Date
LEFRSP01: Listing of Efficacy Variable Based on Investigator Assessment; Safety Analysis Set (Study 54767414MMY2036)
Treatm
ent 
Group
Site ID 
Subject
ID
Measurable 
Disease Type
Best 
Resp.
Date of Best Resp. 
(Study Day)
Date of 
PD 
(Study Day)
Reason 
for PD
Reason 
for PD
Censoring
Date of Last 
Disease 
Assessment 
(Study Day)
PFS
(Month)
Date of Death/
Last Date Known to be 
Alive (Study Day)
OS 
(Month)
Arm A
XX
XX
Serum
CR
2018-06-04 (XX)
XX
2018-06-14 (xx)
2.4+
2018-06-14 (xx)
2.4+
Key: sCR=stringent complete response; CR=complete response; VGPR=very good partial response; PR=partial response; MR=minimal response; SD=stable disease; PD=progression disease; NE=not evaluable.
Key: OS=Overall Survival; PFS=Progression-free Survival; Resp.=Response.
+: Censoring.
Programming notes:
Sort the listing by Treatment group (Arm A, Arm B), Site ID, and Subject ID.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
33
Approved, Date: 25 September 2018
TSFAE-ST01:
Overview of Treatment-emergent Adverse Events; Safety Analysis Set (Study 
54767414MMY2036)
Analysis set: Safety
###
###
###
###
Any TEAE
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
At least one relateda
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
At least one related to daratumumab
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
At least one related to JNJ-63723283
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Maximum toxicity grade
Grade 1
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Grade 2
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Grade 3
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Grade 4
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Grade 5
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Any serious TEAE
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
At least one related a
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
At least one related to daratumumab
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
At least one related to JNJ-63723283
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
TEAE leading to discontinuation of study 
treatment b
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
TEAE leading to discontinuation of 
daratumumab
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
At least one related to daratumumab
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
TEAE leading to discontinuation of JNJ-
63723283
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
At least one related to JNJ-63723283
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
TEAE with outcome of death
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
At least one related to daratumumab
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
At least one related to JNJ-63723283
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Key: TEAE = treatment-emergent adverse event. 
a TEAEs related to at least 1 of the 2 study treatments: daratumumab and JNJ-63723283.
b Includes those subjects indicated as having discontinued treatment due to an adverse event on the end of treatment CRF page.
Note: Adverse events are coded using MedDRA version XX.X. Percentages are calculated with the number of 
subjects in each group as denominator.
Display Specifications
Output Identifier
TSFAE01
Programming Notes:
1.
TEAE with outcome of death are based on an AE outcome equal to Fatal or toxicity grade of 5 from AE page.
2.
An AE is considered to result in discontinuation of study agent if the “action taken regarding study agent” is 
“drug withdrawn” on the AE eCRF page. If an attribute of the AE is missing, it will not be imputed.
3.
An AE is considered to result in discontinuation of study treatment if the reason for termination on the End of 
Treament disposition page is AE.  
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
34
Approved, Date: 25 September 2018
TSFAE-ST02:
Treatment-emergent Adverse Events by System Organ Class and Preferred Term; Safety 
Analysis Set (Study 54767414MMY2036)
Analysis set: Safety
###
###
###
###
Total number of subjects with TEAE
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
MedDRA system organ 
class/preferred term
System organ class
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Preferred term
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
System organ class
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Preferred term
### (xx.x%)
### (xx.x%)
### (xx.x%)
### (xx.x%)
Key: TEAE = treatment-emergent adverse event, 
Note: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event. 
Adverse events are coded using MedDRA Version XX.X. Percentages are calculated with the number of subjects in each group as 
denominator.
Display Specifications
Output Identifier
TSFAE02
Programming Notes:
1.
For any uncoded system organ class, present system organ class in table as “Uncoded”; for any uncoded 
preferred terms, present ‘Uncoded’ and add verbatim in parenthese next to the preferred term. 
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
35
Approved, Date: 25 September 2018
LSFAE01: Listing of Treatment-emergent Adverse Events; Safety Analysis set (Study 54767414MMY2036)
Treatment 
Group
Site 
ID
Subject 
ID
Onset Date 
(Study Day)
End Date 
(Study Day)
Preferred 
Term
SAE?
Toxicity 
Grade
Relationship toa
Action Taken withb
Outcome
IRR Associated 
withc
Immune 
Mediated? 
(Y/N)
A DLT ? 
(Y/N)
Dara
JNJ-283
Dara
JNJ-283
Dara JNJ-283
xxx
xxx
xxx
2014-06-21 (1)2014-06-21 (1)
Cough
No
1
VL
NR
DI
DNC
RECOVERED/
RESOLVED
Y
N
N
N
2014-06-29 (9) 2014-06-30 
(10)
Blood 
blister 
Yes
3
NR
VL
DI
DW
RECOVERED/
RESOLVED
N
N
N
Y
Key: Dara=daratumumab. JNJ-283=JNJ-63723283. SAE = Serious adverse event. IRR=infusion related reaction. DLT=dose-limiting toxicity.
a: NR = Not Related. DO = Doubtful, Poss. = Possible, Prob. = Probable, VL = Very Likely.
b: DI = Drug Interrupted, DNC = Dose Not Changed, DR = Dose Reduced, DW = Drug Withdrawn, NA = Not Applicable, UN = Unknown.
c: Y=Yes. N=No. NA=Not Applicable. UN=Unknown.
Note: Adverse events are coded using MedDRA version XX.X.
Display Specifications
Output Identifier
LSFAE01
Programming notes:
1.
Sort the list by treatment group (Safety run-in, Arm A, Arm B), site ID, subject ID, Onset Date 
Display Specifications
Output Identifier
LSFAE02
Programming notes:
1.
Update ‘Treatment-emergent Adverse Events’ in the title to ‘Treatment-emergent Serious Adverse Events’.
2.
Remove the ‘SAE?’ column
3.
Delete the ‘SAE=Serious adverse event’ in the footnote.
4.
Sort the list by treatment group (Safety run-in, Arm A, Arm B), site ID, subject ID, Onset Date 
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
36
Approved, Date: 25 September 2018
Display Specifications
Output Identifier
LSFAE03
Programming notes:
1.
Update ‘Treatment-emergent Adverse Events’ in the title to ‘Treatment-emergent Grade 3 or 4 Adverse Events’.
2.
Sort the list by treatment group (Safety run-in, Arm A, Arm B), site ID, subject ID, Onset Date 
Display Specifications
Output Identifier
LSFAE04
Programming notes:
1.
Update ‘Treatment-emergent Adverse Events’ in the title to ‘Subjects who Discontinued All Study Treatment Because of 1 or More Treatment-emergent 
Adverse Events’.
2.
Sort the list by treatment group (Safety run-in, Arm A, Arm B), site ID, subject ID, Onset Date 
Display Specifications
Output Identifier
LSFAE05
Programming notes:
1.
Update ‘Treatment-emergent Adverse Events’ in the title to ‘Subjects who Discontinued Any Study Drugs Because of 1 or More Treatment-emergent Adverse 
Events’.
2.
Sort the list by treatment group (Safety run-in, Arm A, Arm B), site ID, subject ID, Onset Date 
Display Specifications
Output Identifier
LSFAE06
Programming notes:
1.
Update ‘Treatment-emergent Adverse Events’ in the title to ‘Infusion Related Reactions’.
2.
Sort the list by treatment group (Safety run-in, Arm A, Arm B), site ID, subject ID, Onset Date 
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
37
Approved, Date: 25 September 2018
Display Specifications
Output Identifier
LSFAE07
Programming notes:
1.
Update ‘Treatment-emergent Adverse Events’ in the title to ‘Immune Mediated Adverse Events’.
2.
Remove the ‘Immune Mediated? (Y/N)’ column.
3.
Sort the list by treatment group (Safety run-in, Arm A, Arm B), site ID, subject ID, Onset Date 
Display Specifications
Output Identifier
LSFAE08
Programming notes:
1.
Update ‘Treatment-emergent Adverse Events’ in the title to ‘Treatment-emergent Adverse Events Leading to Cycle Delay or Dose Modifications’.
2.
Sort the list by treatment group (Safety run-in, Arm A, Arm B), site ID, subject ID, Onset Date 
Display Specifications
Output Identifier
LSFAE09
Programming notes:
1.
Update ‘Treatment-emergent Adverse Events ’Treatment-emergent Adverse Events Leading to Infusion Interrupted, Infusion Rate Decreased or Infusion 
Aborted’.
2.
Sort the list by treatment group (Safety run-in, Arm A, Arm B), site ID, subject ID, Onset Date 
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
38
Approved, Date: 25 September 2018
LSFAE10: Listing of Subjects Who Had New Malignancies; Safety Analysis set (Study 54767414MMY2036)
Treatment 
Group
Site ID Subject 
ID
Line 
Number
Diagnosis
Diagnosis 
Date (Study 
Day)
Existing malignancy 
(Y/N) / Initiation 
Diagnosis Date if ‘Y’ 
(Study Day)
Confirmed by 
pathology (Y/N) /
Diagnosis 
Method if ‘Y’
Stage of 
Disease/Staging 
System
Total No./Dose 
(mg/kg) of Dara
Infusions
Total No./Dose 
(mg)of JNJ-283 
Infusions
Treatment for 
The New 
Malignancy
Outcome
xxx
xxx
xx
1
ACUTE 
MONOBLASTI
C LEUKEMIA
Y/2005-05-01 (-100)
Y/Biopsy
III/ISS
15/300
10/2400
Curative 
Surgery
RECOVERED/R
ESOLVED
Key: Dara= daratumumab. JNJ-283=JNJ-63723283.
LSFDTH-ST01: Listing of Subjects Who Died During the Study; Safety Analysis Set (Study 54767414MMY2036)
Treatment Group
Site ID
Subject ID
Total No. of Dara 
Infusions/Total Dose (mg/kg) 
/Study Day of Last Infusion
Total No. of JNJ-283 
Infusions/Total Dose 
(mg)/Study Day of Last 
Infusion
Date of Death 
(Study Day)
Primary Cause of 
Death
(If ‘AE’, Preferred 
Term)
Relationship toa
Dara
JNJ-283
*Infliximab 5 mg/kg
XX
SSSS-PPPP
20/320/270
8/1920/270
2017-07-21 (xx)
AE(Upper 
respiratory tract 
infection)
NR
NR
Key: Dara=daratumumab. JNJ-283=JNJ-63723283
a: NR = Not Related. DO = Doubtful, Poss. = Possible, Prob. = Probable, VL = Very Likely.
Note: Adverse events are coded using MedDRA version XX.X.
Display Specifications
Output Identifier
LSFDTH01
Programming Notes:
1.
Sort listing based on treatment group (Safety run-in, Arm A, Arm B), site ID, subject ID.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
39
Approved, Date: 25 September 2018
TSFLAB-ST07: Shift Table of Baseline versus Worst Toxicity Grade during Treatment in Hematological Test; Safety Analysis Set (Study 
54767414MMY2036)
Treatment Group and Evaluation at baseline
N
Grade 0
Grade 1
Grade 2
Grade 3
Grade 4
Analysis set: Safety 
###
WBC low (Leukopenia)
Post-baseline
###
Grade 0
##
##
##
##
##
Grade 1
##
##
##
##
##
Grade 2
##
##
##
##
##
Grade 3
##
##
##
##
##
Grade 4
##
##
##
##
##
Etc.
Note: N is the number of subjects with non-missing values for the specific lab test at baseline and at least one postbaseline visit during treatment. The laboratory toxicity grades are derived 
based on the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Version 4.03.
Display Specifications
Output Identifier
TSFLAB01
Programming Notes:
1.
Parameters: Platelets low (Thrombocytopenia), Neutrophils low (Neutropenia), Hemoglobin low (Anemia), and Lymphocytes low (Lymphocytopenia) 
Display Specifications
Output Identifier
TSFLAB02
Programming Notes:
1.
Update ‘Hematology’ in the title to ‘Chemistry’ 
2.
List for parameters: ALT high, AST high, Creatinine high, Sodium high (Hypernatremia), Sodium low (Hyponatremia), Potassium high (Hyperkalemia), 
Potassium low (Hypokalemia), Bilirubin high (hyperbilirubinemia), Alkaline phosphatase high, Corrected calcium high (Hypercalcemia), Corrected calcium 
low (Hypocalcemia), amylase high (hyperamylasemia), total lipase high (hyperlipasemia)
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
40
Approved, Date: 25 September 2018
LSFLAB-ST01: Listing of Hematology Laboratory Values; Safety Analysis Set (Study 54767414MMY2036)
Treatment Group
Site ID
Subject ID
Parameter (Unit)
Visit
Assessment Date 
(Study Day)
Result
Normal Range
xx
xx-xx
Display Specifications
Output Identifier
LSFLAB01
Programming Notes:
1.
Update ‘Hematology’ in the title to ‘Other’
2.
List for parameters: Thyroid Stimulating Hormone; Free triiodothyronine (T3); Total triiodothyronine (T3); Free thyroxine (T4)
3.
Unscheduled results or multiple results taken at the same visit will be reported here.
4.
The standard sort order is Treatment Group, Site ID, Subject ID, Parameter, and Assessment Date.
Display Specifications
Output Identifier
LSFVS01
Programming Notes:
1.
Update ‘Hematology’ in the title to ‘Vital Signs’
2.
List for parameters: Diastolic blood pressure (mmHg), Systolic blood pressure (mmHg) and weight (kg)
3.
Unscheduled results or multiple results taken at the same visit will be reported here.
4.
The standard sort order is Treatment Group, Site ID, Subject ID, Parameter, and Assessment Date.
5.
Remove the ‘Normal Range’ column.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
41
Approved, Date: 25 September 2018
LSFECG-ST01: Listing of ECG Results; Safety Analysis Set (Study 54767414MMY2036)
Treatment Group
Site ID
Subject ID
Visit
Assessment Date 
(Study Day)
Oerall Interpretation
If ‘Abnormal’, Clinically Significant? 
(Y/N)
Display Specifications
Output Identifier
LSFECG01
Programming Notes:
1.
Unscheduled results or multiple results taken at the same visit will be reported here.
2.
The standard sort order is Treatment Group, Site ID, Subject ID, Parameter, and Assessment Date.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
42
Approved, Date: 25 September 2018
TPK-ST07:
Summary of Daratumumab Concentrations (ug/mL); Pharmacokinetic-evaluable Analysis Set
(Study 54767414MMY2036)
Analysis set: pharmacokinetic-evaluable 
analysis set
##
##
##
##
Cycle 1 Day 1
N
###
###
###
###
Mean (SD)
x.xx (x.xxx)
x.xx (x.xxx)
x.xx (x.xxx)
x.xx (x.xxx)
Median
xxx.x
xxx.x
xxx.x
xxx.x
Range
(xxx.x, xxx.x)
(xxx.x, xxx.x)
(xxx.x, xxx.x)
(xxx.x, xxx.x)
CV (%)
xxx
xxx
xxx
xxx
Geometric mean
x.xx 
x.xx 
x.xx 
x.xx 
Cycle 2 Day 1
N
###
###
###
###
Mean (SD)
x.xx (x.xxx)
x.xx (x.xxx)
x.xx (x.xxx)
x.xx (x.xxx)
Median
xxx.x
xxx.x
xxx.x
xxx.x
Range
(xxx.x, xxx.x)
(xxx.x, xxx.x)
(xxx.x, xxx.x)
(xxx.x, xxx.x)
CV (%)
xxx
xxx
xxx
xxx
Geometric mean
x.xx 
x.xx 
x.xx 
x.xx 
Cycle 3 Day 1
N
###
###
###
###
Mean (SD)
x.xx (x.xxx)
x.xx (x.xxx)
x.xx (x.xxx)
x.xx (x.xxx)
Median
xxx.x
xxx.x
xxx.x
xxx.x
Range
(xxx.x, xxx.x)
(xxx.x, xxx.x)
(xxx.x, xxx.x)
(xxx.x, xxx.x)
CV (%)
xxx
xxx
xxx
xxx
Geometric mean
x.xx 
x.xx 
x.xx 
x.xx 
…
Key: SD = standard deviation, CV = coefficient of variation.
Note: Table includes subjects who received at least 1 administration of daratumumab and have at least 1 pharmacokinetic sample 
concentration value after the first infusion.
Note: Predose samples with a time of collection prior to the start of infusion for Cycle 1 Day 1, and up to 6 hours prior to the start of 
infusion for other predose samples will be included from summary statistics. Postdose samples with a time of collection before the 
end of infusion or more than 15 min after the end of infusion will be excluded from summary statistics.
Display Specifications 
Output Identifier
TPKCONC01
Programming notes:
1.
Present all available visits.
2.
For visits of ‘4 weeks after last dose’ and ‘8 weeks after last dose’, data are displayed in the postinfusion 
column.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
43
Approved, Date: 25 September 2018
Display Specifications 
Output Identifier
TPKCONC02
Programming notes:
1.
Change ‘Daratumumab’ in the title to ‘JNJ-63723283’.
2.
Present all available visits.
3.
For visits of ‘4 weeks after last dose’ and ‘8 weeks after last dose’, data are displayed in the postinfusion 
column.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
44
Approved, Date: 25 September 2018
GPK-ST05: Mean and Standard Deviation of Daratumumab Serum Peak and Trough Concentrations 
(ug/mL); Pharmacokinetic-evaluable Analysis Set (Study 54767414MMY2036)
Note: At each time point, concentration values are plotted on linear scale, and the error bars are mean +/- standard 
deviation.
Note: Predose samples with a time of collection before the start of infusion for Cycle 1 Day 1, and up to 6 hours prior to 
the start of infusion for other predose samples will be included from summary statistics. Postdose samples with a time of 
collection before the end of infusion or more than 15 min after the end of infusion will be excluded from summary 
statistics.
Display Specifications 
Output Identifier
GPKCONC01
Programming Notes:
1.
Present all available visits in x-axis. 
2.
Display Specifications 
Output Identifier
GPKCONC02
Programming Notes:
1.
Change ‘Daratumumab’ in the title to ‘JNJ-63723283’
2.
Present all available visits in x-axis. 
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
45
Approved, Date: 25 September 2018
TPKIR-ST01:
Summary of Anti-daratumumab Antibodies Status; Immunogenicity Analysis Set (Study 
54767414MMY2036)
Analysis set: immunogenicity
###
###
###
Subjects with appropriate samplesa
###
###
###
Subjects with baseline positive samplesb,c
### (xx.x%)
### (xx.x%)
### (xx.x%)
Subjects positive for anti-daratumumab 
antibodiesb,d
### (xx.x%)
### (xx.x%)
### (xx.x%)
Peak titer
1:20
###
###
###
    Subjects positive for neutralizing 
antibodies
### (xx.x%)
### (xx.x%)
### (xx.x%)
Subjects negative for anti-daratumumab 
antibodiesb,e
### (xx.x%)
### (xx.x%)
### (xx.x%)
a Subjects with appropriate samples had 1 or more samples obtained after their first daratumumab administration.
b Denominator is subjects with appropriate samples.
c Subjects with baseline samples positive had samples positive for anti-daratumumab antibodies at baseline, regardless of status 
after first daratumumab administration.
d Subjects positive for anti-daratumumab antibodies includes all subjects who were positive (treatment-boosted or treatment-
induced) at any time after their first daratumumab administration. Subjects with baseline positive samples and without increased 
titer after treatment are not considered treatment-boosted.
e Excludes subjects who were positive at any time.
Display Specifications 
Output Identifier
TPKIR01
Programming notes:
1.
Please remove row of “Peak titer” if there is no subject positive for antibodies to daratumumab.
2.
Please remove ‘d’ if there are no subject positive for antibody to daratumumab, and change the label ‘e’ to 
‘d’.
Display Specifications 
Output Identifier
TPKIR02
Programming notes:
1.
Change ‘Daratumumab’ to ‘JNJ-63723283’ in the whole table.
2.
Please remove row of “Peak titer” if there is no subject positive for antibodies to JNJ-63723283.
3.
Please remove ‘d’ if there are no subject positive for antibody to JNJ-63723283, and change the label ‘e’ to 
‘d’.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
46
Approved, Date: 25 September 2018
LPKIR-ST01:
List of Subjects Positive for Anti-daratumumab Antibodies Status; Immune Response-evaluable Analysis Set (Study 54767414MMY2036)
Treatment Group 
Subject ID
Visit/Time Point
Infusion Given?
Infusion Related 
Reaction
Serious
Toxicity 
Grade
Daratumumab 
Conc. (μg/mL)
Antibody to 
Daratumumab Titer
Safety run-in
######
CYCLE 1 DAY 
1/PREDOSE
Yes
Yes
No
1
LLOQ
NEGTIVE
CYCLE 2 DAY 
1/PREDOSE
No
NA
443.7
1:20
Key: NA= not applicable.
Display Specifications
Output Identifier
LPKCONC01
Programming Notes:
1.
Listing sort: Treatment Group, Subject ID, and Visit. 
2.
This listing should include all visits where PK sampling was performed for subjects positive for ADA. The titer column will either present the actual titer value 
(which means they were positive), will be ‘NEGATIVE’ if there is no titer value (which means they were negative at that visit), or will be “NA” if there was no titer 
sample at that visit.
Display Specifications
Output Identifier
LPKCONC02
Programming Notes:
1.
Change the ‘daratumumab’ to ‘JNJ-63723283’ in the listing.
2.
Listing sort: Treatment Group, Subject ID, and Visit. 
3.
This listing should include all visits where PK sampling was performed for subjects positive for ADA. The titer column will either present the actual titer value 
(which means they were positive), will be ‘NEGATIVE’ if there is no titer value (which means they were negative at that visit), or will be “NA” if there was no 
titer sample at that visit.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
47
Approved, Date: 25 September 2018
GBMK01: Plot of Percent of Total Natural Killer Cells in Blood Over Time; Safety Analysis Set (Study 54767414MMY2036)
Programming note: 
1.
Display the treatment groups as ‘Safety Run-in’ or ‘Arm A’, 
2.
Display the scheduled visits for this study.
3.
Update the y-lab as appropriate.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
48
Approved, Date: 25 September 2018
TBMK01: Summary of Percent of Total Natural Killer Cells in Blood Over Time; Safety Analysis Set (Study 54767414MMY2036) 
Change from Baseline 
N 
Mean 
SD 
Med 
Min 
Max 
Base 
Mean 
N 
Mean 
SD 
Med 
Min 
Max 
Percent of total natural killer cells (%)
Safety Run-in
Baseline
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
xxx.xx
Cycle 1 Day 8
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
xxx.xx
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
Cycle 1 Day 15
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
xxx.xx
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
…
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
xxx.xx
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
Arm A
Baseline
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
xxx.xx
Cycle 1 Day 8
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
xxx.xx
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
Cycle 1 Day 15
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
xxx.xx
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
…
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
xxx.xx
xxx
xxx.xx
xxx.xxx
xxx.xx
xx.x
xxx.x
Programming note: 
1.
Display the scheduled visits for this study.
2.
Update the biomarker name in the title as appropriate.
3.
Update the biomarker name in the first row of the table and unit as appropriate.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
49
Approved, Date: 25 September 2018
5.
NARRATIVE CRITERION

Deaths within 30 days of last dose of study treatment 

Discontinuations of study treatment due to treatment-emergent AEs 

Treatment-emergent serious AEs

Adverse events of clinical interest

Infusion-related reaction, Grade 3 or higher

Treatment-emergent Immune-related AE, Grade 3 or higher

Treatment-emergent infections/infestations, SAE or Grade 3 or higher

Treatment-emergent hemorrhage events, SAE or Grade 3 or higher  

Treatment-emergent tumor lysis syndrome, SAE or Grade 3 or higher

New Malignancies

Treatment-emergent anaphylaxis or suspected anaphylaxis

Treatment-emergent for subject who require the DIRA test result to confirm CR/sCR or 
treatment-emergent for subject who has earlier date of CR/sCR due to DIRA

Treatment-emergent intravascular hemolysis

Treatment-emergent interference with cross-matching and red blood cell antibody screening
6.
PROGRAMMING CODE FOR STATISTICAL PROCEDURES (IF REQUIRED)
7.
LIST OF POST HOC OUTPUT (IF REQUIRED)
IDENTIFIER
OUTPUT TITLE
ANALYSIS SET
TO DO
REFERENCE 
LAYOUT
8.
ADDITIONAL ANALYSIS/DEVIATION RULES
Please see DPS_ part 2.
NCT03357952


JNJ-63723283; JNJ-54767414    (DARZALEX®, daratumumab)
Statistical Analysis Plan/Data Presentation Specifications 54767414MMY2036
50
Approved, Date: 25 September 2018
REFERENCES
1.
Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. 
Leukemia. 2006;20(9):1467-1473.
2.
Kumar S, Paiva B, Anderson KC et al. International Myeloma Working Group consensus criteria for response 
and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328-46
3.
Rajkumar SV, Harousseau JL, Durie B, et al. Consensus recommendations for the uniform reporting of clinical 
trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117(18):4691-4695
NCT03357952