A Phase 1b-2, Open-Label Study of JNJ-68284528, A Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Relapsed or Refractory Multiple Myeloma
Phase: PHASE1
Conditions: Multiple Myeloma
Sponsor: Janssen Research & Development, LLC

CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved,  Date: 15 June 2022
Janssen Research & Development*
Clinical Protocol
A Phase 1b-2, Open-Label Study of JNJ-68284528, a Chimeric Antigen Receptor T cell
(CAR-T) Therapy Directed Against BCMA in Subjects with Relapsed or Refractory 
Multiple Myeloma
CARTITUDE-1
Protocol 68284528MMY2001; Phase 1b-2
AMENDMENT 5
JNJ-68284528
*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 Pharmaceutica NV; Janssen, Inc; 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.
This study will be conducted under US Food & Drug Administration IND regulations (21 CFR 
Part 312).
EudraCT NUMBER:         2018-000121-32
Status:
Approved
Date:
15 June 2022
Prepared by:
Janssen Research & Development
EDMS number:
EDMS-ERI-155210182, 6.0
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.
NCT03548207

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved,  Date: 15 June 2022
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 5
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 5
PROTOCOL AMENDMENTS....................................................................................................................... 6
SYNOPSIS.................................................................................................................................................. 31
TIME AND EVENTS SCHEDULE .............................................................................................................. 33
ABBREVIATIONS ...................................................................................................................................... 43
1.
INTRODUCTION................................................................................................................................ 45
1.1.
Multiple Myeloma ........................................................................................................................... 45
1.2.
BCMA............................................................................................................................................. 45
1.3.
CAR-T Therapy.............................................................................................................................. 45
1.4.
JNJ-68284528................................................................................................................................ 46
1.5.
Summary of Clinical Studies .......................................................................................................... 47
1.6.
Overall Rationale for the Study...................................................................................................... 50
1.7.
Potential Safety Risks and Mitigation Strategies ........................................................................... 50
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESES.......................................................................... 52
2.1.
Objectives and Endpoints .............................................................................................................. 52
2.2.
Hypotheses .................................................................................................................................... 54
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 54
3.1.
Overview of Study Design.............................................................................................................. 54
3.2.
Rationale of Dose and Administration Schedule Selection............................................................ 57
3.3.
Dose De-escalation........................................................................................................................ 58
3.4.
Dose Escalation ............................................................................................................................. 59
3.5.
Safety Evaluation Team................................................................................................................. 59
4.
SUBJECT POPULATION.................................................................................................................. 60
4.1.
Inclusion Criteria ............................................................................................................................ 60
4.2.
Exclusion Criteria ........................................................................................................................... 63
5.
INTERVENTION ALLOCATION AND BLINDING ............................................................................ 66
6.
DOSAGE, ADMINISTRATION, AND GUIDANCE............................................................................ 66
6.1.
Study Treatment Administration..................................................................................................... 66
6.1.1.
Criteria for Apheresis.................................................................................................................. 67
6.1.2.
Criteria for Conditioning Regimen (Cyclophosphamide and Fludarabine) Dosing..................... 68
6.1.3.
Evaluation Prior to Administration of JNJ-68284528.................................................................. 69
6.1.4.
JNJ-68284528 Administration .................................................................................................... 70
6.2.
Pre-infusion Supportive Therapy ................................................................................................... 71
6.3.
Management Guidelines for Potential Risks.................................................................................. 71
6.3.1.
Management of Cytokine Release Syndrome............................................................................ 71
6.3.2.
Neurologic Toxicities................................................................................................................... 74
6.3.2.1.
CAR-T Cell-related Neurotoxicity (Immune Effector Cell-Associated Neurotoxicity 
Syndrome [ICANS]) ................................................................................................................. 74
6.3.2.2.
Other Neurotoxicities ............................................................................................................... 76
6.3.3.
Tumor Lysis Syndrome............................................................................................................... 77
6.3.4.
Cytopenia.................................................................................................................................... 78
6.3.5.
Hypogammaglobulinemia ........................................................................................................... 78

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
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Status: Approved,  Date: 15 June 2022
6.3.6.
Infections .................................................................................................................................... 78
6.3.7.
Hypersensitivity Reactions.......................................................................................................... 79
6.3.8.
Second Primary Malignancy....................................................................................................... 79
7.
INTERVENTION COMPLIANCE....................................................................................................... 79
8.
PRESTUDY AND CONCOMITANT THERAPY ................................................................................ 79
8.1.
Permitted Medications.................................................................................................................... 80
8.2.
Prohibited Therapies...................................................................................................................... 80
8.3.
Subsequent Anticancer Therapy.................................................................................................... 81
9.
STUDY EVALUATIONS .................................................................................................................... 81
9.1.
Study Procedures........................................................................................................................... 81
9.1.1.
Overview..................................................................................................................................... 81
9.1.2.
Screening Phase ........................................................................................................................ 82
9.1.3.
Apheresis.................................................................................................................................... 82
9.1.4.
Cyclophosphamide and Fludarabine Conditioning Regimen ..................................................... 82
9.1.5.
JNJ-68284528 Administration .................................................................................................... 82
9.1.6.
Post-treatment Phase................................................................................................................. 82
9.1.6.1.
Post-infusion Period ................................................................................................................ 83
9.1.6.2.
Post-treatment Period.............................................................................................................. 83
9.1.6.3.
Long-term Follow-up................................................................................................................ 83
9.2.
Safety Evaluations ......................................................................................................................... 84
9.3.
Pharmacokinetics and Immunogenicity ......................................................................................... 88
9.3.1.
Evaluations ................................................................................................................................. 88
9.3.2.
Analytical Procedures................................................................................................................. 88
9.3.3.
Pharmacokinetic Parameters ..................................................................................................... 89
9.3.4.
Immunogenicity Assessment/Antibodies to JNJ-68284528 ....................................................... 89
9.4.
Biomarker Evaluations ................................................................................................................... 89
9.4.1.
Pharmacodynamic/Predictive Markers....................................................................................... 90
9.4.2.
Minimal Residual Disease .......................................................................................................... 91
9.5.
Pharmacokinetic/Pharmacodynamic Evaluations.......................................................................... 91
9.6.
Efficacy Evaluations....................................................................................................................... 91
9.6.1.
Myeloma Protein Measurements in Serum and Urine................................................................ 92
9.6.2.
Serum Calcium Corrected for Albumin....................................................................................... 92
9.6.3.
Bone Marrow Examination.......................................................................................................... 92
9.6.4.
Skeletal Survey........................................................................................................................... 93
9.6.5.
Documentation of Extramedullary Plasmacytomas.................................................................... 93
9.7.
Sample Collection and Handling.................................................................................................... 94
9.8.
Patient-reported Outcome Assessments (Phase 2 Only) .............................................................. 94
9.9.
Qualitative Interviews (Phase 2 Only)............................................................................................ 95
9.10.
Medical Resource Utilization.......................................................................................................... 96
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL 
FROM THE STUDY ........................................................................................................................... 96
10.1.
Completion ..................................................................................................................................... 96
10.2.
Discontinuation of Study Treatment............................................................................................... 96
10.3.
Withdrawal from the Study............................................................................................................. 97
10.4.
Withdrawal from the Use of Research Samples ............................................................................ 97
11.
STATISTICAL METHODS................................................................................................................. 97
11.1.
Subject Information ........................................................................................................................ 98
11.2.
Sample Size Determination ........................................................................................................... 98
11.3.
Efficacy Analyses ........................................................................................................................... 99
11.4.
Safety Analyses ........................................................................................................................... 100
11.5.
Pharmacokinetic Analyses........................................................................................................... 101
11.6.
Pharmacokinetic/Pharmacodynamic Analyses............................................................................ 101
11.7.
Immunogenicity Analyses ............................................................................................................ 101

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
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Status: Approved,  Date: 15 June 2022
11.8.
Patient-reported Outcome Assessments (Phase 2 Only) ............................................................ 102
11.9.
Medical Resource Utilization........................................................................................................ 102
12.
ADVERSE EVENT REPORTING .................................................................................................... 102
12.1.
Definitions .................................................................................................................................... 102
12.1.1.
Adverse Event Definitions and Classifications ......................................................................... 102
12.1.2.
Attribution Definitions................................................................................................................ 103
12.1.3.
Severity Criteria ........................................................................................................................ 104
12.2.
Special Reporting Situations........................................................................................................ 105
12.3.
Procedures................................................................................................................................... 105
12.3.1.
All Adverse Events.................................................................................................................... 105
12.3.2.
Serious Adverse Events ........................................................................................................... 106
12.3.3.
Adverse Events of Special Interest........................................................................................... 107
12.3.4.
Pregnancy................................................................................................................................. 108
12.4.
Contacting Sponsor Regarding Safety......................................................................................... 108
13.
PRODUCT QUALITY COMPLAINT HANDLING............................................................................ 108
13.1.
Procedures................................................................................................................................... 109
13.2.
Contacting Sponsor Regarding Product Quality .......................................................................... 109
14.
STUDY TREATMENT INFORMATION ........................................................................................... 109
14.1.
Physical Description of Study Treatment..................................................................................... 109
14.2.
Packaging .................................................................................................................................... 109
14.3.
Labeling........................................................................................................................................ 109
14.4.
Preparation, Handling, and Storage............................................................................................. 109
14.5.
Drug Accountability ...................................................................................................................... 110
15.
STUDY-SPECIFIC MATERIALS..................................................................................................... 110
16.
ETHICAL ASPECTS ....................................................................................................................... 111
16.1.
Study-specific Design Considerations ......................................................................................... 111
16.2.
Regulatory Ethics Compliance..................................................................................................... 112
16.2.1.
Investigator Responsibilities ..................................................................................................... 112
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................. 112
16.2.3.
Informed Consent ..................................................................................................................... 113
16.2.4.
Privacy of Personal Data .......................................................................................................... 114
16.2.5.
Long-term Retention of Samples for Additional Future Research............................................ 115
16.2.6.
Country Selection ..................................................................................................................... 115
17.
ADMINISTRATIVE REQUIREMENTS ............................................................................................ 115
17.1.
Protocol Amendments.................................................................................................................. 115
17.2.
Regulatory Documentation .......................................................................................................... 116
17.2.1.
Regulatory Approval/Notification .............................................................................................. 116
17.2.2.
Required Prestudy Documentation........................................................................................... 116
17.3.
Subject Identification, Enrollment, and Screening Logs .............................................................. 117
17.4.
Source Documentation................................................................................................................. 117
17.5.
Case Report Form Completion .................................................................................................... 118
17.6.
Data Quality Assurance/Quality Control ...................................................................................... 118
17.7.
Record Retention ......................................................................................................................... 119
17.8.
Monitoring .................................................................................................................................... 119
17.9.
Study Completion/Termination..................................................................................................... 120
17.9.1.
Study Completion/End of Study................................................................................................ 120
17.9.2.
Study Termination..................................................................................................................... 120
17.10.
On-site Audits............................................................................................................................... 120
17.11.
Use of Information and Publication.............................................................................................. 121
REFERENCES.......................................................................................................................................... 123
INVESTIGATOR AGREEMENT ............................................................................................................... 164

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
5
Status: Approved,  Date: 15 June 2022
LIST OF ATTACHMENTS
Attachment 1:
Criteria for Response to Multiple Myeloma Treatment............................................. 125
Attachment 2:
Deleted ..................................................................................................................... 127
Attachment 3:
International Myeloma Working Group Diagnostic Criteria ...................................... 128
Attachment 4:
Prior Cancer Therapy for Multiple Myeloma and Refractory Myeloma 
Definition................................................................................................................... 129
Attachment 5:
Eastern Cooperative Oncology Group Performance Status Grade ......................... 130
Attachment 6:
Formulas for Estimating Glomerular Filtration Rate ................................................. 131
Attachment 7:
Serum Calcium Corrected for Albumin..................................................................... 132
Attachment 8:
Hepatitis B Virus Screening...................................................................................... 133
Attachment 9:
Time and Events Schedules for Retreatment with JNJ-68284528 .......................... 134
Attachment 10:
Patient Reported Outcomes (PRO) Measures......................................................... 144
Attachment 11:
Cytokine Release Syndrome ASBMT Consensus Grading System ........................ 153
Attachment 12:
Immune Effector Cell-associated Encephalopathy (ICE) Tool................................. 154
Attachment 13:
Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) ASBMT 
Consensus Grading Systema,b ................................................................................. 155
Attachment 14:
Anticipated Adverse Events...................................................................................... 156
Attachment 15:
Handwriting Adverse Event Toxicity Grading Criteria .............................................. 157
Attachment 16:
Anti-microbial Prophylaxis Recommendations......................................................... 158
Attachment 17:
COVID-19 Guidance on Study Conduct and Vaccine Timing.................................. 159
Attachment 18:
Adverse Event Reporting Guidance for Study 68284528MMY2001........................ 163
LIST OF IN-TEXT TABLES AND FIGURES 
TABLES
Table 1:
Time and Events Schedule for Study Procedures/ Assessments ............................................ 33
Table 2:
Time and Events Schedule for Pharmacokinetic and Biomarker Sampling ............................. 40
Table 3:
Potential Risks and Mitigation Strategies ................................................................................. 51
Table 4: 
Summary of CRS Grade by Weight-adjusted Total CAR-positive T Cell Dose (Legend-
2 Study)..................................................................................................................................... 58
Table 5:
Dose Limiting Toxicity Criteria .................................................................................................. 58
Table 6:
JNJ-68284528 Administration................................................................................................... 70
Table 7:
Pre-infusion Medications .......................................................................................................... 71
Table 8:
Guidelines for the Management of Cytokine Release Syndrome............................................. 73
Table 9:
Guidelines for the Management of CAR-T Cell-related Neurotoxicity (eg, ICANS) ................. 75
Table 10:
Guidelines for the Management of Raised ICP / Cerebral Edemaa.......................................... 76
Table 11: Sample Size Scenarios in Phase 1b......................................................................................... 98
Table 12:
Time and Events Schedule for Study Procedures/ Assessments at Retreatment with 
JNJ-68284528......................................................................................................................... 134
Table 13:
Time and Events Schedule for Pharmacokinetic and Biomarker Sampling for 
Retreatment ............................................................................................................................ 140
FIGURES
Figure 1:
LCAR-B38M Coding Region..................................................................................................... 46
Figure 2:
Schematic Overview of the Study Flow Chart .......................................................................... 56

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
6
Status: Approved,  Date: 15 June 2022
PROTOCOL AMENDMENTS
Protocol Version
Date
Original Protocol
11 April 2018
Amendment 1
20 August 2018
Amendment 2
11 March 2019
Amendment 3
30 July 2019
Amendment 4
20 March 2020
Amendment 5
15 June 2022
Amendments below are listed beginning with the most recent amendment.
Amendment 5 (15 June 2022)
The overall reason for the amendment: The reason for the amendment is to inform investigators that patients 
receiving cilta-cel are possibly at a higher risk of severe/fatal outcomes from COVID-19 infection compared with 
patients who are receiving standard of care therapy, and to provide additional guidance for COVID-19 prevention 
and mitigation. Additional guidance for HLH and additional clarifications were also incorporated.
Applicable Section(s)
Description of Change(s)
Rationale: To present all of the guidance on COVID-19 prevention, outcomes, and mitigations in the same 
document.
Attachment 17: 
COVID-19 Guidance 
on Study Conduct 
and Vaccine Timing
Integrated the COVID-19 guidance, which was provided as a separate document, into 
the protocol as Attachment 17.
Rationale: To clarify the timing for COVID-19 vaccination for cilta-cel recipients, consistent with current 
recommendations across the cilta-cel program.
Attachment 17: 
COVID-19 Guidance 
on Study Conduct 
and Vaccine Timing
Added guidance on COVID-19 vaccine timing for cilta-cel recipients.
Rationale: To provide additional prevention and mitigation guidance for COVID-19 infections in patients treated 
with cilta-cel.
1.7. Potential Safety 
Risks and Mitigation 
Strategies (Table 3)
6.3.6. Infections
Attachment 17: 
COVID-19 Guidance 
on Study Conduct 
and Vaccine Timing
Added guidance on measures to prevent and mitigate COVID-19 infection, including the 
importance of vaccines and other preventative measures, the use of prophylaxis therapy 
(eg, Evusheld, if available), and the use of antiviral therapy (eg, Paxlovid, if available) 
for COVID-19 infection.
Rationale: To expand the reporting timeframe for COVID-19 infections.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
7
Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
Time and Events 
Schedule (Table 1)
9.2. Safety 
Evaluations
12.3.1. All Adverse 
Events
Attachment 9: Time 
and Events Schedules 
for Retreatment with 
JNJ-68284528 (Table 
12)
Added text to indicate that events of COVID-19 infection will be reported during the 
first-year post-infusion of cilta-cel.
Rationale: To expand the reporting timeframe for COVID-19 medications.
Time and Events 
Schedule (Table 1)
8. Prestudy and 
Concomitant Therapy
Attachment 17: 
COVID-19 Guidance 
on Study Conduct 
and Vaccine Timing
Attachment 9: Time 
and Events Schedules 
for Retreatment with 
JNJ-68284528 (Table 
12)
Specified that medications for the prevention and treatment of COVID-19, including 
vaccinations against COVID-19, will be reported until 1 year after cilta-cel infusion.
Rationale: To increase awareness and provide additional guidance about the risk of HLH, consistent with health 
authority feedback.
1.7. Potential Safety 
Risks and Mitigation 
Strategies (Table 3)
6.3.1. Management of 
Cytokine Release 
Syndrome
Added language regarding features of HLH that may put subjects at high risk of 
bleeding and included additional measures to be taken if HLH is suspected.
Rationale: For clarity.
12.3.3. Adverse 
Events of Special 
Interest
Removed stated that “Grade 1 or 2 adverse events of special interest would not qualify 
for expedited reporting unless they meet serious adverse event criteria.”
Rationale: To ensure movement and neurocognitive toxicities (ie, parkinsonism) are communicated in an 
expedited fashion, consistent with health authority advice.
12.3.3. Adverse 
Events of Special 
Interest
Added clarification of the requirement for expedited reporting (within 24 hours) of any 
grade movement and neurocognitive toxicity (ie, parkinsonism).
Rationale: To help ensure adverse events are collected and reported as required.
Attachment 18: 
Adverse Event 
Reporting Guidance
for Study 
68284528MMY2001
Attachment was added to summarize requirements for adverse event and expedited 
adverse event reporting.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
Rationale: To be consistent with current recommendations for RCL assessment across the cilta-cel program.
Time and Events 
Schedule (Table 2)
Attachment 9: Time 
and Events Schedules 
for Retreatment with 
JNJ-68284528 (Table 
13)
Clarified the timing (Study Day in addition to Month) of RCL assessment.
Time and Events 
Schedule (Table 2)
9.1.6.3. Long-term 
Follow-up
9.4. Biomarker 
Evaluations
Attachment 9: Time 
and Events Schedules 
for Retreatment with 
JNJ-68284528 (Table 
13)
Added that, if post-treatment assays are negative for RCL during the first year, 
collection of follow-up samples may be discontinued, and yearly review of medical 
history will be sufficient for the patient. If any post-treatment samples are positive, 
further analysis of the RCL, and more extensive patient follow-up should be undertaken.
Rationale: Request for clarity regarding COVID-19 antibody reporting, including timeframe.
9.2. Safety 
Evaluations
Added a request to provide COVID-19 antibody titers, if available, post cilta-cel 
infusion for up to 1 year.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 15 June 2022
Amendment 4 (20 March 2020)
The overall reason for the amendment: The overall reason for the amendment is to add other neurotoxicities as 
a safety risk and implement additional monitoring and risk minimization measures for JNJ-68284528.
Applicable Section(s)
Description of Change(s)
Rationale: Safety information was updated to include other neurotoxicities.
Time and Events 
Schedules (Table 1 
and Table 12); 3.1 
Overview of Study 
Design
Collection of a handwriting sample and frequency of testing was added to the study 
procedures.
Updated footnote “q” (Table 1) and “n” (Table 12) to include handwriting sample.
Time and Events 
Schedules (Table 1 
and Table 12)
Extended ICE neurologic test to be performed at least daily until ICANS is resolved.
For adverse events, added: Report new neurologic adverse events or exacerbation of 
existing neurologic adverse events up to 12 months after JNJ-68284528 infusion.
1.5 Summary of 
Clinical Studies
Added a summary of data for Study 68284528MMY2001 and a description of 6 cases of 
other neurotoxicities. Added updated information on Legend-2 study and Study 
68284528MMY2002.
1.7 Potential Safety 
Risks and Mitigation 
Strategies; Table 3
Added other neurotoxicities to Table 3 (Potential Risks and Mitigation Strategies) as a 
subsection of neurologic toxicities (changed from neurological adverse events).
Added specific information to CRS rather than just cross reference to Section 6.3.1.
Also updated guidance for cytopenias, infections, and hypogammaglobulinemia
2.1 Objectives and 
Endpoints
Added exploratory objective and endpoints to characterize potential early predictive 
markers for neurotoxicity.
6.1.4. JNJ-68284528 
Administration
Added the following: Hospitalization is required for Grade 2, 3, or 4 CAR-T cell-related 
neurotoxicity (eg, ICANS) temporally associated with CRS. Hospitalization for neurotoxicity 
that is not temporarily associated with CRS, or any other neurologic adverse events, is at the 
discretion of the investigator.
6.3.2 Neurological 
Adverse Events
Divided section into overall neurologic adverse events with sub-sections of CAR-T 
cell-related neurotoxicity (ICANS) (Section 6.3.2.1) and other neurotoxicities (Section 
6.3.2.2)
Added that subjects should be monitored for neurotoxicity for 1 year post JNJ-68284528 
infusion.
6.3.2.1 CAR-T Cell-
related Neurotoxicity 
(Immune Effector 
Cell-Associated 
Neurotoxicity 
Syndrome [ICANS])
Added “Consider performing neuroimaging (eg, MRI)…”
Clarified that hospitalization is required for Grade 2, 3, or 4 CAR-T cell-related 
neurotoxicity temporally associated with CRS.
Added recommendation to rule out alternative etiologies at first sign of neurotoxicity.
6.3.2.2 Other 
Neurotoxicities
New section with guidance to monitor for other neurotoxicities

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
9.2 Safety 
Evaluations
Added the following:
Added handwriting assessments to safety measures
Added neurological adverse events to adverse events that are exception to 100 day 
reporting. New neurological adverse events or exacerbation of existing neurological 
adverse events will be reported during the first year post JNJ-68284528 dose.
Added grading criteria to be used for neurotoxicity and changes in handwriting
For subjects with prior pertinent neurologic disease (eg, stroke, encephalitis) consider 
baseline MRI of the brain and an EEG.
Added a section describing the assessment for qualitative changes in handwriting.
12.3.1. All Adverse 
Events
Added neurological adverse events to the exceptions from reporting until 100 days after 
the last administration of study treatment.
Added “new neurological adverse events or exacerbation of existing neurologic adverse 
events” will be reported during the first year post-dosing JNJ-68284528.
Attachment 15
Handwriting Adverse 
Event Toxicity 
Grading Criteria
Table added for qualitative grading of handwriting sample.
Rationale: Change made to allow for flexibility in assessments.
Time and Events 
Schedules (Table 1 
and Table 12)
Added footnote “s” (Table 1) and “p” (Table 12): Local laboratory assessments may be 
used under specified circumstances (See Section 9.6)
9.6. Efficacy 
Evaluations
Added provision for local laboratory data collection
Rationale: Revised text in the protocol for clarity.
Time and Events 
Schedules (Table 1 and 
Table 12)
Revised as conmeds for adverse events are collected beyond Day 100: Continuous 
from the time of signing of ICF until at least 100 days after last administration of 
any study treatment. Concomitant usage for the treatment of adverse events after 100 
days should be reported.
Time and Events 
Schedules (Table 2 and 
Table 13)
Clarified timing of sample collection for MRD
1.7 Potential Safety Risks 
and Mitigation Strategies; 
Table 3
Added guidance to CRS to “Notify the sponsor if subject is experiencing Grade 2 or 
higher CRS”.
Added guidance for neurologic adverse events to “Notify the sponsor if subject is 
experiencing any grade ICANS”.
Added guidance for neurologic adverse events to “Notify the sponsor if subject is 
experiencing any grade ICANS”.
6.3.4. Cytopenia
Added language for parvovirus B19 testing in subjects with prolonged neutropenia
6.3.5. 
Hypogammaglobulinemia
Added language for IVIG prophylaxis

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
9.4. Biomarker 
Evaluations
Added language for collection of tumor sample for subjects with SPM, 
plasmacytoma sample, and cerebral spinal fluid sample.
Added that if a subject dies and an autopsy is performed, specimens may be 
requested by the sponsor for analysis, as allowed by local regulations.
8. Prestudy and 
Concomitant Therapy
Added that all medications must be recorded “…until at least 100 days after 
infusion of JNJ-68284528
Added: After 100 days, only adverse events that are considered related to study 
drug need to be reported until the end of the study. This includes concomitant 
therapy and any medication used to treat or support adverse events or serious 
adverse events (within or beyond 100 days after infusion).
8.1 Permitted 
Medications
Added that chemotherapy agents used to treat CAR-T cell-related toxicities are 
permitted upon consultation with the sponsor.
8.2 Prohibited Therapies
Removed exception for therapy to treat CAR-T cell-related toxicity from prohibited 
therapies. Added: ‘or protocol-specific therapies which may be used in conjunction 
with JNJ-68284528.
9.4.2. Minimal Residual 
Disease
Added guidance for in the event that a fresh bone marrow aspirate is not collected at 
baseline.
12.3.1. All Adverse 
Events
Added “After 100 days, only adverse events that are considered related to study drug 
need to be reported until the end of the study.”
Revised as follows: “Serious adverse events, including those spontaneously reported 
to the investigator within 100 days after the last administration of any study 
treatment must be reported using the Serious Adverse Event Form.”
Clarified that all deaths not related to disease progression should be reported to the 
sponsor following expedited procedures.
12.3.3 Adverse Events of 
Special Interest
Added other neurotoxicities.
Added events that must be reported to the sponsor using the serious adverse event 
form within 24 hours of awareness.
14.5 Drug Accountability
Added clarification that information in this section relates to study treatment that is 
supplied to investigational sites from the study sponsor.
6.3.6 Infections
Deleted: Consider periodic monitoring for CMV with PCR testing. If PCR is 
positive based on local threshold, clinical judgment and institutional guidelines 
should be followed to decide about initiation of CMV treatment.  
Rationale: Updated information based on current clinical data.
1.7 Potential Safety Risks 
and Mitigation Strategies
Removed statement “Clinical experience with JNJ-68284528 and LCAR-B38M 
CAR-T cells is limited” as to date almost 100 subjects have received an infusion of 
JNJ-68284528.
Added: Longer follow-up and treatment of additional subjects, particularly subjects 
who have received fewer prior therapies than subjects in the Legend-2 and 
68284528MMY2001 studies, may reveal additional risks.
Rationale: Flexibility added to bridging therapy language.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
12
Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
3.1. Overview of 
Study Design
Revised following guidance:
Additional cycles of bridging therapy may be considered based on subject’s clinical 
status and timing of availability of CAR-T product.  Investigator must contact the 
sponsor for approval.
Bridging therapy is now permitted for subjects receiving retreatment, with sponsor 
approval
Time and Events 
Schedule (Table 12)
Since bridging therapy is now permitted for subjects receiving retreatment, added that 
echocardiogram or MUGA scan should be repeated after completion of bridging therapy 
if it includes agents with known cardiotoxicity
Rationale: Grading column added to CRS and ICANS management tables to reflect adoption of ASBMT criteria 
across study protocols.
6.3.1 Management of 
Cytokine Release 
Syndrome; Table 8
6.3.2.1 CAR-T Cell-
related Neurotoxicity 
(ICANS); Table 9
Added column for CRS grade.
Added column for ICANS grade.
Added to row 1 (ICE score 7-9) dexamethasone can be considered for Grade 1 ICANS.
Rationale: Added recommendations for extended anti-microbial usage.
6.3.6. Infections
Added: Extended use of anti-microbial therapies for at least 6 month (or longer as per 
institutional guidelines) or consistent with post ASCT consensus guidelines after CAR-T 
dosing are recommended (see Attachment 16).
Attachment 16
Table with anti-microbial prophylaxis recommendations
Rationale: Corrected an error.
9.3.3. 
Pharmacokinetic 
Parameters
Deleted ‘for each dose level’ from the following statement as all subjects will be 
summarized in 1 group: Pharmacokinetic parameters will be estimated for individuals, 
and descriptive statistics will be calculated for each dose level. 
9.10 Medical 
Resource Utilization
Added “Health economics data such as medical resource utilization data associated 
with medical encounters….”
Added “Health economics data such as costs associated with the medical encounters will 
be collected separately from the eCRF. All health economic data will be used only in a 
de-identified manner.”
Rationale: References were updated.
References
Added reference: MD Anderson Cancer Center. IEC Therapy Toxicity Assessment and 
Management. 2019. Appendix J. https://www.mdanderson.org/documents/for-
physicians/algorithms/clinical-management/clin-management-cytokine-release-web-
algorithm.pdf
Deleted reference: Legend Biotech. Clinical Safety and Efficacy Report. Legend-2 
study. LCAR-B38M-02 or NCT03090659.
Rationale: Minor errors were noted.
Throughout the 
protocol
Minor grammatical, formatting, or spelling changes were made.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
13
Status: Approved,  Date: 15 June 2022
Amendment 3 30 July 2019
The overall reason for the amendment: The overall reason for the amendment is to transition into the Phase 2 
portion of the study, describe the role of the Independent Review Committee (IRC), add the Medical Resource 
Utilization (MRU) assessment, and to add clarity to targeted sections of the protocol.
Applicable Section(s)
Description of Change(s)
Rationale: Updated the protocol title page with the name of the study
Title page
Updated the title of the protocol to include “CARTITUDE-1”.
Rationale: Independent Review Committee added for evaluation of disease status
Synopsis; 2.2 Hypothesis
Synopsis; 2.1 Objectives 
and Endpoints
2.2 Hypotheses
3.1 Overview of Study 
Design;
11.3 Efficacy Analyses
Added language for the inclusion of an Independent Review Committee to evaluate 
disease status.
Clarification added to the study hypothesis: “Treatment with JNJ-68284528 will 
demonstrate acceptable safety and will have significant anti-myeloma activity (ie, 
the lower limit of two-sided 95% confidence interval [CI] for ORR, as assessed by 
the IRC, is greater than 30%) at the targeted recommended Phase 2 dose (RP2D) 
level in subjects with advanced relapsed or refractory multiple myeloma.”
Update to the Evaluations: “Disease status will be evaluated by an Independent 
Review Committee (IRC) according to clinical judgement as guided by the 
IMWG consensus recommendations for multiple myeloma.
The second primary endpoint was updated as follows: ORR (at least a partial 
response [PR] or better) as defined by the International Myeloma Working Group 
(IMWG) response criteria as assessed by the Independent Review Committee 
(IRC).
The following statement was amended to describe the role of the IRC: “Treatment 
with JNJ-68284528 will demonstrate acceptable safety and will have significant anti-
myeloma activity (ie, the lower limit of two-sided 95% confidence interval [CI] for 
ORR, as assessed by the IRC,  is greater than 30%) at the targeted recommended 
Phase 2 dose (RP2D) dose level in subjects with advanced relapsed or refractory 
multiple myeloma. ”The following statement was amended to describe the role of the 
IRC in regard to the evaluation of the primary efficacy analysis: “Disease status will 
be evaluated according to the IMWG consensus recommendations for multiple 
myeloma treatment response criteria (Attachment 1) 10, 11,31. For the primary 
efficacy analysis, the disease status evaluation for each subject will be assessed 
by an Independent Review Committee (IRC). Disease status will be evaluated 
according to clinical judgement guided by the IMWG consensus 
recommendations for multiple myeloma treatment response criteria 
(Attachment 1.) 10, 11,31. The process and convention of the IRC will be detailed 
in a separate charter. Response will be determined using a validated computer 
algorithm.”
The following statement was added: “For efficacy, assessment by the IRC will be 
used as primary.”
Rationale: Changes and corrections made for clarity

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
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Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
T&E Schedule 
(Table 1 and Table 12)
For safety criteria, added a cross reference to Section 6.1.3 (Evaluation Prior to 
Administration of JNJ-68284528).
Added window for Hematology assessment prior to apheresis.
Revised infectious disease assessment to allow for a window of testing prior to 
apheresis for flexibility.
Revised skeletal survey evaluation to “As clinically indicated to assess for document
disease progression or response”.
Footnote “f” (Table 1) and footnote “e” (Table 12) updated to include: “Serology 
results performed as standard of care within 28 days prior to apheresis are 
acceptable.
T&E Schedule 
(Table 1)
Corrected PGIS post-treatment footnote: ‘Xa’ to ‘Xo’.
Footnote “b” updated to include: “For subjects who discontinue the study before Day 
100, including those who have not received an infusion of JNJ-68284528, the 
Day 100 assessments should be performed prior to withdrawal if feasible.” 
6.1. Study Treatment 
Administration
Added subheading for exceptional release criteria.
Rationale: Window added to PK sampling for consistency in collections
T&E Schedule 
(Table 2 and Table 13)
Additional window of “same day as dose of JNJ-68284528 infusion” for the PK 
CAR positive T cell cellular blood sample, the PK CAR transgene levels blood 
sample, and the soluble serum BCMA sample. 
T&E Schedule 
(Table 2)
Clarification to footnote “a”; added “post JNJ-68284528 infusion”.
Rationale: Medical Resource Utilization (MRU) data collection is added to evaluate the total health care 
resources for JNJ-68284528 CAR-T process 
T&E Schedule 
(Table 1 and Table 12);
2.1 Objectives and 
Endpoints;
9.10 Medical Resource 
Utilization; 
11.9 Medical Resource 
Utilization; 
Added Medical Resource Utilization requirements.
Patient Reported Outcome heading updated to include Medical Resource 
Utilization.
Row added to Table 1 for Medical Resource Utilization visit schedule.  
Added footnote “r” to define MRU data collection until Day 180 (± 7 days).
Added an exploratory objective and endpoint.
Added requirements of medical resource utilization
Added method of statistical analysis for medical resource utilization data. 
Rationale: Added kanamycin to hypersensitivity reactions

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
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Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
1.7. Potential Safety 
Risks and Mitigation 
Strategies;
6.3.7 Hypersensitivity 
Reactions
Added kanamycin to list of potential hypersensitivity reactions.
Rationale: Clarification made to retreatment criteria to incorporate guidance for ongoing hematologic vs non-
hematologic toxicity
3.1 Overview of Study 
Design
Modified the eligibility criteria for retreatment to:

Progressive disease (PD) after best response of minimal response (MR) or better. 

No history of Grade 3 or higher toxicities reported

No ongoing Grade 3 or higher hematologic toxicity.

No ongoing Grade 2 non-hematologic toxicity (with the exception of nausea, 
vomiting, hair loss, and constipation).

At least 6 months between first JNJ-68284528 infusion and detection of PD.
Rationale: Revisions made for clarity
6.1.1 Criteria for 
Apheresis;
Added 24-hours prior to apheresis window for results of clinical laboratory values 
required for enrollment.  
6.1.1 Criteria for 
Apheresis; 6.1.2 Criteria 
for Conditioning 
(Cyclophosphamide and 
Fludarabine) Dosing
Added antitumor therapy from exclusion criteria (from Section 4.2) in addition to 
cross reference for clarity.
6.1.2 Criteria for 
Conditioning 
(Cyclophosphamide and 
Fludarabine) Dosing
Clinical laboratory values required for enrollment (Section 4.1), with the following 
exceptions: lymphocyte count of ≥0.3 x 109/L. Transfusion support is permitted to 
maintain a hemoglobin of 8.0 g/dL (5 mmol/L) as needed, and platelets of ≥50 
x 109/L until 3 days before the hematology laboratory test, preceding 
lymphodepletion. and transfusion of platelets and administration of myeloid growth 
factor is permitted until 3 days before the hematology laboratory test preceding 
lymphodepletion. Myeloid growth factors are permitted up to 1 day prior to the start 
of the conditioning regimen. Pegylated myeloid growth factors (ie, pegfilgrastim) are 
prohibited.
9.2 Safety Evaluations
In clinical laboratory test subsection, updated “Blood urea nitrogen” to “Blood urea 
nitrogen/ urea” for countries outside of US.
Rationale: Clarification made to inclusion criteria to better define a regimen. A regimen is a line of therapy
4.1 Inclusion criteria
Modification of inclusion criteria 4.1, 5, and 6 to replace the term “regimen” with 
“line of therapy”.  

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
Rationale: Contraception guidance revised in response to cyclophosphamide labeling.
4.1 Inclusion criteria
4.2 Exclusion criteria
Inclusion criterion #10:  

The timeframe for which subjects must agree to practice a highly 
effective method of contraception has been updated from the time of 
signing the ICF until at least 100 days 1 year after receiving a JNJ-
68284528 infusion.

In addition to the highly effective method of contraception a man must 
also agree to use a barrier method of contraception from the time of 
signing the ICF until at least 100 days 1 year after receiving a JNJ-
68284528 infusion.

Women and men must agree not to donate eggs (ova, oocytes) or sperm, 
respectively, during the study and for 100 days 1 year after the last dose 
of study treatment. 
Exclusion criterion #20:  

Pregnant or breast-feeding, or planning to become pregnant while 
enrolled in this study or within 100 days 1 year after receiving study 
treatment.
Exclusion criterion #21: 

Plans to father a child while enrolled in this study or within 100 days 1 
year after receiving study treatment.
Rationale: Clarification to safety language for consistency
6.1.2 Criteria for 
Conditioning Regimen 
(Cyclophosphamide and 
Fludarabine) Dosing
To be consistent with the revisions to Section 6.1.2., text updated from: “No 
evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection. 
Subjects on anti-infective agents within 7 days prior to apheresis must receive 
approval to proceed from sponsor” to “No signs of active infection. For subjects 
requiring systemic anti-microbial treatment or with temperature ≥38.0 Celsius 
within 7 days prior to the first dose of conditioning regimen, the investigator 
must receive approval to proceed from the sponsor.” 
Rationale: The use of a catheter is no longer applicable
6.1.2 Criteria for 
Conditioning 
(Cyclophosphamide and 
Fludarabine) Dosing
Deleted statement regarding construction of catheter.
Rationale: Modified guidance for dosing delays to ensure subject safety prior to JNJ-68284528 infusion
6.1.3 Evaluation Prior to 
Administration of JNJ-
68284528
JNJ-68284528 Dosing Delays: 
Subjects will be evaluated for safety on the day of JNJ-68284528 infusion. If a 
significant health status change (eg, clinical deterioration, rapidly progressing 
disease, constipation) occurs following the start of the conditioning regimen (see 
Section 6.1.2), the investigator should contact the sponsor prior to dosing.
Infusion of JNJ-68284528 must be delayed if any of the following events occur:
Uncontrolled Signs of active infection. Do not administer JNJ-68284528 to 
subjects with active infection. For subjects requiring systemic anti-
microbial treatment, or with temperature ≥38.0 Celsius within 48 hours 

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
before JNJ-68284528 infusion, investigator must consult with the 
sponsor prior to dosing.
Grade ≥3 non-hematologic toxicities of the cyclophosphamide and 
fludarabine conditioning regimen (except for Grade 3 nausea, vomiting, 
diarrhea, or constipation). Investigator must consult with the sponsor 
prior to dosing.
Rationale: Added language to allow testing of tumor sampling in case of a report of second primary 
malignancies (SPM).
6.3.8 Second Primary 
Malignancy; 9.1.6.3 
Long-term Follow-up
Added sentence “A tumor sample should be collected and DNA, RNA or protein 
analysis may be performed to investigate the presence of lentiviral elements”.  
Rationale: Qualification made to prohibited therapy 
8.2 Prohibited Therapies
Pegylated myeloid growth factors (ie, pegfilgrastim) are prohibited within the first 
100 days after infusion of JNJ-68284528 (Section 6.1.2).
Rationale: Correction of errors
9.1.6.1 Post-Infusion 
Period 
Correction to temperature symbols for reporting fever (> updated to ≥).
Rationale: Clarification to the method of treatment response analysis
9.6 Efficacy Evaluations
The following sentence was deleted: “Disease progression must be consistently 
documented across clinical study sites using the criteria in Attachment 1. The 
sponsor will use a validated computer algorithm to analyze response to treatment.”
Rationale: Clarification to biomarker evaluation language
9.6.3 Bone Marrow 
Examination
Bone marrow aspirate or biopsy (acceptable if aspirate is not possible) will be 
performed for clinical assessments. Bone marrow aspirate will be performed for
and biomarker evaluations. 
Rationale: Clarification to Patient-Reported Outcome Assessments (Phase 2 only)
9.8 Patient-Reported 
Outcome Assessments 
(Phase 2 only)
Language updated as follows: “Full training documentation will be provided to site 
coordinators before the start of data collection. PRO assessments will be conducted 
beyond disease progression or subsequent anticancer therapy. If no site visits are 
scheduled for additional disease evaluations, subjects will have the option of 
completing the PRO assessments after disease progression or subsequent 
anticancer therapy via telephone.”
Rationale: Updates to the efficacy analysis
3.1 Overview of Study 
Design
The sponsor will establish a data cutoff date for clinical study report (CSR) analyses. 
The first primary analysis will be conducted approximately 6 months after the last 
subject received their initial dose of JNJ-68284528. An update of the analysis will 
be provided at approximately 9-12 months after the last subject received their 
initial dose of JNJ-68284528 and at the end of the study which is defined as 2 
years after the last subject has received their initial dose of JNJ-68284528 
(Section 17.9.1). Subjects will be followed for survival after the clinical cutoff for 
the primary CSR.  The data cutoff will be communicated to the sites. Study 
completion/end of study will be defined as no later than 2 years after the last subject 
has received their initial dose of JNJ 68284528 (Section 17.9.1). However, the The
sponsor will monitor subjects treated with JNJ-68284528 for 15 years for 

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
complications of lentiviral integration, including second primary malignancies on a 
long-term follow-up study. 
11.3 Efficacy Analyses
An efficacy analyses end point definition was updated as follows: “Overall response 
rate (ORR) is defined as the proportion of subjects who achieve a PR or better 
according to the IMWG criteria.10,11,31 Response to treatment will be analyzed by a 
validated computerized algorithm.9,29
The following sentence as added to the section: “For efficacy, assessment by the 
IRC will be used as primary.”
The timing of the primary analysis was updated as follows: “The first analysis for 
the primary endpoint, ORR (PR or better), will be conducted approximately at 
6 months after the last subject has received his or her initial dose of JNJ-68284528, 
and will be based on the mITT analysis set. The response rate and its 95% exact
confidence interval (CI) will be calculated based on binomial distribution, and the 
null hypothesis will be rejected if the lower bound of the confidence interval exceeds 
30%. Analysis of VGPR or better response rate, DOR, PFS, and OS will be 
conducted at the same cutoff as the ORR, and an update of these endpoints will be 
provided at approximately 9 -12 months after last subject has received his or her 
initial dose of JNJ-68284528 and at the end of the study, which is defined as 2 
years after the last subject has received his or her initial dose of JNJ-68284528. 
Additional safety data will be collected in a long-term follow-up study.”
Details added regarding the type of analysis are as follows: “A sensitivity analysis 
of ORR will be performed based on the subjects in the mITT analysis set who 
received the JNJ-68284528 product that met all of the pre-specified release 
criteria.
The agreement on ORR between the determination by the IRC and the 
assessment by a validated computerized algorithm developed by the sponsor 
will be evaluated using the kappa statistic and 95% CI will also be provided.”
Rationale: Adverse event template language incorporated for clarity
12.1.3 Severity Criteria
The following statement was added: Any adverse event or serious adverse event 
not listed in the NCI CTCAE Version 5.0 will be graded according to 
investigator clinical judgment by using the standard grades as follows:
Rationale: Clarification regarding reporting of Adverse Event of Special Interest
12.3.3 Adverse Events of 
Special Interest
Change made to the reporting requirements for adverse events of special interest.  
Adverse events of special interest “should be reported to the sponsor in a timely 
manner” replaces text stating “will be reported to the sponsor within 24 hours of 
awareness, and may require enhanced data collection”.
Rationale: Addition to list of study-specific materials
15 Study-Specific 
Materials
Added “Thermal printer and barcode scanner (for sites utilizing Vineti chain of 
custody/chain of identity software in Phase 2)” to end of preexisting list.
Rationale: Added an attachment for anticipated adverse events to fulfil the ICSR requirement from FDA.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
19
Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
Attachment 14:  
Anticipated Adverse 
Events
The attachment of anticipated adverse event was added to specify the definition, 
reporting time of anticipated adverse events, etc.
Rationale: Updates to references
T&E Schedule 
(Table 2 and Table 12);
3.3 Dose De-escalation; 
9.2 Safety Evaluations; 
12.1.3 Severity Criteria; 
Attachment 11; 
Attachment 13 
Update to reference for ASBMT consensus grading for CRS (Lee 2018 changed to 
Lee 2019). 
References
Reference number 9 no longer cited: “Dimopoulos MA, Oriol A, Nahi H, et al. 
Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J 
Med. 2016;375:1319 1331.”
Reference number 22 was updated to: “Lee DW, Santomasso BD, Locke FL, et al. 
ASBMT consensus grading for cytokine release syndrome and neurological toxicity 
associated with immune effector cells. Biol Blood Marrow Transplant.2019 
Apr;25(4):625-638”.
Reference number 29 no longer cited: “Palumbo A, Chanan Khan A, Weisel K, et al. 
Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J 
Med. 2016;375:754 766.”
Rationale: Minor errors were noted
Throughout the protocol
Minor grammatical, formatting, or spelling changes were made.
Amendment 2 (11 March 2019)
The overall reason for the amendment: The overall reason for the amendment is to expand the number of 
subjects enrolled in the Phase 1b portion of the study, update the CRS and neurotoxicity management guidelines, 
update the CRS and neurotoxicity grading system, and add clarity to targeted sections of the protocol.
Applicable Section(s)
Description of Change(s)
Rationale: Revisions made to allow for an expansion in the number of subjects enrolled in the Phase 1b portion 
of the study
Synopsis Overview of 
Study Design and 
Dosage and 
Administration; 
3.1. Overview of 
Study Design;
3.4. Dose Escalation;
11.2. Sample Size 
Determination
The number of subjects enrolled in the Phase 1b portion of the study was expanded from 
“approximately 24” to “at least 24 and up to 50 subjects”.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
Synopsis Dosage and 
Administration;
3.1. Overview of 
Study Design
The following text was also added “ Confirmation of the RP2D will be based on review 
of data from at least 24 subjects who were administered JNJ-68284528. Additional 
subjects (up to 50) will be enrolled in the Phase 1b portion of the study to generate 
supplemental safety and efficacy data at the RP2D.”  
11.2. Sample Size 
Determination
Addition of Table 11 to describe the probabilities of observing the adverse events under 
the assumed true incidence rates of the adverse events with the larger sample sizes.
Rationale: Revisions to the CRS toxicity management recommendations and to incorporate ASBMT consensus 
grading system for CRS 
T&E Schedule 
(Table 1 and 
Table 12);
3.3. Dose De-
escalation;
9.2. Safety 
Evaluations;
12.1.3. Safety Criteria
Attachment 11
Added that CRS will be evaluated according to the new ASBMT consensus grading 
(Lee et al 2018) per new Attachment 11.
6.3.1. Management of 
Cytokine Release 
Syndrome
Revisions to the guidelines for management of CRS in Table 8 to replace CRS grade 
with presenting symptoms. 
Addition of precautionary language in case of severe unresponsive CRS to evaluate for 
HLH/MAS and consider additional interventions.
Revised section title to remove “prevention” to more accurately reflect that the section 
content is for management of CRS
Added additional language around interventions (tocilizumab and other monoclonal 
antibodies targeting cytokines) for CRS.
Attachment 2
Deleted contents of Attachment 2 as CRS grading has been replaced with ASBMT 
consensus grading
Rationale: Revisions to update the neurotoxicity management recommendations, incorporate ASBMT consensus 
grading for Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and include Immune Effector 
Cell-associated Encephalopathy (ICE) Tool.
T&E Schedule 
(Table 1 and 
Table 12);
3.3. Dose De-
escalation;
9.2. Safety 
Evaluations;
12.1.3. Safety 
Criteria;
Attachment 13
Added that CAR-T cell-related neurotoxicity (eg, ICANS) should be graded according 
to the ASBMT consensus grading (Attachment 13).
T&E Schedule 
(Table 1 and Table 
12)
Assessment of ICE test added to Time and Events Schedules Table 1 and Table 11.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
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Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
1.7. Potential Safety 
Risks and Mitigation 
Strategies
Replaced “neurological adverse events” entry in potential risks table with Neurological 
adverse events including CAR-T cell-related neurotoxicity (eg, immune effector cell-
associated neurotoxicity syndrome [ICANS])
Added guidance that hospitalization is required for Grade ≥2 CAR-T cell-related 
neurotoxicity (eg, ICANS).
6.1.4. JNJ-68284528 
Administration;
6.3.2. Neurological 
Adverse Events
Specified that hospitalization is required for Grade 2, 3, or 4 CAR-T cell-related 
neurotoxicity (eg, ICANS) not all neurotoxicity
6.3.2. Neurological 
Adverse Events;
9.2. Safety 
Evaluations;
Attachment 12
Revised section to include definition of ICANS and use of ICE assessment tool. Added 
a description of the neurologic examination and ICE tool to Section 9.2.
Added that at first signs of seizures or raised intracranial pressure/cerebral edema that 
subjects should be transferred to the ICU and treated according to institutional 
guidelines.
Revised Table 9; removed grading assessment and replaced with presenting symptoms.
Management is determined by the most severe event not attributable to any other cause.
Added Table 10 (Guidelines for the management of raised ICP/ cerebral edema).
ICE tool added as Attachment 12
Rationale: Changes made to safety criteria for clarity
T&E Schedule 
(Table 1 and 
Table 12)
Changed “eligibility criteria (predose)” to “safety criteria” (added as separate section) to 
more accurately reflect the assessment.
3.1. Overview of 
Study Design;
6.1.1. Criteria for 
Apheresis
Eligibility criteria required before apheresis now referred to as “safety criteria”. 
Addition of Section 6.1.1 to define the safety criteria to be met before apheresis of the 
subject.
6.1.2. Criteria for 
Conditioning 
Regimen 
(Cyclophosphamide 
and Fludarabine) 
Dosing
Defined cyclophosphamide and fludarabine as conditioning regimen in the title for 
clarity and replaced “cyclophosphamide and fludarabine” with “conditioning regimen” 
for consistency throughout Section 6.1.2.
Revised criterion for corticosteroids to align with changes to exclusion criterion #7. 
Added that the sponsor should be called for approval if a subject receives corticosteroids 
at a dose >10mg per day in the week prior to the start of the conditioning regimen.
Added that myeloid growth factors (but not pegylated myeloid growth factors) are 
permitted up to 1 day prior to the start of the conditioning regimen.
Added cross reference exclusion criterion #4 for washout of bridging therapy.
Rationale: Revisions made to biomarker sample collections in response to emerging data

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
22
Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
T&E Schedule 
(Table 2 and 
Table 13)
Additional collections of immunophenotyping (whole blood) samples on Days 1 (pre-
dose) ,2, 3, 7, 10, 42, 78, and every 4 weeks after Day 100 up to 1 year. Removed 
assessment on Day 184.
Added collection for CyTOF (aspirate) (bone marrow) prior to the first dose of the 
conditioning regimen.
Added sample collection for cytokine profiling on Day 2.
Split “Prior to Subsequent Therapy or Study Completion, Whichever is First” column 
into “At PD” and “At Study Completion for Subjects without PD”
Footnote ‘c’ now only applies to PK CAR positive T-cell, PK transgene levels, and 
ADA samples to state that additional samples are to be collected at CRS or 
neurotoxicity event Grade ≥2.
Added additional CyTOF/PBMC/plasma (whole blood) collections on Day 7 and Day 
10.
T&E Schedule 
(Table 2 and 
Table 13);
9.3.1. Evaluations
Collection of additional cytokine profiling samples at onset of CRS or CAR-T cell-
related neurotoxicity (eg, ICANS) (any grade) and then every 24 hours until event is 
stabilized or resolving at which point additional samples are collected at 24, 48, and 72 
hours or as clinically indicated. Addition of footnote ‘g’ (for cytokine profiling) to Table 
2 and 
Table 13
Rationale: Revisions made for clarity or consistency
T&E Schedule 
(Table 1 and 
Table 12)
Removed the ≤7 day window from the disease characteristics assessment to be 
performed prior to the first dose of conditioning regimen 
Collection of serum 2-microglobulin moved from screening to prior to first dose of 
conditioning regimen to be consistent with collection times of other disease evaluations. 
Additional collection of quantitative immunoglobulins added prior to first dose of
conditioning regimen.
Added “and core biopsy” to “bone marrow aspirate” row title under other disease 
evaluations. Replaced “immunofluorescence” with “flow cytometry” as methodology to 
assess sCR. Revised footnote ‘k’ (Table 1) and ‘j’ (Table 12) to state that bone marrow 
morphology is to be assessed locally at all time points.
T&E Schedule 
(Table 1 and 
Table 12);
9.1.6.1. Post-infusion 
Period
Revised footnote ‘h’ (Table 1) and ‘g’ (Table 12) to indicate that subjects should record 
2 temperatures including their maximum daily temperature in the diary. Clarified in 
footnote that temperature will be checked at least twice a day up to Day 28. Deleted 
reference to temperature collection from Section 9.1.4.1 due to redundancy.
T&E Schedule 
(Table 1 and 
Table 12);
3.1. Overview of 
Study Design;
3.5. Safety Evaluation 
Team;
6.1.4. JNJ-68284528 
Administration
Added clarification that the requirement for hospitalization and local stay will be 
evaluated by the SET.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
T&E Schedule 
(Table 1);
6.1.1. Criteria for 
Apheresis
Screening assessments that should be collected for subjects who undergo a second 
apheresis were identified. Included as footnote ‘a’ in T&E.
Clarified in footnote ‘a’ that the ICF must be signed before any study-related procedures 
are performed and remains in effect if the screening evaluation is not performed within 
the 28 day screening phase.
1.4. JNJ-68284528
Revised the following statement to be consistent with emerging data. “The novel design 
of the BCMA targeting domain facilitates binding of 2 epitopes features dual targeting 
domains on BCMA,…”
2.1. Objectives and 
Endpoints;
9.4 Biomarker 
Evaluations
Revisions to the secondary endpoint of objective to characterize the pharmacokinetics 
and pharmacodynamics of JNJ-68284528 and exploratory endpoint of objective to 
explore whether the infused CAR-positive T cell subsets impact pharmacodynamics, 
safety, and clinical activity of JNJ-68284528. Added CD25+ to list of biomarker 
evaluations.
3.1. Overview of 
Study Design;
3.5. Safety Evaluation 
Team
Text added to clarify the SET meeting interval in Section 3.5. Added to Section 3.1, a 
cross reference to details regarding when SET meetings are to occur.
3.1. Overview of 
Study Design
Clarify that clinical data will be shared with the relevant health authorities before 
administration of JNJ-68284528 to subjects in the Phase 2 portion of the study
3.3. Dose De-
escalation
Clarified that DLTs are those associated with JNJ-68284528
4.1. Inclusion Criteria
Added to criterion #3 that local laboratory assessments may be used to establish
measurable disease at Screening, with local laboratory result ≥125% of requirements
4.2. Exclusion 
Criteria
Revised criterion (#7) on prior corticosteroid use from daily dose to cumulative dose for 
clarity.
Revised criterion (#3) to change to no known active disease present for ≥2 years (change 
from ≥3 years) to be more consistent with ASCO guidance. 
6.1. Study Treatment 
Administration
Added that sponsor approval must be obtained to change the conditioning regimen 
schedule. Removed, due to redundancy, statement regarding re-assessment of eligibility 
criteria if cyclophosphamide and fludarabine is delayed ≥10 weeks.
6.3.7. 
Hypersensitivity 
Reactions
Added for consistency with Table 3 and the Investigator’s Brochure
6.3.8. Second Primary 
Malignancy
Added for consistency with Table 3 and the Investigator’s Brochure
8.1. Permitted 
Medications
Revised language around bisphosphonate recommendation: Bisphosphonates should
may be initiated (if not already being administered) unless contraindicated within 1 
week prior to the first dose of study treatment and continued until disease progression is 
established.
Added therapies intended to treat CAR-T cell-related toxicity (ie, CRS).
Added that myeloid growth factors are permitted up to 1 day prior to the start of the 
conditioning regimen to be consistent with Section 6.1.2.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
24
Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
8.2. Prohibited 
Therapies
Removed “Routine transfusions should not be given on the day of JNJ-68284528 
administration” from list of medications prohibited during the study (ie, routine 
transfusions are allowed on the day of JNJ-68284528 infusion based on institutional 
practice).
Added as an exception to prohibited therapies “part of therapy intended to treat CAR-T 
cell-related toxicity”.
Added guidance that based on the clinical judgment low-dose aspirin may be continued 
for thromboprophylaxis.
Added that Pegylated myeloid growth factors (ie, pegfilgrastim) are prohibited to be 
consistent with Section 6.1.2.
9.4.2. Minimal 
Residual Disease
Revised the following statement “Baseline bone marrow aspirates will be used to define 
the myeloma clones, and post-treatment samples will be used to evaluate MRD 
negativity in those subjects who experience at lease a CR. as MRD testing will be 
performed on all Day 28 samples, not just for subjects in which a CR has been declared.
9.6.1. Myeloma 
Protein 
Measurements in 
Serum and Urine
Revisions for consistency with the guidance provided in the Time and Events Schedule., 
Cross references added to Table 1 and Table 12.
10.3. Withdrawal 
from the Study
For consistency with the addition of the guidance added for risk/benefit consideration in 
the event that a JNJ-68284528 product does not meet pre-specified release criteria 
(Section 6.1), the withdrawal from study language was modified to state “Failure to 
manufacture JNJ-68284528 after 2 apheresis attempts”.
12.3.1. All Adverse 
Events
Removal of terms for adverse events of special interest; now refers to Section 12.3.3 for 
complete information.
12.3.3. Adverse 
Events of Special 
Interest
Edits made for clarity and consistency with other sections of the protocol.
Attachment 6
Modification to the calculation for estimating glomerular filtration rate to standardize 
the calculation and remove reference to online tools.
Rationale: Deletions made due to redundancy
4. Subject Population
Removed “NOTE” at the end of the section. As redundant with addition of Section 6.1.1
9.1.4. 
Cyclophosphamide 
and Fludarabine 
Conditioning 
Regimen
9.1.5. JNJ-68284528 
Administration
Deleted text and added cross reference as content is described elsewhere in the protocol
9.1.6.1. Post-Infusion 
Period
Deleted text that is repetitive with other sections of the protocol, cross referenced to 
Table 6.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
25
Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
Rationale: Correction made to eligibility criteria – documentation of disease progression
4.1. Inclusion Criteria
Criterion #6 revised to state “Subject must have documented evidence of progressive 
disease based on investigator’s determination of response by the IMWG criteria on or 
within 12 months of their last regimen (Attachment 1). Confirmation may be from either 
central or local testing. Also, subjects with documented evidence of progressive disease 
(as above) within the previous 6 months and who are refractory or non-responsive to 
their most recent line of treatment afterwards.”.
Rationale: Change made to exclude subjects with prior history of CNS multiple myeloma because of suspected 
increased risk of neurologic toxicity
4.2. Exclusion 
Criteria
Revised criterion #9 to state “Known active, or prior history of central nervous system 
(CNS) involvement or exhibits clinical signs of meningeal involvement of multiple 
myeloma.”
Rationale: Changes made to incorporate revised HBV and HCV eligibility requirements to add revised HBV 
monitoring criteria 
T&E schedule 
(Table 1 and Table 
12)
Added that events of HBV reactivations should be reported during the first year post-
dosing of LCAR-B38M CAR-T cells. Revised footnotes ‘f’ (Table 1) and ‘e’ (Table 12).
1.7. Potential Safety 
Risks and Mitigation 
Strategies
Added cross reference to hepatitis B virus screening guide in Attachment 8.
4.2. Exclusion 
Criteria;
9.2. Safety 
Evaluations
Removed reference to ASCO guidelines from criterion #14 as it does not represent 
guidance provided in Attachment 8.
Attachment 8
Revised to include guideline for prevention of HBV reactivation specific for subjects 
receiving immunosuppressive therapy
4.2. Exclusion 
Criteria
Revised criterion #15 to include “HCV-RNA quantitation positive” and added guidance 
for subjects with a known history of HCV infection.
6.3.6. Infections
Added warning that HBV reactivation may occur in subjects with drugs directed against 
B cells.
9.2. Safety 
Evaluations
Added HBV monitoring recommendations.
12.3.1. All Adverse 
Events
Added that events of HBV reactivations will be reported during the first year post-
dosing of JNJ-68284528.
Attachment 8
Revised hepatitis screening guide for determining subject eligibility.
Rationale: Revision to the timing of when conditioning regimen should be re-administered upon resolution of 
active infection or Grade ≥3 non-hematologic toxicities of the conditioning regimen, to allow for flexibility
6.1.3. Evaluation 
Prior to 
Administration of 
JNJ-68284528
Updated that the conditioning regimen should be re-administered if resolution of 
infection or Grade ≥3 non-hematologic toxicities of the conditioning regimen to Grade 
≤1 takes more than 14 days (changed from 7 days).
Rationale: Correction to serum calcium corrected for albumin; removal of language that is no longer relevant to 
IMWG.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
9.6.2. Serum Calcium 
Corrected for 
Albumin
Deleted the following: Measurement of free ionized calcium is an acceptable alternative 
to corrected serum calcium for determining hypercalcemia. In this study, free ionized 
calcium levels greater than the ULN indicate hypercalcemia.
Rationale: Additional information provided regarding subject identifiers to be included with infusion bag
14.2. Packaging
16.2.4. Privacy of 
Personal Data
17.3. Subject 
Identification, 
Enrollment, and 
Screening Logs
For tracking and traceability of apheresis material, subject name and date of birth will be 
collected, as allowed by local regulations, will be collected to ensure chain of identity of 
the JNJ-68284528 for each subject.
Rationale: Minor errors were noted
Throughout the 
protocol
Minor grammatical, formatting, or spelling changes were made.
Amendment 1 (20 August 2018)
The overall reason for the amendment: The overall reason for the amendment is to collect additional safety 
information and add clarity to targeted sections of the protocol
Applicable Section(s)
Description of Change(s)
Rationale: Revisions made to collect additional safety information and provide an additional inclusion criterion 
(lower limit of lymphocyte count) that may increase potential for successful manufacture of JNJ-68284528.
T&E Schedule (Table 1 
and Table 10)
Changed window for hematology assessment on day of apheresis from ≤72 hour 
window to “prior to apheresis (same day)”
Added hematology, chemistry, and vital signs assessments on Day 21 (to correspond 
with PK assessments added on Day 21).
T&E Schedule (Table 1 
and Table 10);
6.1.1. Criteria for 
Cyclophosphamide and 
Fludarabine Dosing
Language added to indicate that subjects who receive bridging therapy that includes 
agents with known cardiac toxicity, assessment of cardiac function should be repeated 
within 7 days prior to the start of the conditioning regimen.
4.1. Inclusion Criteria 
(criterion #8);
6.1.1. Criteria for 
Cyclophosphamide and 
Fludarabine Dosing
Added lymphocyte count of ≥0.3 x 109/L to laboratory value criteria at screening to 
allow for successful apheresis.
6.1.1. Criteria for 
Cyclophosphamide and 
Fludarabine Dosing
On the day of the first dose of the conditioning regimen, subjects should be evaluated 
for the presence of an indwelling catheter.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
27
Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
Rationale: Changed the baseline for efficacy assessment to more accurately reflect response to treatment
T&E Schedule (Table 1 
and Table 10)
Samples for serum protein electrophoresis (SPEP) and urine protein electrophoresis 
(UPEP) assessments will be collected to establish baseline disease characteristics 
prior to the first dose of the conditioning regimen.
T&E Schedule (Table 1 
and Table 10);
9.6.5. Documentation of 
Extramedullary 
Plasmacytomas
Revised assessment for extramedullary plasmacytomas to be performed ≤14 days 
prior to the first day of the conditioning regimen instead of at screening.
Rationale: Revision made to the window in the post-treatment period to prevent out of window visits during the 
extended follow-up
T&E Schedule (Table 1)
Window for post treatment visits (every 28 days after Day 100) changed from ±2 days 
to ±7 days
Rationale: Added infectious disease testing at apheresis to comply with local and regional donor requirements
T&E Schedule (Table 1 
and Table 10);
9.2. Study Evaluations
Added testing at the time of apheresis for HIV, hepatitis B, hepatitis C, HTLV, and 
other infectious diseases as applicable per local regulations
Rationale: Patient reported outcomes (PRO) assessments and Qualitative Interviews added to obtain information 
on the benefit of subject’s perceived health-related quality of life in the Phase 2 portion of the study
T&E Schedule (Table 
1);
2.1. Objectives and 
Endpoints;
9.8. Patient-Reported 
Outcomes;
11.8. Patient-Reported 
Outcome Assessments
Added the European Organization for Research and Treatment of Cancer 
(EORTC)-QLQ-C30, EuroQol Five Dimension Questionnaire (EQ-5D-5L), Patient 
Global Impression of Change (PGIC), Patient Global Impression of Severity (PGIS), 
and single items from EORTC QLQ-MY20 assessments to the Phase 2 part of the 
study; included as secondary endpoints.
T&E Schedule (Table 
1);
2.1. Objectives and 
Endpoints;
9.9. Qualitative 
Interviews
Subjects enrolled in the Phase 2 part of the study will be given the option to 
participate in qualitative patient experience interviews.
Exploratory objective added for qualitative interviews.
Attachment 10 (Patient 
Reported Outcome 
Measures)
Added sample PRO assessment documents
Rationale: Correction of errors
T&E Schedule (Table 2
and Table 11)
Correction to collection for minimal residual disease (MRD) assessments in subjects 
with CR will occur “…up to and including disease progression.”
T&E Schedule (Table 
10)
Addition of Day 100X ECOG assessment added to be consistent with main T&E 
(Table 1).
Synopsis (Statistical 
Methods); 
11.2. Sample Size 
Determination
Correction to the following statement: “With 60 subjects, the study will have 90% 
power to declare the ORR is higher than 30% or higher at the 1-sided significance 
level of 0.025.”

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
28
Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
2.1. Objectives and 
Endpoints
PFS and OS added to exploratory endpoint “Correlation between MRD negative rate 
and duration of response, PFS, and OS”, to align with corresponding exploratory 
objective.
3.1. Overview of Study 
Design
Correction to the timing of bridging therapy “(anti-plasma cell directed treatment 
between screening apheresis and the administration of JNJ 68284528 first dose of 
the conditioning regimen)” consistent with what is presented in the diagram of the 
study design (Figure 2).
Rationale: Adjustments made to timing of pharmacokinetic and biomarker sample collections to reduce patient 
burden
T&E Schedule (Table 1, 
Table 2, Table 10, and 
Table 11)
Reduced the number of bone marrow samples to be collected prior to JNJ-68284528 
infusion. A single collection pre-conditioning regimen was added in place of a 
collection at screening and pre-dose. Collection of blood samples adjusted to align 
with changes in bone marrow collections.
Reduced and/or change collection time points for whole blood or serum collections 
for immunophenotyping, CyTOF, and cytokine profiling.
Rationale: Modifications made for clarity or consistency
T&E Schedule (Table 1 
and Table 10)
Window for post-treatment assessments changed from ±2 days to ±7 days.
Clarified that serum M-protein electrophoresis, urine protein electrophoresis, serum 
calcium corrected for albumin and serum FLC and serum/urine immunofixation will 
occur prior to the first dose of conditioning regimen; added ≤7 days.
T&E Schedule (Table 2 
and Table 11)
To be consistent with guidance in Section 9.3.1, added footnote ‘b’ to ADA sample 
(footnote b) to indicate ADA should be collected if CRS or neurotoxicity Grade ≥2 is 
reported.
Added footnote ‘e’ to CyTOF (bone marrow) and CyTOF/PBMC (whole blood)
Moved placement of footnote ‘d’ for flow to avoid giving the impression that a 
sample was to be collected at end of study.
Synopsis
Revised the subject population description, for clarity, to include additional 
information from the inclusion criteria in Section 4.1.
Synopsis;
3.5. Safety Evaluation 
Team;
6.1. Study Treatment 
Administration
The term ‘staggered enrollment’ was changed to ‘staggered dosing’ to more correctly 
describe the observational period between administration of JNJ-68284528 to the first 
and second, second and third, and third and fourth subjects.
Added that administration of the conditioning regimen and dosing with JNJ-68284528 
will be paused between dosing of the sixth subject and conclusion of the first Safety 
Evaluation Team (SET) meeting.
T&E Schedule (Table 2 
and Table 11)
Pharmacokinetic (PK) (chimeric antigen receptor [CAR]-positive T cell assessment) 
to be performed on bone marrow samples collected to assess PK CAR transgene 
levels. Row added to clarify the timing of these assessments. 
3.1. Overview of Study 
Design
Added that subjects who receive retreatment will be monitored in the long-term 
follow-up study for 15 years from the time of last treatment.
4.1. Inclusion Criteria 
(criterion #4)
Added reference to definition of refractory multiple myeloma (IMWG consensus 
criteria).

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
29
Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
4.2. Exclusion Criteria 
(criterion #15)
Criterion modified as follows: “Hepatitis C (anti-hepatitis C virus [HCV] antibody 
positive or HCV RNA quantitation positive) or known to have a history of hepatitis C. 
If antibody positive, further testing of quantitative levels to rule out positivity is 
required.”
6.1. Study Treatment 
Administration
Clarified that if conditioning regimen must be delayed ≥10 weeks after apheresis “the 
subject must undergo full rescreening assessment of eligibility criteria prior to 
dosing (with the exception that a repeat bone marrow collection and re-signing of 
the ICF are not required).
6.2. Pre-infusion 
Supportive Therapy
Clarified in Table 7 that antihistamine and antipyretic refer to diphenhydramine or 
equivalent and acetaminophen or equivalent, respectively.
9.1.1. Overview
Revised approximate blood volume drawn per subject (up to 2 years post treatment) 
to align with revisions in sample collections.
9.1.3. Apheresis
Clarification that the target number of PBMCs collected at apheresis is 6 x 109
PBMCs with a range of 2 to 20 x 109 PBMCs. The volume is no longer specified.
9.4. Biomarker 
Evaluations; 
9.4.1. 
Pharmacodynamic/ 
Predictive Markers
Revisions made to clarify and support the biomarker evaluations to be conducted.
Rationale: Revisions to PK and Immunogenicity sections to align with assay requirements and added sampling 
on Day 21 to expand data collection during the first 3 weeks
T&E Schedule (Table 2 
and Table 11)
PK CAR positive T cell, CAR transgene, and soluble B cell maturation antigen 
(BCMA) assessments added on Day 21. Immunophenotyping, CyTOF/PBMC/plasma 
(whole blood), and cytokine profiling assessments added on Day 21.
T&E Schedule (Table 1 
and Table 10)
Assessments for hematology, chemistry, and vital signs added on Day 21 to 
correspond to the visit added for PK collections.
9.3.1. Evaluations
Revisions made for clarity. Removed detail that is more appropriate for the lab 
manual. 
9.3.2. Analytical 
Procedures;
9.3.4. Immunogenicity 
Assessment/Antibodies 
to JNJ-68284528
Removed statements indicating that immune response analyses (anti-drug antibody 
[ADA]) may be conducted on PK samples for accuracy, ADA cannot be performed 
on PK samples collected in this study, and are noted separately in the time and events 
schedules.
Rationale: Revision made to allow for red blood cell transfusion after screening maintain hemoglobin levels.
4.1. Inclusion Criteria
(criterion #8)
Added a footnote to the clinical laboratory values table stating: “For subjects who 
meet the inclusion criteria at screening, transfusion of RBCs is permitted after 
screening as needed to maintain a hemoglobin level 8.0 g/dL.”
6.1.1. Criteria for 
Cyclophosphamide and 
Fludarabine Dosing
Revision made to first bulleted statement to be consistent with RBC transfusion 
allowance added to the inclusion criteria. “Clinical laboratory values required for 
enrollment (Section 4.1), with the following exceptions: lymphocyte count of ≥0.3 x 
109/L and transfusion of red blood cells or platelets and administration of myeloid 
growth factor is permitted until 3 days before the hematology laboratory test.”
Rationale: Guidance added for risk/benefit consideration in the event that a JNJ-68284528 product does not meet 
pre-specified release criteria.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
30
Status: Approved,  Date: 15 June 2022
Applicable Section(s)
Description of Change(s)
6.1. Study Treatment 
Administration
Guidance added that the sponsor will evaluate the risk/benefit for administration of a 
JNJ-68284528 product that did not meet pre-specified release criteria and determine if 
the supply of the product to the treating physician could be considered.
Rationale: Revision to allow for rescreening of subjects who do not meet all eligibility criteria
9.1.2. Screening Phase
Revised protocol to allow subjects who did not meet all inclusion criteria or who met 
an exclusion criterion to be rescreened once, upon written approval from the sponsor.
Rationale: Revisions made for consistency with the current IMWG criteria
9.6.5. Documentation of 
Extramedullary 
Plasmacytomas; 
Attachment 1. 
Revised to be consistent with IMWG criteria as presented in Kumar 2016.
Rationale: Minor errors were noted
Throughout the protocol
Minor grammatical, formatting, or spelling changes were made.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
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32
Status: Approved,  Date: 15 June 2022
SUBJECT POPULATION
Eligible subjects are 18 years of age and have a documented diagnosis of multiple myeloma according to 
IMWG diagnostic criteria and an Eastern Cooperative Oncology Group (ECOG) Performance Status grade
of 0 or 1. 
Subjects must satisfy all of the following criteria: 1) Measurable disease at screening as defined by any of 
the following: Serum monoclonal paraprotein (M-protein) level 1.0 g/dL or urine M-protein level 
200 mg/24 hours; or Light chain multiple myeloma without measurable disease in the serum or the urine: 
Serum immunoglobulin free light chain 10 mg/dL and abnormal serum immunoglobulin kappa lambda 
free light chain ratio; 2) Received at least 3 prior lines of therapy or are double refractory to a proteasome 
inhibitor (PI) and an immunomodulatory agent (IMiD) (induction with or without hematopoietic stem cell 
transplant and with or without maintenance therapy is considered a single regimen), subjects will have 
undergone at least 1 complete cycle of treatment for each regimen (unless progressive disease [PD] was the 
best response); 3) Received a PI, an IMiD, and anti-CD38 antibody (prior exposure can be from different 
monotherapy or combination regimens); and 4) Documented disease progression during, or within 
12 months, of their most recent anti-myeloma therapy.
DOSAGE AND ADMINISTRATION
A conditioning regimen consisting of cyclophosphamide 300 mg/m2 intravenously (IV) daily and 
fludarabine 30 mg/m2 (IV) daily for 3 days will be administered. JNJ-68284528 IV infusion will take place 
5 to 7 days after the start of the conditioning regimen. In the Phase 1b portion of the study, the target dose 
is 0.75 x 106 CAR-positive viable T cells/kg (range: 0.5-1.0 x 106 CAR-positive viable T cells/kg). In the 
event of excess toxicity, a dose de-escalation to dose level -1 (0.3 x 106 CAR-positive viable T cells/kg 
[range: 0.1-0.5 x 106 CAR-positive viable T cells/kg]) for new subjects will occur. Additionally, a dose 
escalation to dose level 2 (target dose not to exceed a 3-fold dose escalation [2.25 x 106 CAR-positive viable 
T cells/kg, range: ± 30% of the target dose, depending on target dose chosen for dose level 2]) will be 
considered if specified safety criteria are met. Confirmation of the RP2D will be based on review of data 
from at least 24 subjects who were administered JNJ-68284528 in the Phase 1b portion of the study.
Additional subjects (up to approximately 50) will be enrolled in the Phase 1b portion of the study to generate 
supplemental safety and efficacy data at the RP2D.
EVALUATIONS
Safety will be evaluated by adverse events, laboratory test results, vital sign measurements, physical 
examination findings, and assessment of ECOG performance status. Disease status will be evaluated by an 
IRC according to clinical judgement guided by the IMWG consensus recommendations for multiple 
myeloma. Blood and serum samples will be collected for assessment of JNJ-68284528 pharmacokinetics, 
immunogenicity (antibodies to JNJ-68284528), and predictive biomarkers of response or resistance to 
JNJ-68284528.
STATISTICAL METHODS
No formal statistical hypothesis testing will be performed for the Phase 1b portion of the study.
The sample size for the Phase 2 portion of the study assumes that the overall response rate for JNJ-68284528
will be 50%. With 60 subjects, the study will have 90% power to declare the ORR is higher than 30% at 
the 1-sided significance level of 0.025.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
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Status: Approved,  Date: 15 June 2022
Table 1:
Time and Events Schedule for Study Procedures/ Assessments
Screening 
Phase
Apheresis
Cyclophosphamide
and fludarabine 
conditioning 
regimen
JNJ-
68284528 
Infusion
Post Infusion (Day 1 to Day 100)
(any subject who received an infusion of JNJ-68284528 should continue all 
subsequent assessments) a
Post-
treatment
(Day 101 
and up to 
Study 
Completion)
b
≤28 days 
prior to 
apheresis
a
Upon 
enrollment
Day -5,* -4, -3 
(assessments may 
be conducted 
≤72 hours predose)
*Window for start 
of conditioning 
regimen: Day -7 to 
Day -5
Day 1
(Infusion
)
Day 
3
Day 
7 
(± 1 
day)
Day 
10 
(± 1 
day
)
Day 
14 
(± 1 
day
)
Da
y 
21 
(± 1 
day
)
Day 
28 
(± 2 
days)
Day 
42 
(± 2 
days)
Day 
56 
(± 2 
days)
Day 
78 
(± 2 
days)
Day 
100 
(± 2 
days)
b
(every 28 
days after 
day 100)c
(± 7 days)
Concomitant 
medication
Continuous from the time of signing of ICF until at least 100 days after last administration of any study treatment.
Concomitant usage for the treatment of adverse events after 100 days should be reported.
Medications for the prevention and treatment of COVID-19 (including vaccines) and HBV reactivation should be reported until 1 year after cilta-cel infusion 
(Attachment 17).
Abbreviations: aPTT=activated partial thromboplastin time; CR=complete response; sCR=stringent complete response; CRS= cytokine release syndrome; CT=computed tomography; 
D=Day; ECOG=Eastern Cooperative Oncology Group; ECG=electrocardiogram; EORTC-QLQ=European Organization for Research and Treatment of Cancer Quality of Life 
Questionnaire; EQ-5D-5L=EuroQol Five Dimension Questionnaire; FISH=fluorescence in situ hybridization; FLC=free light chain; HBV=hepatitis B virus; ICANS=immune-effector 
cell-associated neurotoxicity syndrome; ICE=immune effector Cell-associated Encephalopathy; ICF=informed consent form; INR=international normalized ratio; IPPI=investigational 
product preparation instructions; MRD=minimal residual disease; MRI=magnetic resonance imaging; MRU=medical resource utilization; MUGA=multiple-gated acquisition; 
PGIC=Patient Global Impression of Change; PGIS=Patient Global Impression of Severity; PRO=patient reported outcome; PT=prothrombin time; SIPPM=site investigational product 
procedures manual; SOC=standard of care; SPEP=serum protein electrophoresis; UPEP=urine protein electrophoresis.
a
ICF must be signed before any study-related procedures are performed, and remains in effect even if the screening evaluation is not performed within the 28-day Screening Phase. 
Evaluations for eligibility determination performed outside the screening window may need to be repeated. For subjects who require a repeat apheresis see Section 6.1.1. for 
assessments should be collected before the second apheresis. If the second apheresis falls outside of the 28 day window, all screening assessments (except bone marrow collection) 
must be repeated.
b
For subjects who discontinue the study before Day 100, including those who have not received an infusion of JNJ-68284528, the Day 100 assessments should be performed prior to 
withdrawal if feasible. Subjects who discontinue after Day 100 but before study completion should have urine and serum disease assessments performed prior to withdrawal if 
feasible at the time of discontinuation, unless performed within 14 days prior to discontinuation. Study completion is defined as 2 years after the last subject has received his or her 
initial dose of JNJ-68284528.
c
Post-treatment assessments to be obtained until progressive disease is documented or the start of subsequent anticancer therapy, with the exception of survival status and subsequent 
anticancer therapy, which are to be collected until study completion.
d
Disease characteristics cytogenetics (full karyotyping or FISH as well as molecular genetics [if applicable]), both of which may originate from prior to or during the screening 
period within 42 days before apheresis, or between apheresis and the conditioning regimen, as applicable. A pathologist/cytogeneticist should complete the cytogenetics data 
collection worksheet.
e
The first 6 subjects enrolled will be hospitalized for at least 2 weeks after infusion of JNJ-68284528. The requirement for hospitalization and local stay will be evaluated by the SET 
for subsequent subjects. For subjects who are hospitalized, hematology and chemistry laboratory evaluations, vital signs, and oxygen saturation should be performed at least daily 
or more as clinically indicated.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
39
Status: Approved,  Date: 15 June 2022
f
Serology results performed as standard of care within 28 days prior to apheresis are acceptable; Hepatitis B: HBsAg, anti-HBc, anti-HBs, HBV DNA quantification (for subjects 
who are anti-HBs positive without history of vaccination or for subjects who are anti-HBs positive and anti-HBc positive); Monitor HBV-DNA, AST/ALT every 3 months for one 
year post-dose of JNJ-68284528. Hepatitis C: HCV antibody, HCV-RNA (for subjects who are anti HCV positive); HIV serology. 
g
Immediately before the start of infusion, at the end of infusion, and 0.5, 1, 2 hours after end of infusion. Monitor until normalized after a CRS event.
h
Temperature will be checked at least twice a day up to Day 28. Subjects will be provided with a thermometer and instructed on the use of the thermometer and entering 2 temperatures 
including their maximum daily temperature in a diary. Diary will be reviewed at each visit, then collected on Day 28 and stored with subject source documents.
i
All subjects will be evaluated for IgG, IgA, IgM. Testing for IgD and IgE will only be performed for subjects with IgD and IgE-type myeloma.
j
UPEP sample collected as part of the standard of care and prior to the subject signing ICF may be used for analysis at the central laboratory. 
k
Bone marrow morphology from an aspirate and core biopsy to be assessed locally at all time points. Additional bone marrow aspirate samples will be collected for biomarkers (see 
Table 2).
l
Results from skeletal survey performed as routine follow-up within 42 days before start of apheresis may be used without these tests being repeated. The skeletal survey is to be 
performed by either roentgenography or low-dose computed tomography (CT) scans without the use of IV contrast. If a CT is used it must be of diagnostic quality. Additional 
imaging (X-ray, CT, or MRI) will be performed as clinically indicated (eg, to document response or progression).
m
Extramedullary plasmacytomas should be assessed for all subjects with a history of plasmacytomas or if clinically indicated prior to the first dose of the conditioning regimen, by 
clinical examination or radiologic imaging.
n
HIV, hepatitis B, hepatitis C, HTLV, and other infectious diseases as applicable per local regulations
o
PRO assessments to be collected every 28 days in the post-treatment Phase. For subjects with disease progression or who initiate subsequent anticancer therapy, PRO assessments 
should be collected every 16 weeks. 
p
Subjects enrolled in the Phase 2 portion of the study will have the option of participating in pre-treatment and post-treatment semi-structured qualitative interviews.
q
Pre-infusion ICE test and handwriting sample should be performed before pre-medication with diphenhydramine
r
Medical resource evaluation data will be collected until Day 180 (± 7 days).
s
Local laboratory assessments may be used under specified circumstances (See Section 9.6).

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
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42
Status: Approved,  Date: 15 June 2022
Table 2:
Time and Events Schedule for Pharmacokinetic and Biomarker Sampling
Screening 
Phase
Apheresis
Cyclophosp
hamide and 
fludarabine 
conditionin
g regimen
JNJ-
68284528 
Infusion
Post Infusion (any subject who received infusion of JNJ-68284528 should continue all 
subsequent assessments) a and Post-treatment (Day 101 up to study completion)
At 
PD
At
Study 
Complet
ion for 
subjects 
without
PD
≤28 days 
prior to 
apheresis
Upon 
enroll-
ment
Day -5,* -4, 
-3
(assessment
s may be 
conducted 
≤72 hours 
predose) b*
Day 1
(Infusion)
Day 
2
Day 
3 
Day 
7 
(± 1 
day)
Day 
10 
(± 1 
day)
Day 
14 
(± 1 
day)
Day 
21 
(± 2 
days)
Day 
28 
(± 2 
days)
Day 
42 
(± 2 
days)
Day 
56 
(± 2 
days)
Day 
78 
(± 2 
days)
Day 
100 
(± 2 
days)
Day 
184
(±7 
days)
MRD 
(aspirate)
(bone 
marrow)
X (prior to 
first dose of 
conditioning 
regimen 
[≤7 days])
Sample should be collected: 

For all dosed subjects at Day 28, and at 6 months, 12 months, 18 months (Day 520), and 24 months 
(Day 744) (± 16 days) regardless of the status of disease measured in blood and urine.

For subjects with suspected CR at the time of CR and then yearly for subjects that remain on study up to 
disease progression.
Cytogenetics 
(bone 
marrow)
X (prior to 
first dose of 
conditioning 
regimen 
[≤7 days])
X
Replication 
Competent 
Lentivirus 
(RCL)
(whole 
blood)
X (prior to 
first dose of 
conditioning 
regimen 
[≤7 days])
Pre-dose
At approximately 3 (Day 84), 6 (Day 168), and 12 (Day 364) months (±1 month); then yearly (±3 months) 
until EOS, and then yearly (±3 months) for up to 15 years after cilta-cel infusion in a separate long-term 
follow-up study. Yearly collection of RCL samples is not required if assessments within the first year are 
negative. Additional samples may be collected triggered by events which may be relevant to RCL per clinical 
assessment.
Cytokine 
profilingg
(serum)
X (prior to 
first dose of 
conditioning 
regimen 
[≤7 days])
Pre-dose, 
2hrs Post 
(±10 
minutes)
X
X
X
X
X
X
X
X
X
X
X
Abbreviations: ADA=anti-drug antibody; BCMA=B-cell maturation antigen; CAR=chimeric antigen receptor; CR = complete response; CRS=cytokine release syndrome; CyTOF=cytometry 
by time of flight; PD= progressive disease; EOI=end of infusion; MRD=minimal residual disease; PBMC=peripheral blood mononuclear cell; PK=pharmacokinetic; sCR=stringent complete 
response 
a
For subjects who discontinue the study post JNJ-68284528 infusion before Day 100, the Day 100 assessments should be performed if feasible.
b
Window for start of conditioning regimen: Day -7 to Day -5
c
Collect additional samples when any of the following are suspected or reported: 1) CRS or CAR-T cell-related neurotoxicity (eg, ICANS) Grade ≥2 (at onset of the event, and 24 and 
72 hours after) or as clinically indicated; and 2) as indicated based on emerging data. 
d
ADA sample should be collected if a subject withdraws from the study after JNJ-68284528 administration but prior to disease progression or study completion.
e
Sample should also be collected at suspected CR
f
Sample should be collected at 12 months, relative to Day 1, for subjects that achieve CR/sCR and remain on study.
g
Collect additional samples when any of the following are suspected or reported: 1) CRS or CAR-T cell-related neurotoxicity (eg, ICANS) (any grade) (at onset of the event, and then 
every 24 hours until CRS or ICANS event has stabilized or is resolving at which time additional collections should occur at 24, 48, and 72 hours) or as clinically indicated; and 2) as 
indicated based on emerging data.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
43
Status: Approved,  Date: 15 June 2022
ABBREVIATIONS
ALL
acute lymphocytic leukemia
ANC
absolute neutrophil count
APRIL
a proliferation inducing ligand
ASBMT
American Society for Blood and Bone Marrow Transplantation
ASCO
American Society of Clinical Oncology
AST
aspartate aminotransferase
BAFF
B-cell activating factor
BCMA
B-cell maturation antigen
BNP
B-type natriuretic peptide
CAR-T
chimeric antigen receptor T (cells)
CBC
complete blood count
CBR
clinical benefit rate
CI
confidence interval
CNS
central nervous system
CR
complete response
CRS
cytokine release syndrome
CSR
clinical study report
CT
computed tomography
CyTOF
cytometry by time of flight 
DLT
dose limiting toxicity
DOR
duration of response
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
EORTC
European Organization for Research and Treatment of Cancer
EQ-5D-5L
EuroQol Five Dimension Questionnaire
FLC
free light chain
eCRF
electronic case report form
eDC
electronic data capture
GCP
Good Clinical Practice
G-CSF
granulocyte colony-stimulating factor
GVHD
graft-versus-host disease
HBV
hepatitis B virus
HCV
hepatitis C virus
HLH/MAS
hemophagocytic lymphohistiocytosis/macrophage activation syndrome
HRQoL
health-related quality of life 
ICANS
Immune effector cell-associated neurotoxicity syndrome
ICE
Immune-effector Cell-associated Encephalopathy
ICF
informed consent form
ICH
International Conference on Harmonisation
IEC
independent ethics committee
Ig
immunoglobulins
IL
interleukin
IMiD
immunomodulatory drug
IMWG
International Myeloma Working Group
IPPI
investigational product preparation instructions
IRB
Institutional Review Board
IRC
Independent Review Committee
IV
intravenous(ly)
LVEF
left ventricular ejection fraction
MedDRA
Medical Dictionary for Regulatory Activities
MR
minimal response
MRD
minimal residual disease
MRI
magnetic resonance imaging
MRU
medical resource utilization
MUGA
multiple-gated acquisition

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
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Status: Approved,  Date: 15 June 2022
NCI CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
NYHA
New York Heart Association
ORR
overall response rate
OS
overall survival
PBMC
peripheral blood mononuclear cell
PD
progressive disease
PFS
progression-free survival
PGIC
Patient Global Impression of Change
PGIS
Patient Global Impression of Severity
PI
proteasome inhibitor 
POEMS 
polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes
PQC
product quality complaint
PR
partial response
PRO
patient reported outcomes
QIg
quantitative immunoglobulin
RBC
red blood cell
RCL
replication competent lentivirus
RP2D
recommended Phase 2 dose
sBCMA
soluble BCMA
sCR
stringent complete responses
SET
safety evaluation team
SIPPM
site investigational product procedures manual
SPEP
serum protein electrophoresis
TCR
T cell receptor
TLS
tumor lysis syndrome
TNF-R
tumor necrosis factor receptor
TTR
time to response
ULN
upper limit of normal
UPEP
urine M-protein quantitation by electrophoresis
VGPR
very good partial response
β-hCG
β human chorionic gonadotropin

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
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Status: Approved,  Date: 15 June 2022
1.
INTRODUCTION
1.1.
Multiple Myeloma
Multiple myeloma is characterized by the production of monoclonal immunoglobulin (Ig) proteins 
or protein fragments (M proteins)that have lost their function.20,28 The proliferation of multiple 
myeloma cells leads to subsequent displacement of normal bone marrow hematopoietic precursors
and overproduction of M-proteins. Hallmarks of multiple myeloma include osteolytic lesions, 
anemia, increased susceptibility to infections, hypercalcemia, renal insufficiency or failure, and 
neurological complications.17,28
Treatment options for multiple myeloma have substantially improved over time and vary 
depending on the aggressiveness of the disease, underlying prognostic factors, physical condition 
of the patient, and existing co-morbidities. Therapeutic options include agents such as proteasome 
inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies, and stem cell 
transplantation.
Despite these therapeutic achievements, the disease recurs and remains incurable. Thus, there is a
need for novel therapeutic approaches when the disease is resistant to available therapy.
1.2.
BCMA
B cell maturation antigen (BCMA, also known as CD269 and TNFRSF17) is a 20 kilodalton, 
type III membrane protein that is part of the tumor necrosis receptor superfamily.31 BCMA is 
predominantly expressed in B-lineage cells and plays a critical role in B cell maturation and 
subsequent differentiation into plasma cells.31 BCMA binds 2 ligands that induce B cell 
proliferation: a proliferation inducing ligand (APRIL; CD256) and B-cell activating factor (BAFF;
CD257).3,9,29 Upon binding of BCMA monomers to the APRIL trimer, activation and 
phosphorylation of p38MAPK, ELK, and NF-κB are triggered through intracellular tumor necrosis 
factor receptor (TNF-R)-associated factor (TRAF) molecules leading to pro-survival gene 
regulation.5,14,16
In multiple myeloma cell lines and patient samples, BCMA is more stably expressed specifically 
on the B cell lineage than CD138, a key plasma cell marker which is also expressed on normal 
fibroblasts and epithelial cells.27 The expression characteristics of BCMA make it an ideal 
therapeutic target in the treatment of multiple myeloma.13,31
1.3.
CAR-T Therapy
Chimeric antigen receptor T (CAR-T) cell therapy uses modified autologous T cells that are
activated in an MHC-independent manner upon binding to their target. This results in lysis of the 
targeted cells. Kymriah® (tisagenlecleucel), a CD19 directed CAR-T cell-based immunotherapy, 
is approved in the US for the treatment of pre-B acute lymphocytic leukemia (ALL) that is 
refractory or in second or later relapse for patients up to 25 years of age. Yescarta(axicabtagene 
ciloleucel), another CD19 directed CAR-T based therapy, is approved in the US for the treatment 
of adult patients with relapsed or refractory large B-cell lymphoma. An ongoing Phase 1 clinical 
study with bb2121, a BCMA-directed CAR-T immunotherapy, demonstrated promising results for 

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 15 June 2022
1.5.
Summary of Clinical Studies 
The nonclinical pharmacology program was designed to characterize the biological activity and 
mechanism of action of LCAR-B38M CAR-T cells. In vitro mechanistic proof-of-principle studies 
have assessed target engagement with respect to:

On-target binding (ie, binding of VHH to BCMA)

Off-tumor target activity (ie, in human non-myeloma cell lines, including lung, liver, breast, 
brain, embryonic kidney and kidney expressing hERG)

On-tumor target activity (ie, in human multiple myeloma cell lines)
In vivo studies have evaluated the safety and efficacy of LCAR-B38M CAR-T cells.
Refer to the Investigator’s Brochure for a complete description of the nonclinical study 
information.
Legend-2
Legend-2 is a first-in-human, single-arm, open-label, multicenter study to determine the safety and 
efficacy of LCAR-B38M CAR-T cells used to treat subjects with relapsed or refractory multiple 
myeloma. The study was conducted in China by Legend Biotech. Study enrollment was completed 
in November 2017; 74 subjects have been treated on this study. The clinical cutoff for the analysis 
presented here was 06 February 2018 with updated survival, efficacy data, and CRS grading 
provided as of 31 December 2018. As of the 31 December 2018 update, the median follow-up was 
17.41 months (range: 0.4–32.2 months).
All subjects had relapsed or refractory multiple myeloma with a median of 3 (range: 1-9) prior 
lines of therapy including PI therapy (73%), IMiD (87.8%), and both PI and IMiD (64.9%). Prior 
autologous stem cell transplant (ASCT) was reported for 24.3% of subjects. The median age at 
study entry was 54.5 years (range: 27-74 years). The median follow-up was 6.31 months (range: 
0.4 – 20.7 months). The median number of LCAR-B38M CAR-positive viable T cells 
administered was 0.513 x 106 CAR-positive viable T cells/kg (range: 0.07-2.10 x 106 CAR-
positive viable T cells/kg).
Of the 74 subjects included in the Legend 2 study, 68 (91.8%) subjects had an adverse event of 
CRS (median time to onset 9 days [range: 1-19 days]), including Grade 1 for 37 subjects, Grade 2 
for 25 subjects, Grade 3 for 5 subjects, and Grade 5 for 1 subject. The fatal event of CRS occurred 
in a 40-year-old female who experienced CRS and tumor lysis syndrome (TLS) and died on Day 13
after receiving the LCAR-B38M CAR-T cell infusion. For most subjects, symptoms of CRS were 
mild and reversible. Grade 1 neurotoxicity was reported for 1 subject.
Cytopenias (thrombocytopenia and neutropenia) were common, however, prolonged Grade 4 
cytopenias with duration exceeding 35 days were infrequent. Infection events were reported in 
7 (9.5%) subjects; however, the rate did not appear to exceed that expected for subjects with 
multiple myeloma.

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Relapsed or Refractory Multiple Myeloma
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Status: Approved,  Date: 15 June 2022
In addition to the subject who died from CRS, 1 subject had a fatal adverse event related to 
treatment with LCAR-B38M CAR-T cells. A 54-year old male with a history of coronary artery 
disease and extensive anthracycline therapy who experienced CRS with a maximum Grade of 2, 
and died on Day 22 after LCAR-B38M CAR-T infusion due to a potential acute pulmonary 
embolism and potential acute coronary syndrome.
Although the Legend-2 study was conducted in China, one 56-year old male, Caucasian subject 
from the United States was treated. The subject received similar prior therapy (5 prior lines of 
therapy including PI, IMiD, and anti-CD38 antibody treatment) as is required on this study. He
experienced Grade 3 CRS after LCAR-B38M CAR-T cell infusion. The CRS resolved after 
treatment with anti-IL-6 receptor antibody and TNFα inhibitor. The subject achieved a stringent 
complete response (sCR).
As of the 31 December 2018 update, the overall response rate (complete response [CR]+very good 
partial response [VGPR]+partial response [PR]) was 87.8%. Complete response was achieved by 
54 (73.0%) subjects and 49 (66.2%) subjects were negative for MRD as assessed by bone marrow 
8-color flow cytometry assay. The Kaplan-Meier estimate of median duration of response was 
22 months (95% confidence interval [CI]: 11.79-29.14). The median PFS for the overall 
population was 16 months (95% CI: 10.61-28.16) and among the 49 subjects achieving 
MRD-negative CR, the median duration of response was 28 months. Administering the CAR-T 
cells as a split dose did not appear to have a different safety or efficacy profile compared with 
administering it as a single dose (See Section 3.2). There was no apparent association between 
response and the number of total viable T cells or CAR-positive viable T cells infused.
Study 68284528MMY2001 (study data generated following initiation of the conduct of this
protocol)
As of the 24 June 2019 data cutoff, 25 subjects had received an infusion of JNJ-68284528 in the 
Phase 1b portion of Study 68284528MMY2001. The safety profile is consistent with observations 
from the Legend-2 study. 

Twenty-four of the 25 subjects who received JNJ-68284528 had at least 1 treatment-emergent 
adverse event (TEAE). 

The most commonly reported TEAEs (>20% of subjects) were CRS (88.0%), neutropenia 
(80.0%), anemia (76.0%), thrombocytopenia (72.0%), leukopenia (40.0%), lymphopenia 
(28.0%), fatigue (24.0%), headache (24.0%), cough (24.0%), and diarrhea (20.0%)

Grade 3 or 4 TEAEs were reported for 24 of the 25 subjects. 

The most commonly reported Grade 3 or 4 TEAEs (>10% of subjects) were neutropenia 
(76.0%), anemia (48%), thrombocytopenia (60.0%), leukopenia (40.0%), lymphopenia 
(16.0%), and CRS (16.0%). 

Serious adverse events were reported for 6 subjects: 

One subject had serious TEAEs of Grade 3 CAR-T cell-related encephalopathy syndrome 
(CRES) and Grade 3 CRS.

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
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Status: Approved,  Date: 15 June 2022

One subject had serious TEAEs of CRS, with Grade 5 hemophagocytic 
lymphohistiocytosis (HLH) secondary to CRS, and Grade 4 acute kidney injury.

One subject had serious TEAEs of Grade 4 thrombocytopenia and Grade 3 pneumonia.

One subject had a serious TEAE of Grade 2 mental status change.

One subject had a serious TEAE of Grade 3 encephalitis.

One subject had serious TEAEs of Grade 1 CRS and Grade 1 confusional state.

One subject died on Day 99 due to CRS, with Grade 5 HLH secondary to CRS. 

Twenty-two of the 25 subjects (88.0%) experienced CRS. Three subjects experienced Grade 3 
CRS and 1 subject experienced Grade 5 CRS (as noted above).

CAR-T cell-related neurotoxicity was reported in 4 subjects. One subject had Grade 3 CRES, 
the second subject had Grade 1 neurologic adverse events (dysarthria, slow mentation, gait 
disturbance, and somnolence), the third subject had Grade 1 CRES, and the fourth subject had 
a Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) event (difficulty 
in finding words). All events occurred in the setting of CRS.
The median duration of follow-up for the 21 subjects who received JNJ-68284528 and had at least 
1 post-dose disease evaluation as of 24 June 2019 was 2.99 months (range: 1.3 to 9.9 months). 
Among these 21 subjects, 19 subjects achieved at least a partial response (PR) with an ORR (PR 
or better) of 90.5% (including unconfirmed responses) with 13 subjects (61.9%) having VGPR or 
better and 6 subjects (28.6%) having CR or better. A stringent complete response (sCR) was 
achieved by 4 subjects. Fifteen subjects had post-baseline bone marrow samples available for 
MRD assessment. All 10 subjects (100%) evaluable at the 10-5 sensitivity level were negative for 
MRD by next generation flow cytometry and/or next generation sequencing (NGS; Adaptive v 
2.0). Two subjects were indeterminate at 10-5 due to insufficient cell counts but were MRD 
negative at the sensitivity threshold of 10-4 by NGS. No clone identification could be performed 
in 3 subjects by NGS. Follow-up for response continues, however these preliminary data suggest 
compelling efficacy in this population of heavily pre-treated subjects.
Other Neurotoxicities
As of 06 March 2020, neurotoxicity with symptoms suggestive of Parkinsonian features that 
occurred after a period of recovery from CRS and/or ICANS have been observed in 6 subjects 
from Study 68284528MMY2001 (n=97). Among 6 subjects, 3 subjects had confirmed 
Parkinsonian-like symptoms with some shared features in their clinical presentation have been 
observed, with initial presentation between Day 19 and Day 101 after JNJ-68284528 infusion. 
Symptoms include altered mental status, feeling or appearing agitated, personality changes (such 
as being more withdrawn, expressing little emotion), lack of facial expression, being less 
communicative (answering questions with 1-word), difficulty with short term memory, slowing of 
movements, difficulty performing simple tasks (such as buttoning a shirt), difficulty swallowing, 
joint or muscle stiffness or inflexibility, shuffling gait (walking very slowly with small steps and 
heavy feet), restlessness, impaired balance, bradykinesia, slight cogwheeling/rigidity in 
extremities, micrographia (small handwriting) and impaired ability to perform activities of daily 
living (ADLs). On exam, all 3 subjects presented with symptoms described as Parkinsonian. The 

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
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Status: Approved,  Date: 15 June 2022
brain MRI showed no acute abnormalities in these subjects. The remaining 3 subjects had a mixed 
presentation of neurotoxicities (including some Parkinsonian-like symptoms) which presented 
with complicating comorbidities. All 6 subjects referenced above had previously experienced CRS 
(4 Grade 2, 2 Grade 3 all of which resolved) and 5 out of 6 subjects had ICANS (3 Grade 1, 1 
Grade 2, 1 Grade 3). Three subjects referenced above have died. Although these subjects also 
experienced other adverse events which may have contributed to the cause of death, such as 
infection and sepsis, the role of neurotoxicity cannot be ruled out.
Study 68284528MMY2002 (study data generated following initiation of the conduct of the 
protocol)
Study 68284528MMY2002 is a Phase 2, open-label, multicenter study in China (sponsored by 
Legend Biotech HK Limited and Janssen R&D; Investigational New Drug holder is Legend 
Biotech) to evaluate the efficacy and safety of LCAR-B38M CAR-T cells in adult subjects with 
relapsed or refractory multiple myeloma. Approximately 60 subjects will be enrolled into the 
study. The primary objective is to evaluate the efficacy of LCAR-B38M CAR-T cells. 
The first subject was dosed on 22 March 2019. As of 9 Dec 2019, 25 subjects were enrolled into 
the study and 13 subjects received LCAR-B38M CAR-T cells. Of the 12 subjects analyzed in the 
second safety evaluation team meeting, 12 subjects were reported with CRS, 1 subject had 
Grade 1, 5 had Grade 2, 5 had Grade 3, and 1 had Grade 4 CRS. The median onset to CAR-T 
infusion was 7 days (range: 2-8) and median duration of CRS was 5 days (range: 4-8). One subject 
received an infusion of LCAR-B38M CAR-T cells on 06 May 2019 and died on 12 May 2019 due 
to hemorrhage secondary to thrombocytopenia. The investigator attributed the thrombocytopenia, 
CRS, and acute renal failure to LCAR-B38M CAR-T cell therapy. The CRS events experienced 
by other subjects all resolved. No neurotoxicity has been reported as of the cutoff date. Further 
details are provided in the most recent edition of the Investigator’s Brochure.
1.6.
Overall Rationale for the Study 
BCMA is a cell surface antigen highly expressed on cells of the B cell lineage. Comparative studies 
show a lack of BCMA in most normal tissues and absence of expression on CD34-positive 
hematopoietic stem cells.7,15 This selective expression and the biological importance for the 
proliferation and survival of myeloma cells makes BCMA a promising target for CAR-T based 
immunotherapy, JNJ-68284528. Results in 74 subjects from the Legend-2 study indicate an ORR 
of 87.8% with a CR rate of 64.9%. The observed response rates and the reversible adverse events 
for most subjects, support further investigation of this approach in the current study.
1.7.
Potential Safety Risks and Mitigation Strategies
The potential risks of JNJ-68284528 are identified from the following: 1) results of nonclinical 
studies; 2) mechanism of action; and 3) previous clinical experience with LCAR-B38M CAR-T 
cells. Longer follow-up and treatment of additional subjects, particularly subjects who have 
received fewer prior therapies than subjects in the Legend-2 and 68284528MMY2001 studies, may 
reveal additional risks. 

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Objectives 
Endpoints 
To describe pre-trial goals and 
expectations as well as post-treatment 
experience of JNJ-68284528 using 
semi-structured qualitative interviews 
(Phase 2 only)
Description of the subject experience with 
JNJ-68284528 through a content analysis of the 
qualitative interview transcripts.
To characterize the impact of JNJ-
68284528 CAR-T process on medical 
resource utilization 
Number of subjects with type and length of inpatient 
stay and overall medical encounters 
To characterize potential early clinical, 
translational, and imaging markers for 
neurotoxicity (predictive markers)
Qualitative changes in handwriting assessment
Tmax, Cmax, and phenotypic analysis of CAR-T cells
Neuroimaging (CT/MRI)
2.2.
Hypotheses
Treatment with JNJ-68284528 will demonstrate acceptable safety and will have significant anti-
myeloma activity (ie, the lower limit of two-sided 95% confidence interval [CI] for ORR, as 
assessed by the IRC, is greater than 30%) at the targeted recommended Phase 2 dose (RP2D) dose 
level in subjects with advanced relapsed or refractory multiple myeloma.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a Phase 1b-2, open-label, multicenter study of JNJ-68284528 administered to adult subjects
with relapsed or refractory multiple myeloma. The aim of the study is to evaluate the safety and 
efficacy of JNJ-68284528. At least 24 and up to approximately 50 subjects will be enrolled in the 
Phase 1b portion of the study in which a RP2D of JNJ-68284528 will be established. Confirmation
of the RP2D will be based on review of data from at least 24 subjects who were administered JNJ-
68284528. Additional subjects (up to approximately 50) will be enrolled in the Phase 1b portion 
of the study to generate supplemental safety and efficacy data at the RP2D.
Safety evaluation team (SET) meetings will be convened as described in Section 3.5. All available 
data including safety, pharmacodynamic, pharmacokinetic, and efficacy data from subjects 
enrolled in Phase 1b study will be considered. The SET or sponsor may also determine that 
additional subjects are required to further evaluate safety and dose prior to proceeding to the Phase 
2 portion of the study. Before administration of JNJ-68284528 in the Phase 2 portion of the study, 
clinical data will be shared with the relevant health authorities. The planned sample size for the 
Phase 2 portion will be approximately 60 subjects.
During the Screening Phase, all subjects will provide written consent for study participation and 
will be screened for study eligibility within 28 days prior to apheresis. Safety criteria that must be 
met prior to starting apheresis are presented in Section 6.1.1.
Eligible subjects will undergo apheresis for collection of peripheral blood mononuclear cells 
(PBMC). Study enrollment is defined at the day of apheresis. JNJ-68284528 will be generated 

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from T cells selected from the apheresis. Subjects for whom apheresis or manufacturing fails will 
be allowed a second attempt at apheresis. 
Bridging therapy (anti-plasma cell directed treatment between apheresis and the first dose of the 
conditioning regimen) will be allowed when clinically indicated (ie, to maintain disease stability 
while waiting for manufacturing of JNJ-68284528), with the permission of the sponsor. Additional 
cycles of bridging therapy may be considered based on subject’s clinical status and timing of 
availability of CAR-T product. Investigator must contact the sponsor for approval. Bridging 
therapy must be a short-term treatment which previously generated at least a response of stable 
disease for the subject. The sponsor will not permit subjects who are found to be in CR after 
bridging therapy to receive JNJ-68284528.
After meeting safety criteria for treatment (Section 6.1.2), subjects will be administered a 
conditioning regimen of IV cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 
3 days. JNJ-68284528 will be administered at a total targeted dose of 0.75 x 106 CAR-positive 
viable T cells/kg (range: 0.5-1.0 x 106 CAR-positive viable T cells/kg) 5 to 7 days after start of the 
conditioning regimen (Section 6.1). This is a dose range informed by the Legend-2 study as 
described in Section 3.2. In the event of excess toxicity, a dose de-escalation to dose level -1 
(0.3 x 106 CAR-positive viable T cells/kg [range: 0.1-0.5 x 106 cells/kg]) for new subjects will 
occur (Section 3.3). Additionally, a dose escalation to dose level 2 (target dose not to exceed a 
3-fold dose escalation [2.25 x 106 CAR-positive viable T cells/kg, range: ±30%, depending on 
target dose chosen for dose level 2]) will be considered if specified safety criteria are met
(Section 3.4).
The first 6 subjects enrolled in the Phase 1b portion of the study will be hospitalized for at least 
2 weeks after receiving an infusion of JNJ-68284528. Hospitalization and local stay requirements 
for subsequent subjects will be based on recommendations by the SET.
For the primary efficacy analysis, the disease status evaluation for each subject will be assessed 
by an Independent Review Committee (IRC). Disease status will be evaluated according to clinical 
judgement guided by the IMWG consensus recommendations for multiple myeloma treatment 
response criteria (Attachment 1). 11,12,32 The process and convention of the IRC will be detailed in 
a separate charter.
Safety evaluations will include a review of adverse events, laboratory test results, vital sign 
measurements, physical examination findings, handwriting assessments, and assessment of 
Eastern Cooperative Oncology Group (ECOG) performance status grade. The safety profile will 
be evaluated at SET meetings during the Phase 1b portion of the study. Follow up of subjects for 
disease progression and survival will continue during the Posttreatment Phase. All study 
evaluations will be conducted according to the Time and Events Schedules (Table 1 and 
Table 2).
The sponsor will establish a data cutoff date for clinical study report (CSR) analyses. The first
analysis will be conducted approximately 6 months after the last subject receives their initial dose 
of JNJ-68284528. An update of the analysis will be provided at approximately 9-12 months after 

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
No ongoing Grade 3 or higher hematologic toxicity.

No ongoing Grade 2 non-hematologic toxicity (with the exception of nausea, vomiting, hair 
loss, and constipation).

At least 6 months between first JNJ-68284528 infusion and detection of PD.
Subjects must satisfy all inclusion and exclusion criteria (Section 4), except for exclusion criteria 1 
and 2, to be eligible for retreatment. A maximum of 1 retreatment may occur per subject. Bridging 
therapy prior to retreatment may be considered based on subject’s clinical status and timing of 
availability of CAR-T product.  Investigator must contact the sponsor for approval.
A staggered strategy for retreatment will be applied. There must be an observation period of at 
least 2 weeks between retreatment with JNJ-68284528 to the first and second subject, the second 
and third, and third and fourth subjects, respectively.
Time and events schedules for retreatment are provided in Attachment 9 (Table 12 and 
Table 13). Subjects who received retreatment with JNJ-68284528 and are in follow-up at the end 
of the study (2 years after the last subject receives the initial dose of JNJ-68284528) will be 
monitored in the long-term follow-up study for 15 years from the time of last treatment (see 
Section 9.1.6.3). 
3.2.
Rationale of Dose and Administration Schedule Selection
The conditioning regimen of cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 
3 doses will lead to lymphodepletion and help promote CAR-T cell expansion in the subject.
Cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 before JNJ-68284528 infusion (Day 1) 
is consistent with the lymphodepletion regimen used in the marketed CAR-T products Kymriah19
and Yescarta34. 
JNJ-68284528 will be administered at a targeted infused dose of 0.75 x 106 CAR-positive viable 
T cells/kg (range: 0.5-1.0 x 106 CAR-positive viable T cells/kg with a maximum total dose of 1.0 x 
108 CAR-positive viable T cells) for this Phase 1b-2 study. This dose is informed by the Legend-
2 clinical study performed at 4 study sites across China. The number of viable CAR-positive T 
cells prepared for the 74 subjects from the Legend-2 study ranged from 0.07 to 2.10 x 106 CAR-
positive viable T cells/kg (mean 0.642 x 106 cells/kg, median 0.513 x 106 cells/kg).
Across all 74 subjects, the safety profile supports doses up to 1.5 x 106 cells/kg with regards to 
occurrence of CRS (Table 4). Analysis of the safety of doses above 1.5 x 106 in the Legend-2 study 
is not possible due to the very small number of subjects who received a dose above this 
concentration. As discussed in Section 1.4, the JNJ-68284528 drug product expresses the same 
CAR protein and is produced using a modified manufacturing process relative to the drug product 
used in the Legend-2 study. Differences in clinical activity and safety profiles due to the updated 
manufacturing process are possible. Thus, the targeted infused dose (post-freeze) of 0.75 x 106
CAR-positive viable T cells/kg proposed for JNJ-68284528 was reduced to half of the prepared
dose (pre-freeze) of 1.5 x 106 cells/kg supported by the safety analysis summarized in Table 4. 
Acknowledging that each CAR-T cell product may have unique factors that influence the safety 

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If >1 out of the first 6 subjects at any dose level meets DLT criteria during the 21-day evaluation 
period, a dose de-escalation to a target dose (dose level -1) of 0.3 x 106 CAR-positive viable 
T cells/kg (range: 0.1-0.5 x 106 cells/kg) for future subjects will be mandated as determined by the 
SET (see Section 3.5). For the duration of the Phase 1b portion of the study, a dose de-escalation 
will be mandated if, at the time of the SET meeting, DLT criteria are met for 20% of subjects for 
any dose level reaching the evaluation milestone (eg, 6, 12, or 18 subjects). 
Adverse events should be evaluated according to National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI-CTCAE Version 5.0), with the exception of CRS and CAR-T 
cell-related neurotoxicity (eg, ICANS). CRS should be evaluated according to the ASBMT
consensus grading (Lee 2019)22 (Attachment 11). CAR-T cell-related neurotoxicity (eg, ICANS) 
should be graded using the ASBMT consensus grading (Attachment 13). Assessments for ICE 
should be performed as specified in the Time and Events Schedule (Table 1 and Table 12) in both 
the Phase 1b and Phase 2 portions of the study.
3.4.
Dose Escalation
At the time of the SET meeting, if fewer than 20% of subjects enrolled in the study at the target 
starting dose (dose level 1) meets DLT criteria during the 21-day dose de-escalation evaluation 
period described above, the SET may approve a dose escalation (dose level 2). The target dose 
level and range for dose level 2 will be decided by the SET after review of all available safety, 
pharmacokinetic, pharmacodynamic, and preliminary efficacy data, and will not exceed a 3-fold 
dose escalation of the initial target dose (2.25 x 106 CAR-positive viable T cells/kg [range: ±30%, 
depending on target dose chosen for dose level 2]) (see Table 6). Dose escalation beyond dose 
level 2 will not be permitted. After dose escalation, the same criteria for dose de-escalation 
described in Section 3.3 will be used for mandated de-escalation back to 0.75 x 106 cells/kg (dose 
level 1).
The RP2D will be confirmed by the SET after evaluation of safety, preliminary efficacy, 
pharmacokinetic, and pharmacodynamic data from at least 24 Phase 1b subjects. The RP2D will 
be a dose level examined in Phase 1b at which <20% of subjects experienced a DLT. If there is 
more than one dose level that meets this safety threshold, the preliminary overall response rate 
among subjects that have had at least two post-infusion efficacy assessments will be considered 
with additional consideration given to the rate and level of JNJ-68284528 CAR-T cell persistence.
3.5.
Safety Evaluation Team
To ensure safety monitoring and sponsor oversight of the study, the sponsor will establish a SET. 
The SET will be chaired by the sponsor Study Responsible Physician. Membership will include 
the study principal investigators, a sponsor clinical scientist, safety physician, statistician, clinical 
pharmacologist, and additional sponsor staff, as appropriate. SET meetings will occur only during 
the Phase 1b portion of the study. Written documentation of meeting outcomes will be maintained 
by the sponsor. Decisions with the potential to impact subjects’ safety (eg, unfavorable change in 
risk/benefit assessment) will be promptly communicated to regulatory authorities and study sites 
as appropriate.

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SET meetings will occur approximately after 6 subjects at the same dose level have completed the 
21-day dose evaluation period: 1) during the Phase 1b study to evaluate for escalation and de-
escalation of dose level after completion of the DLT evaluation period of every 6 subjects through 
24 subjects and every 12 subjects thereafter, and 2) after SET evaluation of at least 24 subjects 
evaluated, administration of JNJ-68284528 to subjects in the Phase 2 portion of the study may
begin concurrently with ongoing administration of JNJ-68284528 to subjects in the Phase 1b 
portion of the study. Ad-hoc SET meetings may be convened at the discretion of the sponsor. 
Administration of the conditioning regimen and dosing with JNJ-68284528 will be paused 
between dosing of the sixth subject and the conclusion of the first SET meeting. These meetings 
will ensure the safety of subjects is maintained prior to continued dosing of subjects and will 
consider the need to reduce the dose and if it is safe to escalate the dose for upcoming subjects. 
This SET will consider all available treatment emergent data (eg, pharmacokinetic, 
pharmacodynamics, safety, efficacy) for these decisions. The SET may advise on modifications in 
study conduct, including whether hospitalization, local stay, or staggered dosing with
JNJ-68284528 is required for subsequent subjects or stopping further enrollment if treatment-
emergent toxicity is believed to result in an unfavorable risk-benefit profile. All SET decisions 
will be communicated to all study sites and archived in writing in the Trial Master File.
4.
SUBJECT POPULATION
Screening for eligible subjects will be performed within 28 days prior to apheresis. The inclusion 
and exclusion criteria for enrolling subjects in this study are described in the following 
2 subsections. If there is a question about the inclusion or exclusion criteria, the investigator must 
consult with the Study Responsible Physician, Study Responsible Scientist or delegate and resolve 
any issues before enrolling a subject in the study. Waivers are not allowed.
4.1.
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study: 
1.
18 years of age.
2.
Documented diagnosis of multiple myeloma according to IMWG diagnostic criteria
(Attachment 3).
3.
Criterion modified per Amendment 2
3.1. Measurable disease at Screening as defined by any of the following:

Serum monoclonal paraprotein (M-protein) level 1.0 g/dL or urine M-protein 
level 200 mg/24 hours; or

Light chain multiple myeloma without measurable disease in the serum or the 
urine: Serum immunoglobulin free light chain 10 mg/dL and abnormal serum 
immunoglobulin kappa lambda free light chain ratio.

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Note: Local laboratory assessments may be used to establish measurable disease at 
Screening, with local laboratory result ≥125% of requirements
4.
Criterion modified per Amendment 1
4.1. Criterion modified per Amendment 3
4.2. Received at least 3 prior multiple myeloma treatment lines of therapy or are double 
refractory to an IMiD and PI (refractory multiple myeloma as defined by IMWG consensus 
criteria30). Note: induction with or without hematopoietic stem cell transplant and with or 
without maintenance therapy is considered a single line of therapy.

Undergone at least 1 complete cycle of treatment for each line of therapy, unless PD 
was the best response to the line of therapy.
5.
Criterion modified per Amendment 3
5.1 Received as part of previous therapy a PI, an IMiD, and an anti-CD38 antibody (prior 
exposure can be from different monotherapy or combination lines of therapy).
6.
Criterion modified per Amendment 2
6.1. Criterion modified per Amendment 3
6.2. Subject must have documented evidence of progressive disease based on investigator’s 
determination of response by the IMWG criteria on or within 12 months of their last line 
of therapy (Attachment 1). Confirmation may be from either central or local testing. Also, 
subjects with documented evidence of progressive disease (as above) within the previous 
6 months and who are refractory or non-responsive to their most recent line of therapy
afterwards are eligible.
7.
ECOG Performance Status grade of 0 or 1 (Attachment 5).

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
Who is sexually active with a woman who is pregnant must use a condom
Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, 
during the study and for 1 year after the last dose of study treatment. 
Note: Hormonal contraception may be susceptible to interaction with the study treatment, 
which may reduce the efficacy of the contraceptive method.
11.
Subject must sign an ICF indicating that he or she understands the purpose of procedures 
required for the study and is willing to participate in the study. Consent is to be obtained 
prior to the initiation of any study-related tests or procedures that are not part of standard-
of-care for the subject’s disease.
12.
Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
4.2.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study:
1.
Prior treatment with CAR-T therapy directed at any target. 
2.
Any therapy that is targeted to BCMA.
3.
Criterion modified per Amendment 2
3.1. Diagnosed or treated for invasive malignancy other than multiple myeloma, except:

Malignancy treated with curative intent and with no known active disease present 
for 2 years before enrollment; or 

Adequately treated non-melanoma skin cancer without evidence of disease.
4.
Prior antitumor therapy as follows, prior to apheresis:

Targeted therapy, epigenetic therapy, or treatment with an investigational drug or 
used an invasive investigational medical device within 14 days or at least 5 half-
lives, whichever is less.

Monoclonal antibody treatment for multiple myeloma within 21 days. 

Cytotoxic therapy within 14 days. 

Proteasome inhibitor therapy within 14 days. 

Immunomodulatory agent therapy within 7 days.

Radiotherapy within 14 days. However, if the radiation portal covered 5% of the 
bone marrow reserve, the subject is eligible irrespective of the end date of 
radiotherapy.

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5.
Toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 
or less except for alopecia or peripheral neuropathy.
6.
The following cardiac conditions:

New York Heart Association (NYHA) stage III or IV congestive heart failure

Myocardial infarction or coronary artery bypass graft (CABG) 6 months prior to 
enrollment

History of clinically significant ventricular arrhythmia or unexplained syncope, not 
believed to be vasovagal in nature or due to dehydration

History of severe non-ischemic cardiomyopathy

Impaired cardiac function (LVEF <45%) as assessed by echocardiogram or 
multiple-gated acquisition (MUGA) scan (performed 8 weeks of apheresis).  
7.
Criterion revised per Amendment 2
7.1. Received a cumulative dose of corticosteroids equivalent to ≥70 mg of prednisone 
within the 7 days prior to apheresis
8.
Received either of the following:

An allogenic stem cell transplant within 6 months before apheresis. Subjects who 
received an allogeneic transplant must be off all immunosuppressive medications 
for 6 weeks without signs of graft-versus-host disease (GVHD).  

An autologous stem cell transplant 12 weeks before apheresis 
9.
Criterion modified per Amendment 2
9.1. Known active, or prior history of central nervous system (CNS) involvement or 
exhibits clinical signs of meningeal involvement of multiple myeloma.
10.
Stroke or seizure within 6 months of signing ICF.
11.
Plasma cell leukemia at the time of screening (>2.0 x 109/L plasma cells by standard 
differential), Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, 
organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary AL 
amyloidosis.
12.
Seropositive for human immunodeficiency virus (HIV).
13.
Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis.

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14.
Criterion modified per Amendment 2
14.1. Hepatitis B infection as defined according to Attachment 8). In the event the 
infection status is unclear, quantitative levels are necessary to determine the infection 
status.
15.
Criterion modified per Amendment 1
15.1. Criterion modified per Amendment 2
15.2. Hepatitis C infection defined as (anti-hepatitis C virus [HCV] antibody positive 
or HCV-RNA positive) or known to have a history of hepatitis C. For subjects with 
known history of HCV infection, confirmation of sustained virologic response [SVR] 
is required for study eligibility, defined as ≥24 weeks after completion of antiviral 
therapy.
16.
Supplemental oxygen use to maintain adequate oxygenation.
17.
Known life threatening allergies, hypersensitivity, or intolerance to JNJ-68284528 or 
its excipients, including DMSO (refer to Investigator’s Brochure).
18.
Serious underlying medical condition, such as:

Evidence of serious active viral, bacterial, or uncontrolled systemic fungal 
infection

Active autoimmune disease or a history of autoimmune disease within 3 years

Overt clinical evidence of dementia or altered mental status
19.
Any issue that would impair the ability of the subject to receive or tolerate the planned 
treatment at the investigational site, to understand informed consent or 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.
20.
Criterion modified per Amendment 3
20.1 Pregnant or breast-feeding, or planning to become pregnant while enrolled in this 
study or within 1 year after receiving study treatment.
21.
Criterion modified per Amendment 3
21.1 Plans to father a child while enrolled in this study or within 1 year after receiving 
study treatment.

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22.
Major surgery within 2 weeks prior to apheresis, or has surgery planned during the study 
or within 2 weeks after study treatment administration. (Note: subjects with planned 
surgical procedures to be conducted under local anesthesia may participate.) 
5.
INTERVENTION ALLOCATION AND BLINDING
Randomization will not be used in this study. Subjects will receive study treatment if all 
inclusion/exclusion criteria are met. As this is an open-label study, blinding procedures are not 
applicable.
6.
DOSAGE, ADMINISTRATION, AND GUIDANCE
For this study, study treatment refers to both cyclophosphamide/fludarabine and JNJ-68284528. 
All dosing information must be recorded in the Dosage Administration page of the electronic case 
report form (eCRF). 
6.1.
Study Treatment Administration
Approximately 4 weeks after apheresis, and after the site is notified in writing by the Janssen team 
that manufacture and quality testing of JNJ-68284528 has been completed, each subject will 
receive a conditioning regimen of intravenous (IV) cyclophosphamide 300 mg/m2 and fludarabine 
30 mg/m2 at 3 daily doses; sponsor approval must be obtained to change the conditioning regimen 
schedule. JNJ-68284528 will be administered as a single infusion 5 to 7 days after the start of the 
conditioning regimen (the first day of conditioning is Day -7 to Day -5, and the day of JNJ-
68284528 infusion is Day 1). Cyclophosphamide and fludarabine should be administered using 
administration procedures and supportive care according to the site’s standard of care. JNJ-
68284528 should be administered as described in the site investigational product procedures 
manual (SIPPM) and investigational product preparation instructions (IPPI).
A strategy of staggered dosing with JNJ-68284528 will be applied. There must be an observation 
period of at least 4 weeks between administration of JNJ-68284528 to the first and second subject, 
and an observation period of at least 2 weeks between administration of JNJ-68284528 to the 
second and third and third and fourth subjects, respectively. No observation periods are mandated 
after the fourth subject receives JNJ-68284528. Administration of the conditioning regimen and 
dosing with JNJ-68284528 will be paused between JNJ-68284528 dosing of the sixth subject and 
conclusion of the first SET meeting.
Exceptional Release Criteria
In the event a JNJ-68284528 product that did not meet pre-specified release criteria is produced 
during the manufacturing procedures, the sponsor will evaluate the risk/benefit for administration 
of the affected product and determine if the supply of the product to the treating physician could 
be considered. If required, approval from the relevant health authorities for use of the product will 
be obtained. In the event the supply of the affected product is deemed appropriate, the investigator 
should inform the study subject that the product did not meet release specifications prior to 
administration.

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6.1.1.
Criteria for Apheresis
The investigator should contact the sponsor if evidence of rapid disease progression or suspected 
CNS involvement is observed between screening and apheresis. Subjects must meet the following 
criteria to proceed with apheresis:

Clinical laboratory values required for enrollment (inclusion criterion 8, Section 4.1) resulted 
within 24-hours prior to apheresis

No plasma cell leukemia at the time of apheresis (>2.0 x 109/L plasma cells by standard 
differential) (exclusion criterion 11, Section 4.2).

ECOG performance status grade of 0 or 1

Negative pregnancy test for women of childbearing potential up to 72 hours prior to apheresis

No antitumor therapy within timeframe detailed in Section 4.2 and presented below:

Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an 
invasive investigational medical device within 14 days or at least 5 half-lives, whichever 
is less.

Monoclonal antibody treatment for multiple myeloma within 21 days. 

Cytotoxic therapy within 14 days. 

Proteasome inhibitor therapy within 14 days. 

Immunomodulatory agent therapy within 7 days.

Radiotherapy within 14 days. However, if the radiation portal covered ≤5% of the bone 
marrow reserve, the subject is eligible irrespective of the end date of radiotherapy.

Cumulative dose of corticosteroids should not exceed equivalent to ≥70 mg prednisone within 
the 7 days prior to the first dose of conditioning regimen

No evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection. 
Subjects on anti-infective agents within 7 days prior to apheresis must receive approval to 
proceed from sponsor.

No major surgery 2 weeks prior to apheresis

No live, attenuated vaccines ≤4 weeks prior to apheresis

No supplemental oxygen use to maintain adequate oxygenation

No new arrhythmia or other cardiac adverse events unless controlled with medical 
management and approved by the medical monitor
For subjects who require a repeat apheresis, the following screening assessments should be 
collected before the second apheresis: weight, hematology laboratory assessments, chemistry 
laboratory assessments, and echocardiogram or MUGA (if clinically indicated). If the second 
apheresis falls outside of the 28-day window, all screening assessments (except bone marrow 
collection) must be repeated).

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6.1.2.
Criteria for Conditioning Regimen (Cyclophosphamide and 
Fludarabine) Dosing
The investigator should contact the sponsor if evidence of rapid disease progression is observed 
between apheresis and cyclophosphamide and fludarabine dosing. Subjects must meet the 
following criteria to proceed with cyclophosphamide and fludarabine dosing:

Clinical laboratory values required for enrollment (Section 4.1), with the following exception: 
lymphocyte count of ≥0.3 x 109/L. Transfusion support is permitted to maintain a hemoglobin 
of ≥8.0 g/dl (≥5mmol/L) as needed, and platelets of ≥50 x 109/L until 3 days before the 
hematology laboratory test, preceding lymphodepletion. Myeloid growth factors are permitted 
up to 1 day prior to the start of the conditioning regimen. Pegylated myeloid growth factors 
(ie, pegfilgrastim) are prohibited.

Echocardiogram or MUGA scan for subjects who receive bridging therapy that includes 
agents with known cardiac toxicity, including but not limited to anthracyclines and
carfilzomib (per prescribing information), verification of non-impaired cardiac function 
(LVEF ≥45%) should be performed after completion of bridging therapy and prior to the first 
dose of the conditioning regimen.

ECOG performance status grade of 0 or 1

Negative pregnancy test for women of childbearing potential up to 72 hours prior to the first 
dose of the conditioning regimen

No antitumor therapy within timeframe detailed in Section 4.2 and presented below:

Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an 
invasive investigational medical device within 14 days or at least 5 half-lives, whichever 
is less.

Monoclonal antibody treatment for multiple myeloma within 21 days. 

Cytotoxic therapy within 14 days. 

Proteasome inhibitor therapy within 14 days. 

Immunomodulatory agent therapy within 7 days.

Radiotherapy within 14 days. However, if the radiation portal covered 5% of the bone 
marrow reserve, the subject is eligible irrespective of the end date of radiotherapy.

No active Grade 3 toxicity to any bridging therapy

No cumulative dose of corticosteroids equivalent to ≥70 mg prednisone within the 7 days prior 
to conditioning regimen dosing. The sponsor should be called for approval if a subject receives 
corticosteroids at a dose >10 mg per day in the week prior to the start of the conditioning 
regimen.

No signs of active infection. For subjects requiring systemic anti-microbial treatment or with 
temperature ≥38.0 Celsius within 7 days prior to the first dose of conditioning regimen, the 
investigator must receive approval to proceed from the sponsor.

No major surgery 2 weeks prior to conditioning regimen dosing

No live, attenuated vaccines within 4 weeks prior to conditioning regimen dosing

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
No supplemental oxygen use to maintain adequate oxygenation 

No new arrhythmia or other cardiac adverse events unless controlled with medical 
management and approved by the medical monitor

Washout from bridging therapy completed as specified in Section 4.2, criterion 4.
Subjects should be evaluated for the presence of an indwelling catheter prior to the first dose of 
the conditioning regimen. 
6.1.3.
Evaluation Prior to Administration of JNJ-68284528
JNJ-68284528 Dosing Delays: 
Subjects will be evaluated for safety on the day of JNJ-68284528 infusion. If a significant health 
status change (eg, clinical deterioration, rapidly progressing disease) occurs following the start of 
the conditioning regimen (see Section 6.1.2), the investigator should contact the sponsor prior to 
dosing. 
Infusion of JNJ-68284528 must be delayed if any of the following events occur:

Signs of active infection. Do not administer JNJ-68284528 to subjects with active infection. 
For subjects requiring systemic anti-microbial treatment, or with temperature ≥38.0 Celsius 
within 48 hours before JNJ-68284528 infusion, investigator must consult with the sponsor 
prior to dosing.

Grade 3 non-hematologic toxicities of cyclophosphamide and fludarabine conditioning 
(except for Grade 3 nausea, vomiting, diarrhea, or constipation). Investigator must consult 
with the sponsor prior to JNJ-68284528 dosing.
If resolution of these events to Grade ≤1 takes more than 14 days, the conditioning regimen should 
be re-administered (cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 days) after 
a minimum of 21 days following the first dose of the first conditioning regimen
(cyclophosphamide and fludarabine).

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6.1.4.
JNJ-68284528 Administration
JNJ-68284528 will be administered as summarized in Table 6.
Table 6:
JNJ-68284528 Administration
Dose
JNJ-68284528 will be administered in one infusion. The target dose is 0.75 x 106 CAR-
positive viable T cells/kg (range: 0.5-1.0 x 106 CAR-positive viable T cells/kg) as described 
in Section 3.2. The maximum total dose of cells to be administered to any subject is 1.0 x 108
CAR-positive viable T cells (ie, the maximum weight adjusted dose calculated for a 100-kg
subject). If the dose level is de-escalated to dose level -1 or escalated to dose level 2, the 
maximum total dose of cells would be adjusted accordingly as the maximum weight adjusted 
dose (CAR-positive viable T cells/kg) calculated for a 100-kg subject at that dose level. The
dose and administration schedule may be altered for safety purposes based on emerging data.  
If after apheresis and CAR-T cell preparation the quantity of JNJ-68284528 manufactured is 
not sufficient for dosing at the lower end of the dosing range, dosing for that subject may 
proceed, provided that a measurable quantity of JNJ-68284528 CAR-positive viable T cells 
that pass quality testing are generated.
Route/Regimen
JNJ-68284528 IV infusion is to be administered under the supervision of site staff. Refer to 
the IPPI for JNJ-68284528 infusion instructions.
Dosing Instructions
The actual dose for study treatment administration will be based on the subject’s weight (kg)
at apheresis. 
Schedule of Administration 
One intravenous infusion
Hospitalization 
Requirements
The first 6 subjects enrolled will be hospitalized for at least 2 weeks after receiving an 
infusion of JNJ-68284528 and will be asked to remain within a 1-hour travel time of the 
hospital and in the company of a competent adult at all times for 1 additional week after 
discharge.
Subjects who are not hospitalized will be asked to remain within a 1-hour travel time of the 
hospital and in the company of a competent adult at all times for the 2 weeks following study 
treatment. Hospitalization and local stay requirements will be evaluated by the SET for 
subsequent subjects.
At the first sign of CRS (such as fever), subjects should be immediately hospitalized for 
evaluation. Further details regarding management of CRS are described in 
Table 8.
Hospitalization is required for Grade 2, 3, or 4 CAR-T cell-related neurotoxicity (eg, ICANS)
temporally associated with CRS. Hospitalization for neurotoxicity that is not temporarily 
associated with CRS, or any other neurologic adverse events, is at the discretion of the 
investigator.
Vital Sign and Clinical 
Safety Monitoring
Monitor vital signs as indicated in the Time and Events Schedule (Table 1).

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6.2.
Pre-infusion Supportive Therapy
Prior to JNJ-68284528 infusion, subjects should receive premedication as noted below (Table 7). 
Corticosteroids should not be used during pre-infusion. 
Table 7:
Pre-infusion Medications
Medication
Dose
Administration
Antihistamine
diphenhydramine (50 mg) or 
equivalent
Oral – administer 1 hour (±15 minutes) prior to JNJ-68284528 infusion
Or
IV– start infusion 30 minutes (±15 minutes) prior to JNJ-68284528 
infusion
Antipyretic
acetaminophen (650 mg to 
1,000 mg) or equivalent
Oral or IV - administer 30 minutes (±15 minutes) prior to 
JNJ-68284528 infusion
6.3.
Management Guidelines for Potential Risks 
6.3.1.
Management of Cytokine Release Syndrome
In the Legend-2 study, CRS was reported in approximately 92% of subjects who received LCAR-
B38M CAR-T cells. Most events were Grade 1 or Grade 2. All events of CRS started with fever 
after the infusion of CAR-T therapy (See Section 1.5). Of the subjects who developed CRS, 
approximately 84% experienced transiently increased aspartate aminotransferase (AST). AST 
increase was Grade 3 or Grade 4 in 31% and 6% of subjects with CRS, respectively. Subjects 
should be monitored for increased AST, and consumptive coagulopathy, indicated by an increase 
in D-dimers and a decrease in fibrinogen if CRS is suspected.
Symptoms indicative of CRS may include, but are not limited to, fever (with or without rigors), 
arthralgia, nausea, vomiting, tachypnea, hypoxia, tachycardia, hypotension, headache, confusion, 
tremor, delirium, dyspnea, pulmonary edema, and capillary leak.21 Potentially life-threatening 
complications of CRS may include cardiac dysfunction, adult respiratory distress syndrome, 
neurologic toxicity, renal failure, hepatic failure, and disseminated intravascular coagulation.
Laboratory testing to monitor for disseminated intravascular coagulation, a manifestation of CRS, 
should be carried out in addition to daily monitoring of chemistry and hematology assessments 
(including ferritin and CRP) when fever or other signs of potential CRS are present (see Table 1). 
In addition, pulmonary, renal and hepatic function will be monitored closely (see Table 1). 
Cytokine release syndrome will be captured as an adverse event of special interest (see 
Section 12.3.3).
Rarely, severe CRS can evolve into a presentation consistent with hemophagocytic 
lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) that may require additional 
therapy. In these cases, laboratory testing may reveal high serum levels of ferritin, lactate 
dehydrogenase, soluble CD25, and cytokines (such as IFNγ and IL-6), and low serum levels of 
fibrinogen (Neelapu 2018)25. Severe thrombocytopenia, low fibrinogen, and often DIC may be 
features of HLH, all of which combined may increase the risk of severe bleeding in these subjects. 
If HLH is suspected, anticoagulation should be avoided or modified based on institutional 

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guidelines depending on platelet count and renal function. Subjects with HLH should have their 
platelet count and coagulation parameters very closely monitored and maximal support should be 
provided to avoid major bleeding complications. For example, consider platelet transfusion if 
platelets are less than 50 × 109/L. Under these circumstances, investigators should consider treating 
the subject in the ICU, so that maximal monitoring and support can be carried out during this 
period.
Trained clinical personnel should be prepared to intervene in the event of CRS. Resources 
necessary for resuscitation (ie, agents such as epinephrine and aerosolized bronchodilator; medical 
equipment such as oxygen, tracheostomy equipment, and a defibrillator) should be readily 
available. Tocilizumab must be available prior to administration of JNJ-68284528. Vital signs and 
laboratory parameters must be monitored at regular intervals until normal. Additional specimens 
for pharmacokinetic and pharmacodynamic testing should be collected as per the schedule outlined 
in Table 2. 
Infection and CRS may have a similar presentation. Therefore, investigators are strongly 
encouraged to evaluate for an infection at the first signs or symptoms of CRS. Cultures and 
imaging should be obtained: the clinical signs and symptoms should determine which tests are 
appropriate. 
Recommendations for the clinical management of CRS are provided in Table 8. At the first sign 
of CRS (such as fever) subjects should be immediately hospitalized for evaluation. The use of 
myeloid growth factors, particularly granulocyte colony-stimulating factor (G-CSF), should be 
avoided during CRS. Tocilizumab intervention may be considered with presenting symptom of 
fever per investigator discretion when other sources of fever have been eliminated and early 
tocilizumab should be considered in subjects at high risk of severe CRS (for example, high baseline 
tumor burden, early fever onset, or persistent fever after 24 hours of symptomatic treatment). Other 
monoclonal antibodies targeting cytokines (for example, anti-IL1 and/or anti-TNF) may be used 
based on institutional practice, especially for cases of CRS which does not respond to tocilizumab. 
Therapy directed at reduction or elimination of CAR-T cells, including chemotherapy, may be 
considered in consultation with the sponsor for subjects who develop high grade CRS with 
laboratory findings overlapping with HLH/MAS (including hyperferritinemia) that remains severe 
or life-threatening following prior therapies, including tocilizumab and corticosteroids.

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Supportive care for CRS (including but not limited to anti-pyretic agents, IV fluid support, 
vasopressors, supplemental oxygen) should be administered according to the clinical 
manifestations of the subject’s illness. Similarly, ancillary testing such as B-type natriuretic 
peptide (BNP) assessment, echocardiograms, arterial blood gas, assessments of coagulation 
laboratory tests, should be performed if clinically indicated. 
6.3.2.
Neurologic Toxicities
Based on the specific mode-of-action of JNJ-68284528, severe or serious neurological toxicities 
(including CAR-T cell-related neurotoxicity, eg, ICANS [Immune Effector Cell-Associated 
Neurotoxicity Syndrome]) may occur (Section 6.3.2.1). Subjects should be monitored for 
neurotoxicity for 1-year post JNJ-68284528 infusion (Section 6.3.2.2). 
6.3.2.1.
CAR-T Cell-related Neurotoxicity (Immune Effector Cell-Associated 
Neurotoxicity Syndrome [ICANS])
Subjects should have the Immune Effector Cell-associated Encephalopathy (ICE) Assessment 
Tool (ICE-Tool; Attachment 12) performed at baseline (within 24 hours prior to infusion of 
JNJ-68284528 infusion) and daily after the first symptoms of CAR-T cell-related neurotoxicity 
(eg, ICANS) are suspected and until resolution. Consider performing ICE-Tool more frequently 
until neurotoxicity symptoms resolve. Consider performing neuroimaging (eg, magnetic resonance 
imaging [MRI]) at screening and/or neurology consultation if pre-existing disease is suspected; 
see Section 9.2 Safety Evaluation.
Subjects should be monitored for neurological toxicities including, but not restricted to, speech 
disorders, aphasia, convulsions, disturbances in consciousness, confusion, disorientation, or 
coordination and balance disorders. If these or other neurological toxicities are observed, 
regardless of causality, then the sponsor’s medical monitor must be consulted. Hospitalization is 
required for Grade 2, 3, or 4 CAR-T cell-related neurotoxicity (eg, ICANS) temporally associated 
with CRS.
At the first sign of neurotoxicity, neurology consultation and evaluation should be considered for 
all neurological toxicities. Rule out alternative etiologies including infectious etiologies (eg, viral 
origin such as, human herpesvirus [HHV] HHV-6, HHV-7) if clinically indicated. Subjects who 
have a lumbar puncture as part of their neurologic work up should have a sample of cerebral spinal 
fluid for additional testing (eg, pharmacokinetic or biomarkers) as clinically indicated. For signs 
of seizures or raised intracranial pressure (ICP)/cerebral edema, consider neuroimaging (CT/MRI), 
transfer the subject to the intensive care unit (ICU) and treat according to institutional guidelines 
or practices.
General management for CAR-T cell-related neurotoxicity (eg, ICANS) with or without 
concurrent CRS is summarized in Table 9. All neurological adverse events, including CAR-T 
related neurotoxicity (eg, ICANS), will be captured as an adverse event of special interest (see 
Section 12.3.3).

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
difficulty with short term memory

slowing of movements

difficulty performing simple tasks

difficulty swallowing

joint or muscle stiffness or inflexibility

shuffling gait

restlessness

micrographia
Early detection, workup and intervention, may be important to prevent neurologic toxicity from 
worsening. The following is a list of potential diagnostics that should be considered in subjects 
with new neurologic symptoms:

Positron emission tomography/computerized tomography (PET/CT) of the brain and/or brain 
MRI with perfusion and an electroencephalogram (EEG) 

Lumbar puncture to rule out infection (in particular John Cunningham virus [JCV], herpes 
zoster virus [HZV], herpes simplex virus [HSV]-1/2, HHV-6, HHV-7, Epstein-Barr virus 
[EBV], cytomegalovirus [CMV]).

Serologic testing for HHV-6 and HHV-7 by PCR for viremia. 

CSF flow cytometry and cytology should be considered to rule out leptomeningeal disease. 

Cerebral spinal fluid (CSF) analysis to rule out paraneoplastic syndromes. 

Thiamine level (consider empiric thiamine replacement while awaiting results)24
Therapy directed at reduction or elimination of CAR-T cells, including chemotherapy, may be 
considered in consultation with the sponsor for subjects who develop neurotoxicity that remains 
unresponsive to other interventions.
Per Section 9.4 of the protocol, if cerebral spinal fluid (CSF) or other relevant biological sample 
analysis is clinically indicated, a sample of CSF may be requested for additional analysis by the 
sponsor, as allowed by local regulations.
Per section 9.7of the protocol, qualitative changes in handwriting since baseline are being explored 
by the sponsor as a potential early clinical predictive marker for neurotoxicity.
6.3.3.
Tumor Lysis Syndrome
Although TLS is uncommon in subjects with multiple myeloma, one subject in the Phase 1 
Legend-2 Study experienced fatal TLS. Subjects must be monitored closely for symptoms of TLS. 
Management of TLS, including hyperkalemia, hyperuricemia, hyperphosphatemia, and 
hypocalcemia, is highly recommended. It is also required that high-risk subjects, ie, those with a 
high tumor burden (60% plasma cell infiltrate on the bone marrow biopsy or aspirate [whichever
is higher] or a subject with multiple extramedullary disease sites or plasmacytomas), be treated

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prophylactically in accordance with local standards (eg, extra hydration; diuretics; allopurinol 
300 mg daily and primary or secondary uricosuric agents, as indicated). TLS will be captured as 
an adverse event of special interest (see Section 12.3.3).
6.3.4.
Cytopenia
Subjects may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and 
JNJ-68284528 infusion. In the Legend-2 study, Grade 3 and 4 cytopenias included leukopenia 
(25.7%), thrombocytopenia (18.9%), anemia (14.9%), and neutropenia (2.7%). Prolonged 
neutropenia may increase the risk of infection. Blood counts should be monitored after 
JNJ-68284528
infusion. The use of myeloid growth factors, particularly granulocyte 
colony-stimulating factor (G-CSF), should be avoided during CRS.
Parvovirus B19 monitoring by PCR should be considered in subjects experiencing prolonged 
neutropenia or a decline in neutrophil counts following recovery.
6.3.5.
Hypogammaglobulinemia
Hypogammaglobulinemia 
may 
occur 
in 
subjects 
receiving 
JNJ-68284528. 
Monitor 
immunoglobulin levels after treatment as detailed in the Time and Events Schedule (Table 1) and 
more frequently if clinically indicated and treat according to local guidelines, including 
administration of immunoglobulin replacement and monitoring for infection.
Subjects with IgG < 400 mg/dL and recurrent infections may receive prophylactic IVIG as per 
institutional guidelines.
6.3.6.
Infections
Administration of JNJ-68284528 may increase the risk of infection due to cytopenias or 
hypogammaglobulinemia. Subjects should be monitored frequently for infection and should have 
blood cultures obtained and empiric antibiotics administered per institutional standards. Extended 
use of anti-microbial therapies for at least 6 month (or longer as per institutional guidelines) or 
consistent with post ASCT consensus guidelines after CAR-T dosing are recommended (see 
Attachment 16). Perform screening for HBV, HCV, and HIV and monitor as clinically indicated
(see HBV monitoring recommendations in Section 9.2 and Attachment 8, and initiate treatment as 
appropriate. HBV reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and 
death, may occur in subjects treated with drugs directed against B cells such as JNJ-68284528. 
HBV reactivation has occurred in subjects who appear to have resolved hepatitis B infection.
Subjects receiving cilta-cel are possibly at a higher risk of severe/fatal outcomes from COVID-19 
infection compared with patients who are receiving standard of care therapy. Subjects should be 
reminded of the importance of vaccines and other preventative measures. Investigators should 
consider prophylaxis (eg, Evusheld, if available) and antiviral medications (eg, Paxlovid, if 
available) for patients diagnosed with COVID-19 infection, as noted in Attachment 17.

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6.3.7.
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of JNJ-68284528. Serious hypersensitivity 
reactions including anaphylaxis, may be due to dimethyl sulfoxide (DMSO), dextran 40, or 
residual ampicillin or kanamycin in JNJ-68284528. Subjects should be treated urgently per 
institutional standards, avoiding corticosteroid use if possible. Subjects should receive 
premedication prior to JNJ-68284528 dosing as noted in Section 6.2.
6.3.8.
Second Primary Malignancy
Second primary malignancy is a theoretical possibility due to the risk of lentiviral insertion. Second 
primary malignancies should be managed per institutional standards. Second primary 
malignancies must be reported during the duration of the study, irrespective of when they occur, 
and subsequently will be collected in a long-term follow-up study yearly until 15 years post dosing 
of JNJ-68284528. A tumor sample should be collected and DNA, RNA or protein analysis may be 
performed to investigate the presence of lentiviral elements.
7.
INTERVENTION COMPLIANCE
Apheresis and infusion of JNJ-68284528 will be done in the controlled environment of a qualified 
clinical site, under the direct observation of qualified study-site personnel. The details of 
administration will be recorded in the eCRF (including date, dose of cells, start, and stop times of 
the IV infusion, and volume infused). Precautions associated with the use of the study treatment 
and concomitant medications will be reviewed by the sponsor.
Refer to the SIPPM for a description of the chain of identity and chain of custody procedures 
associated with the apheresis product and JNJ-68284528.
8.
PRESTUDY AND CONCOMITANT THERAPY 
Throughout the study, investigators may prescribe concomitant medications or treatments (except 
for those listed in Section 8.2) deemed necessary to provide adequate supportive care. All 
medications (including prescription and over-the-counter products, and transfusions of blood 
products) different from the study treatment must be recorded throughout the study beginning with 
the signing of the ICF until at least 100 days after infusion of JNJ-68284528, or until the start of 
subsequent systemic anticancer treatment, if earlier. After 100 days, only adverse events that are 
considered related to study drug need to be reported until the end of the study. This includes 
concomitant therapy and any medication used to treat or support adverse events or serious adverse 
events (within or beyond 100 days after infusion). Exceptions include medications used to prevent 
(including vaccines) and treat COVID-19 and HBV reactivation, which should be reported until 1 
year after cilta-cel infusion, regardless of severity or causality (Attachment 17). Recorded
information will include a description of the type of the drug, dosing regimen, route of 
administration, duration of treatment, and its indication. All medications, including details of 
previous anticancer treatment, should be documented in the appropriate section of the eCRF.
Anti-myeloma therapy (medications which the subject has previously received) is permitted during 
bridging therapy (see Section 3.1) (Attachment 4).

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8.1.
Permitted Medications
The following are examples of supportive therapies that may be used during the study:

Standard 
supportive 
care 
therapies 
(antiemetics, 
antidiarrheals, 
anticholinergics, 
antispasmodics, antipyretics, antihistamines, analgesics, antibiotics and other antimicrobials, 
histamine receptor [H2] antagonists or proton pump inhibitors, and other medications intended 
to treat symptoms or signs of disease) and therapies intended to treat CAR-T cell-related 
toxicity (ie, CRS) as clinically indicated, according to institutional standards and as deemed 
necessary by the investigator.

Bisphosphonates may be initiated (if not already being administered) unless contraindicated 
within 1 week prior to the first dose of study treatment and continued until disease progression 
is established. In the case of severe adverse events such as hypercalcemia, bisphosphonates 
may be administrated as clinically indicated, according to institutional standards and as 
deemed necessary by the investigator.

Hematopoietic growth factor support and transfusions (irradiated blood products) are 
permitted to treat symptoms or signs of neutropenia, anemia or thrombocytopenia according 
to local standards of care. Non-pegylated myeloid growth factors are permitted up to 1 day 
prior to the start of the conditioning regimen (Section 6.1.2).

Documented infectious complications should be treated with oral or IV antibiotics or other 
anti-infective agents as considered appropriate by the treating investigator, according to 
standard institutional practice. 

Chemotherapy agents used to treat CAR-T cell-related toxicities are permitted upon 
consultation with the sponsor (see Section 6.3).
8.2.
Prohibited Therapies
The following medications are prohibited during the study. The sponsor must be notified in 
advance (or as soon as possible thereafter) of any instances in which prohibited therapies are (to 
be) administered.

Corticosteroid use should be avoided, except for the treatment of CRS or CAR-T cell-related 
neurotoxicity (eg, ICANS), as described in Table 8 and Table 9. Alternative therapies, if 
feasible, should be given prior to corticosteroids.

Any chemotherapy, anticancer immunotherapy (other than JNJ-68284528), or experimental 
therapy, except as described in Section 3.1 (bridging therapy), or protocol- specific therapies 
which may be used in conjunction with JNJ-68284528.

While in follow-up, emergency orthopedic surgery or radiotherapy is generally prohibited, but 
may be allowed in the absence of disease progression. Cases must be discussed and approved 
by the sponsor. Such emergency radiotherapy may consist of localized radiotherapy for pain 
control or for stabilization of an extensive bone lesion at high risk of pathologic fracture or 
damage to surrounding tissues.

Nonsteroidal anti-inflammatory agents should be avoided to minimize the risk of exacerbation 
of potential sub-clinical myeloma-related kidney disease. Based on the investigator’s clinical 
judgement, low-dose aspirin may be continued for thromboprophylaxis.

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
Other immunosuppressant agents unless used as protocol-specified pre- or post-treatment 
medications to treat an adverse event (eg, CRS).

Vaccination with live, attenuated vaccine after signing consent and in the 4 weeks prior to 
the infusion of JNJ-68284528, and for 100 days after infusion of JNJ-68284528.

The use of IV contrast infusions should be avoided to prevent myeloma-related kidney 
disease. If administration of IV contrast is necessary, then adequate precautions including 
hydration are indicated.

Pegylated myeloid growth factors (ie, pegfilgrastim) are prohibited within the first 100 days 
after infusion of JNJ-68284528 (Section 6.1.2).
8.3.
Subsequent Anticancer Therapy
Subsequent anticancer therapy administered after JNJ-68284528 should be only administered after 
confirmed PD per IMWG criteria and recorded in the eCRF. The start and end date and best 
response should be documented in the eCRF, if available.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
The Time and Events Schedules summarizes the frequency and timing of procedures and 
assessments applicable to this study (Table 1 and Table 2); for subjects who are eligible for 
retreatment with JNJ-68284528, follow the Time and Events Schedules in Attachment 9
(Table 12 and Table 13).
All planned assessments, including laboratory tests, on the day of JNJ-68284528 dosing must be 
completed and the results reviewed prior to the start of the infusion. Treatment decisions will be 
based on safety assessments performed at the local laboratory and disease assessments performed 
at the central laboratory.
If multiple assessments are scheduled for the same timepoint, it is recommended that procedures 
be performed in the following sequence: electrocardiogram (ECG), vital signs, blood draw. Blood 
collections for biomarkers and pharmacokinetic assessments should be kept as close to the
specified time as possible. Actual dates and times of assessments will be recorded in the source 
documents and the laboratory requisition form. Within 24 hours of study treatment infusion, if the 
study treatment is infused peripherally, blood samples must be drawn from a vein contralateral to 
the arm into which JNJ-68284528 is infused. If the study treatment is infused via a central vein 
line, blood samples over the subsequent 24 hours must be drawn from a vein in either arm. 
The approximate volume of blood drawn from each subject in this study (up to 2 years’ post-
treatment) is 958 mL. Repeat or unscheduled samples may be taken for safety reasons or for 
technical issues with the samples. 

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Based on emerging data, adjustments to the planned schedule of assessments may be made by the 
sponsor to protect subject safety. These decisions will be documented in writing by the SET (see 
Section 3.5)
and appropriately communicated to participating investigators prior to 
implementation.
9.1.2.
Screening Phase
All subjects must sign an ICF prior to the conduct of any study-related procedures. The screening 
phase begins when the first screening assessment is performed. Screening procedures will be 
performed up to 28 days before apheresis. If an assessment was performed as part of the subject’s 
routine clinical evaluation and not specifically for this study, it does not need to be repeated after 
signed informed consent has been obtained provided the assessments fulfill the study requirements 
and are performed within the specified timeframe prior to the first dose of study treatment. 
Retesting of abnormal screening values that lead to exclusion are allowed only once during the 
screening phase (to reassess eligibility). The last result obtained prior to apheresis will be used to 
determine eligibility. Subjects who do not meet all inclusion criteria or who meet an exclusion 
criterion may, at the discretion of the investigator, be rescreened once upon the sponsor’s written 
approval. Subjects who are to be rescreened must sign a new informed consent before rescreening. 
Rescreening and subsequent activities must be conducted in accordance with protocol defined time 
windows.
9.1.3.
Apheresis
Prior to apheresis, review of safety assessments should be completed per Time and Events 
Schedules (Table 1 and Table 2). Apheresis should be performed according to institutional 
standards, with a collection target of 6 x 109 PBMCs (range: 2 to 20 x 109 PBMCs); two apheresis 
collections may be performed to attain this target. Instructions for processing and shipping 
apheresis product are provided in the SIPPM.
9.1.4.
Cyclophosphamide and Fludarabine Conditioning Regimen
At the completion of manufacture and quality testing of JNJ-68284528, notification will be sent to 
the clinical site. Prior to dosing with cyclophosphamide and fludarabine, review of eligibility, 
safety assessments and disease characteristics should be completed per Section 6.1. The details 
regarding safety monitoring and study visits during this phase are included in the Time and Events 
Schedules (Table 1 and Table 2). 
9.1.5.
JNJ-68284528 Administration
Administration of JNJ-68284528 is fully described in Table 6.
9.1.6.
Post-treatment Phase 
The post-treatment phase starts after the completion of JNJ-68284528 infusion and includes the 
post-infusion period and the post-treatment period.

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9.1.6.1.
Post-infusion Period
The post-infusion period starts after the completion of JNJ-68284528 infusion on Day 1 and lasts 
until Day 100. Any subject who receives an infusion of JNJ-68284528 should continue all 
subsequent post-infusion assessments as per the Time and Events Schedules (Table 1 and 
Table 2). During this period, subjects will be monitored closely for safety and disease assessments. 
Subjects will be asked to check their temperature at least twice daily (entering 2 temperatures 
including their maximum daily temperature on the provided diary) and will be instructed to report 
any fever (≥100.4oF or ≥38oC) to the study doctor immediately to initiate monitoring for 
development of CRS. 
Hospitalization requirements are described in Table 6. Subjects will be provided a "wallet (study) 
card" with pertinent information about the study and be asked to carry this card with them for the
duration of the post-infusion and post-treatment period.
9.1.6.2.
Post-treatment Period
The post-treatment period starts on Day 101 and lasts until study completion, defined as 2 years 
after the last subject has received his or her initial dose of JNJ-68284528. Assessments are to be 
performed per the Time and Events Schedules (Table 1 and Table 2), and include safety and 
disease assessments every 28 days. Disease evaluation should continue to be performed until 
confirmed disease progression, death, start of a new anticancer treatment, withdrawal of consent
for study participation, or end of the study, whichever occurs first. Once disease progression is 
confirmed, subsequent disease assessment is not required unless the subject receives retreatment 
with JNJ-68284528 (see Attachment 9).
After disease progression is documented, survival status and subsequent anticancer therapy will 
be obtained every 16 weeks until the end of study, unless the subject has died, is lost to follow-up, 
or has withdrawn consent. If the information is obtained via telephone contact, written 
documentation of the communication must be available for review in the source documents. If the 
subject has died, the date and cause of death will be collected and documented on the eCRF, if or 
when available. Where allowed by local law, public records may be used to document death or to 
obtain survival status.
9.1.6.3.
Long-term Follow-up
Second primary malignancies will be reported for the duration of the study, defined as 2 years after 
the last subject has received his or her initial dose of JNJ-68284528. Following completion of this 
study, assessment for replication competent lentivirus (RCL) and second primary malignancies 
will continue for up to 15 years after dosing with JNJ-68284528 on a follow-up study. In addition, 
subjects who received retreatment with JNJ-68284528 and are in follow-up at the end of the study
(2 years after the last subject receives his or her initial dose of JNJ-68284528) will be monitored
in this long-term follow-up study. A tumor sample should be collected and DNA, RNA or protein 
analysis may be performed to investigate the presence of lentiviral elements.

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9.2.
Safety Evaluations
Safety will be measured by adverse events, laboratory test results, vital sign measurements, 
physical examination findings (including neurological examination), assessment of ICE-Tool 
scores, handwriting assessments, and assessment of ECOG performance status grade. Clinically 
relevant changes occurring during the study must be recorded on the adverse event section of the 
eCRF. 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. 
Safety monitoring assessments may be performed more frequently, if clinically indicated.  
The study will include the following evaluations of safety according to the time points provided in 
the Time and Events Schedules (Table 1 and Table 2).
Adverse Events
Adverse events (except for neurological adverse events, second primary malignancy, HBV 
reactivation, and COVID-19 infection) will be reported (or, when appropriate, by a caregiver, 
surrogate, or the subject's legally acceptable representative) from the time a signed and dated 
informed consent is obtained until 100 days after last administration of any study treatment or until 
the start of subsequent anticancer therapy, if earlier. Second primary malignancies will be reported 
for the duration of the study and, subsequently, will be collected on a long-term follow-up study 
yearly until 15 years’ post dosing of JNJ-68284528. Events of HBV reactivations and COVID-19 
infections, and new neurological adverse events or exacerbation of existing neurological adverse 
events will be reported during the first year post-dosing of JNJ-68284528. See Attachment 18 for 
additional adverse event reporting guidance for this study.
Adverse events will be followed by the investigator as specified in Section 12, Adverse Event 
Reporting and graded according to the National Cancer Institute Common Terminology Criteria 
for Adverse Events (NCI-CTCAE Version 5.0), with the exception of CRS and CAR-T cell-related 
neurotoxicity (eg, ICANS). CRS should be evaluated according to the ASBMT consensus grading 
(Lee 2019)22 (Attachment 11). CAR-T cell-related neurotoxicity (eg, ICANS) should be graded 
using the ASBMT consensus grading (Attachment 13). Subjects with Grade 3 or higher toxicity 
or unresolved adverse events that lead to treatment discontinuation will continue to be assessed 
until recovery to Grade 1 or baseline, the event is deemed irreversible, the end of the study, or a 
maximum of 6 months, whichever comes first. 
In addition to capturing ICANS and CRS adverse events (graded by ASTCT consensus grading), 
all individual symptoms of CRS (eg, fever, hypotension) and ICANS (eg, depressed level of 
consciousness, seizures) must be captured as individual adverse events and graded by CTCAE 
criteria. Neurotoxicity that is not temporarily associated with CRS, or any other neurologic adverse 
events that do not qualify as ICANS, will be graded by CTCAE criteria. Events of neurotoxicity 
or exacerbation of existing neurologic adverse events will be reported for 1-year post infusion of 
JNJ-68284528.
Changes in handwriting (ie, micrographia, dysgraphia, or agraphia) should be graded using the 
criteria outlined in Attachment 15 and reported as an adverse event in the eCRF. Should a subject 

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Physical Examination 
The screening physical examination will include, at a minimum, subject’s height, general
appearance, examination of the skin, ears, nose, throat, lungs, heart, abdomen, extremities, 
musculoskeletal system, and lymphatic system. Thereafter, a symptom-directed physical 
examination will be conducted as clinically indicated at subsequent timepoints. Abnormalities will 
be recorded in the appropriate section of the eCRF. Body weight will be measured prior to infusion 
of JNJ-68284528 (see the Time and Events Schedule Table 1). Clinically significant post-baseline 
abnormalities should be recorded as adverse events.
ECOG Performance Status
The ECOG performance status scale will be used to grade changes in the subject’s daily living 
activities (Attachment 5) and will be assessed as noted in the Time and Events Schedule Table 1.
Neurologic Examination (Phase 1b and Phase 2)
Magnetic resonance imaging (MRI) at screening or neurology consultation should be considered 
if pre-existing disease is suspected. For subjects with prior pertinent neurologic disease (eg, stroke, 
encephalitis) consider baseline MRI of brain and an EEG. At the first sign of neurotoxicity, 
neurology consultation and evaluation should be considered. CAR-T cell-related neurotoxicity (eg,
ICANS) should be graded using ASBMT consensus grading. Other neurological adverse events 
not associated with ICANs should be graded based on CTCAE version 5.0 throughout both phases 
of the study. Findings from neurological testing that support CAR-T cell-related neurotoxicity 
(eg, ICANS) should be reported in the CRF.
Immune-effector Cell-associated Encephalopathy (ICE) Tool Scores
The ICE test was developed to provide objectivity for the grading of multiple overlapping 
encephalopathy terms currently included on the approved CAR-T products (Lee 2019)22
(Attachment 12). The ICE tool will be collected as noted in the Time and Events Schedule (Table 
1 and Table 12) to guide management throughout both phases of the study. It will also be used to
grade the severity of ICANS (Attachment 13). All ICE-Tool scores, must be reported in the eCRF. 
Handwriting Assessment
Qualitative changes in handwriting since baseline are being explored by the sponsor as a potential 
early clinical predictive marker for neurotoxicity. Currently no standardized CTCAE toxicity 
gradings are available in the NCI-CTCAE v5.0. for these type of changes in handwriting. 
Therefore, the sponsor has developed a handwriting assessment criterion to assess subjects for 
occurrence of the following types of changes in handwriting: micrographia, dysgraphia, or 
agraphia, as potential early indicators for neurotoxicity (Attachment 15).
Handwriting assessments will be collected on a writing log according to the Time and Events 
Schedule (Table 1) and as instructed by the sponsor. Subjects unable to write at baseline are 
excused from this assessment during study. The sponsor’s medical monitor should immediately be 
notified when changes in handwriting are detected. This will prompt discussion about additional 
assessments to further evaluate for other neurotoxicity symptoms, further workup, as well as the 

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potential initiation of interventions. All cases of handwriting abnormalities (ie, micrographia, 
dysgraphia, or agraphia) must be reported as an adverse event in the eCRF. Should a subject 
experience a serious CAR-T associated neurotoxicity (either ICANS or other neurotoxicity), then 
a copy of the handwriting assessment log should be submitted with the serious adverse event
report.
9.3.
Pharmacokinetics and Immunogenicity
The goal of the pharmacokinetic assessment of JNJ-68284528 in this study is to evaluate 
pharmacokinetic parameters, and immunogenicity effects on the pharmacokinetic profiles and 
parameter values. Pharmacokinetic/pharmacodynamics, dose-response (safety and efficacy) 
relationships will be explored. The recommended dose regimen for dose expansion will be 
determined based on information including the pharmacokinetic and pharmacodynamic 
information obtained in Phase 1b. Immunogenicity assessments will also be utilized in these 
evaluations. See Section 9.1.1 for sample collection instructions.
9.3.1.
Evaluations 
Blood and serum samples will be collected for JNJ-68284528 pharmacokinetics, and 
immunogenicity (antibodies to JNJ-68284528) assessment as specified in the Time and Events 
Schedule (Table 2). Also, pharmacokinetic and immunogenicity samples will be collected at the 
time onset of suspected CRS or CAR-T cell-related neurotoxicity (eg, ICANS) regardless of 
causality (as specified in Table 2 and Table 13). In addition, pharmacokinetic and immunogenicity 
samples will be collected following the end of study treatment as shown in Table 2. The exact 
dates and times of blood sampling must be recorded on the laboratory requisition form. Refer to 
the Laboratory Manual for sample collection requirements. Collected samples must be stored 
under specified controlled conditions for the temperatures indicated in the Laboratory Manual.
Venous blood samples will be collected for measurement of CAR-T positive cellular concentration 
and transgene levels of JNJ-68284528.
Bone marrow samples will be collected for measurement of transgene levels and cellular 
concentrations of JNJ-68284528 (see Time and Events schedules, Table 2 and Table 13). 
Blood samples will be collected for exploratory evaluations of soluble circulating BCMA 
(sBCMA). This data may be used for mechanistic pharmacokinetic/pharmacodynamic modeling.
Additional information about the collection, handling, and shipment of biological samples can be 
found in the Laboratory Manual.
9.3.2.
Analytical Procedures
Pharmacokinetics
Post-dose blood and bone marrow samples will be analyzed to determine CAR-T positive cellular 
concentration and transgene levels of JNJ-68284528 using specific and sensitive assay methods 
that are validated by or under the supervision of the sponsor.

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Immunogenicity
The detection and characterization of antibodies to JNJ-68284528 will be performed using a 
validated assay method by or under the supervision of the sponsor. Other analyses may be 
performed to characterize immunogenicity.
9.3.3.
Pharmacokinetic Parameters
Blood and bone marrow samples will be collected for the measurement of JNJ-68284528 cellular 
concentrations and transgene levels for pharmacokinetic analyses (Time and Events Schedule
Table 2). Pharmacokinetic parameters will be estimated for individuals, and descriptive statistics 
will be calculated. Correlation of Cmax and AUC with dose may also be explored. Pharmacokinetic 
parameters include, but are not limited to, AUCinf, AUC(0-t), AUCtau, Cmax, half-life, and Tmax
parameters will be calculated if sufficient data are available for estimation.
9.3.4.
Immunogenicity Assessment/Antibodies to JNJ-68284528
Antibodies to JNJ-68284528 will be evaluated in serum samples collected during the Treatment 
Phase (Table 2). Additionally, serum samples should also be collected at the final visit from 
subjects who discontinued treatment or were withdrawn from the study. These samples will be 
tested by the sponsor or sponsor's designee.
JNJ-68284528 transgene concentration will also be determined to aide in the interpretation of 
immunogenicity data. These samples will be stored and evaluated if deemed necessary.
Serum samples will be screened for antibodies binding to JNJ-68284528 and the titer of confirmed 
positive samples will be reported. Other analyses may be performed to verify the stability of 
antibodies to JNJ-68284528 or further characterize the immunogenicity of JNJ-68284528. 
9.4.
Biomarker Evaluations
Biomarker assessments will focus on several objectives: 1) evaluate infused CAR-T cell subsets 
and activation markers including, but not limited to, CD4+, CD8+, CD25+, central memory, 
effector memory cells; 2) determine the ability of JNJ-68284528 to induce MRD negativity in 
subjects with relapse/refractory multiple myeloma who have achieved CR; 3) serum or plasma
proteomic profiling of cytokines (such as IL-6, IL-15, and IL-10) and other immune related 
proteins (such as perforin and granzymes); 4) immunophenotyping of biomarkers of 
response/resistance on myeloma cells (such as BCMA and PD-L1); 5) determine the clinical 
benefit (ORR, DOR, TTR, PFS, and OS) of JNJ-68284528 in subjects with cytogenetic 
modifications (del17p, t(4;14), t(14;16), or other high-risk molecular subtypes); and 
6) immunophenotyping of immune cells subsets such as CD4+ and CD8+ T cells, regulatory T 
cells, B and NK cells. Additional biomarker samples may be collected to help understand an 
unexplained adverse event including but not limited to serum or peripheral blood mononuclear 
cells (PBMCs) from whole blood. Additional sample(s) for cytokines will be collected as clinically 
indicated (Table 2).
The potential presence of RCL will be evaluated from whole blood samples of subjects treated 
with JNJ-68284528. RCL will be evaluated using a qPCR assay against the lentiviral vesicular 

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stomatitis virus-G gene yearly for up to 15 years in the present study or a separate long-term 
follow-up study.. If all post-infusion samples for an individual subject are negative for RCL during 
the first year after treatment, no additional samples will be collected and RCL assessments will be 
terminated. Yearly review of medical history will generally be sufficient for the subject. If any 
post-infusion samples are positive, further RCL analysis and more extensive subject follow-up 
should be undertaken. Additional event triggered testing for RCL may be conducted as clinically 
indicated, as specified in the Schedule of Activities (SoA).
Peripheral blood mononuclear cells will be retained for exploratory analysis of the immune system 
which may include retroviral insertion analysis, T cell receptor (TCR) analysis (both clonality 
and/or diversity of TCR), functional in vitro assays, or other. Biomarker analyses are dependent 
upon the availability of appropriate biomarker assays and may be deferred or not performed if 
during or at the end of the study it becomes clear that the analysis will have no scientific value, or 
if there are not enough samples or not enough 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 the intended utility of the data.
Based on emerging scientific evidence, the sponsor may request additional material from 
previously collected bone marrow samples during or after study completion for a retrospective 
analysis. For subjects diagnosed with a SPM, a tumor sample should be collected. Additionally, 
the sponsor should receive a sample of plasmacytoma if a plasmacytoma biopsy is performed for 
any reason, including during screening. Subjects who have a lumbar puncture as part of their 
neurologic work up should have cerebral spinal fluid for additional test by the sponsor. In this case, 
such analyses would be specific to research related to the study treatment(s) or diseases being 
investigated. If a subject dies and an autopsy is performed, specimens may be requested by the 
sponsor for analysis, as allowed by local regulations.
9.4.1.
Pharmacodynamic/Predictive Markers 
The baseline of the JNJ-68284528 subsets and dynamic changes/persistence and activation of 
CAR-positive viable T cells may be associated with the depth and durability of response. An 
evaluation of these cell populations may be performed by flow cytometry or cytometry by time of 
flight (CyTOF) or both and correlated with response. Additional immunophenotyping may be 
performed on bone marrow aspirate and whole blood samples to evaluate expression of biomarkers 
on myeloma cells (such as BCMA and PD-L1) and immune cell populations (such as CD4+ and 
CD8+ T cells) by flow cytometry, or CyTOF, or next generation sequencing (whole exome and 
RNA sequencing) or both. T cell receptor (TCR) sequencing may be performed to study T cell 
clonality that may affect drug response. Samples may be characterized by gene expression 
profiling and somatic mutation analysis by next generation sequencing (whole exome and RNA 
sequencing) to evaluate potential biomarkers that may correlate with response. Samples may be 
evaluated by other similar technologies to evaluate protein or RNA expression or for somatic DNA 
analysis.
Circulating serum biomarkers present following chemotherapy conditioning and following 
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Evaluation of cytokines (such as IL-6, IL-15, IL-10, and IFN-) and other circulating proteins 
(such as granzymes and perforin) will be analyzed to identify potential pharmacodynamic and 
predictive biomarkers of response or resistance.
9.4.2.
Minimal Residual Disease 
Minimal residual disease (MRD) negativity is being evaluated as a potential surrogate for PFS and 
OS in multiple myeloma treatment. MRD will be monitored in subjects using next generation 
sequencing (NGS) on bone marrow aspirate DNA. Baseline bone marrow aspirates will be used to 
define the myeloma clones, and post-treatment samples will be used to evaluate MRD negativity. 
A fresh bone marrow aspirate will be collected prior to the first dose of conditioning regimen (≤7 
days). If the NGS MRD method is unavailable, or determined to be scientifically inferior, then 
alternative methods for MRD assessment may be utilized. Additional timepoints for MRD 
assessment are reflected in the Time and Events schedule (Table 2).
In the event fresh bone marrow aspirate will not be collected at Baseline, or if the fresh aspirate 
does not yield a usable clone, non-decalcified diagnostic tissue (bone marrow aspirate slides or 
formalin-fixed paraffin embedded tissue) should be collected for calibration of myeloma cells to 
facilitate the assessment of the MRD endpoints by NGS.
9.5.
Pharmacokinetic/Pharmacodynamic Evaluations 
Pharmacokinetic/pharmacodynamic modeling will be explored to understand and characterize the 
dose-response relationship.
9.6.
Efficacy Evaluations 
Disease evaluations must be performed as specified in the Time and Events Schedule Table 1. 
Disease evaluations will be performed by a central laboratory (additional samples may be collected 
for analysis by the local laboratory) until disease progression, death, start of a new anticancer 
treatment, withdrawal of consent for study participation, or end of the study, whichever occurs 
first. However, if a subject receives retreatment with JNJ-68284528 after a confirmed disease 
progression (see Section 3.1), then disease evaluations will continue according to the Time and 
Events schedule provided in Attachment 9. This study will use the IMWG-based response 
criteria.30 If it is determined that the study treatment interferes with the immunofixation assay, CR 
will be defined as the disappearance of the original M-protein associated with multiple myeloma 
on immunofixation, and the determination of CR will not be affected by unrelated M-proteins 
secondary to the study treatment.11
For quantitative immunoglobulin (QIg) at baseline, M-protein, immunofixation, and free-light 
chain (FLC) measurements in serum and 24-hour urine, the investigator will use results provided 
by the central laboratory. Disease progression must be consistently documented across clinical 
study sites using the criteria in Attachment 1. 
All efforts should be made to collect efficacy data centrally. However, local laboratory data may 
be collected if central laboratory data is not available at a particular timepoint, however this does 
not include screening assessments. Documentation of the local laboratory data should be sent to 

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the Principal Investigator and filed in the medical record. It is the Principal Investigator’s 
responsibility to ascertain that these results are reviewed and entered into the subject’s medical 
record and the eCRF.
9.6.1.
Myeloma Protein Measurements in Serum and Urine
Blood and 24-hour urine samples for M-protein measurements will be sent to and analyzed by a 
central laboratory. Only one serum and one 24-hour urine sample per time point are required by 
the central laboratory to perform the following tests. Assessments will be performed as specified 
in the Time and Events Schedule (Table 1 and Table 12).

Serum quantitative Ig 

Serum protein electrophoresis (SPEP)

Serum immunofixation electrophoresis

Serum FLC assay (for subject in suspected CR/sCR and every disease assessment for subjects
with serum FLC only disease)

24-hour urine M-protein quantitation by electrophoresis (UPEP)

Urine immunofixation electrophoresis 

Serum β2-microglobulin 
Blood and 24-hour urine samples will be collected as specified in the Time and Events Schedule 
Table 1 and Table 12 until the development of confirmed disease progression. Disease progression 
based on one 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. 
Serum and urine immunofixation and serum free light chain assays 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 non-quantifiable). For subjects with light chain multiple myeloma, 
serum and urine immunofixation tests will be performed routinely as per the Time and Events 
Schedule (Table 1 and Table 12).
9.6.2.
Serum Calcium Corrected for Albumin
Blood samples for calculating serum calcium corrected for albumin will be collected and analyzed 
centrally until the development of confirmed disease progression. Development of hypercalcemia 
(corrected serum calcium >11.5 mg/dL [>2.9 mmol/L]) may indicate disease progression or 
relapse if it is not attributable to any other cause. 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 7.
9.6.3.
Bone Marrow Examination
Bone marrow aspirate or biopsy (acceptable if aspirate is not possible) will be performed for 
clinical assessments. Bone marrow aspirate will be performed for biomarker evaluations. Clinical 
staging (morphology, cytogenetics, and immunohistochemistry or immunofluorescence or flow 

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cytometry) should be done by a local laboratory. A portion of the bone marrow aspirate will be 
sent to the central laboratory for immunophenotyping and to monitor BCMA, checkpoint ligand 
expression in CD138-positive multiple myeloma cells, and checkpoint expression on T cells. If 
feasible, bone marrow aspirate also will be performed to confirm CR and sCR and at disease 
progression. In addition, MRD will be evaluated as specified in the Time and Events schedules.
9.6.4.
Skeletal Survey
A 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 during 
the screening phase and evaluated by the local laboratory by either roentgenography (“X-rays”) or 
low-dose computed tomography (CT) scans without the use of IV contrast. If a CT scan is used it 
must be of diagnostic quality. Following JNJ-68284528 infusion, and before disease progression 
is confirmed, X-rays or CT scans should be performed locally, whenever clinically indicated based 
on symptoms, to document response or progression. Magnetic resonance imaging (MRI) is an 
acceptable method for evaluation of bone disease, and may be included at the discretion of the 
investigator; however, it does not replace the skeletal survey (see the disease response criteria in 
Attachment 1). If a radionuclide bone scan is used at screening, in addition to the complete skeletal 
survey, then both methods must be used to document disease status. These tests must be performed 
at the same time. Note: a radionuclide bone scan does not replace a complete skeletal survey.
If a subject presents with disease progression manifested by symptoms of pain due to bone 
changes, then 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 no repeat confirmatory X-rays are necessary. If 
changes are equivocal, then a repeat X-ray is needed in 1 to 3 weeks.
9.6.5.
Documentation of Extramedullary Plasmacytomas
Sites of known extramedullary plasmacytomas must be documented ≤14 days prior to the first 
dose of the conditioning regimen. Clinical examination or MRI may be used to document 
extramedullary sites of disease. CT scan evaluations are an acceptable alternative if there is no 
contraindication to the use of IV contrast. Positron emission tomography scan or ultrasound tests 
are not acceptable to document the size of extramedullary plasmacytomas. However, PET/CT 
fusion scans can be used to document extramedullary plasmacytomas if the CT component of the 
PET/CT fusion scan is of sufficient diagnostic quality.
Extramedullary plasmacytomas should be assessed for all subjects with a history of 
plasmacytomas or if clinically indicated at ≤14 days prior to the first dose of the conditioning 
regimen, by clinical examination or radiologic imaging. Assessment of measurable sites of 
extramedullary disease will be performed, measured, and evaluated locally every 4 weeks (for 
physical examination) for subjects with a history of plasmacytomas or as clinically indicated 
during treatment for other subjects until development of confirmed CR or confirmed disease 
progression. If assessment can only be performed radiologically, then evaluation of extramedullary 
plasmacytomas may be done every 12 weeks. The methodology used for evaluation of each disease 

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site should be consistent across all visits. Irradiated or excised lesions will be considered not 
measurable, and will be monitored only for disease progression.
To qualify for VGPR or PR/ minimal response (MR), the sum of products of the perpendicular 
diameters of the existing extramedullary plasmacytomas must have decreased by over 90% or at 
least 50%, respectively, and new plasmacytomas must not have developed (see the disease 
response criteria in Attachment 1). 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 the longest diameter of previous lesion >1 cm in short axis must have increased 
at least 50%, or a new plasmacytoma must have developed. When 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%, then the criterion for disease progression is met.
9.7.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory 
requisition form. Instructions for the collection, handling, storage, and shipment of samples are 
found in the Laboratory Manual that will be provided. Collection, handling, storage, and shipment 
of samples must be under the specified, and where applicable, controlled temperature conditions 
as indicated in the Laboratory Manual. Refer to the Time and Events Schedule 
(Table 1 and Table 2) for the timing and frequency of all sample collections.
9.8.
Patient-reported Outcome Assessments (Phase 2 Only)
The subjects’ HRQoL (disease-related symptoms, functioning, and general well-being) will be 
captured using patient-reported outcome (PRO) measures. The PRO measures will be administered
for the Phase 2 part of the study, during site visits, to understand how the PRO endpoints change 
over time. These measures will be administered according to the Time and Events Schedule (Table 
1); to be completed by the subjects before any clinical tests, procedures, or other consultations that 
would influence subject’s perceptions of their current health state. The PRO measures will be 
provided in the local language. If a subject requires assistance completing the PRO assessment, a 
study coordinator may assist but should not prompt the subject in selecting their response. At 
completion, the study coordinator should verify that the questionnaires are completed in full or 
document the reason for missing information. Full training documentation will be provided to site 
coordinators before the start of data collection. PRO assessments will be conducted beyond disease 
progression or subsequent anticancer therapy. If no site visits are scheduled for additional disease 
evaluations, subjects will have the option of completing the PRO assessments after disease 
progression or subsequent anticancer therapy via telephone.
Samples of the PRO measures are provided in Attachment 10:

EORTC QLQ-C30

EORTC QLQ-MY20: 4 single items

EQ-5D-5L

PGIS 

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
PGIC 
The EORTC-QLQ-C30 version 3 includes 30 items in 5 functional scales (physical, role, 
emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, 
nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, 
diarrhea, and financial difficulties). The recall period is 1 week (“past week”) and responses are 
reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. 
A higher score represents greater HRQoL, better functioning, and more (worse) symptoms. The 
EORTC QLQ-C30 has been widely used among patients with multiple myeloma. Reliability, 
validity, and clinically meaningful change have been demonstrated.32,33 The EORTC QLQ-MY20 
was designed to use alongside the EORTC QLQ-C30 to address issues of more relevance to 
myeloma patients.8 Four single items from the EORTC QLQ-MY20 will be administered to assess 
emotional health status (feel restless or agitated, thinking about your illness, worried about dying, 
worried about health in the future). Recall, response options, and interpretation are similar to the 
EORTC QLQ-C30.
The EQ-5D-5L is a generic measure of health status. For purposes of this study, the EQ-5D-5L 
will be used to generate utility scores for use in cost-effectiveness analyses. The EQ-5D-5L is a 
5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression plus a visual analog scale rating “health today” with 
anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The 
scores for the 5 separate questions are categorical and cannot be analyzed as cardinal numbers. 
However, the scores for the 5 dimensions are used to compute a single utility score ranging from 
zero (0.0) to 1 (1.0) representing the general health status of the individual (values less than 0 are 
possible when using the UK scoring algorithm). The EQ-5D-5L asks respondents to select their 
response based on their current health (“today”) and takes less than 5 minutes to complete.
The Patient Global Impression of Severity (PGIS) is a single item to assess severity of pain. 
Subjects are asked to rate the severity of their current pain on a 5-point verbal rating scale. The 
Patient Global Impression of Change (PGIC) is a single item to assess the subject’s perception in 
change of their overall health status using a 7-point verbal rating scale. The PGIC is only 
administered post-infusion.
9.9.
Qualitative Interviews (Phase 2 Only)
Subjects enrolled in Phase 2 portion of the study will have the option of participating in pre-
treatment (at screening) and post-treatment (Day 100 and approximately 6 months post infusion 
with JNJ-68284528) semi-structured interviews.
Pre- and post-treatment interviews have been used in early phase clinical trials to inform 
exploratory insight into subject experiences. The data from these interviews will not be reconciled 
with the safety database of the study. These interviews are semi-structured and are designed to 
allow subjects to provide their own impressions of JNJ-68284528 and not be restricted to items 
included in standard questionnaires. Interviewers will be trained on the interview guide and
provided with note-taking pages to capture subject responses. Interviews will take place in the 

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local language and will be audiotaped with approval of the subject for transcription and content 
analysis. The content analysis will present the qualitative themes that emerge from the narrative 
data.
9.10.
Medical Resource Utilization
Health economics data such as medical resource utilization data, associated with medical 
encounters, will be collected in the CRF by the investigator and study-site personnel for all Phase 2 
subjects throughout the study. Protocol-mandated procedures, tests, and encounters are excluded. 
As per Table 1, all medical care encounters since the previous collection will be collected for all 
Phase 2 subjects. Medical resource evaluation data will be collected until Day 180 (± 7 days). 
Health economics data such as costs associated with the medical encounters will be collected 
separately from the eCRF. All health economic data will be used only in a de-identified manner.
The data collected may be used to conduct exploratory economic analyses and will include:

Number and duration of medical care encounters, including surgeries, radiographic 
diagnostics, laboratory tests, and other selected procedures (inpatient and outpatient)

Duration of hospitalization (total days length of stay, including duration by wards; eg, 
intensive care unit)

Number and character of diagnostic and therapeutic tests and procedures

Outpatient medical encounters and treatments (including physician or emergency room visits, 
tests and procedures, and medications)
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ 
WITHDRAWAL FROM THE STUDY
10.1.
Completion
A subject will be considered to have completed the study if he or she dies before the end of the 
study, has not been lost to follow-up or has not withdrawn consent for study participation before 
the end of the study, defined as 2 years after the last subject has received his or her initial dose of 
JNJ-68284528.
10.2.
Discontinuation of Study Treatment 
A subject should not receive JNJ-68284528 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

Grade 3 nonhematologic toxicity related to cyclophosphamide and fludarabine occurs, and 
precludes retreatment with cyclophosphamide and fludarabine prior to JNJ-68284528 infusion 
per Section 6.1

The subject received concurrent (non-protocol) anticancer treatment (with exception of 
sponsor-approved bridging therapy)

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
Confirmed disease progression per IMWG criteria (Attachment 1) between the time of 
conditioning therapy and infusion of JNJ-68284528. 

Subject refuses further study treatment

Noncompliance with study treatment or procedure requirements
The primary reason for treatment discontinuation will be documented in the eCRF and source 
documents, and the subject should be followed per standard of care until recovery from bridging 
therapy or cyclophosphamide and fludarabine conditioning regimen. If a subject's study treatment 
is discontinued for any reason, this will not result in automatic withdrawal of the subject from the 
study.
10.3.
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

Failure to manufacture JNJ-68284528 after 2 apheresis attempts

The sponsor discontinues the study 
The reason(s) for subject withdrawal will be recorded on the eCRF and source documents. If 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.
If a subject withdraws consent following dosing with JNJ-68284528, study assessments for the 
last visit in the post-infusion period (Table 1: Day 100; Table 2: Day 100) should be completed 
prior to withdrawal of consent, if feasible.
10.4.
Withdrawal from the Use of Research Samples
Withdrawal from the use of samples is future research
The subject may withdraw consent for use of samples for future research (refer to Section 16.2.5, 
Long-Term Retention of Samples for Additional Future Research). If this occurs, then samples 
will be destroyed after they are no longer needed for the clinical study. Details of sample retention
for research are presented in the ICF.
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. 

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Continuous variables will be summarized using the number of observations, mean, standard 
deviation, coefficient of variation, median, and range as appropriate. Categorical values will be 
summarized using the number of observations and percentages as appropriate.
The efficacy and safety data will be summarized separately for Phase 1b and Phase 2 part. Pooling 
of the two parts maybe considered when appropriate. Specific details will be provided in the 
Statistical Analysis Plan. 
11.1.
Subject Information
The analysis populations for this study are defined as follows:

Modified Intent-To-Treat (mITT) Analysis Set: This set consists of subjects who received 
a JNJ-68284528 infusion at the targeted RP2D dose and will be considered as the primary 
analysis set for all efficacy summaries.

All Treated Analysis Set: This set consists of subjects who received JNJ-68284528 infusion
and will be considered as the primary analysis set for safety summaries.

Pharmacokinetic Analysis Set: This set consists of all subjects who received JNJ-68284528
infusion and have at least 1 post-dose pharmacokinetic sample.

Immunogenicity Analysis Set: This set consists of all subjects who received JNJ-68284528
infusion and have at least 1 post-dose immunogenicity sample.
11.2.
Sample Size Determination
At least 24 and up to approximately 50 subjects will be treated in Phase 1b part to establish the 
RP2D and assess safety. With 24 treated subjects, if the true incidence rate of certain adverse 
events (refer to Table 3) is 10%, the probability of observing at least one subject experiencing 
event is more than 90%. The probability of detecting at least one subject experiencing a certain 
adverse event under the assumed true incidence rate based on plausible sample sizes is provided
in Table 11.
Table 11: 
Sample Size Scenarios in Phase 1b
Sample Size in Phase 1b
True incidence rate of the adverse 
event
Probability of observing at least one subject 
experiencing the adverse event
24
10%
92%
40
6%
91.6%
50
5%
92.3%
For therapies available to treat subjects with relapsed or refractory multiple myeloma at the time 
that this protocol was written (including daratumumab), the reported ORR is 30% or less.
The sample size for the Phase 2 portion of the study assumes that the overall response rate will be 
at least 50%. With 60 subjects treated with JNJ-68284528 in the Phase 2 portion of the study, there 
will be approximately 90% power to declare the ORR is higher than 30% at the 1-sided 
significance level of 0.025. 

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11.3.
Efficacy Analyses 
Endpoint Definitions:
Overall response rate (ORR) is defined as the proportion of subjects who achieve a PR or better 
according to the IMWG criteria.10,11,30
VGPR or better response rate (sCR+CR+VGPR) is defined as the proportion of subjects who 
achieve a VGPR or better response according to the IMWG criteria.10,11,30
Duration of response (DOR) will be calculated among responders (with a PR or better response) 
from the date of initial documentation of a response (PR or better) to the date of first documented 
evidence of progressive disease, as defined in the IMWG criteria. Relapse from CR by positive 
immunofixation or trace amount of M-protein is not considered as disease progression. Disease 
evaluations will continue beyond relapse from CR until disease progression is confirmed. For 
subjects who have not progressed, data will be censored at the last disease evaluation before the 
start of any subsequent anti-myeloma therapy.
Time to response (TTR) is defined as the time between date of the initial infusion of JNJ-68284528
and the first efficacy evaluation that the subject has met all criteria for PR or better. For subjects
without response, data will be censored either at the date of progressive disease, or in the absence 
of progressive disease, at the last disease evaluation before the start of subsequent anti-myeloma 
therapy.
Progression-free survival (PFS) defined as the time from the date of the initial infusion of 
JNJ-68284528 to the date of first documented disease progression, as defined in the IMWG 
criteria, or death due to any cause, whichever occurs first. For subjects who have not progressed 
and are alive, data will be censored at the last disease evaluation before the start of any subsequent 
anti-myeloma therapy.
Overall survival (OS) is measured from the date of the initial infusion of JNJ-68284528 to the date 
of the subject’s death. If the subject is alive or the vital status is unknown, then the subject’s data 
will be censored at the date the subject was last known to be alive.
For efficacy, assessment by the IRC will be used as primary.
The first analysis for the primary endpoint, ORR (PR or better), will be conducted approximately 
at 6 months after the last subject has received his or her initial dose of JNJ-68284528, and will be 
based on the mITT analysis set. The response rate and its 95% exact confidence interval (CI) will 
be calculated based on binomial distribution, and the null hypothesis will be rejected if the lower 
bound of the confidence interval exceeds 30%. Analysis of VGPR or better response rate, DOR, 
PFS, and OS will be conducted at the same cutoff as the ORR, and an update of these endpoints 
will be provided at approximately 9-12 months after the last subject has received his or her initial 
dose of JNJ-68284528 and at the end of the study, which is defined as 2 years after the last subject
has received his or her initial dose of JNJ-68284528. Additional safety data will be collected in a 
long-term follow-up study.

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A sensitivity analysis of ORR will be performed based on the subjects in the mITT analysis set 
who received the JNJ-68284528 product that met all of the pre-specified release criteria.
The agreement on ORR between the determination by the IRC and the assessment by a validated 
computerized algorithm developed by the sponsor will be evaluated using the kappa statistic and 
95% CI will also be provided.
The distribution (median and Kaplan-Meier curves) of DOR will be provided using Kaplan-Meier 
estimates for subjects who achieved response during the study. Similar analysis will be performed 
for OS, PFS, and TTR for the mITT analysis set. 
11.4.
Safety Analyses
All safety analyses are to be performed on data from the all treated analysis set. The baseline value 
for safety assessment is defined as the value collected at the time closest to, but prior to, the start 
of JNJ-68284528 infusion. The safety parameters to be evaluated are the incidence, severity, and 
type of adverse events, clinically significant changes in the subject’s physical examination 
findings, vital signs measurements, and clinical laboratory results. Exposure to investigational 
product and reasons for discontinuation of study treatment will be tabulated. Adverse events will 
be summarized by system organ class, preferred term, worst grade experienced by the subject, and 
by dose level.
Adverse Events
The verbatim terms used in the eCRF 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 after JNJ-68284528 infusion or that are a consequence of a 
pre-existing condition that has worsened since baseline. All reported treatment-emergent 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 dose group.
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those 
subjects who die, experience an adverse event of special interest, discontinue treatment due to an 
adverse event, or who experience a severe or a serious adverse event.
Adverse events that occur after administration of the conditioning regimen and before 
JNJ-68284528 infusion will be summarized and listed separately.
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 or Data Presentation 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 time 
point. Worst toxicity grade during treatment will be presented according to NCI-CTCAE Version 
5.0. Change from baseline to the worst toxicity grade experienced by the subject during the study 

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will be provided as shift tables. A listing of subjects with any laboratory results outside the 
reference ranges will be provided.
Electrocardiogram 
The interpretation of the ECGs as determined by a qualified physician (investigator or qualified 
designee) will be summarized at scheduled time points.
Vital Signs
Descriptive statistics of temperature, pulse/heart rate, respiratory rate, and blood pressure (systolic 
and diastolic) values and changes from baseline will be summarized at each scheduled time point. 
The percentage of subjects with values beyond clinically important limits will be summarized.
11.5.
Pharmacokinetic Analyses
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. Descriptive statistics will be used to summarize 
CAR-T positive cell count and transgene level at each sampling timepoint.

Description on the planned analyses for Cmax, AUC, Tmax, 

Responder vs. non-responder analyses
If sufficient data are available, population-PK analysis of peripheral JNJ-68284528 cellular 
concentration and transgene level-time data of JNJ-68284528 may be performed. 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. Exposure-response analyses may also be 
performed; if performed, details will be provided in a separate analysis plan and report.
11.6.
Pharmacokinetic/Pharmacodynamic Analyses
If sufficient data are available, then other PK/pharmacodynamic modeling may be performed, 
including exploring the relationship between JNJ-68284528 cellular concentrations, transgene 
levels, pharmacodynamic markers (eg, sBCMA, M-protein) and endpoints of clinical efficacy and 
safety. If performed, details and results of the analysis will be presented in a separate report.
11.7.
Immunogenicity Analyses
The incidence of anti-JNJ-68284528 antibodies will be summarized for all subjects who receive 
JNJ-68284528 and have appropriate samples for detection of antibodies to JNJ-68284528
(ie, subjects with at least 1 sample obtained after the infusion of JNJ-68284528). The results will 
be summarized by dose level for subjects with appropriate samples for the detection of antibodies 
to JNJ-68284528.
Immunogenicity analyses will be descriptive in nature and will include the number and percentage 
of subjects who developed anti-JNJ-68284528 antibodies. The effect of anti-JNJ-68284528
antibodies on pharmacokinetics, safety, and efficacy may also be evaluated.

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11.8.
Patient-reported Outcome Assessments (Phase 2 Only)
The EORTC QLQ-C30, EORTC QLQ-MY20 (4 items), EQ-5D-5L utility and visual analog 
scores, PGIC, and PGIS will be descriptively summarized at each time point. Meaningful and 
sustained improvement in subject’s HRQoL comparative to their baseline health status will be 
evaluated using established meaningful change thresholds.12 Within-group change of the PRO 
endpoints will be assessed by change from baseline (screening phase) using mixed models for 
repeated measures. 
11.9.
Medical Resource Utilization
Medical resource utilization data will be summarized in descriptive statistics of medical encounters 
(eg, length of stay, inpatient, outpatient, test, and reason). 
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.
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 
Conference 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 European 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 treatment 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-68284528, the expectedness of an adverse event 
will be determined by whether or not it is listed in the Investigator's Brochure. 
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.
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.

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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. 
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.
12.1.3.
Severity Criteria
An assessment of severity grade will be made by the investigator according to the NCI CTCAE
Version 5.0, with the exception of CRS and CAR-T cell-related neurotoxicity (eg, ICANS). CRS 
should be evaluated according to the ASBMT consensus grading (Lee 2019)22 (Attachment 11). 
CAR-T cell-related neurotoxicity (eg, ICANS) should be graded using the ASBMT consensus 
grading (Attachment 13). Any adverse event or serious adverse event not listed in the NCI CTCAE 
Version 5.0 will be graded according to investigator clinical judgment by using the standard grades 
as follows:
Grade 1
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.
Grade 2
Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living.*
Grade 3
Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily 
living.**
Grade 4
Life-threatening consequences; urgent intervention indicated.
Grade 5
Death related to adverse event.
Activities of Daily Living (ADL)
*
Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc.
**
Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden.

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12.2.
Special Reporting Situations
Safety events of interest on a sponsor study treatment that may require expedited reporting or 
safety evaluation include, but are not limited to:

Overdose of a sponsor study treatment

Suspected abuse/misuse of a sponsor study treatment

Accidental or occupational exposure to a sponsor study treatment

Medication error involving a sponsor product (with or without subject/subject exposure to the 
sponsor study treatment, eg, name confusion)

Exposure to a sponsor study treatment from breastfeeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that 
meets the criteria of a serious adverse event should be recorded on the serious adverse event page 
of the eCRF.
12.3.
Procedures
12.3.1.
All Adverse Events
All adverse events (with the exception of neurological adverse events, second primary 
malignancies, see Section 12.3.3, HBV reactivation, and COVID-19 infection) and special 
reporting situations, whether serious or non-serious, will be reported from the time a signed and 
dated ICF is obtained until 100 days after last administration of any study treatment or until the 
start of subsequent systemic anticancer therapy, if earlier, and may include contact for follow-up 
of safety. After 100 days, only adverse events that are considered related to study drug need to be 
reported until the end of the study. Events of HBV reactivations and COVID-19 infection, and
new neurological adverse events or exacerbation of existing neurologic adverse events will be 
reported during the first year post-dosing of JNJ-68284528. Adverse events of special interest are 
defined in Section 12.3.3. Anticipated adverse events are defined in Attachment 14.
Serious adverse events, including those spontaneously reported to the investigator must be reported 
using the Serious Adverse Event Form. The sponsor will evaluate any safety information that is 
spontaneously reported by an investigator beyond the time frame specified in the protocol. All 
events that meet the definition of a serious adverse event will be reported as serious adverse events, 
regardless of whether they are protocol-specific assessments. See Attachment 18 for additional 
adverse event reporting guidance for this study.
All adverse events, regardless of seriousness, severity, or presumed relationship to study treatment, 
must be recorded using medical terminology in the source document and the eCRF. 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 eCRF their opinion concerning the 
relationship of the adverse event to study therapy. All measures required for adverse event 

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management must be recorded in the source document and reported according to sponsor 
instructions.
Exceptions:

Expected progression of disease should not be considered an adverse event (or serious adverse 
event). However, if determined by the investigator to be more likely related to the study 
treatment than the underlying disease, the clinical signs or symptoms of progression and the
possibility that the study treatment is enhancing disease progression, should be reported per 
the usual reporting requirements (see Section 12.1).
All deaths not related to disease progression, regardless of attribution, should be reported to the 
sponsor following expedited reporting procedures.
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. 
The investigator (or sponsor where required) must report suspected unexpected serious adverse 
reactions to the appropriate Independent Ethics Committee/Institutional Review Board (IEC/IRB) 
that approved the protocol unless otherwise required and documented by the IEC/IRB.
For all studies with an outpatient phase, including open-label studies, the subject must be provided 
with a "wallet (study) card" and instructed to carry this card with them for the duration of the study 
indicating the following (at minimum):

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
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).

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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 treatment 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:

Routine monitoring hospitalizations post-infusion required per protocol

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 eCRF). 
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.
12.3.3.
Adverse Events of Special Interest
Cytokine release syndrome, neurotoxicity (including CAR-T cell-related neurotoxicity 
[eg, ICANS] and other neurotoxicities), TLS, and second primary malignancy of any grade will 
be followed as part of standard safety monitoring activities by the sponsor, regardless of severity 
or causality. These events should be reported to the sponsor in a timely manner, irrespective of 
seriousness (eg, serious and nonserious adverse events). Events of CRS, TLS, and neurotoxicity
(any grade) must be reported until 100 days after last administration of any study treatment or until 
the start of subsequent anticancer therapy, if earlier, and followed until recovery or until there is 
no further improvement. 
Second primary malignancies must be reported for the duration of the study, irrespective of 
treatment emergent status, and subsequently will be collected in a long-term follow-up study 
yearly until 15 years post dosing of JNJ-68284528.

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The following events must be reported to the sponsor using the Serious Adverse Event Form within 
24 hours of awareness of the event, irrespective of seriousness or causality (eg, serious and 
nonserious adverse events): 

≥Grade 3 CRS,

≥Grade 3 neurotoxicity, 

≥Grade 3 tumor lysis syndrome, 

Any grade movement and neurocognitive toxicity (ie, parkinsonism),

Any grade second primary malignancies.
Adverse events of special interest that are considered to be non-serious by the investigator are to 
be included on the serious adverse event form and in the eCRF. All adverse events of special 
interest of any grade should be followed until recovery or until there is no further improvement.
12.3.4.
Pregnancy
All initial reports of pregnancy in female subjects or partners of male subjects must be reported to 
the sponsor by the study-site personnel within 24 hours of their knowledge of the event using 
appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous 
abortion, fetal death, stillbirth, congenital anomalies, and 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 discontinue further study treatment. Because the 
effect of the study treatment on sperm is unknown, pregnancies in partners of male subjects included 
in the study will be reported as noted above. 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.

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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.
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 TREATMENT INFORMATION
14.1.
Physical Description of Study Treatment
JNJ-68284528
therapy is a BCMA-directed genetically modified autologous T cell 
immunotherapy that involves reprogramming a subject’s T cells with a transgene encoding a 
chimeric antigen receptor (CAR) to identify and eliminate BCMA-expressing malignant and 
normal cells. Upon binding to BCMA-expressing cells, the CAR transmits a signal to promote T 
cell expansion, activation, target cell elimination, and persistence of the JNJ-68284528.
14.2.
Packaging
JNJ-68284528 will be provided in an infusion bag with specific subject identifiers. 
JNJ-68284528 will be provided in an infusion bag with specific subject identifiers, this will include 
subject number and subject apheresis identification number or donor identification number (DIN), 
subject name and subject date of birth, as allowed by local regulations.
14.3.
Labeling
Study treatment labels will contain information to meet the applicable regulatory requirements.
14.4.
Preparation, Handling, and Storage 
JNJ-68284528 is provided in a single-dose unit containing CAR-positive viable T cells based on 
the subject weight reported at the time of apheresis.
JNJ-68284528 therapy contains human cells genetically modified with a lentiviral vector. Follow 
local biosafety guidelines applicable for handling and disposal of such products. The product is 
prepared from autologous blood collected by apheresis. JNJ-68284528 may carry a risk of 
transmitting infectious viruses to healthcare professionals handling the product. Accordingly, 
healthcare professionals should employ universal precautions to avoid potential transmission of 
infectious diseases when handling the product.

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Detailed instructions for storage conditions and handling will accompany clinical drug supplies to 
the clinical study sites. The storage conditions and expiry dates are indicated on the label. Refer to 
the IPPI for additional guidance on study treatment preparation, handling, and storage.
14.5.
Drug Accountability
Information in this section relates to study treatment that is supplied to investigational sites from 
the study sponsor.
The investigator is responsible for ensuring that all study treatment received at the site is 
inventoried and accounted for throughout the study. The study treatment administered to the 
subject must be documented on the drug accountability form. All study treatment will be stored 
and disposed of according to the sponsor's instructions. Study-site personnel must not combine 
contents of the study treatment containers.
Study treatment 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 under appropriate environmental 
conditions. Unused study treatment 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 treatment will 
be documented on the drug return form.
Potentially hazardous materials such as used ampules, needles, syringes, infusion bags, 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 treatment 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 treatment will be 
supplied only to subjects participating in the study. The investigator agrees neither to dispense the 
study treatment 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:

Study protocol

Investigator's Brochure

ECG machine and manual

IPPI/SIPPM (includes apheresis and cell processing instructions)

Laboratory Manual

Interactive web response system manual

Electronic data capture (eDC) manual

Sample ICF

Subject diaries and instructions/educational materials

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
PRO instruments and completion guidelines (Phase 2)

Thermal printer and barcode scanner (for sites utilizing Vineti chain of custody/chain of 
identity software in Phase 2)
16.
ETHICAL ASPECTS
16.1.
Study-specific Design Considerations 
Thorough scientific evaluation of any promising treatment before market authorization is an 
ethical requirement. In the continuing search for medications with improved efficacy and safety 
profiles, it is necessary to fully investigate and understand new products before exposure to the 
public. As discussed in Section 1.5, 74 subjects with relapsed or refractory multiple myeloma have 
received treatment with LCAR-B38M CAR-T cells in a clinical study setting. An analysis of safety 
data for these subjects demonstrated a manageable safety profile consistent with its known 
mechanism of action. In view of the Legend 2 study results and the prognosis for the subject 
population being considered for this study, a positive risk-benefit profile is anticipated. Subjects 
will be closely monitored throughout the study, as discussed throughout this protocol, for both 
safety and clinical benefit.
Apheresis risks may include hypotension, faintness, blurry vision, dizziness, coldness, sweating, 
infection, abnormal blood clotting, allergic reaction, bleeding, seizures, abdominal cramps, and 
tingling in the limbs. Subjects will be closely monitored during the procedure and will be evaluated 
for hospitalization in the case of CRS.
The blood sample collection scheme was designed to collect the minimum number of blood 
samples that accurately and completely describe the pharmacokinetic/pharmacodynamic 
characteristics of the study treatment. This minimizes the number of venipunctures and the total 
volume of blood collected from each subject during the study. The volume of blood to be drawn 
is considered to be customary and acceptable for subjects participating in a cancer clinical study 
and is deemed reasonable over the timeframe of the study, based upon the standard of the American 
Red Cross. 
Potential subjects will be fully informed of the risks and requirements of the study prior to enrollment 
and, during the study, subjects will be given any additional information that may affect their decision 
to continue participation. They will be told that their consent to participate in the study is voluntary 
and may be withdrawn at any time with no reason given and without penalty or loss of benefits to 
which they would otherwise be entitled. Only subjects who are fully able to understand the risks, 
benefits, and potential adverse events of the study, and provide their consent voluntarily will be 
enrolled.

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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.
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

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
If applicable, new or revised subject recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable

New edition(s) of the Investigator's Brochure and amendments/addenda

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)

Reports of adverse events that are serious, unlisted/unexpected, and associated with the study 
treatment

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 must give written consent according to local requirements after the nature of the study 
has been fully explained. The ICF(s) must be signed before performance of any study-related 
activity. The ICF(s) that is/are used must be approved by both the sponsor and by the reviewing 
IEC/IRB and be in a language that the subject can read and understand. The informed consent 
should be in accordance with principles that originated in the Declaration of Helsinki, current ICH 
and GCP guidelines, applicable regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential subjects 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 

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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 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 physician may also 
recontact the subject for the purpose of obtaining consent to collect information about his or her 
survival status.
The subject 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 the subject's personally dated signature. After having obtained the consent, a copy of the ICF 
must be given to the subject.
If the subject 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 is obtained.
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 disclosures 
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place. 
For tracking and traceability of the apheresis material and investigational product, subject name 
and date of birth, as allowed by local regulations, will be collected to ensure chain of identity of 
the investigational product for the subject. Sponsor personnel whose responsibilities require access 
to personal data agree to keep the identity of subjects confidential.
The informed consent obtained from the subject 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.

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Exploratory biomarker, pharmacokinetic, and immunogenicity research is not conducted under 
standards appropriate for the return of data to subjects. In addition, the sponsor cannot make 
decisions as to the significance of any findings resulting from exploratory research. Therefore, 
exploratory research data will not be returned to subjects or investigators, unless required by law 
or local regulations. Privacy and confidentiality of data generated in the future on stored samples 
will be protected by the same standards applicable to all other clinical data.
16.2.5.
Long-term Retention of Samples for Additional Future Research 
Samples, including apheresis product, collected in this study and JNJ-68284528 that was 
manufactured but not administered to a subject may be stored for up to 15 years (or according to 
local regulations) for additional research. Samples will only be used to understand JNJ-68284528, 
understand multiple myeloma, understand differential drug responders, and develop tests/assays 
related to JNJ-68284528. 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 10.4, 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 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.

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During the study, when 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 eCRF 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 treatment 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

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:

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
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 (as allowed by local regulations). In cases where the subject is not enrolled into 
the study, the date seen and date of birth (as allowed by local regulations) will be used.
For tracking and traceability of the apheresis material and investigational product, subject name 
and date of birth, as allowed by local regulations, will be collected to ensure chain of identity of 
the investigational product for the subject.
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 treatment administration information; and date of 
study completion and reason for early discontinuation of study treatment or withdrawal from the 
study, if applicable. 
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring guidelines 
(or other equivalent document).
The 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:

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
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 
eCRF 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 eCRF. Data in this system may be 
considered source documentation.
17.5.
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each subject in electronic format. 
All eCRF entries, corrections, and alterations must be made by the investigator or authorized 
study-site personnel. The investigator must verify that all data entries in the eCRF are accurate and 
correct.
The study data will be transcribed by study-site personnel from the source documents onto an 
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any 
such worksheets will become part of the subject's source documents. Data must be entered into 
eCRF in English. The eCRF 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.
If necessary, queries will be generated in the eCRF tool. If corrections to an eCRF are needed after 
the initial entry into the eCRF, this can be done in either of the following ways:

Investigator and study-site personnel can make corrections in the eCRF tool at their own 
initiative or as a response to an auto query (generated by the eCRF tool).

Sponsor or sponsor delegate can generate a query for resolution by the investigator and study-
site personnel.
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, periodic monitoring visits by the sponsor, and where 
applicable direct transmission of clinical laboratory data from a central laboratory into the 

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sponsor's data base. Written instructions will be provided for collection, handling, storage, and 
shipment of samples. 
Guidelines for eCRF completion will be provided and reviewed with study-site personnel before 
the start of the study. The sponsor will review eCRF 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 eCRF 
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.
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 eCRF 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 

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eCRF 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. 
17.9.
Study Completion/Termination
17.9.1.
Study Completion/End of Study
The end of the study will be defined as 2 years after the last subject has received his or her initial 
dose of JNJ-68284528. 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 treatment 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 

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with regulatory guidelines and company policy. These audits will require access to all study 
records, including source documents, for inspection. Subject privacy must, however, be respected. 
The investigator and study-site personnel are responsible for being present and available for 
consultation during routinely scheduled study-site audit visits conducted by the sponsor or its 
designees. 
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part 
of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor if he or she has 
been contacted by a regulatory agency concerning an upcoming inspection.
17.11. Use of Information and Publication 
All information, including but not limited to information regarding JNJ-68284528 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-68284528, 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 CSR 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 for the study. Results of exploratory biomarker analyses 
performed after the CSR has been issued will be reported in a separate report and will not require 
a revision of the CSR. 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 

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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 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 18 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 ICMJE Recommendations for the Conduct, Reporting, Editing and Publication of 
Scholarly Work in Medical Journals, which state that the named authors must have made a 
significant contribution to the conception or design of the work; or the acquisition, analysis, or 
interpretation of the data for the work; and drafted the work or revised it critically for important 
intellectual content; and given final approval of the version to be published; and agreed to be 
accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity 
of any part of the work are appropriately investigated and resolved.
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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Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. 
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Frigyesi I, Adolfsson J, Ali M, et al. Robust isolation of malignant plasma cells in multiple myeloma. Blood. 
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Hatzoglou A, Roussel J, Bourgeade MF, et al. TNF receptor family member BCMA (B cell maturation) 
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Hsi ED, Steinle R, Balasa B, et al. CS1, a potential new therapeutic antibody target for the treatment of 
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Kimberley FC, Hahne M, Medema JP. "APRIL hath put a spring of youth in everything": Relevance of APRIL 
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Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple 
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Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release 
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b
In some cases it is possible that the original M protein light-chain isotype is still detected on immunofixation 
but the accompanying heavy-chain component has disappeared; this would not be considered as a CR even 
though the heavy-chain component is not detectable, since it is possible that the clone evolved to one that 
secreted only light chains. Thus, if a patient has IgA lambda myeloma, then to qualify as CR there should be 
no IgA detectable on serum or urine immunofixation; if free lambda is detected without IgA, then it must be 
accompanied by a different heavy chain isotype (IgG, IgM, etc.).
c
Clarifications to the criteria for coding progressive disease: bone marrow criteria for progressive disease are 
to be used only in subjects without measurable disease by M-protein and by FLC levels; “25% increase” 
refers to M-protein, and FLC, and does not refer to bone lesions, or soft tissue plasmacytomas and the 
“lowest response value” does not need to be a confirmed value.
Notes: All response categories (CR, sCR, VGPR, PR, MR, and progressive disease) require 2 consecutive 
assessments made at any time before the institution of any new therapy; CR, sCR, VGPR, PR, MR, and stable 
disease 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 progressive disease, serum M-component increases of ≥1 g/dL are sufficient to define relapse if 
lowest M-component is ≥5 g/dL.
Source: Adapted from Durie (2015) and Rajkumar (2011)11,30, Kumar (2016)18

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Attachment 2:
Deleted 
Attachment content removed in Amendment 2

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Attachment 3:
International Myeloma Working Group Diagnostic Criteria
Diagnostic criteria for myeloma must be met when the patient was diagnosed. Multiple myeloma is defined 
as clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytomaa and 
any one or more of the following myeloma defining events:

Myeloma defining events:

Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative 
disorder, specifically:
o
C: Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of 
normal or >2.75 mmol/L (>11 mg/dL)
o
R: Renal insufficiency: creatinine clearance <40 mL per minb or serum creatinine 
>177 μmol/L (>2 mg/dL)
o
A: Anemia: hemoglobin value of >20 g/L below the lower limit of normal, or a hemoglobin 
value <100 g/L 
o
B: Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CTc,d

Any one or more of the following biomarkers of malignancy: 

Clonal bone marrow plasma cell percentagea ≥60%

Involved:uninvolved serum free light chain ratioe ≥100

>1 focal lesions on MRI studiesf
a
Clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, 
immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably 
be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the 
highest value should be used.
b
Measured or estimated by validated equations. 
c
If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish 
from solitary plasmacytoma with minimal marrow involvement.
d
PET-CT=18F-fluorodeoxyglucose PET with CT.
e
These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The 
involved free light chain must be ≥100 mg/L. 
f
Each focal lesion must be 5 mm or more in size.
Source: Rajkumar (2011)30

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Attachment 4:
Prior Cancer Therapy for Multiple Myeloma and Refractory Myeloma Definition
Prior Therapy
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. 
Refractory Myeloma
Refractory myeloma is defined as disease that is nonresponsive while on primary or salvage therapy, or 
progresses within 60 days of last therapy. Nonresponsive disease is defined as either failure to achieve 
minimal response or development of progressive disease (PD) while on therapy. There are 2 categories of 
refractory myeloma: “relapsed-and-refractory myeloma” and “primary refractory myeloma.”
Relapsed and refractory myeloma
Relapsed and refractory myeloma is defined as disease that is nonresponsive while on salvage therapy, or 
progresses within 60 days of last therapy in patients who have achieved minimal response (MR) or better 
at some point previously before then progressing in their disease course.
Source: Rajkumar (2011)30

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Attachment 6:
Formulas for Estimating Glomerular Filtration Rate
Modified Diet in Renal Disease (MDRD) Formula 
For serum creatinine in mg/dL, the estimated glomerular filtration rate (eGFR) for the MDRD formula is:
eGFR (MDRD) mL/min per 1.73m2= 175 x [serum creatinine (mg⁄dL)]-1 154 x [age]-0 203 x [1.212 if 
black] x [0.742 if female]
For serum creatinine in µmol/L, the eGFR for the MDRD formula is:
eGFR (MDRD) mL/min per 1.73m2= 175 x [serum creatinine (mol/L)/88.4]-1 154 x [age]-0 203 x [1.212 
if black] x [0.742 if female] 
Sources: 
Levey (2006)23

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Attachment 7:
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 (1999)6

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effector cell-associated neurotoxicity syndrome; ICE=immune effector Cell-associated Encephalopathy; ICF=informed consent form; INR=international normalized ratio; 
IPPI=investigational product preparation instructions; MRD=minimal residual disease; MRI=magnetic resonance imaging; MUGA=multiple-gated acquisition; PRO=patient reported 
outcome; PT=prothrombin time; SIPPM=site investigational product procedures manual; SOC=standard of care; SPEP=serum protein electrophoresis; UPEP=urine protein 
electrophoresis.
a
For subjects who discontinue the study before Day 100X, the Day 100X assessments should be performed prior to withdrawal of consent if feasible. Subjects who discontinue after 
Day 100X but before study completion should have urine and serum disease assessments performed prior to withdrawal of consent if feasible at the time of discontinuation, unless 
performed within 14 days prior to discontinuation. For subjects who receive retreatment with JNJ-68284528 and are in follow-up at the end of the study (2 years after the last 
subject receives the initial dose of JNJ-68284528), monitoring will continue in the long-term follow-up study (Section 9.1.6.3).
b
Post-treatment assessments to be obtained until progressive disease is documented or the start of subsequent anticancer therapy, with the exception of survival status and 
subsequent anticancer therapy, which are to be collected until study completion.
c
Disease characteristics cytogenetics (full karyotyping or FISH as well as molecular genetics [if applicable]), both of which may originate from prior to or during the screening 
period within 42 days before apheresis, or between apheresis and the conditioning regimen, as applicable.
d
For subjects who are hospitalized for potential CRS, hematology and chemistry laboratory evaluations should be performed at least daily or more as clinically indicated
e
Serology results performed as standard of care within 28 days prior to apheresis are acceptable. Hepatitis B: HBsAg, anti-HBc, anti-HBs, HBV DNA quantification (for subjects 
who are anti-HBs positive without history of vaccination or for subjects who are anti-HBs positive and anti-HBc positive); Monitor HBV-DNA, AST/ALT every 3 months for one 
year post-dose of JNJ-68284528. Hepatitis C: HCV antibody, HCV-RNA (for subjects who are anti HCV positive); HIV serology
f
Immediately before the start of infusion, at the end of infusion, and 0.5, 1, 2 hours after end of infusion. Monitor until normalized after a CRS event
g
Temperature will be checked at least twice a day up to Day 28X. Subjects will be provided with a thermometer and instructed on the use of the thermometer and entering 
2 temperatures including their maximum daily temperature in a diary. Diary will be reviewed at each visit, then collected on Day 28 and stored with subject source documents. 
h
All subjects will be evaluated for IgG, IgA, IgM. Testing for IgD and IgE will only be performed for subjects with IgD and IgE-type myeloma.
i
UPEP sample collected as part of the standard of care and prior to the subject signing ICF may be used for analysis at the central laboratory. 
j
Bone marrow morphology from an aspirate and core biopsy to be assessed locally at all time points. Additional bone marrow aspirate samples will be collected for biomarkers (see 
Table 13).
k
Results from skeletal survey performed as routine follow-up within 42 days before start of apheresis may be used without these tests being repeated. The skeletal survey is to be 
performed by either roentgenography or low-dose computed tomography (CT) scans without the use of IV contrast. If a CT is used it must be of diagnostic quality. Additional 
imaging (X-ray, CT, or MRI) will be performed as clinically indicated (eg, to document response or progression).
l
Extramedullary plasmacytomas should be assessed for all subjects with a history of plasmacytomas or if clinically indicated prior to the first dose of the conditioning regimen, by 
clinical examination or radiologic imaging.
m
HIV, hepatitis B, hepatitis C, HTLV, and other infectious diseases as applicable per local regulations.
n
Pre-infusion ICE test and handwriting sample should be performed before pre-medication with diphenhydramine
o
Medical resource evaluation data will be collected until Day 180X (± 7 days)
p
Local laboratory assessments may be used under specified circumstances (see Section 9.6)

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Screening 
Phase
Apheresis
Cyclophosp
hamide and 
fludarabine 
conditioning 
regimen
JNJ-
68284528 
Infusion
Post Infusion (any subject who received infusion of JNJ-68284528 should continue all 
subsequent assessments) a and Post-treatment (Day 101X up to study completion)
At 
PD
At End 
of Study 
for 
subjects 
without
PD
≤28 days 
prior to 
apheresis
If 
perform-
ed
Day -5X,* -
4X, -3X 
(assessments 
may be 
conducted 
≤72 hours 
predose) b
Day 1X
(Infusion)
Day 
2X
Day 
3X 
Day 
7X 
(± 1 
day)
Day 
10X 
(± 1 
day)
Day 
14X 
(± 1 
day)
Day 
21X 
(± 2 
days)
Day 
28X 
(± 2 
days
)
Day 
42X 
(± 2 
days)
Day 
56X 
(± 2 
days)
Day 
78X 
(± 2 
days
)
Day 
100X 
(± 2 
days)
Day 
184X
(±7 
days)
CyTOF/ 
PBMC/ 
Plasma 
(whole 
blood)
X
X
X
X
X
X
X
X
X
X
Xe,f
MRD 
(aspirate)
(bone 
marrow)
X (prior to 
first dose of 
conditioning 
regimen 
[≤7 days])
Sample should be collected: 

For all dosed subjects at Day 28X, and at approximately 6X, 12X, 18X, 24X months regardless of the status 
of disease measured in blood and urine

For subjects with suspected CR at the time of CR and then yearly for subjects that remain on study up to 
disease progression.
Cytogeneti
cs (bone 
marrow)
X (prior to 
first dose of 
conditioning 
regimen 
[≤7 days])
X
Replicatio
n 
Competent 
Lentivirus 
(RCL)
(whole 
blood)
X (prior to 
first dose of 
conditioning 
regimen 
[≤7 days])
Pre-dose
At approximately 3X (Day 84), 6X (Day 168), and 12X (Day 364) months (±1 month); then yearly (±3 months) 
until EOS, and then yearly (±3 months) for up to 15 years after cilta-cel infusion in a separate long-term follow-
up study. Yearly collection of RCL samples is not required if assessments within the first year are negative. 
Additional samples may be collected triggered by events which may be relevant to RCL per clinical assessment.
Cytokine 
profilingg
(serum)
X (prior to 
first dose of 
conditioning 
regimen 
[≤7 days])
Pre-dose,
2hrs Post 
(±10 
minutes)
X
X
X
X
X
X
X
X
X
X
X

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Abbreviations: ADA=anti-drug antibody; BCMA=B-cell maturation antigen; CAR=chimeric antigen receptor; CR = complete response; CRS=cytokine release syndrome; 
CyTOF=cytometry by time of flight; PD= progressive disease; EOI=end of infusion; MRD=minimal residual disease; PBMC=peripheral blood mononuclear cell; PK=pharmacokinetic; 
sCR=stringent complete response
a
For subjects who discontinue the study before Day 100X, the Day 100X assessments should be performed if feasible.
b
Window for start of conditioning regimen: Day -7 to Day -5
c
Collect additional samples when any of the following are suspected or reported: 1) CRS or CAR-T cell-related neurotoxicity (eg, ICANS) Grade ≥2 (at onset of the event, and 24 and 
72 hours after) or as clinically indicated; and 2) as indicated based on emerging data. 
d
ADA sample should be collected if a subject withdraws from the study after JNJ-68284528 administration but prior to disease progression or study completion.
e
Sample should also be collected at suspected CR
f
Sample should be collected at 12 months, relative to Day 1X, for subjects that achieve CR/sCR and remain on study.
g
Collect additional samples when any of the following are suspected or reported: 1) CRS or CAR-T cell-related neurotoxicity (eg, ICANS) (any grade) (at onset of the event, and then 
every 24 hours until CRS or ICANS event has stabilized or is resolving at which time additional collections should occur at 24, 48, and 72 hours) or as clinically indicated; and 2) as 
indicated based on emerging data.

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Attachment 10:
Patient Reported Outcomes (PRO) Measures
EORTC QLQ-C30

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Single Items from the EORTC QLQ MY20

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EQ-5D-5L

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Patient Global Impression of Severity (PGIS)

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Patient Global Impression of Change (PGIC)

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Attachment 12:
Immune Effector Cell-associated Encephalopathy (ICE) Tool
Immune Effector Cell-Associated Encephalopathy (ICE) Toola
Orientation: Orientation to year, month, city, hospital: 

4 points
Naming: Name 3 objects (eg, point to clock, pen, button): 

3 points
Following commands: (eg, Show me 2 fingers or Close your eyes and stick out your tongue): 

1 point
Writing: Ability to write a standard sentence (eg, Our national bird is the bald eagle): 

1 point
Attention: Count backwards from 100 by ten: 

1 point
a: ICE-Tool Scoring:

Score 10: No impairment

Score 7-9: Grade 1 ICANS

Score 3-6: Grade 2 ICANS

Score 0-2: Grade 3 ICANS

Score 0 due to patient unarousable and unable to perform ICE assessment: Grade 4 ICANS

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Attachment 13:
Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) ASBMT 
Consensus Grading Systema,b
Neurotoxicity 
Domain
Grade 1
Grade 2
Grade 3
Grade 4
ICE Score
7-9
3-6
0-2
0 (patient is 
unarousable and 
unable to perform 
ICE).
Depressed Level of 
Consciousness
Awakens 
spontaneously.
Awakens to 
voice.
Awakens only to tactile 
stimulus.
Patient is 
unarousable or
requires vigorous or
repetitive tactile 
stimuli
to arouse. Stupor or
coma.
Seizure
N/A
N/A
Any clinical seizure,
focal or generalized, that
resolves rapidly; or
Non-convulsive
seizures on EEG that 
resolve with
intervention.
Life-threatening
prolonged seizure 
(>5 min); or
Repetitive clinical 
or electrical seizures
without return to
baseline in between.
Motor Findings
N/A
N/A
N/A
Deep focal motor
weakness such as
hemiparesis or
paraparesis.
Raised 
Intracranial 
Pressure / 
Cerebral Edema
N/A
N/A
Focal/local edema on 
neuroimaging.
Diffuse cerebral 
edema on 
neuroimaging; or
Decerebrate or
decorticate 
posturing; or
Cranial nerve VI 
palsy; or 
Papilledema; or
Cushing's triad.
a: Toxicity grading according to Lee et al 2019
b: ICANS grade is determined by the most severe event (ICE score, level of consciousness, seizure, motor findings, 
raised ICP/cerebral edema) not attributable to any other cause.
Note: all other neurological adverse events (not associated with ICANS) should continue to be graded with CTCAE 
Version 5.0 during both phases of the study

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Attachment 14:
Anticipated Adverse Events
Anticipated Event
An anticipated event is an adverse event that commonly occurs independent of exposure to the drug under 
investigation.
For the purposes of this study the following serious adverse events will be considered anticipated events:

Anaemia

Bleeding

Bone diseases

Hypercalcaemia

Hyperuricemia

Infection

Neutropenia

Renal failure and insufficiency

Thrombocytopenia
These anticipated events will be periodically analyzed in aggregate by the sponsor during study conduct.  
The sponsor will prepare a safety report in narrative format if the aggregate analysis indicates that the 
anticipated event occurs more frequently in the treatment group than in the general disease population and 
the sponsor concludes there is a reasonable possibility that the drug under investigation caused the 
anticipated event.
The plan for monitoring and analyzing the anticipated events is specified in a separate Anticipated Events 
Safety Monitoring Plan. The assessment of causality will be made by the sponsor’s safety assessment 
committee.
The sponsor assumes responsibility for appropriate reporting of the listed anticipated events according to 
the requirements of the countries in which the studies are conducted.

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Attachment 15:
Handwriting Adverse Event Toxicity Grading Criteria
Adverse Event Term
Grade 1
Grade 2
Micrographia:
abnormally small or 
cramped handwriting
Mildly smaller letters 
or reduced spacing 
(eg, <50% decrease 
from baseline)
Moderate to severely 
smaller letters or reduced 
spacing (eg, >=50% 
decrease from baseline)
Dysgraphia:
illegible writing or 
writing that takes an 
unusually long time or 
great effort
Mildly slower 
writing, impaired 
straightness of line, 
difficulty in 
completing task from 
baseline; most words 
are legible
Moderate to severely 
slower writing, impaired 
straightness of line, 
difficulty in completing 
task from baseline; most 
words are illegible
Agraphia:
pathologic loss of the 
ability to write
Able to write part of 
a sentence (3 or more 
words); noted change 
from baseline
Able to write just 1 to 2 
words, or unable to write 
any words; noted change 
from baseline

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Attachment 16:
Anti-microbial Prophylaxis Recommendations
Subjects should receive antimicrobial prophylaxis as per recommendations below or per institutional 
standards.
Prophylaxis
Therapy 
Start 
Stop 
Anti-Bacterial 
Fluoroquinolones (Levofloxacin - 500 
mg PO or IV daily, or equivalent)
Suggested Alternative for subjects 
with allergy to quinolones:
Cefpodoxime -  200 mg PO twice a 
day
At neutropenia onset
(ANC < 500/μL)
At Neutropenia 
resolution (for example, 
ANC ≥ 500/µL)
Anti-Fungal
Fluconazole - 400 mg daily
(or equivalent) 
Alternatives: Caspofungin or 
Micafungin
Prolonged neutropenia > 3 weeks –
Consider switching to Posaconazole, 
or as per institutional guidelines
At neutropenia onset 
(ANC < 500/μL)
At Neutropenia 
resolution (for example, 
ANC ≥ 500/µL)
Anti-Viral
Acyclovir – 400 - 800 mg PO twice a 
day2 (dose to be adjusted as per 
institutional guidelines)
Alternative:
Valacyclovir - 500 mg PO twice a day
Day 1 of infusion
Suggested for at least 12 
months post infusion 
Pneumocystis
Pneumonia (PCP)
Trimethoprim-sulfamethoxazole – 1 
DS tablet PO daily or 1 SS tablet PO 
daily
Alternatives:
Pentamidine (as per institutional 
guidelines), or
Dapsone – 100 mg PO daily or 50 mg 
PO BID,
or
Atovaquone – 1500 PO daily
Day 1 of infusion
Suggested duration: 6 
months OR until CD4 
count ≥ 200 cells/µL, 
(whichever is longer)
Consider CMV serology at baseline, monitor with PCR testing as clinically indicated per institutional
guidance

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Attachment 17:
COVID-19 Guidance on Study Conduct and Vaccine Timing
GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 
site personnel being reassigned to critical tasks. 
In alignment with recent health authority guidance, the sponsor is providing options for study 
related participant management in the event of disruption to the conduct of the study. This guidance 
does not supersede any local or government requirements or the clinical judgement of the 
investigator to protect the health and well-being of participants and site staff. 
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent 
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each 
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments 
should be performed if required and as feasible. Participants will also be questioned regarding 
general health status to fulfill any physical examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow up. Modifications to protocol-required assessments may be 
permitted via COVID-19 Appendix after consultation with the participant, investigator, and the 
sponsor. Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations. Discontinuations of study interventions and withdrawal from the study should 
be documented with the prefix “COVID-19-related” in the case report form (CRF). 
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance. 
If a participant has tested positive for COVID 19, the investigator should contact the sponsor’s 
responsible medical officer to discuss plans for study intervention and follow-up. Modifications 
made to the study conduct as a result of the COVID-19 pandemic should be summarized in the 
clinical study report.
Testing for COVID-19 should be performed according to local guidance. If a participant has tested 
positive for COVID-19, the following should be reported in the EDC tool:

all cases of COVID-19, regardless of severity or causality (including asymptomatic 
COVID-19) up to 1 year after cilta-cel infusion

all medications given to prevent (including vaccines) or treat COVID-19 up to 1 year after 
cilta-cel infusion

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GUIDANCE SPECIFIC TO THIS PROTOCOL:
These emergency provisions are meant to ensure subject safety on study while site capabilities are 
compromised by COVID-19-related restrictions. As restrictions are lifted and the acute phase of 
the COVID-19 pandemic resolves, sites should revert to original protocol conduct as soon as 
feasible.
Study Visits and Assessments

At the discretion of the investigator and with sponsor approval, study visits may be performed 
remotely via telemedicine technology that connects study subjects to their research 
coordinators and investigators. Blood sample collection may be performed at the subject’s 
home by mobile study personnel (ie, nurses and mobile phlebotomist). Home health nursing 
can either be centrally sourced via sponsor agreement with a vendor, or done via site contract 
with a visiting nurse service independent of the sponsor.

For subjects who are unable to come to the site for scheduled visits and/or if site capabilities 
are compromised by COVID-19 related restrictions, contact (eg, telephone, videoconference, 
or other channels) with the subject should be made in advance, to collect information on the 
subject’s current health status and any new or ongoing adverse events and concomitant 
medications. Normal study procedures should be followed for the applicable visits as closely 
as possible even if lab assessments and physical exams are performed locally. Where local 
laboratories are used, it is important to ensure appropriate documentation of laboratory 
reference ranges. The remote contact with the subject (as allowable per local regulations), the 
local laboratory results, and the sponsor discussion should be documented in the subject 
source record. Similarly, at a minimum, a comment must be entered in the Comments eCRF 
clearly designating as “COVID-19-related” and acknowledging the discussion between the 
investigator and the sponsor.

For subjects eligible to receive retreatment, original protocol conduct must be followed until 
Day 100. 

All deviations from protocol-required assessments should be documented in detail within the 
subject’s source record and should be clearly designated as “COVID-19-related”. It must be 
documented if a visit is conducted remotely. Source documentation should detail how each 
assessment was collected (eg, remote vs. on-site, central vs. local laboratory, vital signs taken 
at home by caretaker vs. delegated in-home nursing).

Consenting and re-consenting of subjects will be performed as applicable for the measures 
taken (including also remote consenting by phone or video consultation) and according to 
local guidance for informed consent applicable during the COVID-19 pandemic.
The above measures are recommended for consideration on a temporary basis during the 
COVID-19 pandemic to ensure that subject assessments continue as outlined in the protocol 
without imposing health risk to subjects, their families, and site staff. Every effort should be made 
to complete all protocol-required assessments. 

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GUIDANCE ON COVID-19 VACCINE TIMING, AND COVID-19 PREVENTION AND 
TREATMENT FOR CILTA-CEL RECIPIENTS
It is recommended that participants receive prophylactic COVID-19 vaccination when locally 
available, at the discretion of investigator judgement or institutional practice, and in compliance 
with the cilta-cel study protocol and local labels for the vaccine.  Below is general guidance for 
consideration.
Many vaccines against COVID-19 are being developed with different technologies and platforms 
and may have safety and efficacy profiles that are not fully characterized even after preliminary 
health authority approval. However, the benefit-risk ratio of receiving a COVID-19 vaccine among 
patients with multiple myeloma participating in cilta-cel studies is considered to be positive and 
should be considered for administration while in compliance with the cilta-cel study protocol and 
when not otherwise contraindicated for use in the vaccine label.
Per protocol, live attenuated vaccines must be completed at least 6 weeks prior to lymphodepletion 
therapy or initiated at least 100 days after cilta-cel infusion. There are no specific timing 
restrictions for inactivated vaccines, which include vaccines which use alternative technology like 
mRNA or replication-incompetent viral vectors, per protocol. Enrollment into an interventional 
clinical trial for an experimental vaccine is prohibited during study. Any vaccination, including 
COVID-19 vaccinations, must be recorded on the Concomitant Medication page of the eCRF. 
No data is currently available to suggest that COVID-19 vaccines pose specific or additional safety 
risk beyond other vaccines for cancer patients undergoing treatment.  Theoretically, a diminished 
immune response may occur in immunocompromised patients, and therefore these patients may 
have reduced vaccine effectiveness.
While not specifically required per protocol, it is encouraged to complete the COVID-19 vaccine 
series at least 2 weeks prior to lymphodepletion, and to delay vaccination for at least 3 months 
after cilta-cel infusion, to maximize immune response.
Several organizations and journals have published recommendations for COVID-19 vaccine 
administration in cancer patients, including:

European Society for Blood and Marrow Transplantation (EBMT)
https://www.ebmt.org/covid-19-and-bmt 

American Society for Transplantation and Cellular Therapy (ASTCT) 
https://www.hematology.org/covid-19/ash-astct-covid-19-vaccination-for-hct-and-car-t-cell-
recipients

National Comprehensive Cancer Network (NCCN) 
https://www.nccn.org/covid-19/pdf/COVID-19_Vaccination_Guidance_V2.0.pdf

Centers for Disease Control and Prevention (CDC) 
https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html  

JNJ-68284528
Relapsed or Refractory Multiple Myeloma
Clinical Protocol 68284528MMY2001 – Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
162
Status: Approved,  Date: 15 June 2022

Nature Reviews Clinical Oncology: COVID-19 vaccine guidance for patients with cancer 
participating in oncology clinical trials. Desai A, Gainor JF, Hegde A, et al. (March 15, 2021). 
DOI:   10.1038/s41571-021-00487-z

https://www.nature.com/articles/s41571-021-00487-z
Investigators should inform patients that emerging data from another cilta-cel study show that 
patients receiving cilta-cel are possibly at higher risk of severe/fatal outcomes from COVID-19 
infection compared with patients receiving standard of care therapy (Section 6.3.6).
Based on guidance from the organizations listed above, the following measures should be 
implemented to minimize subjects’ risk of severe COVID-19 infection: 

Subjects, particularly those who are less than 6 to 9 months from cilta-cel infusion, should be 
reminded that the ongoing pandemic is still putting them at risk of contracting COVID-19. 
Investigators should ask subjects to continue to limit their risk of exposure to infected 
individuals as much as possible and strictly adhere to prevention measures such as proper 
masking, hand hygiene, social distancing, and avoiding travel and public transportation to the 
extent possible.

Investigators should discuss with subjects the importance of COVID-19 vaccines in the 
prevention of severe illness, hospitalization, and death from COVID-19. Subjects should 
assume that any vaccination administered prior to lymphodepletion and cilta-cel infusion no 
longer provides protection. For this reason, it is strongly recommended that all subjects 
receive a full COVID-19 vaccination series (eg, a primary series of 3 vaccines and a 4th 
booster dose for mRNA vaccines; note: mRNA vaccines are recommended), no sooner than 
3 months after cilta-cel infusion, regardless of vaccination status prior to cilta-cel. In addition, 
if not already vaccinated, caregivers, family, and household contacts should be advised to 
receive COVID-19 vaccination as well.

Investigators should consider prophylaxis (eg, Evusheld, if available in the region) to reduce 
subjects’ risk of severe/fatal COVID during the first 6 to 9 months after cilta-cel. It is critical 
that subjects understand that multiple myeloma patients (even those who have not received 
CAR-T therapy) may not seroconvert until after the 3rd vaccine dose and as a result they may 
remain at a very high risk of severe COVID-19 for at least 2 to 3 months after starting 
vaccination 2.

Investigators should instruct subjects to notify them or study site staff immediately if they are 
diagnosed with COVID 19, even if they are asymptomatic, so that appropriate treatment 
measures can be determined.

If available in the region, antivirals (eg, Paxlovid or other available agents) should be 
considered early after COVID-19 diagnosis. Subjects may remain asymptomatic or have 
minimal symptoms for a period of time prior to deteriorating. Investigators should make 
subjects aware that these drugs may potentially significantly lower their risk of severe
COVID-19.

CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved,  Date: 30 April 2020
Janssen Research & Development *
Clinical Protocol
COVID-19 Appendix
Protocol Title
A Phase 1b-2, Open-Label Study of JNJ-68284528, a Chimeric Antigen Receptor T cell 
(CAR-T) Therapy Directed Against BCMA in Subjects with Relapsed or Refractory 
Multiple Myeloma
Protocol 68284528MMY2001; Phase 1b-2
JNJ-68284528
*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; Janssen Biopharma Inc.; 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.
This study will be conducted under United States (US) sites of this study will be conducted under 
US Food & Drug Administration Investigational New Drug (IND) regulations (21 CFR 
Part 312).]
Status:
Approved  
Date:
30 April 2020
Prepared by:
Janssen Research & Development, LLC
EDMS number:
EDMS-RIM-48939, 1.0
THIS APPENDIX APPLIES TO ALL CURRENT APPROVED VERSIONS OF PROTOCOL
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.
NCT03548207

COVID-19 Appendix
JNJ-68284528
Clinical Protocol 68284528MMY2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved,  Date: 30 April 2020
COVID-19 APPENDIX
GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 
site personnel being reassigned to critical tasks. 
In alignment with recent health authority guidance, the sponsor is providing options for study 
related participant management in the event of disruption to the conduct of the study. This guidance 
does not supersede any local or government requirements or the clinical judgement of the 
investigator to protect the health and well-being of participants and site staff. 
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent 
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each 
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments 
should be performed if required and as feasible. Participants will also be questioned regarding 
general health status to fulfill any physical examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow up. Modifications to protocol-required assessments may be 
permitted via COVID-19 Appendix after consultation with the participant, investigator, and the 
sponsor. Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations. Discontinuations of study interventions and withdrawal from the study should 
be documented with the prefix “COVID-19-related” in the case report form (CRF). 
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance. 
If a participant has tested positive for COVID 19, the investigator should contact the sponsor’s 
responsible medical officer to discuss plans for study intervention and follow-up. Modifications 
made to the study conduct as a result of the COVID-19 pandemic should be summarized in the 
clinical study report.

COVID-19 Appendix
JNJ-68284528
Clinical Protocol 68284528MMY2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
3
Status: Approved,  Date: 30 April 2020
GUIDANCE SPECIFIC TO THIS PROTOCOL:
These emergency provisions are meant to ensure subject safety on study while site capabilities are 
compromised by COVID-19-related restrictions. As restrictions are lifted and the acute phase of 
the COVID-19 pandemic resolves, sites should revert to original protocol conduct as soon as 
feasible.
Study Visits and Assessments

At the discretion of the investigator and with sponsor approval, study visits may be performed 
remotely via telemedicine technology that connects study subjects to their research 
coordinators and investigators. Blood sample collection may be performed at the subject’s 
home by mobile study personnel (ie, nurses and mobile phlebotomist). Home health nursing 
can either be centrally sourced via sponsor agreement with a vendor, or done via site contract 
with a visiting nurse service independent of the sponsor.

For subjects who are unable to come to the site for scheduled visits and/or if site capabilities 
are compromised by COVID-19 related restrictions, contact (eg, telephone, videoconference, 
or other channels) with the subject should be made in advance, to collect information on the 
subject’s current health status and any new or ongoing adverse events and concomitant 
medications. Normal study procedures should be followed for the applicable visits as closely 
as possible even if lab assessments and physical exams are performed locally. Where local 
laboratories are used, it is important to ensure appropriate documentation of laboratory 
reference ranges. The remote contact with the subject (as allowable per local regulations), the 
local laboratory results, and the sponsor discussion should be documented in the subject 
source record. Similarly, at a minimum, a comment must be entered in the Comments eCRF 
clearly designating as “COVID-19-related” and acknowledging the discussion between the 
investigator and the sponsor.

For subjects eligible to receive retreatment, original protocol conduct must be followed until 
Day 100. 

All deviations from protocol-required assessments should be documented in detail within the 
subject’s source record and should be clearly designated as “COVID-19-related”. It must be 
documented if a visit is conducted remotely. Source documentation should detail how each 
assessment was collected (eg, remote vs. on-site, central vs. local laboratory, vital signs taken 
at home by caretaker vs. delegated in-home nursing).

Consenting and re-consenting of subjects will be performed as applicable for the measures 
taken (including also remote consenting by phone or video consultation) and according to 
local guidance for informed consent applicable during the COVID-19 pandemic.
The above measures are recommended for consideration on a temporary basis during the 
COVID-19 pandemic to ensure that subject assessments continue as outlined in the protocol 
without imposing health risk to subjects, their families, and site staff. Every effort should be made 
to complete all protocol-required assessments.