A Phase 2, Open-Label, Multicenter, Basket Study Evaluating the Efficacy of Brexucabtagene Autoleucel in Adults With Rare B-cell Malignancies (ZUMA-25)
Phase: PHASE2
Conditions: Relapsed/Refractory Waldenstrom Macroglobulinemia, Relapsed/Refractory Richter Transformation, Relapsed/Refractory Burkitt Lymphoma, Relapsed/Refractory Hairy Cell Leukemia
Sponsor: Kite, A Gilead Company

 
CLINICAL STUDY PROTOCOL
Protocol Title:
A Phase 2, Open-Label, Multicenter, Basket Study 
Evaluating the Efficacy of Brexucabtagene Autoleucel in 
Adults with Rare B-cell Malignancies (ZUMA-25) – 
Master Protocol
Protocol Number: 
KT-US-568-0138 (ZUMA-25) – master protocol
Note:
This master protocol should be used in conjunction with the 
substudy protocols KT-US-568-0138-A, KT-US-568-0138-B, 
KT-US-568-0138-C and KT-US-568-0138-D. 
Note: Substudies KT-US-586-0138-A and KT-US-568-
0138-D were terminated early by the Sponsor (effective 
21 June 2023).
Indication:
Adult subjects with rare B-cell malignancies, defined in 
separate disease specific substudies:
•
Substudy A – relapsed/refractory Waldenstrom 
macroglobulinemia: terminated early by Sponsor 
(effective 21 June 2023)
•
Substudy B – relapsed/refractory Richter transformation
•
Substudy C – relapsed/refractory Burkitt lymphoma
•
Substudy D – relapsed/refractory hairy cell leukemia: 
terminated early by Sponsor (effective 21 June 2023)
Kite Investigational Product:
Brexucabtagene autoleucel
Kite IND Number:
028542
EU CT Number:
Substudy A- 2022-501259-10-00: terminated early by 
Sponsor (effective 21 June 2023)
Substudy B- 2022-501260-18-00
Substudy C- 2022-501261-46-00
Substudy D- 2022-501262-21-00: terminated early by 
Sponsor (effective 21 June 2023)
Clinical Trials.gov Identifier:
NCT05537766
Sponsor:
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
United States of America

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Contact Information:
The medical monitor name and contact information is 
provided on the Key Study Team Contact List 
Protocol Version/Date:
Original: 23 May 2022
Amendment History:
Amendment 1.0: 20 July 2022
Amendment 1.1: 12 January 2023
Amendment 2.0: 01 March 2023
Amendment 3.0: 17 August 2023
Country-specific 
Requirements:
Country-specific requirements are listed in Appendix 12.4
This study will be conducted under United States (US) Food and Drug Administration (FDA) 
Investigational New Drug (IND) application regulations (21 Code of Federal Regulations 
Part 312); however, sites located in the European Economic Area, and Switzerland are not 
included under the IND application and are not considered to be IND application sites.
This study will be conducted in compliance with this protocol and in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki, and that are consistent with 
International Council for Harmonisation (ICH) Good Clinical Practice (GCP) and applicable 
regulatory and local requirements.
CONFIDENTIALITY STATEMENT
This document contains confidential information of Kite Pharma, Inc., a wholly owned subsidiary of 
Gilead Sciences Inc. This document must not be disclosed to anyone other than the study site research 
staff, collaborators, and members of the Institutional Review Board/Independent Ethics Committee, a 
scientific review board, or an equivalent. The information in this document cannot be used for any 
purpose other than the conduct of the clinical investigation without the prior written consent of 
Kite Pharma, Inc. 

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TABLE OF CONTENTS
CLINICAL STUDY PROTOCOL..................................................................................................................................1
TABLE OF CONTENTS................................................................................................................................................3
LIST OF IN-TEXT TABLES .........................................................................................................................................7
LIST OF IN-TEXT FIGURES........................................................................................................................................7
PROTOCOL SYNOPSIS................................................................................................................................................8
STUDY SCHEMA........................................................................................................................................................21
LIST OF ABBREVIATIONS.......................................................................................................................................22
1.
INTRODUCTION................................................................................................................................................25
1.1.
Brexucabtagene Autoleucel.....................................................................................................................25
1.2.
Summary of Relevant Nonclinical and Clinical Studies With Brexucabtagene Autoleucel...................25
1.2.1.
Nonclinical Studies With Brexucabtagene Autoleucel .........................................................25
1.2.2.
Clinical Studies With Brexucabtagene Autoleucel ...............................................................25
1.3.
Disease Background ................................................................................................................................26
1.3.1.
Disease Indication-specific Information................................................................................27
1.4.
Study Rationale .......................................................................................................................................27
1.5.
Benefit/Risk Assessment for the Study ...................................................................................................28
1.6.
Compliance..............................................................................................................................................28
2.
OBJECTIVES AND ENDPOINTS......................................................................................................................29
3.
STUDY DESIGN.................................................................................................................................................31
3.1.
Study Design ...........................................................................................................................................31
3.1.1.
Rationale for Study Design Elements....................................................................................32
3.2.
Study Treatments.....................................................................................................................................34
3.2.1.
Leukapheresis........................................................................................................................34
3.2.2.
Bridging Therapy (Optional; for RT and BL Subjects Only)................................................34
3.2.3.
Lymphodepleting Chemotherapy ..........................................................................................34
3.2.4.
Brexucabtagene Autoleucel...................................................................................................35
3.2.5.
Auxiliary Medicinal Products................................................................................................35
3.3.
Duration of Subject Participation ............................................................................................................35
3.4.
End-of-Study Definition..........................................................................................................................35
3.5.
Long-term Follow-up ..............................................................................................................................36
3.6.
Study Discontinuation Criteria................................................................................................................36
3.7.
Number of Participating Study Sites .......................................................................................................36
3.8.
Source Data .............................................................................................................................................36
4.
SUBJECT POPULATION...................................................................................................................................37
4.1.
Number of Subjects and Subject Selection .............................................................................................37
4.2.
Eligibility Criteria....................................................................................................................................37
4.2.1.
Inclusion Criteria Common to all Indications .......................................................................37
4.2.2.
Exclusion Criteria Common to all Indications ......................................................................39
4.3.
Subject Withdrawal .................................................................................................................................40
4.3.1.
Reasons for Removal From Treatment..................................................................................41
4.3.2.
Reasons for Removal From Study.........................................................................................41
4.4.
Replacement of Subjects .........................................................................................................................42
5.
STUDY TREATMENT........................................................................................................................................43
5.1.
Description of Study Treatment ..............................................................................................................43

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5.1.1.
Bridging Chemotherapy ........................................................................................................43
5.1.2.
Lymphodepleting Chemotherapy ..........................................................................................43
5.1.3.
Brexucabtagene Autoleucel...................................................................................................44
5.2.
Packaging, Labeling, Storage, and Handling of Study Treatment ..........................................................45
5.2.1.
Brexucabtagene Autoleucel Packaging, Labeling, Storage, and Handling...........................45
5.3.
Dosage and Administration .....................................................................................................................45
5.4.
Prior and Concomitant Medications........................................................................................................45
5.5.
Excluded Medications .............................................................................................................................45
5.5.1.
Washout Periods Prior to Leukapheresis/Enrollment............................................................45
5.5.2.
Excluded Medications or Medications to be Used With Caution After 
Leukapheresis/Enrollment.....................................................................................................46
5.6.
Accountability and Return of Study Treatment.......................................................................................47
5.6.1.
Accountability of Study Treatment .......................................................................................47
5.6.2.
Return or Disposal of Study Treatment.................................................................................47
6.
STUDY ASSESSMENTS COMMON TO ALL SUBSTUDIES ........................................................................48
6.1.
Demographic Data...................................................................................................................................48
6.2.
Medical and Treatment History...............................................................................................................48
6.3.
Safety Assessments .................................................................................................................................48
6.3.1.
Adverse Events......................................................................................................................49
6.3.2.
Clinical Laboratory Tests ......................................................................................................49
6.3.3.
Physical Examination ............................................................................................................51
6.3.4.
Weight ...................................................................................................................................51
6.3.5.
Vital Signs .............................................................................................................................51
6.3.6.
Neurologic Examinations ......................................................................................................52
6.3.7.
Performance Status (Eastern Cooperative Oncology Group Score)......................................52
6.3.8.
Cardiac Function ...................................................................................................................52
6.3.9.
Brain MRI..............................................................................................................................53
6.3.10.
Lumbar Puncture ...................................................................................................................53
6.3.11.
Patient-reported Outcomes ....................................................................................................53
6.3.12.
Concomitant Therapies and Procedures ................................................................................54
6.3.13.
Pregnancy Testing .................................................................................................................54
6.3.14.
Serology Testing....................................................................................................................55
6.3.15.
HIV Viral Load and CD4 Count ...........................................................................................55
6.3.16.
Other Safety Assessments .....................................................................................................55
6.4.
Disease Assessments ...............................................................................................................................56
6.5.
Bone Marrow Aspirate / Biopsy requirements for Subjects With Unexplained Cytopenias or 
Suspicion of Hemophagocytic Lymphohistiocytosis ..............................................................................56
6.6.
Pharmacokinetic Assessments.................................................................................................................56
6.7.
Pharmacodynamic Assessments..............................................................................................................56
6.8.
Other Assessments...................................................................................................................................57
6.8.1.
Central Confirmation of Diagnosis .......................................................................................57
6.8.2.
Exploratory Assessments.......................................................................................................57
6.8.3.
Survival Data.........................................................................................................................57
7.
STUDY PROCEDURES......................................................................................................................................58
7.1.
Subject Informed Consent .......................................................................................................................58
7.1.1.
Informed Consent for Optional Research..............................................................................58
7.2.
Subject ID Assignment............................................................................................................................58
7.3.
Screening .................................................................................................................................................59
7.3.1.
Rescreening ...........................................................................................................................59
7.4.
Enrollment ...............................................................................................................................................59
7.5.
Pretreatment Period .................................................................................................................................60
7.5.1.
Leukapheresis........................................................................................................................60

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7.5.2.
Bridging Therapy (Optional; for RT and BL Subjects Only)................................................61
7.5.3.
Baseline Disease Assessment Post Bridging (Optional; for RT and BL 
Subjects Only) and Post-Ibrutinib (Optional; for WM Subjects Only).................................61
7.5.4.
Lymphodepleting Chemotherapy ..........................................................................................61
7.6.
Treatment Period (Day 0 to Day 7) .........................................................................................................63
7.6.1.
Brexucabtagene Autoleucel Premedications (Day 0)............................................................64
7.6.2.
Infusion of Brexucabtagene Autoleucel (Day 0) and 
Assessments/Procedures to be Performed Before (Days −1 or 0) and 
After (Days 1 to 7) Infusion ..................................................................................................64
7.6.3.
Monitoring After Brexucabtagene Autoleucel Infusion........................................................64
7.6.4.
Requirements for Workup for Potential Infectious and/or Inflammatory 
States .....................................................................................................................................65
7.7.
Post-treatment Follow-Up Period............................................................................................................66
7.7.1.
Post-treatment Assessment Visits..........................................................................................66
7.7.2.
Evaluation Visit After Disease Progression ..........................................................................67
7.7.3.
Follow-up Assessments and Procedures for Enrolled Subjects Who Did 
Not Receive Brexucabtagene Autoleucel or Whose Disease Progressed 
After Brexucabtagene Autoleucel Treatment........................................................................67
7.8.
Assessments and Procedures for Subjects with Disease Progression .....................................................68
7.9.
Follow-up Assessments and Procedures for Subjects who Undergo an Allogeneic Stem Cell 
Transplant after Brexucabtagene Autoleucel Treatment.........................................................................68
7.10.
Care After Completion of Participation in the Study ..............................................................................69
7.11.
Subsequent Anticancer Therapy..............................................................................................................69
7.12.
Instructions for Follow-up and Data to be Collected for Subjects Withdrawn From 
Treatment/Study ......................................................................................................................................69
7.13.
Sample Storage........................................................................................................................................70
8.
ADVERSE EVENTS AND TOXICITY MANAGEMENT................................................................................71
8.1.
Definitions of AEs and SAEs..................................................................................................................71
8.1.1.
Adverse Events......................................................................................................................71
8.1.2.
Dose Limiting Toxicities.......................................................................................................71
8.1.3.
SAEs......................................................................................................................................73
8.1.4.
Targeted Adverse Events and Serious Adverse Events.........................................................74
8.2.
Pregnancies..............................................................................................................................................74
8.3.
Clinical Laboratory and Vital Sign Abnormalities..................................................................................75
8.3.1.
Abnormal Clinical Laboratory Findings ...............................................................................75
8.3.2.
Abnormal Vital Sign Values .................................................................................................75
8.4.
Assessments of AE and SAE Severity and Causality .............................................................................75
8.4.1.
Assessment of AE/SAE Severity...........................................................................................76
8.4.2.
Assessment of AE/SAE Relationship to Brexucabtagene Autoleucel and 
Study Procedures...................................................................................................................77
8.5.
Hospitalization and Prolonged Hospitalization.......................................................................................77
8.6.
Investigator Requirements and Instructions for Reporting AEs, SAEs, and Deaths to the 
Sponsor....................................................................................................................................................77
8.6.1.
Reporting Adverse Events and Serious Adverse Events.......................................................77
8.6.2.
Reporting Deaths...................................................................................................................81
8.6.3.
Reporting Adverse Events, Serious Adverse Events, and Deaths 
Associated With Disease Progression...................................................................................82
8.7.
Sponsor Reporting Requirements (Includes Reporting of SAEs and Deaths) ........................................82
8.8.
Toxicity Management..............................................................................................................................83
8.8.1.
Toxicities Associated With Brexucabtagene Autoleucel Treatment.....................................83
8.9.
Special Situations Reports.......................................................................................................................83
8.9.1.
Definitions of Special Situations...........................................................................................83
8.9.2.
Instructions for Reporting Special Situations........................................................................84

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8.10.
Safety Review Team, Data Safety Monitoring Board, and Criteria to Pause Enrollment ......................85
8.10.1.
Safety Review Team..............................................................................................................85
8.10.2.
Data Safety Monitoring Board ..............................................................................................86
8.10.3.
Criteria to Pause Enrollment .................................................................................................86
9.
STATISTICAL CONSIDERATIONS.................................................................................................................88
9.1.
Statistical Analysis Plan ..........................................................................................................................88
9.2.
Hypothesis ...............................................................................................................................................88
9.3.
Definition of Study Endpoints.................................................................................................................88
9.3.1.
Definitions of Primary Endpoints..........................................................................................88
9.3.2.
Definition of Secondary Endpoints .......................................................................................88
9.3.3.
Definition of Other Endpoints of Interest..............................................................................90
9.4.
Determination of Sample Size.................................................................................................................90
9.5.
Access to Individual Subject Treatment Assignments and Minimization of Bias ..................................90
9.6.
Planned Analyses.....................................................................................................................................91
9.6.1.
Interim Analysis and Early Stopping Guidelines ..................................................................91
9.6.2.
Primary Analysis ...................................................................................................................91
9.6.3.
Final Analysis........................................................................................................................91
9.6.4.
Long-term Data Analysis ......................................................................................................91
9.6.5.
Analysis Conventions............................................................................................................91
9.7.
Demographic Data and Baseline Characteristics ....................................................................................92
9.8.
Efficacy Analysis.....................................................................................................................................92
9.8.1.
Disease Response Rate..........................................................................................................92
9.8.2.
Best Objective Response .......................................................................................................93
9.8.3.
Duration of Response ............................................................................................................93
9.8.4.
Progression-free Survival ......................................................................................................93
9.8.5.
Overall Survival.....................................................................................................................93
9.9.
Safety Analysis........................................................................................................................................93
9.10.
Multiplicity Adjustment ..........................................................................................................................94
9.11.
Pharmacokinetics Analysis......................................................................................................................94
9.12.
Pharmacodynamics Analysis...................................................................................................................94
9.13.
Patient-reported Outcome Analysis.........................................................................................................94
10.
RESPONSIBILITIES...........................................................................................................................................95
10.1.
Investigator Responsibilities ...................................................................................................................95
10.1.1.
Financial Disclosure ..............................................................................................................95
10.1.2.
IRB/IEC Approvals ...............................................................................................................95
10.1.3.
Informed Consent ..................................................................................................................95
10.1.4.
Confidentiality.......................................................................................................................96
10.1.5.
Study Files and Retention of Records ...................................................................................97
10.1.6.
Electronic Case Report Forms...............................................................................................98
10.1.7.
Access to Study Information .................................................................................................99
10.1.8.
Protocol Compliance .............................................................................................................99
10.2.
Sponsor Responsibilities .........................................................................................................................99
10.2.1.
Protocol Modifications ..........................................................................................................99
10.2.2.
Study Report and Publications ............................................................................................100
10.2.3.
Financing and Insurance......................................................................................................100
10.3.
Joint Investigator/Sponsor Responsibilities ..........................................................................................100
10.3.1.
Good Clinical Practice.........................................................................................................100
10.3.2.
Quality Control and Quality Assurance ..............................................................................100
10.3.3.
Ethics ...................................................................................................................................101
10.3.4.
Study Discontinuation .........................................................................................................101
11.
REFERENCES...................................................................................................................................................102

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12.
APPENDICES....................................................................................................................................................105
12.1.
Sponsor and Investigator Signature Page..............................................................................................106
12.2.
Schedules of Assessment.......................................................................................................................107
12.3.
Childbearing Potential and Birth Control..............................................................................................108
12.3.1.
Definition of Childbearing Potential ...................................................................................108
12.3.2.
Birth Control Methods That May Be Considered as Highly Effective ...............................108
12.3.3.
Unacceptable Birth Control Methods..................................................................................109
12.4.
Country-specific Regulatory Agency Requirements.............................................................................110
12.4.1.
Requirement for a Multidisciplinary Consultation Meeting Before Subject 
Inclusion in France..............................................................................................................110
12.4.2.
Post-infusion Monitoring.....................................................................................................110
12.4.3.
Pregnancy testing.................................................................................................................110
12.5.
Immune Effector Cell-associated Encephalopathy Score......................................................................111
12.6.
Patient-reported Outcomes ....................................................................................................................112
12.6.1.
European Organisation for Research and Treatment of Cancer Quality of 
Life Questionnaire C30 Version 3.0....................................................................................112
12.6.2.
European Quality of Life 5-dimension 5-level Questionnaire ............................................112
12.7.
Practical Body Weight Calculation for Subjects Whose Body Mass Index (BMI) is > 35 kg/m2........113
12.8.
Pandemic Risk Assessment and Mitigation Plan ..................................................................................114
12.9.
Tabulated List of Investigational Medicinal Products and Auxiliary Medicinal Products ...................117
12.10. Protocol Amendment History................................................................................................................119
12.10.1.
Amendment 1.0 (dated 20 July 2022) .................................................................................119
12.10.2.
Amendment 1.1- EU-specific Protocol Amendment (dated 12 January 
2023)....................................................................................................................................120
12.10.3.
Amendment 2.0 (dated 01 March 2023)..............................................................................123
12.10.4.
Amendment 3.0 (dated 17 August 2023) ............................................................................128
LIST OF IN-TEXT TABLES
Table 1.
Dose Limiting Toxicities.........................................................................................................19
Table 2.
Recommendations Based on DLTs .........................................................................................20
Table 3.
Objectives and Endpoints ........................................................................................................29
Table 4.
Clinical Laboratory Tests for Safety Assessments Common Across All Substudies..............49
Table 5.
Reporting Requirements for Concomitant Medications and Procedures ................................54
Table 6.
Dose-limiting Toxicities..........................................................................................................72
Table 7.
Recommendations Based on Dose Limiting Toxicities ..........................................................73
Table 8.
Severity Grading of AEs..........................................................................................................76
Table 9.
Reporting Requirements for AEs ............................................................................................79
Table 10.
Reporting Requirements for SAEs ..........................................................................................80
Table 11.
Definitions of Secondary Endpoints........................................................................................88
Table 12.
Definitions of Other Endpoints of Interest ..............................................................................90
Table 13.
Analysis Sets............................................................................................................................92
Table 14.
Immune Effector Cell-associated Encephalopathy Scorea ....................................................111
Table 15
List of Investigational Medicinal Products............................................................................117
Table 16.
List of Auxiliary Medicinal Products ....................................................................................117
LIST OF IN-TEXT FIGURES
Figure 1.
Study and Treatment Schema..................................................................................................21

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PROTOCOL SYNOPSIS
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
Protocol Title: A Phase 2, Open-Label, Multicenter, Basket Study Evaluating the Efficacy of 
Brexucabtagene Autoleucel in Adults with Rare B-cell Malignancies (ZUMA-25) – 
Master Protocol
Indication: Adult subjects with rare B-cell malignancies, defined in separate, disease-specific 
substudies:
•
Substudy A – relapsed/refractory (r/r) Waldenstrom macroglobulinemia (WM): terminated 
early by Sponsor, effective 21 June 2023
•
Substudy B – r/r Richter transformation (RT)
•
Substudy C – r/r Burkitt lymphoma (BL)
•
Substudy D – r/r hairy cell leukemia (HCL): terminated early by Sponsor, effective 
21 June 2023
Kite IND Number: 028542
EU CT Numbers: 
Substudy A- 2022-501259-10-00: terminated early by Sponsor, 
effective 21 June 2023)
Substudy B- 2022-501260-18-00
Substudy C- 2022-501261-46-00
Substudy D- 2022-501262-21-00: terminated early by Sponsor, 
effective 21 June 2023)
ClinicalTrials.gov Identifier: NCT05537766
Kite Investigational Product: Brexucabtagene Autoleucel
Other Investigational Product/IND Number: Not applicable
IDE Number: Not applicable
Number of Study Sites Planned: Approximately 25 
Objectives and Endpoints: The objectives and endpoints that are common to all indications 
are detailed in the table below. Additional objectives and endpoints that are specific to the 
indications being studied are detailed in the respective protocol of each substudy.

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Primary Objective
Primary Endpoint
•
To evaluate the efficacy of brexucabtagene 
autoleucel in subjects with rare B-cell 
malignancies, by determining the Response Rates 
as defined within the substudies by central 
assessment.
•
Response rates by central assessment as defined 
in each substudy 
Secondary Objectives
Secondary Endpoints
•
To evaluate the Complete Response (CR) by 
central assessment as defined within each 
substudy.
•
CR rate by central assessment as defined in each 
substudy 
•
Determine response durability
•
Duration of Response
•
Determine survival status
•
Overall Survival
•
Determine survival status without progression
•
Progression-free survival
•
Determine the time to next treatment (TTNT) after 
administration of brexucabtagene autoleucel
•
TTNT defined as the time from enrollment (for 
Full Analysis Set [FAS]) or brexucabtagene 
autoleucel infusion (for modified intention to 
treat [mITT]) to the initiation of subsequent 
anticancer therapy/treatment
•
Determine the time to first response
•
Time to first response from brexucabtagene 
autoleucel infusion to the first response as 
defined in the substudy
•
Determine the time to best response
•
Time to best response from brexucabtagene 
autoleucel infusion to the best response as 
defined in the substudy
•
Evaluate the safety of brexucabtagene autoleucel 
in subjects with rare B-cell malignancies
•
Incidence of adverse events (AEs) and common 
terminology criteria for adverse events 
(CTCAE) grade changes in safety laboratory 
values
•
Incidence of AEs defined as dose-limiting 
toxicities (DLTs)
•
Incidence of antibodies to brexucabtagene 
autoleucel (immunogenicity)
•
Incidence of replication-competent retrovirus 
(RCR) in peripheral blood mononuclear cells 
(PBMCs) at baseline and after brexucabtagene 
autoleucel infusion
•
To evaluate the effect of brexucabtagene 
autoleucel on patient reported outcomes (PROs) 
and quality of life assessments
•
Changes over time in the PRO assessment 
domains, EORTC-QLQ-C30 and EQ-5D-5L

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Exploratory Objectives
Exploratory Endpoints
•
To evaluate the pharmacokinetic profile of 
brexucabtagene autoleucel in subjects with rare B-
cell malignancies 
•
Levels of chimeric antigen receptor (CAR) T 
cells in blood and association with clinical 
outcomes (efficacy and toxicity)
•
Levels of blood B cells and relationship with 
pharmacokinetic profile and clinical outcome 
•
To evaluate the pharmacodynamic profile of 
brexucabtagene autoleucel in subjects with rare B-
cell malignancies
•
Levels of serum analytes (including cytokines 
and chemokines) in blood and relationship with 
events of interest (eg, cytokine release syndrome 
(CRS) and neurotoxicity).
•
To explore the phenotypic and functional 
characteristics of brexucabtagene autoleucel in 
subjects with rare B-cell malignancies 
•
Product characteristics, including T-cell 
phenotypes and relationship with clinical 
outcome
•
To explore immunogenicity against 
brexucabtagene autoleucel
•
Incidence of anti-brexucabtagene autoleucel 
CAR reactivity
Study Design:
This is a Phase 2, open-label, multicenter study evaluating the efficacy of brexucabtagene 
autoleucel in adult subjects with rare B-cell malignancies.
This study will use a basket study design with separate, indication-specific substudies. The 
study was originally designed to include r/r WM, r/r RT, r/r BL, and r/r HCL. However, the 
study is designed to have the flexibility to independently open and close individual substudies. 
Following the early termination of the r/r WM (Substudy A) and r/r HCL (Substudy D) 
substudies (effective 21 June 2023), subjects are only to be recruited to the r/r RT and r/r BL 
substudies. 
This master protocol contains details regarding all elements of the study that are common 
across each of the indications. In contrast, each of the separate substudy protocols contain 
additional information that is unique to an individual indication (ie, WM, RT, BL or HCL). A 
substudy-specific schedule of assessments (SOA) is located in each of the respective substudy 
protocols. The KT-US-568-0138 master protocol and relevant substudy protocol should be 
referenced in parallel.
Initially, 1 subject will be enrolled and infused in each substudy. No additional subjects will be 
enrolled within a substudy until the subject has been monitored for at least 28 days 
post-infusion. Subsequently, an additional 2 subjects in each substudy can be enrolled in 
parallel. After these initial 3 subjects in an individual substudy have been evaluated for at least 
28 days, the Safety Review Team will make recommendations on further substudy conduct.

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The screening period will have a duration of up to 28 days and will begin on the date a subject 
signs the Institutional Review Board/Independent Ethics Committee approved informed 
consent form and continues through to either confirmation of enrollment (ie, commencement 
of leukapheresis), until a subject withdraws consent before enrollment, or it is determined that 
a subject is a screen failure (ie, does not meet the study eligibility criteria, as defined in the 
KT-US-568-0138 master protocol and respective substudy protocol).
To reduce the risk of Bruton’s tyrosine kinase (BTK) inhibitor withdrawal symptoms and IgM 
flare, subjects in the WM substudy will be allowed ibrutinib through screening and for up to 
30 hours (5 half-lives) prior to starting lymphodepleting chemotherapy. Subjects in the RT 
substudy, if already receiving a BTK inhibitor, may also receive ibrutinib through screening 
and leukapheresis, at the discretion of the investigator.
Informed consent must be obtained before completion of any non-standard of care, 
study-specific procedures. Procedures that are part of the standard of care are not considered 
study-specific procedures and may be performed before obtaining consent and used to confirm 
eligibility.
A subject is considered as enrolled in the study at the commencement of leukapheresis. 
Subjects must have undergone screening procedures and their results must have been 
confirmed by the investigator to meet the study eligibility criteria at screening. For laboratory 
tests performed after screening and before initiation of leukapheresis, allowance will be made 
for an expected normal variation of ±5% of laboratory test value cutoffs noted in the inclusion 
criteria. If there is a need to repeat leukapheresis for a subject, they must continue to meet the 
study eligibility criteria (or be within ±5% of the laboratory test value cutoffs noted in the 
inclusion criteria) before the leukapheresis procedure is performed. (The ±5% cutoffs do not 
apply to the hematological parameters listed in the common inclusion criteria #4 if lower 
values are attributable to underlying disease).
After enrollment/leukapheresis, subjects in the RT and BL substudies may receive optional, 
protocol-defined bridging therapy at the discretion of the investigator. If bridging therapy has 
been administered, a new baseline disease assessment is required, as outlined in the SOA in 
the respective substudies.
Subjects will undergo lymphodepleting chemotherapy with fludarabine (30 mg/m2/day) and 
cyclophosphamide (500 mg/m2/day) for 3 consecutive days from Day -5 to Day -3 (see 
Section 3.2.3 for details) followed by 2 rest days (Day -2 and Day -1).
On Day 0, subjects will receive a single infusion of brexucabtagene autoleucel administered 
intravenously (IV) at a target dose of either 2 × 106 anti-CD19 CAR T cells/kg or 
1 × 106 anti-CD19 CAR T cells/kg, depending on the safety review team recommended dose 
(or a flat dose of 2 x 108 or 1 x 108, respectively, anti-CD19 CAR T cells in subjects 
> 100 kg), with an initial hospitalization period of at least 7 days; this is considered as the 
treatment period. From Day 7 to Day 28, subjects will be required to stay within close vicinity 
to the clinic, with immediate access to urgent care by the investigator.

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After completing the treatment period, all subjects will be followed during the post-treatment 
follow-up period. Counting from Day 0 (the day of brexucabtagene autoleucel infusion), 
subjects will return to the clinic for evaluation at Day 14, Day 28, Week 8, Month 3, then 
every 3 months up to Month 12. Additional substudy-specific visits will occur as outlined 
below:
•
RT and BL: Month 18 and Month 24
•
WM and HCL: every 6 months up to 36 months and then annually up to 60 months
Disease response will be assessed as appropriate for each indication and as described in each 
substudy protocol.
An SOA for each indication is provided in each of the respective substudy protocols.
The study schema is provided in Figure 1.
Number of Subjects Anticipated to be Enrolled and Treated:
A total of approximately 90 subjects will be enrolled and treated across 2 separate substudies 
as detailed below.
•
r/r WM: 60 subjects: Study terminated early by Sponsor, effective 21 June 2023
•
r/r RT: 60 subjects
•
r/r BL: 30 subjects
•
r/r HCL: 20 subjects: Study terminated early by Sponsor, effective 21 June 2023
Target Population:
Male or female adults ≥ 18 years of age and with rare B-cell malignancies defined in the 
respective substudy protocols:
•
Substudy A – r/r WM: Study terminated early by Sponsor, effective 21 June 2023
•
Substudy B – r/r RT
•
Substudy C – r/r BL
•
Substudy D – r/r HCL: Study terminated early by Sponsor, effective 21 June 2023 

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Duration of Treatment and of Study Participation:
Subjects will receive a single infusion of brexucabtagene autoleucel.
The duration of treatment for individual subjects will vary depending on a subject’s screening 
requirements, response to treatment, their survival and their indication. Subjects with RT and 
BL will be followed for approximately 24 months after the brexucabtagene autoleucel 
infusion, and subjects with WM and HCL will be followed for approximately 60 months after 
the brexucabtagene autoleucel infusion. Thereafter, subjects who received brexucabtagene 
autoleucel will transition to a separate long-term follow-up (LTFU) study (KT-US-982-5968) 
to continue follow-up out to 15 years from the time of the initial infusion.
Subjects who were enrolled but who did not receive brexucabtagene autoleucel will also be 
followed for the duration described above but will not be required to transition to the LTFU 
study. Of note, such subjects will have reduced follow-up requirements excluding disease 
response assessments but including survival status and subsequent anticancer therapy, as 
outlined in Section 7.7.3 and Section 7.11, respectively. 
Eligibility Criteria Common to all Substudies:
To be enrolled in the study, subjects must meet all the following inclusion criteria that are 
common to each of the substudies. Subjects must also meet additional disease-specific 
inclusion criteria, as specified in Section 4.2.1 of the respective substudy protocols.
Inclusion Criteria Common to all Substudies:
1) Male or female 18 years of age or older and who have provided written informed consent
2) Presence of toxicities due to prior therapy must be stable and recovered to Grade 1 or 
lower (except for clinically nonsignificant toxicities such as alopecia)
3) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4) Adequate hematological function (unless lower values are attributable to underlying 
disease) as indicated by:
Absolute neutrophil count ≥ 500/μL
Platelet count ≥ 50,000/μL
Hemoglobin level ≥ 8 g/dL
Absolute lymphocyte count ≥ 100/μL
5) Adequate renal, hepatic, pulmonary, and cardiac function defined as:
Creatinine clearance (as estimated by Cockcroft-Gault formula) ≥ 60 mL/min
Serum alanine aminotransferase and aspartate aminotransferase levels ≤ 2.5 × upper 
limit of normal (ULN) or ≤ 5 × ULN if documented liver involvement
Total bilirubin levels ≤ 1.5 × ULN, except in subjects with Gilbert’s syndrome

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Cardiac ejection fraction ≥ 50% and no evidence of pericardial effusion as determined 
by an echocardiogram or multigated acquisition scan and no clinically significant 
electrocardiogram findings
No clinically significant pleural effusion
Baseline oxygen saturation > 92% on room air
6) The following washout periods must be satisfied prior to leukapheresis/enrollment:
Corticosteroid therapy at a pharmacologic dose (≥ 5 mg/day of prednisone or 
equivalent doses of other corticosteroids) must be avoided for 7 days before 
leukapheresis
BTK inhibitors (eg, ibrutinib or acalabrutinib), must be avoided at least 1 week or 
5 half-lives, whichever is shorter, before leukapheresis unless otherwise specified in 
the subprotocols
Anti-neoplastic drugs used in previous therapy must be avoided within 1 week or 
5 half-lives (whichever is shorter) prior to leukapheresis
Systemic inhibitory/stimulatory immune checkpoint molecule therapy (eg, ipilimumab, 
nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists) must be 
avoided at least 3 half-lives prior to leukapheresis
Alemtuzumab must be avoided at least 6 months prior to enrollment
PEG-asparaginase must be avoided at least 3 weeks prior to enrollment
Cladribine and pentostatin must be avoided 3 months prior to enrollment
Donor lymphocyte infusion within 28 days prior to enrollment
Any treatment with immunosuppressive antibody used within 4 weeks prior to 
enrollment (eg, anti-CD20, anti-tumor necrosis factor, anti-interleukin [IL] 6 or 
anti-IL6 receptor) unless this treatment is included in prior or bridging regimens, in 
which case a washout period of 7 days is required prior to leukapheresis
7) Females of childbearing potential must have a negative serum or urine pregnancy test 
(females who have undergone surgical sterilization or who have been postmenopausal for 
at least 2 years are not considered to be of childbearing potential)
Exclusion Criteria Common to all Substudies:
To be enrolled in the study, subjects must not meet any of the following exclusion criteria that 
are common to each of the substudies. Subjects must also not meet any of the additional 
disease-specific exclusion criteria, as specified in Section 4.2.2 of the respective substudy 
protocols.
1) Prior CAR therapy or other genetically modified T-cell therapy
2) Prior treatment with any anti-CD19 therapy
3) History of severe immediate hypersensitivity reaction attributed to aminoglycosides

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4) History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine
5) Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or 
requiring IV antimicrobials for management. Simple urinary tract infection and 
uncomplicated bacterial pharyngitis are permitted if responding to active treatment. 
Patients with a simple urinary tract infection and uncomplicated bacterial pharyngitis and 
responding to active treatment are eligible only if the patient satisfies the criteria of being 
afebrile (ie, temperature lower than 38oC) for at least 24 hours prior to the investigator 
confirming a patient’s eligibility
6) HIV-positive patients, unless taking appropriate anti-HIV medications, having an 
undetectable viral load by quantitative polymerase chain reaction (qPCR) and a CD4 count 
>200 cells/uL
7) Acute or chronic active hepatitis B or hepatitis C infection. Subjects with a history of 
hepatitis infection must have cleared their infection as determined by standard serological 
and genetic testing per current Infectious Diseases Society of America guidelines or 
applicable country guidelines
8) Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling 
Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central 
venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted
9) History or presence of detectable cerebrospinal fluid malignant cells or brain metastases, 
unless otherwise specified in the substudy eligibility criteria
10) History or presence of central nervous system (CNS) disorder, such as cerebrovascular 
ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS 
involvement, posterior reversible encephalopathy syndrome, or cerebral edema with 
confirmed structural defects by appropriate imaging. History of stroke or transient 
ischemic attack within 12 months before enrollment. Subjects with seizure disorders 
requiring active anticonvulsive medication
11) Presence of cardiac atrial or cardiac ventricular lymphoma involvement
12) History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other 
clinically significant cardiac disease within 12 months before enrollment
13) Requirement for urgent therapy due to tumor mass effects (eg, blood vessel compression, 
bowel obstruction, or transmural gastric involvement)
14) Presence of primary immunodeficiency
15) History of autoimmune disease (eg, Crohn’s disease, rheumatoid arthritis, systemic lupus) 
resulting in end organ injury or requiring systemic immunosuppression/systemic disease 
modifying agents within the last 2 years
16) History of deep vein thrombosis or pulmonary embolism requiring therapeutic 
anticoagulation within 6 months before enrollment
17) Any medical condition likely to interfere with assessment of safety or efficacy of study 
treatment

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18) History of severe immediate hypersensitivity reaction to any of the agents/excipients used 
in this study
19) Live vaccine ≤6 weeks before the planned start of the lymphodepleting chemotherapy 
regimen and anticipation of need for such a vaccine during the first 12 months after 
brexucabtagene autoleucel infusion
20) Females who are pregnant or breastfeeding (because of the potentially dangerous effects of 
the preparative chemotherapy on the fetus or infant). Females who have undergone surgical 
sterilization or who have been postmenopausal for at least 2 years are not considered to be 
of childbearing potential
21) Not willing to practice birth control from the time of consent through 12 months after 
completion of the brexucabtagene autoleucel infusion
22) In the investigator’s judgment, the subject is unlikely to complete all study-specific visits 
or procedures, including follow-up visits, or comply with the study requirements for 
participation
Study Procedures/Frequency:
Study procedures common to all of the indications are described in the KT-US-568-0138 
master protocol, and any procedures unique to the specific indication are described in the 
respective substudy protocols.
All procedures and their frequencies are outlined in the SOAs within the substudy protocols 
(substudy protocol Section 12.2).
Subjects will undergo procedures including, but not limited to, the collection of informed 
consent, medical history, physical exam, neurological examination, ECOG performance status, 
disease staging, and blood draws. Subjects will also undergo cardiac function assessment.
Females of childbearing potential will undergo either urine or serum pregnancy testing.
All subjects will be asked to report concomitant therapies, AEs, and subsequent anticancer 
therapy routinely throughout the conduct of the study.
Subjects will undergo leukapheresis for the collection of PBMCs necessary for 
brexucabtagene autoleucel manufacturing. Lymphodepletion chemotherapy will be followed 
by 2 rest days and then an infusion of brexucabtagene autoleucel.
Additional blood draws for the assessment of cytokines, anti-brexucabtagene autoleucel 
antibodies, and RCR are to be performed as clinically indicated and are detailed in the 
respective substudy SOAs.
The post-treatment follow-up period will include physical examinations, disease response 
assessments, and survival status.

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Study Assessments:
The study assessments that are common to all indications and that are managed the same way 
across all substudies are described here in the KT-US-568-0138 master protocol. Assessments 
that are unique to a specific indication or that are managed differently depending on the 
indication (eg, lumbar puncture and disease response assessments) are described in the study 
assessment section of the respective substudy protocols.
Study assessments described in this section are to be performed according to the schedule 
presented in the respective SOA for each substudy.
Safety:
Safety assessments will include collection of AEs, clinical laboratory tests, physical 
examinations, weight, vital signs, neurologic examinations, ECOG performance status, cardiac 
function, brain magnetic resonance imaging (if applicable), lumbar puncture (if applicable), 
collection of concomitant medications, and assessment of the presence of anti-brexucabtagene 
autoleucel antibodies and RCR, as described in the following sections.
Safety assessments will be conducted according to the schedule presented in the SOA of each 
respective substudy.
Efficacy:
Disease assessments will be performed as specified in Section 6 of the respective substudy 
protocols and at the time points specified in the substudy protocol SOAs.
Pharmacokinetics/Pharmacodynamics:
PBMC samples for pharmacokinetic assessments will be drawn according to the schedule 
presented in the substudy protocol SOAs.
Pharmacokinetic assessments include the monitoring of levels of brexucabtagene autoleucel 
CAR T cells in blood over time.
Serum (and plasma) samples for pharmacodynamic assessments will be drawn according to 
the schedule presented in the substudy protocol SOAs.
Pharmacodynamic assessments will include monitoring levels of analytes in serum over time. 
Analytes can include, but are not limited to, homeostatic/proliferative cytokines (eg, IL-2, 
IL-7, IL-5), inflammatory/immune-modulating cytokines, correlates of acute phase response 
(eg, C-reactive protein, ferritin, sIL-2Rα), chemokines, and immune-effector molecules (eg, 
perforin, granzyme A and granzyme B).

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Investigational Product and Study Treatments, Dose, and Mode of Administration:
Substudy A – r/r WM: terminated early by Sponsor (effective 21 June 2023)
•
Optional Ibrutinib treatment is allowed through screening and leukapheresis if required 
(investigator discretion) to reduce the risk of BTK inhibitor withdrawal symptoms and 
IgM flare. Refer to Section 3.1.1.1 of the WM substudy protocol for details.
Substudy B – r/r RT
•
Optional bridging therapy is allowed between leukapheresis and lymphodepletion if 
required (investigator discretion) to limit rapid disease progression. In addition, ibrutinib 
treatment is allowed to continue through screening and leukapheresis if required 
(investigator discretion). Refer to Section 7.2 of the RT substudy protocol for details.
Substudy C – r/r BL
•
Optional bridging therapy is allowed between leukapheresis and lymphodepletion if 
required (investigator discretion) to limit rapid disease progression. Refer to Section 7.2 of 
the BL substudy protocol for details.
Substudy D – r/r HCL: terminated early by Sponsor (effective 21 June 2023)
•
No additional treatment between enrollment and lymphodepletion is allowed.
Lymphodepletion Therapy:
All subjects will receive a 3-day lymphodepleting chemotherapy regimen consisting of 
fludarabine (30 mg/m2/day) and cyclophosphamide (500 mg/m2/day) on Day -5, Day -4, and 
Day -3, followed by 2 rest days (Day -2 and Day -1).
Brexucabtagene Autoleucel Infusion:
All subjects will receive a single infusion of brexucabtagene autoleucel administered IV at a 
target dose of either 2 × 106 anti-CD19 CAR T cells/kg or 1 × 106 anti-CD19 CAR T cells/kg 
(depending on required dose reduction as assessed by the safety review team) on Day 0. For 
subjects weighing > 100 kg, a maximum flat dose of 2 × 108 anti-CD19 CAR T cells 
(or 1 × 108 anti-CD19 CAR T cells if dose reduction is required) will be administered.
Safety Review Team and Data Safety Monitoring Board:
A Safety Review Team (SRT) that is internal to the study sponsor and in collaboration with at 
least 1 study investigator will review safety and efficacy data and make recommendations 
regarding further study conduct, progression and/or dose modification in each substudy after 
3 or 6 subjects have been treated with the initial dose (2 × 106 anti-CD19 CAR T cells/kg of 
body weight or a maximum flat dose of 2 × 108 anti-CD19 CAR T cells for subjects weighing 
> 100 kg) and followed for 28 days (Section 8.10.1). In case of DLTs, the SRT can 
recommend i) to proceed with the starting dose; ii) to include an additional 3 subjects for 
evaluation prior to recommending dose; or iii) that the remaining patients to be dosed with 
1 x 106 anti-CD19 CAR T cells/kg or a maximum flat dose of 1 × 108 anti-CD19 CAR T cells 
for subjects weighing > 100 kg (with a subsequent SRT to be held after at least 3  subjects 
have been treated and followed for 28 days). Only subjects treated with the selected target 
dose will be included in the evaluable subject population for the primary analysis.

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DLTs are defined as the following brexucabtagene autoleucel-related events with onset within 
the first 28 days after the infusion of brexucabtagene autoleucel.
Table 1.
Dose Limiting Toxicities 
Dose-limiting Toxicities
Exceptions
Any brexucabtagene autoleucel related 
Grade 5 event
•
Grade 5 disease progression
Hematologic toxicity Grade 4 does not 
recover to Grade ≤ 2 by Day 28
•
Any hematologic toxicity Grade 4 attributable to underlying 
disease
•
Lymphopenia
Grade 3 or 4 thrombocytopenia lasting of 
any duration if accompanied by Grade 2 
or higher bleeding
•
None
All brexucabtagene autoleucel related 
Grade 4 nonhematologic toxicities 
including opportunistic infections and 
complications associated with HIVa
•
None
Any brexucabtagene autoleucel related 
Grade 3 neurotoxicity including ICANS, 
regardless of duration
•
None
All brexucabtagene autoleucel related 
Grade 3 nonhematological toxicities 
lasting ≥ 7 days including opportunistic 
infections and complications associated 
with HIVa
•
Grade 3 fever
•
Grade 3 aspartate aminotransferase, alanine aminotransferase, 
alkaline phosphatase, bilirubin, or other liver function test 
elevation, provided there is resolution to Grade 2 or lower 
within 14 days
•
Grade 3 nausea and/or anorexia
•
Grade 3 febrile neutropenia returning to baseline within 
2 weeks
•
Grade 3 insomnia, fatigue, and malaise
•
Grade 3 infection that improves to Grade 2 or lower within 
2 weeks
•
Grade 3 TLS including associated manifestations attributable 
to TLS (eg, electrolyte abnormalities, renal function, or 
hyperuricemia)
All brexucabtagene autoleucel related 
Grade 3 cardiac and/or pulmonary events 
of any duration
•
Grade 3 cardiac and/or pulmonary events if related to CRS 
and improves to Grade 2 or lower within 72 hours
Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome; 
ICANS, immune effector cell-associated neurotoxicity syndrome; ICE, immune effector cell-associated encephalopathy; 
NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; TLS, tumor lysis syndrome
Notes: Adverse events are graded using the NCI CTCAE v5.0. CRS and neurotoxicity is graded according to the ASTCT 
consensus grading for CRS and ICANS {Lee 2019}. The severity of individual signs/symptoms of CRS and neurological 
events will be graded according to NCI CTCAE v5.0 for those signs/symptoms that are not part of the grading scale.
a
Infections associated with HIV and AIDS such as (but not exclusive to): Candidiasis of bronchi, trachea, or lungs, 
extrapulmonary Cryptococcosis, Cytomegalovirus disease (other than liver, spleen or nodes), Histoplasmosis, 
disseminated or extrapulmonary, Mycobacterium avium complex, kansasii or other species (disseminated or 
extrapulmonary), Pneumocystis jirovecii pneumonia or complications such as HIV-associated Encephalopathy

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Table 2.
Recommendations Based on DLTs 
Number of Subjects With a Dose Limiting Toxicity in a Cohort
Potential Recommendation
0 of 3 subjects or if 1 DLT occurred in the initial 3 subjects and 
no DLT occurs in the subsequent 3 subjects
If the dose is determined tolerable, then this will be 
the recommended dose.
1 of 3 subjects
Enrol 3 more subjects at the same dose level.
≥ 2 of 3 subjects or if 1 DLT occurred in the initial 3 subjects and 
≥1 DLT occurs in the subsequent 3 subjects
The lower dose level will be established as the 
recommended dose (if assessed to be tolerable 
and recommended by the SRT).
An independent Data Safety Monitoring Board (DSMB) will review safety data throughout the 
study duration to make study conduct recommendations based on an overall assessment of risk 
versus benefit after the target dose for each substudy is confirmed by the SRT. There will be a 
single interim analysis in each substudy. The DSMB will review safety and efficacy data 
against the non-binding futility rules as described in each substudy.
Statistical Methods:
Hypothesis: Brexucabtagene autoleucel will improve the disease response rates compared with 
pre-specified historical control data, as described within each substudy.
Sample Size Calculation: The sample size and power considerations are based on a systemic 
literature review of historical control response rates for each indication, and each substudy is 
designed to be independent of each other without data borrowing across the substudies.
The type-1 and type-2 errors are controlled for each substudy. No multiplicity adjustment is 
made on global type-1 error across the substudies, as the primary goal of this basket study is to 
determine the treatment effect of brexucabtagene autoleucel separately in each substudy rather 
than generalizing the treatment effect evaluation between all the studied indications. 
Nevertheless, a low type-1 error (0.025, 1-sided) and high statistical power (≥ 80%) has been 
planned for each substudy.
Of the indications under investigation, HCL and BL have the lowest incidence and, as such, 
slower accrual for these substudies is likely to be encountered. A sample size of 20 and 30 was 
selected for HCL and BL, respectively, based on the anticipated slower rate of enrollment and 
a goal of acquiring clinically meaningful results for the HCL and BL substudies within a 
reasonable timeframe.
The statistical considerations for each of the indications are described in detail in each 
respective substudy.
This study will be conducted in compliance with this protocol; the International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines of 
Good Clinical Practice, including archiving of essential documents; and all applicable regulatory 
and local requirements.
This study will be conducted under United States Code of Federal Regulations Title 21 Part 312 
or equivalent.

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STUDY SCHEMA
Figure 1.
Study and Treatment Schema 
Abbreviations: BL, Burkitt lymphoma; CAR, chimeric antigen receptor; HCL, hairy cell leukemia; LTFU, long-term follow-up; 
SOC, standard of care; RT, Richter transformation; WM, Waldenstrom macroglobulinemia
a
Refer to the substudy protocols for details of the use of ibrutinib through screening and leukapheresis (WM and RT subjects 
only).
b
Bridging therapy (RT and BL subjects only) will be administered at the discretion of the investigator. If prescribed, bridging 
therapy will be administered after leukapheresis and completed at least 7 days or 5 half-lives, whichever is shorter, before 
initiation of lymphodepleting chemotherapy. Refer to specific substudies for details.
c
A single infusion of brexucabtagene autoleucel administered intravenously at a target dose of 2 x 106 or 1 x 106 anti-CD19 
CAR T cells/kg, in case of required dose reduction, depending on the safety review team recommended dose. For subjects 
weighing > 100 kg a maximum flat dose of 2 x 108 or 1 x 108 anti-CD19 CAR T cells will be administered in case of 
required dose reduction.
d
Refer to Section 12.4 for requirements by country regulatory agencies.
e
Subjects with RT and BL will be followed for approximately 24 months after the brexucabtagene autoleucel infusion and 
subjects with WM and HCL will be followed for approximately 60 months after the brexucabtagene autoleucel infusion. 
Thereafter, subjects who received brexucabtagene autoleucel will transition to a separate LTFU study, KT-US-982-5968, to 
continue follow-up out to 15 years (refer to Section 3.5).
-
-
Optional Bridging 
Lymphodepleting 
Investigational 
:c 
Therapy'> 
Chemotherapy 
Product 
.s 
-~ 
Treatment Period 
"" 
Refer to specific 
Administered on Day -
Q., 
Cl.I 
Substudy 
5, Day -4, and Day -3 
Day Oto Day 7 
Q. 
-= 
= 
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0: 
.s 
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Fludarabine 
On Day 0, a single 
= 
after leukapheresis and 
(30 mg/m2/day) 
infusion of 
= 
= 
Cl.I 
= 
Cl.I 
I----. 
1-------
stopped no later than 
I----. 
and 
brexucabtagene 
i------. 
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-
... 
7 days or 5 half-Ii ves, 
Cyclophosphamide 
autoleucel at a target 
(.I 
= 
= 
tl.l 
Cl.I 
ivhichever is shorter, 
(500 mglm2/day) 
dose of 2 x 10~ 
Cl.I 8 
before initiation of 
anti-CD19 CAR T 
-
0: 
= 
lymphodepleting 
Followed by rest days 
cells/kg< 
Cl.I 
a 
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on Day-2 and Day- ! 
-
i;.;i 
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Followed by 
"' = 
monitoring to Day 7d 
Q., 
-
-

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LIST OF ABBREVIATIONS
AE
adverse event
ALL
acute lymphoblastic leukemia
ANC
absolute neutrophil count
ASTCT
American Society for Transplantation and Cellular Therapy
BL
Burkitt lymphoma
BMI
body mass index
BTK
Bruton’s tyrosine kinase
CAR
chimeric antigen receptor 
CBC
complete blood count
CFR
Code of Federal Regulations
CI
confidence interval
CLL
chronic lymphocytic leukemia
CNS
central nervous system
CPF
cell processing facility 
CR
Complete response/remission 
CRO
contract research organization
CRP
C-reactive protein
CRS
cytokine release syndrome
CSF
cerebrospinal fluid
CT 
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
DLBCL
diffuse large B-cell lymphoma
DLT
dose-limiting toxicity
DOR
duration of response
DSMB
Data Safety Monitoring Board
ECG
electrocardiogram
ECHO
echocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EDC
electronic data capture
EORTC-QLQ-30
European Organisation for Research and Treatment of Cancer Quality of Life Cancer 
Patients Questionnaire
EQ-5D-5L
European Quality of Life 5-Dimension 5-Level Scale
eSAE
electronic serious adverse event 
EU
European Union
FAS
full analysis set
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GP
general practitioner

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GVHD
graft-versus-host disease
HCL
hairy cell leukemia
HCLc
classic hairy cell leukemia 
HCLv
variant hairy cell leukemia 
HCP
healthcare provider
HLH
hemophagocytic lymphohistiocytosis
IB
Investigator’s Brochure
ICANS
immune effector cell-associated neurotoxicity syndrome
ICF
informed consent form
ICH
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use
ID
identification
IEC
Independent Ethics Committee
IL
interleukin
IND
Investigational New Drug
IP
investigational product
IPM
Investigational Product Manual
IRB
Institutional Review Board
IV
intravenous(ly)
KM
Kaplan Meier
LDH
lactate dehydrogenase
LTFU
long-term follow-up
MCL
mantle cell lymphoma
mITT 
modified intent-to-treat
MRI
magnetic resonance imaging
MUGA
multigated acquisition scan
MZL
marginal zone lymphoma
NCI
National Cancer Institute
NHL
non-Hodgkin lymphoma
ORR
objective response rate
OS
overall survival
PBMC
peripheral blood mononuclear cell
PCR
polymerase chain reaction
PD
progressive disease
PFS
progression-free survival
PO
orally
PR
partial response/remission
PRO
patient-reported outcome
qPCR
quantitative polymerase chain reaction
QTc
corrected QT  

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r/r
relapsed/refractory
RCR
replication-competent retrovirus
RT
Richter transformation
SAE
serious adverse event
SAP
statistical analysis plan
SOA
schedule of assessments
SOC
standard of care
SRT
safety review team
SUSAR
suspected unexpected serious adverse reaction
TEAE
treatment-emergent adverse event
TNF
tumor necrosis factor
TTNT
time to next treatment
ULN
upper limit of normal
US
United States
VAS
visual analog scale
WBC
white blood cell
WM
Waldenstrom macroglobulinemia

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1.
INTRODUCTION
1.1.
Brexucabtagene Autoleucel
The brexucabtagene autoleucel chimeric antigen receptor (CAR) T-cell product consists of a 
single-chain antibody fragment against CD19 linked to the CD28 costimulatory and CD3ζ T-cell 
activation domains {Jackson 2016}. Following CAR engagement with CD19+ target cells, CD3ζ 
activation induces the downstream signaling cascade that leads to T-cell activation, proliferation, 
and acquisition of effector functions {Roberts 2018}. The intracellular CD28 domain provides a 
costimulatory signal that works in concert with the primary CD3ζ signal to augment T-cell 
function, including interleukin (IL)-2 production {Finney 1998}. Together, these signals 
stimulate proliferation of the CAR T cells and direct killing of target cells. In addition, activated 
T cells secrete cytokines, chemokines, and other molecules that can recruit and activate 
additional antitumor immune cells {Restifo 2012}.
Refer to the current Investigator’s Brochure (IB) for additional information on brexucabtagene 
autoleucel.
1.2.
Summary of Relevant Nonclinical and Clinical Studies With Brexucabtagene 
Autoleucel
1.2.1.
Nonclinical Studies With Brexucabtagene Autoleucel
Human T cells transduced with the vector carrying an anti-CD19 CAR construct identical to that 
used in the production of brexucabtagene autoleucel were previously evaluated for CAR 
expression, phenotypic markers, and cytokine production after co-culture with CD19+ target 
cells {Kochenderfer 2009}. In this previous study, transduced cells produced cytokines upon 
stimulation with CD19+ targets, but not with CD19– targets, and results of cytotoxicity assays 
demonstrated that anti-CD19 CAR T cells killed primary chronic lymphocytic leukemia (CLL) 
cells in a dose-dependent and CD19-specific manner.
Anti-murine CD19 CAR T cells were assessed using a mouse lymphoma model comprising 
immunocompetent C3H mice and syngeneic 38c13 B-cell lymphoma cells expressing murine 
CD19. Results showed that treatment with anti-murine CD19 CAR T cells eradicated established 
lymphoma masses and increased survival (up to 50 days) compared to control groups.
Refer to the current IB for additional information.
1.2.2.
Clinical Studies With Brexucabtagene Autoleucel
Brexucabtagene autoleucel is being evaluated for the treatment of B-cell leukemias and 
lymphomas. In 2020, results from the KTE-C19-102 (ZUMA-2) study led to the accelerated 
approval of brexucabtagene autoleucel by the United States (US) Food and Drug Administration 
(FDA) for the treatment of adult patients with relapsed/refractory (r/r) mantle cell lymphoma 
(MCL). The European Medicines Agency (EMA) also granted conditional approval of 
brexucabtagene autoleucel for the treatment of adult patients with r/r MCL after 2 or more lines 

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of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor. In 2021, based on the 
results from the KTE-C19-103 (ZUMA-3) study, brexucabtagene autoleucel received FDA 
approval for the treatment of adult patients with r/r B-cell precursor acute lymphoblastic 
leukemia (ALL).
ZUMA-2 (NCT0260313) was a single-arm, open-label, multicenter study in 82 adult subjects 
with r/r MCL. Among the 60 efficacy-evaluable subjects, the objective response rate was 
87% (52/60 subjects), including 37 subjects (62%) achieving a complete remission (CR). The 
median duration of response for subjects who achieved CR ranged from 1.9+ to 29.2+ months. 
The most common (≥ 10%) Grade 3 or higher adverse events (AEs) were anemia, neutropenia, 
thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, fever, 
hyponatremia, hypertension, infection with pathogen unspecified, pneumonia, hypocalcemia, and 
lymphopenia. Serious adverse reactions occurred in 66% of subjects.
ZUMA-3 (NCT02614066) was a single-arm, open-label, multicenter study in 78 adult subjects 
with r/r B-cell precursor ALL. Efficacy was established on the basis of CR within 3 months after 
brexucabtagene autoleucel infusion and the duration of CR. Twenty-eight (51.9%) of the 
54 efficacy-evaluable subjects achieved CR, and with a median follow-up for responders of 
7.1 months, the median duration of CR was not reached. The most common (≥ 10%) Grade 3 or 
4 AEs were fever, febrile neutropenia, hypotension, encephalopathy, cytokine release syndrome, 
hypoxia, and infection with pathogen unspecified.
Refer to the current IB for additional information on other ongoing clinical studies being 
conducted with brexucabtagene autoleucel.
1.3.
Disease Background
This Phase 2, multicenter, open-label, basket study aims to evaluate the efficacy of anti-CD19 
CAR T-cell therapy in adults with rare B-cell malignancies with a high unmet medical need, 
including r/r Waldenstrom macroglobulinemia (WM) {Grunenberg 2019}, r/r Richter 
transformation (RT) {Rossi 2018}, r/r Burkitt lymphoma (BL) {Short 2017, Tiacci 2015}, and 
r/r hairy cell leukemia (HCL) {Tiacci 2015}. 
Note: Substudies in WM and HCL were terminated early by the Sponsor, effective 21 June 
2023.
Despite advances in therapeutic options, outcomes for subjects with these rare B-cell 
malignancies remain poor. Commonly, these indications arise from the B-cell lineage expressing 
the transmembrane protein CD19, thus providing a potential therapeutic target which has been 
explored in other malignancies such as multiple subtypes of non-Hodgkin lymphoma (NHL), 
CLL or ALL {Davila 2016}. CD19 expression begins at the pro-B-cell stage and continues 
throughout B-cell differentiation {Anderson 1984, Nadler 1983, Uckun 1990, Uckun 1988}.
Two CD19-targeted CAR T-cell therapies have been developed by Kite – axicabtagene 
ciloleucel (YESCARTA®) and brexucabtagene autoleucel (TECARTUS®). These therapies 
consist of autologous patient T cells that have been engineered ex vivo to express a CAR 
targeting CD19 on the cell surface of normal and malignant B cells. Both therapies differ in that 

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during the brexucabtagene autoleucel manufacturing process the harvested T cells in the 
leukapheresis product are enriched by binding to magnetic beads coated with anti-CD4 and anti-
CD8 antibodies. This enrichment step is needed for use in certain B-cell malignancies in which 
circulating lymphoblasts are a common feature. Separating T cells from the CD19-expressing 
tumor cells ensures no circulating tumor cells are transduced, and prevents tumor cells from 
potentially driving expansion and exhaustion of the CAR T cells or causing relapse due to 
epitope masking {Ruella 2016, Ruella 2018}. Since circulating lymphoma/leukemia cells may be 
present in subjects diagnosed with the diseases being evaluated under study protocol 
KT-US-568-0138, brexucabtagene autoleucel was selected as the investigational therapy.
The background information and rationale for the investigation of brexucabtagene autoleucel in 
each indication is described in the respective substudy protocol.
1.3.1.
Disease Indication-specific Information
Refer to the respective sections of each substudy protocol for background information regarding 
the epidemiology (Section 1.1.1), diagnosis (Section 1.1.2), frontline treatment (Section 1.1.3) 
and second-line treatment (Section 1.1.4) of WM (substudy KT-US-568-0138-A), Section 1.1.3 
of RT (substudy KT-US-568-0138-B), BL (substudy KT-US-568-0138-C) and HCL (substudy 
KT-US-568-0138-D). 
Note: Substudies in WM and HCL were terminated early by the Sponsor, effective 21 June 
2023.
1.4.
Study Rationale
Treatment options for patients with r/r WM, r/r RT, r/r BL, and r/r HCL are limited and historical 
outcomes are poor.
For third line and beyond WM subjects, prior therapy must have included a BTK inhibitor. Also, 
chemotherapy and/or use of a proteasome inhibitor must have been attempted. For third line and 
beyond HCL, subjects must have received at least 2 prior lines of therapy, including at least a 
PNA and moxetumomab pasudotox (if eligible and available). For r/r RT and r/r BL subjects, no 
established standard of care exists, and mean survival is less than 12 months. For all study 
indications, no established standard of care exists, and only subjects who have exhausted the 
available approved treatment options will be included in this study. Accordingly, the unmet 
medical need for these subjects is significant.
Immunotherapy, which is based on the enhancement of an immune response against the tumor, is 
a promising approach to treat many cancer types. T cells play an important role in killing 
diseased cells throughout the body, but need to possess the appropriate tumor specificity, be 
present in sufficient numbers, and overcome any local immunosuppressive factors to be 
effective. CAR T cells may address these issues and are a promising approach for cancer 
therapy.

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Brexucabtagene autoleucel is an engineered autologous T-cell immunotherapy by which a 
patient’s own T cells are collected and subsequently genetically altered to recognize CD19 that is 
expressed on the cell surface of B-cell malignancies. In ZUMA-2 and ZUMA-3, which 
investigated the safety and efficacy of brexucabtagene autoleucel in adult patients with r/r MCL 
and r/r ALL, respectively, brexucabtagene autoleucel provided significant and clinically 
meaningful outcomes with a positive benefit/risk profile. Similar outcomes were attained with 
axicabtagene ciloleucel in adult NHL patients.
Accordingly, having shown significant clinical benefit of brexucabtagene autoleucel in subjects 
with more frequent B-cell malignancies, the goal of the KT-US-568-0138 study is to assess the 
safety and efficacy of brexucabtagene autoleucel in subjects diagnosed with relatively rare B-cell 
malignancies with high unmet medical need. As such, this study will assess the safety and 
efficacy of brexucabtagene autoleucel in subjects with r/r WM, r/r RT, r/r BL, and r/r HCL (with 
comparisons to historical controls).
Note: Substudies in WM and HCL were terminated early by the Sponsor, effective 21 June 
2023.
1.5.
Benefit/Risk Assessment for the Study
The positive benefit/risk profile of CD19-directed CAR T-cell therapies such as brexucabtagene 
autoleucel and axicabtagene ciloleucel has been established in various aggressive and indolent r/r 
NHLs, r/r MCL and r/r adult ALL, while currently under investigation in r/r pediatric ALL. The 
proposed indications are in alignment with the described expression of the CD19 antigen, and the 
well-established mechanism of action of brexucabtagene autoleucel.
The safety profile of brexucabtagene autoleucel and its administration as a single dose following 
lymphodepletion chemotherapy is well established, with most AEs occurring within 30 days of 
infusion. AEs, which can be severe (even fatal), are typically well defined, reversible (severe 
AEs), and manageable with no apparent long-term consequences other than B-cell aplasia in 
most individuals. The most common events reported with brexucabtagene autoleucel to date 
{Kite Pharma Inc 2021} include, but are not limited to, cytopenias, infections, CRS, and 
neurologic events. Strategies have been developed to monitor for early detection and manage the 
risks associated with these AEs.
Refer to the current version of the IB for a summary of the findings from nonclinical studies and 
the known and potential benefits and risks associated with brexucabtagene autoleucel T-cell 
therapy.
1.6.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory and local legal requirements.

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2.
OBJECTIVES AND ENDPOINTS
The primary and secondary objectives of the study and associated endpoints that are common to 
all the substudies are detailed in Table 3.
Additional substudy-specific objectives and endpoints are provided in Section 2 of each 
respective substudy protocol.
Table 3.
Objectives and Endpoints
Primary Objective
Primary Endpoint
•
To evaluate the efficacy of brexucabtagene 
autoleucel in subjects with rare B-cell 
malignancies, by determining the Response Rates 
as defined within the substudies by central 
assessment
•
Response rates by central assessment as defined in 
each substudy 
Secondary Objectives
Secondary Endpoints
•
To evaluate the CR by central assessment as 
defined within each substudy.
•
CR rate by central assessment as defined in each 
substudy 
•
Determine response durability
•
DOR
•
Determine survival status 
•
OS
•
Determine survival status without progression
•
PFS
•
Determine the TTNT after administration of 
brexucabtagene autoleucel
•
TTNT defined as the time from enrollment (for 
Full Analysis Set [FAS]) or brexucabtagene 
autoleucel infusion (for modified intention to treat 
[mITT]) to the initiation of subsequent anticancer 
therapy/treatment
•
Determine the time to first response
•
Time to first response from brexucabtagene 
autoleucel infusion to the first response as defined 
in the substudy
•
Determine the time to best response
•
Time to best response from brexucabtagene 
autoleucel infusion to the best response as defined 
in the substudy
•
To evaluate the safety of brexucabtagene 
autoleucel in subjects with rare B-cell 
malignancies
•
Incidence of AEs and CTCAE grade changes in 
safety laboratory values
•
Incidence of AEs defined as DLTs
•
Incidence of antibodies to brexucabtagene 
autoleucel (immunogenicity)
•
Incidence of RCR in PBMCs at baseline and after 
brexucabtagene autoleucel infusion
•
To evaluate the effect of brexucabtagene 
autoleucel on patient reported outcomes (PROs) 
and quality of life assessments
•
Changes over time in the PRO assessment 
domains, EORTC-QLQ-C30 and EQ5D-5L

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Exploratory Objectives
Exploratory Endpoints
•
To evaluate the pharmacokinetic profile of 
brexucabtagene autoleucel in subjects with rare B-
cell malignancies
•
Levels of CAR T cells in blood and association 
with clinical outcomes (efficacy and toxicity)
•
Levels of blood B cells and relationship with 
pharmacokinetic profile
•
To evaluate the pharmacodynamic profile of 
brexucabtagene autoleucel in subjects with rare B-
cell malignancies
•
Levels of serum analytes (including cytokines and 
chemokines) in blood and relationship with 
toxicity (eg, CRS and neurotoxicity)
•
To explore the phenotypic and functional 
characteristics of brexucabtagene autoleucel in 
subjects with rare B-cell malignancies
•
Product characteristics, including T-cell 
phenotypes and relationship with clinical outcome
•
To explore immunogenicity against 
brexucabtagene autoleucel
•
Incidence of anti-brexucabtagene autoleucel CAR 
reactivity
Abbreviations: AE, adverse event; CAR, chimeric antigen receptor; CR, complete response; CRS, cytokine release syndrome; 
CTCAE, Common Terminology Criteria for Adverse Events; DLT, dose limiting toxicity; DOR, duration of response; FAS, full 
analysis set; mITT, modified intent-to-treat; OS, overall survival; PFS, progression-free survival; PBMC, peripheral blood 
mononuclear cell; RCR, replication-competent retrovirus; TTNT, time to next treatment.

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3.
STUDY DESIGN
3.1.
Study Design
This Phase 2, open-label, multi-center study will use a basket study design with individual 
indication-specific substudies for r/r WM, r/r RT, r/r BL and r/r HCL.
Note: Substudies in WM and HCL were terminated early by the Sponsor, effective 21 June 
2023.
This master protocol contains details regarding all elements of the study that are common across 
each of the indications. In contrast, each of the separate substudy protocols contain additional 
information that is unique to an individual indication (ie, WM, RT, BL or HCL). A 
substudy-specific schedule of assessments (SOA) is provided in each of the respective substudy 
protocols. Both the KT-US-568-0138 master protocol and relevant substudy protocol should be 
referenced in parallel. The study is designed to have the flexibility to independently open and 
close individual substudies.
Initially, 1 subject will be enrolled and infused per substudy. After the first subject is enrolled 
and infused, no additional subjects will be enrolled in an individual substudy until the first 
subject has been monitored for at least 28 days after the brexucabtagene autoleucel infusion. 
Subsequently, an additional 2 subjects in each substudy can be enrolled in parallel. After these 
3 initial subjects in a substudy have undergone evaluation for at least 28 days after the 
brexucabtagene autoleucel infusion, a Safety Review team (Section 8.10.2) will review the safety 
data and make recommendations on further study conduct, progression, and/or dose modification 
in each substudy.
The screening period will have a duration of up to 28 days and will begin on the date a subject 
signs the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved 
informed consent form (ICF) and continues through confirmation of enrollment (ie, 
commencement of leukapheresis), or until a subject withdraws consent before enrollment, or it is 
determined that a subject is a screen failure (ie, does not meet the study eligibility criteria; see 
Section 4.2).
If required to reduce risk of BTK inhibitor withdrawal symptoms and IgM flare, subjects in the 
WM substudy already receiving a BTK inhibitor will be allowed to receive ibrutinib through 
screening and up to 5 half-lives (30 hours) prior to starting lymphodepleting chemotherapy. 
Subjects in the RT substudy, if already receiving a BTK inhibitor, may also receive ibrutinib 
through screening and leukapheresis at the discretion of the investigator.
After enrollment/leukapheresis, subjects in the RT and BL substudies may receive optional 
protocol-defined bridging therapy, at the investigator’s discretion. If bridging therapy has been 
administered, a new baseline disease assessment is required, as outlined in the SOA of the 
respective substudies.

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Subjects will undergo lymphodepleting chemotherapy with fludarabine (30 mg/m2/day) and 
cyclophosphamide (500 mg/m2/day) for 3 consecutive days from Day -5 to Day -3 (see Section 5 
for details) followed by 2 rest days (Day -2 and Day -1).
On Day 0, subjects will receive a single infusion of brexucabtagene autoleucel administered 
intravenously (IV) at a target dose of either 2 × 106 anti-CD19 CAR T cells/kg or 
1 × 106 anti-CD19 CAR T cells/kg, depending on the safety review team recommended dose (or 
a flat dose of 2 × 108 or 1 × 108, respectively, anti-CD19 CAR T cells in subjects > 100 kg). In 
combination with an initial mandatory hospitalization period of at least 7 days; this is considered 
as the treatment period (refer to Section 12.4 for country-specific post-infusion monitoring 
requirements). Subjects will be required to stay within close vicinity to the clinic, with 
immediate access to urgent care by the investigator until after Day 28.
After completing the treatment period, all subjects will be followed in the post-treatment 
follow-up period. Counting from Day 0 (the day of brexucabtagene autoleucel infusion), subjects 
will return to the clinic for evaluation at Day 14 and Day 28, Week 8, Month 3, and then every 
3 months up to Month 12. Additional substudy-specific visits will occur as outlined below:
•
RT and BL: Month 18 and Month 24
•
WM and HCL: every 6 months up to 36 months, and then annually up to 60 months
Thereafter, subjects will transition to a separate long-term follow-up (LTFU) study 
(KT-US-982-5968) to continue follow-up out to 15 years (refer to Section 3.5).
Disease response will be assessed as appropriate to each indication and as described in each 
substudy protocol.
The study schema is provided in Figure 1.
An SOA for each indication is provided in the respective substudy protocol.
3.1.1.
Rationale for Study Design Elements
The rationale for the study design elements that apply universally across each of the specified 
disease indications are detailed below. For study design elements that are unique to a specific 
substudy (eg, use of ibrutinib in WM and RT), a detailed rationale is provided within the 
respective substudy protocol.
3.1.1.1.
Rationale for Lymphodepleting Chemotherapy
Lymphodepleting chemotherapy regimens have been shown to have multiple mechanisms 
benefiting CAR T-cell therapy, including eliminating sinks for homeostatic cytokines, such as 
IL-2, IL-7, and IL-15, eradicating immunosuppressive elements, such as regulatory T cells and 
myeloid-derived suppressor cells, inducing costimulatory molecules and downregulating 
indoleamine 2,3-dioxygenase in tumor cells, and promoting expansion, function, and persistence 
of adoptively transferred T cells {Becnel 2019}. Furthermore, studies have indicated that 
CAR T-cell expansion over the first month may be associated with response and/or durability of 
the CAR T-cell treatment{Neelapu 2017a}.

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The combination of cyclophosphamide and fludarabine is a potent lymphodepleting regimen 
{Gattinoni 2005}. A combination of cyclophosphamide (500 mg/m2/day) and 
fludarabine (30 mg/m2/day) administered on Day -5, Day -4 and Day -3 prior to CAR T-cell 
infusion has been shown to be efficacious and safe in in previous studies {Neelapu 2017b}.
3.1.1.2.
Rationale for use of Brexucabtagene Autoleucel
Two CD19-targeted CAR T-cell therapies (Axicabtagene ciloleucel [YESCARTA®] and 
brexucabtagene autoleucel [TECARTUS®]) have been developed by Kite. These therapies 
consist of autologous patient T cells that have been engineered ex vivo to express a CAR 
targeting CD19 on the cell surface of normal and malignant B cells. The 2 therapies differ in that 
during the brexucabtagene autoleucel manufacturing process the harvested T cells in the 
leukapheresis product are enriched by binding to magnetic beads coated with anti-CD4 and 
anti-CD8 antibodies. This enrichment step is needed for use in certain B-cell malignancies in 
which circulating lymphoblasts are a common feature. Separating T cells from the 
CD19-expressing tumor cells ensures no circulating tumor cells are transduced and prevents 
tumor cells from potentially driving expansion and exhaustion of the CAR T cells or causing 
relapse due to epitope masking {Ruella 2018}. Since circulating lymphoma/leukemia cells may 
be present in subjects diagnosed with the diseases being evaluated under study protocol 
KT-US-568-0138, brexucabtagene autoleucel was selected as the investigational therapy.
3.1.1.3.
Rationale for the Starting Dose of Brexucabtagene Autoleucel
Three dose levels for brexucabtagene autoleucel (0.5 × 106, 1 × 106, and 2 × 106 anti-CD19 CAR 
T cells/kg) have been explored in several indications including r/r MCL (ZUMA-2), adult 
(ZUMA-3) and pediatric r/r ALL/NHL (ZUMA-4). In this study, the starting dose of 
2 × 106 anti-CD19 CAR T cells/kg has been selected as a dose with a known efficacy profile for 
adults with r/r MCL and an established safety profile{TECARTUS 2021}.
While the 0.5 × 106 anti-CD19 CAR T cells/kg dose explored in the ZUMA-3 study 
demonstrated diminished efficacy compared to the higher dose levels, efficacy has been shown 
with both higher doses. The safety profile of brexucabtagene autoleucel has been well 
established for dose levels of 1 × 106 and 2 × 106 anti-CD19 CAR T cells/kg dose through the 
acquisition of extensive clinical study data (as of 23 January 2022, a total of 295 subjects had 
received brexucabtagene autoleucel in clinical studies), as well as in the clinical post-approval 
setting (as of 23 January 2022, the estimated exposure in the commercial setting was 661 patients 
and an additional 168 patients in the compassionate use setting). Moreover, clinical data on 
axicabtagene ciloleucel in refractory diffuse large B-cell lymphoma (DLBCL) from ZUMA-1 
(NCT02348216) and second line DLBCL in ZUMA-7 (NCT03391466) suggest that the dose of 
2 × 106 anti-CD19 CAR T cells/kg is both safe and efficacious in aggressive NHL subtypes 
similar to RT and BL {Chen 2019}. WM and HCL are indolent NHL subtypes with WM, having 
biological similarities to marginal zone lymphoma (MZL) {Rinaldi 2011} with partially 
overlapping genomic profiles {Sun 2016}. MZL was studied in ZUMA-5 using the 
2 × 106 anti-CD19 CAR T cells/kg dose and showed a positive benefit/risk profile. HCL is 
considered biologically distinct, but shows similar indolent characteristics as follicular 
lymphoma, MZL, and MCL for which the dose of 2 × 106 anti-CD19 CAR T cells/kg is well 
established{Berger 2005, Jacobson 2021a, Jacobson 2021b, YESCARTA 2021}.

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To further evaluate the safety of brexucabtagene autoleucel in these rare indications, a Safety 
Review Team (SRT) will assess the safety data of the first 3 to 6 patients included in each 
substudy as an additional safety measure. Each of the  indications (ie, WM, RT, BL, and HCL) 
are considered as distinct diseases and, as such, each substudy will be evaluated independently in 
regard to SRT and subsequent Data Safety Monitoring Board (DSMB) assessments. However, 
should a new safety signal be observed in any of the first 3 patients within each substudy during 
the dose limiting toxicity (DLT) period, the SRT may recommend dose de-escalation. Further 
details including DLT definitions are provided in Section 8.1.2.
3.2.
Study Treatments
Study treatments that apply to all of the disease indications are described here. For treatments 
that are unique to a specific substudy, details are provided within the respective substudy 
protocol. This includes optional bridging therapy (RT and BL subjects only), and ibrutinib as an 
optional treatment option through screening and leukapheresis (WM and RT subjects only).
3.2.1.
Leukapheresis
Subjects will undergo leukapheresis to obtain PBMCs for the manufacture of brexucabtagene 
autoleucel. Approximately 12 to 15-liters of apheresis material will be processed with a goal to 
target approximately 5 × 109 to 10 × 109 mononuclear cells. Leukapheresed cells obtained from 
subjects at participating study sites will be packaged for expedited shipment to the cell 
processing facility (CPF) for the manufacture of brexucabtagene autoleucel, as described in the 
Investigational Product Manual (IPM). Refer to Section 7.5.1 for more information regarding the 
leukapheresis procedure.
3.2.2.
Bridging Therapy (Optional; for RT and BL Subjects Only)
Bridging therapy is applicable to RT and BL subjects only. Please refer to Section 7.2 of the RT 
substudy protocol, and Section 7.1 of the BL substudy protocol for details.
3.2.3.
Lymphodepleting Chemotherapy
All subjects will receive lymphodepleting chemotherapy with cyclophosphamide 
(500 mg/m2/day) and fludarabine (30 mg/m2/day) administered on Day −5, Day −4, and Day −3, 
followed by 2 rest days (Day -2 and Day -1).
If, after the start of the lymphodepletion regimen, the creatinine clearance falls below 
70 mL/min, subsequent doses of fludarabine will be adjusted according to institutional 
guidelines.
Refer to Section 7.5.4 for details about the lymphodepleting chemotherapy procedures.

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3.2.4.
Brexucabtagene Autoleucel
On Day 0, a single infusion of brexucabtagene autoleucel will be administered IV at a target dose 
of 2 × 106 anti-CD19 CAR T cells/kg or a maximum flat dose of 2 × 108 anti-CD19 CAR T cells 
for subjects weighing > 100 kg. In case of DLTs, the SRT may recommend the dose 
administered to be reduced to 1 × 106 anti-CD19 CAR T cells/kg or a flat dose of 
1 × 108 anti-CD19 CAR T cells in subjects > 100 kg.
Refer to Section 8.10.1 for details of the SRT and Section 8.1.2 for details of DLTs.
Instructions associated with administration of brexucabtagene autoleucel are provided in 
Section 7.6.
Brexucabtagene autoleucel is the Investigational Medicinal Product (IMP) being assessed in this 
study (Appendix 12.9). Brexucabtagene autoleucel has been granted marketing authorization in 
numerous regions, including the US, EU, Canada, Great Britain, and Switzerland, and will be 
used in this study for new indications.
3.2.5.
Auxiliary Medicinal Products
All other medications described throughout the Master Protocol and subprotocols are considered 
auxiliary medicinal products. Auxiliary products are used in accordance with their authorized 
product information in any given country (eg, Package Insert, SmPC) and institutional 
guidelines. The identified and potential risks, and risk minimization, should be managed as 
described within either the authorized product information and/or in accordance with 
institutional guidelines. A list of all auxiliary medicinal products is provided in Appendix 12.9.
3.3.
Duration of Subject Participation
The duration of treatment for individual subjects will vary depending on their indication, 
screening requirements, response to treatment, and survival status. Subjects with RT and BL will 
be followed for approximately 24 months and subjects with WM and HCL will be followed for 
approximately 60 months. Thereafter, subjects who received brexucabtagene autoleucel will 
transition to the separate Kite LTFU study (KT-US-982-5968) to continue follow-up out to 
15 years (refer to Section 3.5).
Subjects who were enrolled but who did not receive brexucabtagene autoleucel will also be 
followed for the durations described above but will not be required to transition to the LTFU 
study. Of note, such subjects will have reduced follow-up requirements excluding disease 
response assessments but including survival status and subsequent anticancer therapy, as outlined 
in Section 7.7.3 and Section 7.11.
3.4.
End-of-Study Definition
The end-of-study is defined for each substudy as the time when the last remaining  subject within 
the specific substudy has completed their last visit (last patient last visit; LPLV) and either 
transitions to a separate LTFU study (Section 3.5), or when the last remaining subject, while still 

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a participant in the specific substudy, is considered lost to follow-up, withdraws full consent, or 
dies, whichever occurs earlier. In addition, the sponsor may decide to terminate an individual 
substudy or the whole study at any time.
3.5.
Long-term Follow-up
Subjects who have received an infusion of brexucabtagene autoleucel and who have completed 
the Post Treatment Follow Up Period either at Month 24 (RT and BL) or Month 60 (WM and 
HCL), or if a substudy is terminated early by Kite (eg, due to lack of efficacy), will transition to 
a separate Kite LTFU study (KT-US-982-5968).
Subjects will continue to be monitored for occurrence of late-onset targeted AEs/serious AEs 
(SAEs) suspected to be possibly related to brexucabtagene autoleucel and presence of 
replication-competent retrovirus (RCR) and vector elements, as appropriate, for up to 15 years 
from the time of the initial brexucabtagene autoleucel infusion (refer also to Section 7.7). In the 
LTFU study, subjects will continue assessments at time points contiguous with their time point 
in this study. The need for prolonged follow-up is based on the potential persistence of gene 
transfer vectors in treated subjects and a need to understand and mitigate the potential risks of 
late onset AEs that could be the potential consequence of this emerging technology.
3.6.
Study Discontinuation Criteria
The SRT and/or DSMB can make a recommendation to the sponsor to discontinue the study 
early based on the guidelines in the SRT and DSMB charters, respectively. The DSMB will 
review the data accrued from each substudy and provide ongoing recommendations on study 
conduct to the Kite Head of Cell Therapy Clinical Development (or designee). The 
recommendations may include continuing a substudy without modification, continuing a 
substudy with modification, stopping a substudy, or communicating that additional data are 
required for review.
Refer to Section 8.10.1 (SRT) and/or Section 8.10.2 (DSMB) for more information. The sponsor 
reserves the right to terminate this study at any time for reasonable medical or administrative 
reasons.
3.7.
Number of Participating Study Sites
Approximately 25 study sites located in the US and Europe will participate in this study. During 
the conduct of the study, additional regions, countries, or study sites may be added, as necessary.
3.8.
Source Data
The source data for this study will be obtained from original documents/records and central 
laboratory, local laboratory, specialty laboratory (for pharmacokinetics and/or 
pharmacodynamics data), and/or medical record data.

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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 90 subjects will be enrolled and treated across the separate substudies.
Approximately 60 subjects with r/r WM who have received at least 2 lines of prior therapy will 
be enrolled and treated. Additional WM-specific eligibility criteria are detailed in the WM 
substudy protocol.
Approximately 60 subjects with r/r RT who have received 1 line of prior therapy will be enrolled 
and treated. Additional RT-specific eligibility criteria are detailed in the RT substudy protocol.
Approximately 30 subjects with r/r BL who have received at least 1 line of prior therapy will be 
enrolled and treated. Additional BL-specific eligibility criteria are detailed in the BL substudy 
protocol.
Approximately 20 subjects with r/r HCL who have received at least 2 lines of prior therapy will 
be enrolled and treated. Additional HCL-specific eligibility criteria are detailed in the HCL 
substudy protocol.
Note: Substudies in WM and HCL were terminated early by the Sponsor, effective 21 June 
2023
4.2.
Eligibility Criteria
4.2.1.
Inclusion Criteria Common to all Indications
To be enrolled in the study, subjects must meet all the following inclusion criteria that are 
common to each of the substudies. Subjects must also meet additional disease specific- inclusion 
criteria, as specified in Section 4.2.1 of the respective substudy protocols.
1)
Male or female 18 years of age or older and who have provided written informed consent
2)
Presence of toxicities due to prior therapy must be stable and recovered to Grade 1 or lower 
(except for clinically nonsignificant toxicities such as alopecia)
3)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4)
Adequate hematological function (unless lower values are attributable to underlying 
disease) as indicated by:
Absolute neutrophil count (ANC) ≥ 500/μL
Platelet count ≥ 50,000/μL
Hemoglobin level ≥ 8 g/dL

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5)
Absolute lymphocyte count ≥ 100/μL
6)
Adequate renal, hepatic, pulmonary, and cardiac function defined as:
Creatinine clearance (as estimated by Cockcroft-Gault formula) ≥ 60 mL/min
Serum alanine aminotransferase and aspartate aminotransferase levels ≤ 2.5 × upper limit 
of normal (ULN) or ≤ 5 × ULN if documented liver involvement
Total bilirubin levels ≤ 1.5 × ULN, except in subjects with Gilbert’s syndrome
Cardiac ejection fraction ≥ 50% and no evidence of pericardial effusion as determined by 
an echocardiogram (ECHO) or multigated acquisition scan (MUGA) and no clinically 
significant electrocardiogram (ECG) findings
No clinically significant pleural effusion
Baseline oxygen saturation > 92% on room air
7)
The following washout periods must be satisfied prior to leukapheresis/enrollment:
Corticosteroid therapy at a pharmacologic dose (≥ 5 mg/day of prednisone or equivalent 
doses of other corticosteroids) must be avoided for 7 days before leukapheresis
BTK inhibitors (eg, ibrutinib or acalabrutinib), must be avoided at least 1 week or 
5 half-lives, whichever is shorter, before leukapheresis unless otherwise specified in the 
subprotocols
Anti-neoplastic drugs used in previous therapy must be avoided within 1 week or 
5 half-lives (whichever is shorter) prior to leukapheresis
Systemic inhibitory/stimulatory immune checkpoint molecule therapy (eg, ipilimumab, 
nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists) must be 
avoided at least 3 half-lives prior to leukapheresis
Alemtuzumab must be avoided at least 6 months prior to enrollment
PEG-asparaginase must be avoided at least 3 weeks prior to enrollment
Cladribine and pentostatin must be avoided 3 months prior to enrollment
Donor lymphocyte infusion within 28 days prior to enrollment
Any treatment with immunosuppressive antibody used within 4 weeks prior to enrollment 
(eg, anti-CD20, anti-tumor necrosis factor [TNF], anti-interleukin [IL] 6 or anti-IL6 
receptor) unless this treatment is included in prior or bridging regimens, in which case a 
washout period of 7 days is required prior to leukapheresis

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8)
Female subjects of childbearing potential must have a negative serum or urine pregnancy 
test (females who have undergone surgical sterilization or who have been postmenopausal 
for at least 2 years are not considered to be of childbearing potential)
4.2.2.
Exclusion Criteria Common to all Indications
Subjects enrolled in the study must not meet any of the following exclusion criteria that are 
common to all indications. In addition, subjects must also not meet any of the disease -specific 
exclusion criteria, detailed in the respective substudy protocols:
1)
Prior CAR therapy or other genetically modified T-cell therapy
2)
Prior treatment with any anti-CD19 therapy
3)
History of severe immediate hypersensitivity reaction attributed to aminoglycosides
4)
History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine
5)
Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or 
requiring IV antimicrobials for management. Simple urinary tract infection and 
uncomplicated bacterial pharyngitis are permitted if responding to active treatment. 
Patients with a simple urinary tract infection and uncomplicated bacterial pharyngitis and 
responding to active treatment are eligible only if the patient satisfies the criteria of being 
afebrile (ie, temperature lower than 38oC) for at least 24 hours prior to the investigator 
confirming a patient’s eligibility
6)
HIV-positive patients, unless taking appropriate anti-HIV medications, having an 
undetectable viral load by quantitative polymerase chain reaction (qPCR) and a CD4 count 
> 200 cells/uL
7)
Acute or chronic active hepatitis B or hepatitis C infection. Subjects with a history of 
hepatitis infection must have cleared their infection as determined by standard serological 
and genetic testing per current Infectious Diseases Society of America guidelines or 
applicable country guidelines
8)
Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling 
Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central 
venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted
9)
History or presence of detectable cerebrospinal fluid (CSF) malignant cells or brain 
metastases, unless otherwise specified in the substudy eligibility criteria
10)
History or presence of central nervous system (CNS) disorder, such as cerebrovascular 
ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS 
involvement, posterior reversible encephalopathy syndrome, or cerebral edema with 
confirmed structural defects by appropriate imaging. History of stroke or transient ischemic 
attack within 12 months before enrollment. Subjects with seizure disorders requiring active 
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11)
Presence of cardiac atrial or cardiac ventricular lymphoma involvement
12)
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other 
clinically significant cardiac disease within 12 months before enrollment
13)
Requirement for urgent therapy due to tumor mass effects (eg, blood vessel compression, 
bowel obstruction, or transmural gastric involvement)
14)
Presence of primary immunodeficiency
15)
History of autoimmune disease (eg, Crohn’s disease, rheumatoid arthritis, systemic lupus) 
resulting in end organ injury or requiring systemic immunosuppression/systemic disease 
modifying agents within the last 2 years
16)
History of deep vein thrombosis or pulmonary embolism requiring therapeutic 
anticoagulation within 6 months before enrollment
17)
Any medical condition likely to interfere with assessment of safety or efficacy of study 
treatment
18)
History of severe immediate hypersensitivity reaction to any of the agents/excipients used 
in this study
19)
Live vaccine ≤ 6 weeks before the planned start of the lymphodepleting chemotherapy 
regimen and anticipation of need for such a vaccine during the first 12 months after 
brexucabtagene autoleucel infusion
20)
Females who are pregnant or breastfeeding (because of the potentially dangerous effects of 
the preparative chemotherapy on the fetus or infant). Females who have undergone surgical 
sterilization or who have been postmenopausal for at least 2 years are not considered to be 
of childbearing potential
21)
Not willing to practice birth control from the time of consent through 12 months after 
completion of the brexucabtagene autoleucel infusion
22)
In the investigator’s judgment, the subject is unlikely to complete all study-specific visits 
or procedures, including follow-up visits, or comply with the study requirements for 
participation
4.3.
Subject Withdrawal
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the physician or at their institution.
Subjects can decline to continue receiving protocol-required treatment and/or other 
study-specific procedures at any time during the study but continue to participate in certain 
follow-up elements of the study (Section 7.12). This is referred to as partial withdrawal of 
consent. Refer to Section 7.12 for instructions on follow-up and data to be collected.

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Withdrawal of full consent from the study means that the subject does not wish to receive further 
protocol-required treatment or undergo study-specific procedures, and the subject does not wish 
to continue further study follow-up. Subject data collected up to withdrawal of consent will be 
retained and included in the analysis of the study and, where permitted by local regulations, 
publicly available data (death records) can be included after withdrawal of consent. The 
investigator is to discuss with the subject appropriate procedures for withdrawal from the study.
As part of the study, sites may be asked to conduct searches of public records, such as those 
establishing survival status, if available and per local guidance and regulations, to obtain survival 
data for any subject for whom the survival status is not known. Moreover, per local guidance and 
regulations, sites may be also asked to retrieve autopsy reports to confirm status of disease at the 
time of death.
The investigator and/or sponsor can also decide to withdraw a subject from the investigational 
product (IP) and/or other protocol-required therapies, study-specific procedures, or the study as a 
whole at any time before study completion.
4.3.1.
Reasons for Removal From Treatment
Reasons for removal of a subject from the protocol-required treatment or study-specific 
procedures include any of the following:
•
AE (eg. an AE occurring prior to dosing, such as uncontrolled infections, stroke, bleeding 
etc., resulting in the subject no longer being eligible to proceed to dosing with 
brexucabtagene autoleucel or an AE occurring post-dosing precluding further study-specific 
procedures per Investigator discretion)
•
Withdrawal by subject
•
Investigational medicinal product (IMP) not available (eg, including, but not limited to, 
manufacturing failure or IMP with reduced cell viability (out of specification))
•
Lost to follow-up
•
Death
•
Termination of the substudy/study by the sponsor
•
Other (eg, noncompliance)
4.3.2.
Reasons for Removal From Study
Reasons for removal of a subject from the study are as follows:
•
Withdrawal by subject
•
Lost to follow-up

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•
Death
•
Termination of the substudy/study by the sponsor
•
Other (eg, investigator decision or noncompliance. Investigator decision for removal of 
patient from the study can be justified in cases where the potential risks of continuing the 
study treatment(s) and protocol-required assessments outweigh the potential benefit for an 
individual patient posing unacceptable safety risks and/or affect assessments of the clinical 
status to a significant degree)
4.4.
Replacement of Subjects
Subjects will continue to be enrolled until the specified number of subjects receiving the SRT 
recommended dose is attained in the DLT-evaluable or the modified intent-to-treat (mITT) set 
(subjects who discontinued before the DLT assessment will be replaced). Subjects who have a 
DLT assessment and later discontinue before the end of study will not be replaced. Refer to 
Section 9.6.5 for the definition of the DLT-evaluable or mITT set.

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5.
STUDY TREATMENT
5.1.
Description of Study Treatment
5.1.1.
Bridging Chemotherapy
Bridging therapy is only applicable to RT and BL subjects. Please refer to Section 7.2 of the 
respective substudy protocols for details.
5.1.2.
Lymphodepleting Chemotherapy
Lymphodepleting chemotherapy will be used to induce lymphocyte depletion and create an 
optimal environment for the in vivo expansion of brexucabtagene autoleucel. The 
lymphodepleting regimen used for this study will be fludarabine and cyclophosphamide.
Lymphodepleting chemotherapy will be supplied by the study site. Refer to the current product 
label for guidance on packaging, storage, preparation, administration and toxicity management 
associated with the administration of the chemotherapy agents described below. Any 
consideration for changes to the lymphodepleting chemotherapy dose should be discussed with 
the Kite medical monitor.
5.1.2.1.
Fludarabine
Fludarabine phosphate is a synthetic purine nucleoside that differs from physiologic nucleosides 
in that the sugar moiety is arabinose instead of ribose or deoxyribose. Fludarabine is a purine 
antagonist antimetabolite.
If, after the start of the lymphodepletion regimen, the creatinine clearance falls below 
70 mL/min, subsequent doses of fludarabine will be adjusted according to institutional 
guidelines.
Refer to the most recent version of the package insert for specific details surrounding the 
administration of fludarabine.
5.1.2.2.
Cyclophosphamide
Cyclophosphamide is a nitrogen mustard-derivative alkylating agent. Following conversion to 
active metabolites in the liver, cyclophosphamide functions as an alkylating agent; the drug also 
possesses potent immunosuppressive activity. The serum half-life after IV administration ranges 
from 3-12 hours; the drug and/or its metabolites can be detected in the serum for up to 72 hours 
after administration.
Refer to the most recent version of the package insert for specific details surrounding the 
administration of cyclophosphamide.

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Mesna (sodium-2-mercaptoethanesulfonate; C2H5NaO3S2) is a detoxifying agent used to reduce 
the risk ofhemonhagic cystitis induced by chemotherapy. 
Mesna will be administered around the time of the cyclophosphamide dose according to 
institutional standards. 
Refer to the most recent version of the brexucabtagene autoleucel package inse1i for specific 
details sunounding the administration of mesna. 
5.1.3. 
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5.2.
Packaging, Labeling, Storage, and Handling of Study Treatment
5.2.1.
Brexucabtagene Autoleucel Packaging, Labeling, Storage, and Handling
Refer to the IPM for details about brexucabtagene autoleucel formulation, packaging and 
labeling, instructions for storage and handling of brexucabtagene autoleucel, and ordering of 
clinical supplies.
5.3.
Dosage and Administration
Refer to Section 3.2.4 for brexucabtagene autoleucel planned dose levels. Refer to Section 7.6.2 
for assessments and procedures to be performed on the day of brexucabtagene autoleucel 
administration.
Refer to the IPM for details and instructions on administration of brexucabtagene autoleucel.
Administration or dosing errors (eg, whether the complete volume in the bag was administered to 
the subject) should be documented in the subject’s source documentation and respective 
electronic case report form (eCRF).
5.4.
Prior and Concomitant Medications
During the study, investigators may prescribe any concomitant medications or treatment deemed 
necessary to provide adequate supportive care, including growth factor support (eg, granulocyte 
colony-stimulating factor), routine anti-emetic prophylaxis, and anti-HIV medication, except 
those medications listed in Section 5.5.
5.5.
Excluded Medications
5.5.1.
Washout Periods Prior to Leukapheresis/Enrollment
The following washout periods must be satisfied prior to leukapheresis/enrollment:
•
Corticosteroid therapy at a pharmacologic dose (≥ 5 mg/day of prednisone or equivalent 
doses of other corticosteroids) must be avoided for 7 days before leukapheresis.  
•
Systemic corticosteroids must be avoided as premedication in subjects for whom CT scans 
with contrast are contraindicated (eg, subjects with contrast allergy or impaired renal 
clearance) if the administration is within 7 days before leukapheresis or 5 days before 
brexucabtagene autoleucel administration (washout period). 
•
BTK inhibitors (eg, ibrutinib or acalabrutinib) must be avoided at least 1 week or 
5 half-lives, whichever is shorter, before leukapheresis unless otherwise specified in the 
subprotocols
•
Anti-neoplastic drugs used for prior therapy must be avoided within 1 week or 5 half-lives 
(whichever is shorter) prior to leukapheresis

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•
Systemic inhibitory/stimulatory immune checkpoint molecule therapy (eg, ipilimumab, 
nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists) must be avoided 
at least 3 half-lives prior to leukapheresis
•
Alemtuzumab must be avoided at least 6 months prior to enrollment
•
PEG-asparaginase must be avoided at least 3 weeks prior to enrollment
•
Cladribine and pentostatin must be avoided 3 months prior to enrollment
•
Donor lymphocyte infusion within 28 days prior to enrollment
•
Any treatment with immunosuppressive antibody used within 4 weeks prior to enrollment 
(eg, anti-CD20, anti-TNF, anti-IL 6 or anti-IL6 receptor) unless this treatment is included in 
prior or bridging regimens, in which case a washout period of 7 days is required prior to 
leukapheresis
5.5.2.
Excluded Medications or Medications to be Used With Caution After 
Leukapheresis/Enrollment
Corticosteroid therapy at a pharmacologic dose (≥ 5 mg/day of prednisone or equivalent doses of 
other corticosteroids) should be avoided for 5 days before infusion of brexucabtagene autoleucel.
Moreover, corticosteroids and other immunosuppressive drugs should also be avoided for 
3 months after brexucabtagene autoleucel administration unless used to manage brexucabtagene 
autoleucel-related toxicities or discussed with the Kite medical monitor.
Vaccination with live viral vaccines is not recommended for at least 6 weeks prior to the start of 
lymphodepleting chemotherapy, during brexucabtagene autoleucel treatment, and for 12 months 
after treatment with brexucabtagene autoleucel. Please refer to the current IB for additional 
information about vaccination, including COVID-19 vaccines.
Therapeutic doses of systemic anticoagulants, such as unfractionated heparin and low-molecular 
weight heparin, should be avoided whenever possible for subjects who are at risk of bleeding due 
to thrombocytopenia.
Treatments for underlying disease, such as chemotherapy, immunotherapy, targeted agents, 
radiation, high-dose corticosteroids (other than those defined/allowed in this master protocol and 
substudy protocols), and other investigational agents are prohibited, except as needed for 
treatment of disease progression after brexucabtagene autoleucel administration.
If permissibility of a specific medication/treatment is in question, contact the Kite medical 
monitor. Please refer to the IB for additional information about excluded medications.

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5.6.
Accountability and Return of Study Treatment
5.6.1.
Accountability of Study Treatment
Refer to the IPM for details about accountability of brexucabtagene autoleucel.
5.6.2.
Return or Disposal of Study Treatment
Unused study drug should remain in storage (at ≤ –150° C) until further instruction from Kite to 
either return the study drug or dispose of the study drug on site. Kite must approve the disposal of 
unused study drug bags on site. Refer to the IPM for details.
The study monitor will review the study treatment records at periodic intervals.

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6.
STUDY ASSESSMENTS COMMON TO ALL SUBSTUDIES
The study assessments that are common to all indications and that are managed the same way 
across all substudies are described here. Assessments that are unique to a specific indication or 
that are managed differently depending on the indication (eg, lumbar puncture and disease 
response assessments) are described in the study assessment section of the substudy protocols.
Study assessments described in this section are to be performed according to the schedule 
presented in the respective SOA for each substudy.
Note: Substudies in WM and HCL were terminated early by the Sponsor, effective 21 June 
2023
6.1.
Demographic Data
Demographic data will be collected at screening for each subject as per country and local 
regulations and guidelines. Where applicable, demographic data may include sex, year of birth, 
race, ethnicity, and country of enrollment with the intent to assess the possible association of 
demographics with subject safety and treatment effectiveness.
6.2.
Medical and Treatment History
Relevant medical history before the start of AE reporting (ie, from before enrollment 
[leukapheresis]) will be collected at screening. Relevant medical history is defined as data about 
the subject’s concurrent medical condition that would be typically shared in a referral letter. All 
findings will be recorded in the eCRFs.
In addition to the medical history, all history related to a subject’s disease, treatment, and 
response to treatment will be collected and must date back to the original diagnosis. Any prior 
treatment received, as outlined in the substudy protocol, must be documented. Additionally, for 
the RT substudy, prior treatment received for CLL must also be collected. For subjects who are 
being referred from another clinic or institution to the participating study site, copies of the 
subject’s chart should be obtained.
Please also refer to Section 6 of the respective substudy protocols for substudy-specific 
requirements.
6.3.
Safety Assessments
Safety assessments will include collection of AEs, clinical laboratory tests, physical 
examinations, weight, vital signs, neurologic examinations, ECOG performance status, cardiac 
function, brain magnetic resonance imaging (MRI) (if applicable), lumbar puncture (if 
applicable), collection of concomitant medications, and assessment of the presence of 
anti-brexucabtagene autoleucel antibodies and RCR, as described in the following sections.

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Safety assessments will be conducted according to the SOA for each respective substudy.
6.3.1.
Adverse Events
All AEs, SAEs, and DLTs will be collected at each study visit, as indicated in the SOA for each 
substudy. Subjects will be asked about any AEs that might have occurred since the last study 
visit.
6.3.2.
Clinical Laboratory Tests
6.3.2.1.
Laboratory Tests for Safety and Pharmacokinetic/Pharmacodynamic Assessments
Clinical laboratory tests using blood, serum, urine or CSF (if applicable) samples will be 
performed to assess safety. Additional samples may be collected as needed for further safety 
testing.
All clinical laboratory test assessments listed in Table 4 will be performed across all substudies 
at the local laboratory except for assays for anti-brexucabtagene autoleucel antibodies and RCR 
which will be performed at the central laboratory.
(Note: In addition to collection of blood samples for assessment at the local laboratory of 
complete blood count [CBC] with differential, blood samples will also be sent to the central 
laboratory at various timepoints identified in the substudy SOAs. This will occur in parallel with 
sampling for pharmacokinetic, pharmacodynamic and exploratory assessments Refer to the 
central laboratory manual for details.
Table 4.
Clinical Laboratory Tests for Safety Assessments Common Across All 
Substudies
Serum Chemistries (Serum)
Hematology (Blood)
Other 
Albumin
Alanine aminotransferase
Alkaline phosphatase
Aspartate aminotransferase
Bicarbonate (CO2) total (as clinically 
indicated)
Bilirubin total and direct
Blood urea nitrogen or urea
Calcium total
Chloride
Creatinine
Creatinine clearance (as estimated by 
Cockcroft Gault formula) (screening 
only)
Glucose
Inorganic phosphorus
Absolute lymphocyte count
CBC with differential
CD4 cell count (HIV positive 
patients only)
PBMCs:
RCR (central laboratory)
qPCR for HIV viral load (HIV 
positive patients only)
Serum:
Anti-brexucabtagene autoleucel 
CAR antibodies (central laboratory)
C-reactive protein
Ferritin
Pregnancy test
Serology anti-HIV1+2 test (at 
screening only)
HIV positive patients serologic 
testing for hepatitis B and hepatitis 
C (at screening only)
CSF:
Presence of malignant cells (if 
applicable)

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Serum Chemistries (Serum)
Hematology (Blood)
Other 
Lactate (as clinically indicated)
Lactate dehydrogenase
Magnesium total
Potassium
Sodium
Uric acid
Abbreviations: CAR, chimeric antigen receptor; CBC, complete blood count; CSF, cerebrospinal fluid; PBMC, peripheral blood 
mononuclear cell; qPCR, quantitative polymerase chain reaction; RCR, replication-competent retrovirus.
Notes: All laboratory tests listed above, except for anti-brexucabtagene autoleucel antibodies, and RCR, are performed at the 
local laboratory.
•
Per institutional guidelines, CBC with differential must include WBC count, neutrophils or 
ANC (including bands according to standard of care), lymphocytes or absolute lymphocyte 
count, hemoglobin, and platelets.
•
Lactate dehydrogenase (LDH) should continue to be monitored after the baseline assessment, 
as clinically indicated.
•
C-reactive protein (CRP) and ferritin will also be tested at the central laboratory as part of the 
pharmacodynamics evaluation (ie, analytes including cytokines; refer to Section 6.7) at the 
time points listed in the respective substudy SOAs (for subprotocol A and subprotocol C, 
refer to Table 4 and Table 5. For subprotocol B and subprotocol D, refer to Table 5 and 
Table 6 in the respective substudy protocols).
•
Refer to Section 6.3.16.2 for information on RCR testing.
•
A urine or serum sample will be collected and assessed locally for females of childbearing 
potential. If the screening pregnancy test (β-human chorionic gonadotropin) is positive, the 
subject should not be enrolled. If a standard-of-care pregnancy test is collected during the 
course of the study and the result is positive, the investigator should report the pregnancy to 
Kite per instructions specified in Section 8.9.2.1. If a female partner of a male subject 
becomes pregnant during the conduct of the study, the pregnancy must be reported to Kite 
per instructions specified in Section 8.9.2.1. Refer to Section 12.4.3 for details regarding 
pregnancy testing of European Union (EU) and Swiss subjects before both leukapheresis and 
lymphodepleting chemotherapy.
•
If the blood urea nitrogen test cannot be performed by the local laboratory, urea should be 
analyzed.
•
At European study sites, serologic tests (ie, HIV, hepatitis B virus, hepatitis C virus, and 
syphilis) will be done per institutional guidelines and EU/CH regulations. Testing may be 
done within 30 days before leukapheresis/enrollment and/or on the day of 
leukapheresis/enrollment.
•
HIV positive patients must undergo tests for viral load by qPCR and CD4 count.

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Refer to Section 6.3.14 for information regarding serology testing.
If a subject is re-admitted to the hospital after the initial 7-day hospitalization period with any 
brexucabtagene autoleucel-related AEs, blood samples for assessment of brexucabtagene 
autoleucel CAR T cells and cytokines will be collected on the day of hospital re-admission and 
then weekly through, and including, the day of discharge, unless the collection overlaps with a 
scheduled one, as per the respective substudy SOA. Blood samples for assessment of 
brexucabtagene autoleucel CAR T cells and cytokines must also be collected at the time of 
disease progression prior to starting any subsequent anticancer therapy.
6.3.2.2.
Laboratory Tests associated with Evaluating Disease Response
Refer to the respective substudy protocol (Section 6) and substudy SOA for specific laboratory 
testing associated with evaluating disease response.
6.3.3.
Physical Examination
Physical examinations will be performed at screening and at the time points noted in the 
respective substudy SOA.
Physical examination will include assessments of splenomegaly, hepatomegaly, 
lymphadenopathy, including (if applicable) Waldeyers ring (throat area, tonsils, adenoids and 
other lymphoid tissue).
Subjects with symptoms related to CRS should undergo physical examination at least daily until 
symptoms resolve to baseline.
Clinically significant adverse changes (as determined by the investigator) when compared with 
the baseline examination will be reported as AEs.
6.3.4.
Weight
Weight (plus height at screening) will be collected at screening and at the time points noted in 
the respective substudy SOA.
6.3.5.
Vital Signs
Vital signs including blood pressure, heart rate, respiration rate, oxygen saturation, and 
temperature will be collected. Vital signs will be monitored as indicated in the SOA for each 
substudy.
In addition to the time points indicated in the SOA for each substudy, it is recommended that 
vital signs are monitored during and after the brexucabtagene autoleucel infusion and then 
routinely per institutional guidelines. Vital signs may be monitored more frequently as clinically 
indicated.

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6.3.6.
Neurologic Examinations
To establish a baseline the subject’s neurological status will be evaluated at screening.
Neurological examinations, including an immune effector cell-associated encephalopathy 
cognition assessment as outlined by the American Society for Transplantation and Cellular 
Therapy (ASTCT) immune effector cell-associated neurotoxicity syndrome (ICANS) consensus 
grading {Lee 2019} will be performed according to the time points specified in the substudy 
SOAs.
A neurological assessment (which may include the Mini-Mental Status Exam) should be 
performed prior to brexucabtagene autoleucel infusion on treatment Day 0, then continue every 
other day during the minimum 7-day hospitalization period (refer to Section 12.4 for specific 
requirements of country regulatory agencies regarding duration of observation period). If a 
subject has extended hospitalization after Day 7, a neurologic assessment will continue to be 
performed as clinically indicated. Neurologic examinations performed on Day 0 to Day 7 can be 
done by a licensed physician or equivalent who is not necessarily an investigator in the study.
Any abnormalities of the following should be recorded: level of consciousness, orientation, 
vision, cranial nerves and brain stem functions, pyramidal and extra pyramidal motor system, 
reflexes, muscle tone and trophic findings, coordination, sensory system, neuropsychological 
findings (eg, speech, cognition, and emotion).
Refer to Section 8.4.1.1 and Section 8.8 for information on the grading and management of 
neurotoxicity events. Grading should be continued daily during any period of Grade 2 or higher 
neurologic events until symptoms return to baseline.
During the hospitalization period for subjects treated with brexucabtagene autoleucel, the 
frequency of evaluations of neurological status may need to be increased. Changes in 
neurological status should be reported as an AE if considered clinically significant at the 
discretion of the investigator.
6.3.7.
Performance Status (Eastern Cooperative Oncology Group Score)
Performance status as measured by the ECOG scale will be performed at the time points 
specified in the respective substudy SOA to quantify the subject’s general well-being and ability 
to perform activities of daily life.
6.3.8.
Cardiac Function
6.3.8.1.
Echocardiogram/Multigated Acquisition Scan
Cardiac function (defined as the left ventricular ejection fraction), as measured by ECHO or 
MUGA, will be assessed during the screening period to confirm study eligibility. No evidence of 
clinically significant pericardial effusion, as required by eligibility, will also be confirmed.

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If the last chemotherapy regimen the subject received is not considered cardiotoxic, an ECHO or 
MUGA performed within 28 days before signing the ICF may be used for eligibility. If the last 
chemotherapy regimen the subject received is considered cardiotoxic, then an ECHO or MUGA 
performed after the subject received their last chemotherapy treatment and within 28 days before 
signing the ICF may be used for confirmation of eligibility.
6.3.8.2.
Electrocardiogram
To establish a baseline, an ECG will be performed at screening. ECG assessments will include 
partial response (PR) duration, QRS duration, QT duration, and RR duration, and corrected QT 
(QTc) interval. The QTc interval will be calculated using Fridericia’s formula {Fridericia 2003}.
6.3.9.
Brain MRI
Brain MRIs will be performed as specified in Section 6.2 of the substudy protocols and the 
substudy SOAs.
6.3.10.
Lumbar Puncture
Lumbar puncture will be performed as specified in Section 6.3 of the respective substudy 
protocols and the substudy SOAs.
6.3.11.
Patient-reported Outcomes
The patient-reported outcomes (PROs) to be used in this study include the European 
Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients 
Questionnaire (EORTC QLQ-C30) and European Quality of Life 5-Dimension 5-Level Scale 
(EQ-5D-5L). A description of each PRO is provided in Section 12.6.
The time points at which the PROs should be administered are provided in the SOAs for each 
respective substudy. These PROs are expected to be completed by all subjects who remain 
on-study at the scheduled assessments, up to and until disease progression.
All PRO measures will be scored using their published administration and scoring manual. For 
items with missing responses, the response will be managed as per the scoring manual.
The PROs are to be completed by the subject before any study-specific assessments or 
procedures are performed (excluding blood draws), before a subject receives any disease status 
information, and on Day 0 prior to the brexucabtagene infusion.
The sponsor will provide training for relevant site personnel for the administration of the 
questionnaires, so that subjects fill in the questionnaires as completely and accurately as 
possible. It is important that the significance and relevance of the data are explained carefully to 
participating subjects so that they are motivated to comply with data collection {Fallowfield 
1987}. The measures are self-reported, and the subject must complete the questionnaires in 
private and should not be given help from relatives or study staff; help in interpreting the 
questions is not allowed. A subject may be exempt from completing the questionnaire if he or 
she is unable to read the questionnaire in 1 of the country languages available.

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6.3.12.
Concomitant Therapies and Procedures
Information about concomitant therapies and procedures will be collected at the timepoints 
specified in the respective substudy SOAs. Reporting requirements for concomitant medications 
are provided in Table 5. Specific concomitant medication collection requirements and 
instructions are included in the eCRF completion guidelines. Refer to Section 5.4 and Section 5.5 
for information about allowed/excluded medications.
Table 5.
Reporting Requirements for Concomitant Medications and 
Procedures
Subjects Who Are:
Not Enrolled 
(ie, Screen Failures, or Not 
Leukapheresed)
Enrolled, 
but Do Not Receive 
Brexucabtagene Autoleucel
Enrolled 
and Received Brexucabtagene Autoleucel
Concomitant medications 
related to serious adverse 
event(s) will be recorded from 
the date of the signing of the 
screening ICF through 30 days 
after the last study-specific 
screening procedure.
Concomitant medications will 
be recorded from the date of 
signing of the ICF until 
30 days after the last 
study-specific procedure has 
occurred (eg, leukapheresis or 
lymphodepleting 
chemotherapy) or until the 
initiation of a new anticancer 
therapy, whichever occurs 
first.
•
Concomitant medications and procedures, 
including oxygen, blood products, 
intubation, and dialysis, will be recorded 
from the date of signing of the ICF until 
3 months after completing treatment with 
brexucabtagene autoleucel.
•
After the 3-month follow-up period, targeted 
concomitant medications and other 
medicinal products will be recorded for 60 
months after the brexucabtagene autoleucel 
infusion, or until disease progression or 
subsequent therapy, whichever occurs first 
(for the RT and BL subjects reporting after 
24 months will continue within the LTFU 
protocol).
•
Targeted concomitant medications include 
gammaglobulin, immunosuppressive drugs, 
anti-infective drugs, vaccinations, and 
anticancer therapies (eg, chemotherapy, 
immunotherapy, targeted therapy, hormone 
therapy, stem cell transplant/BMT, 
high-dose corticosteroids, radiation, surgery, 
and investigational products).
•
All concomitant medications used to treat 
targeted AEs should be recorded throughout 
the study.
Abbreviations: AE, adverse event; BL, Burkitt lymphoma; BMT, bone marrow transplant; ICF, informed consent form; LTFU, 
long-term follow-up; RT, Richter transformation.
6.3.13.
Pregnancy Testing
Pregnancy testing in females of childbearing potential (Refer to Section 12.3.1 for the definition 
of childbearing potential) will occur at the time points indicated in the respective substudy 
SOAs. Refer to Section 3 for details regarding pregnancy testing of EU/CH subjects.

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6.3.14.
Serology Testing
For all subjects, serology anti-HIV1+2 test at screening, unless available HIV test results within 
3 months prior to enrolment, or if the subject has been confirmed to be HIV positive prior to 
screening.
For HIV positive subjects, testing for hepatitis B and hepatitis C at screening (refer to 
Section 4.2.2 for exclusion criteria related to hepatitis B or hepatitis C infection).
At EU/CH study sites, serologic tests (ie, HIV, hepatitis B virus, hepatitis C virus, and syphilis) 
will be done per institutional guidelines and EU/CH regulations. Serology testing may be done 
within 30 days before leukapheresis/enrollment and/or on the day of leukapheresis/ enrolment.
6.3.15.
HIV Viral Load and CD4 Count
Subjects who are HIV positive who are taking appropriate anti-HIV medications with an 
undetectable viral load by qPCR and with a CD4 count > 200 cells/µL at screening will be 
eligible to participate in the study. For subjects who are HIV positive, screening for active 
Hepatitis B and Hepatitis C virus is required. Moreover, regular assessments of viral load and 
CD4 counts will be performed according to the respective substudy SOAs.
6.3.16.
Other Safety Assessments
6.3.16.1.
Antibodies to Brexucabtagene Autoleucel
The presence of antibodies against the brexucabtagene autoleucel CAR will be assessed in serum 
samples, prior to leukapheresis (baseline), on Day 28 post-infusion, and then at Month 3, 
Month 6, Month 9 and Month 12, as per the respective substudy SOAs. The evaluation will be 
performed by a central laboratory. Refer to the central laboratory manual for further details.
6.3.16.2.
Replication-Competent Retrovirus
As brexucabtagene autoleucel comprises retroviral vector-transduced T cells, the presence of 
RCR in the blood of treated subjects will be monitored as per the substudy SOAs. The evaluation 
of RCR will be performed by a central laboratory. Refer to the central laboratory manual for 
further details.
Peripheral blood mononuclear cells (PBMCs) for RCR testing will be collected at baseline 
(before the start of brexucabtagene autoleucel infusion) and at Month 3, Month 6, and Month 12. 
Thereafter, samples will only be collected and tested if an RCR event is clinically suspected 
and/or a subject tests positive for RCR at any time point within the first year. If the latter, 
samples/testing for RCR will continue per physician/investigator discretion.
If a subject dies of a suspected retrovirus-associated disease or develops a new malignancy 
suspected to be associated with brexucabtagene autoleucel during the study or long-term 
follow-up, a blood sample and tumor biopsy may be obtained and sent to the central laboratory 
to assay for brexucabtagene autoleucel CAR T cells and/or RCR.

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Assessments in the Event of a Secondaiy Malignancy 
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In the case of a secondaiy malignancy, eve1y effort will be made to obtain a biopsy sample of the 
neoplastic tissue or the pe1i inent autopsy tissue to strut a diagnostic workflow, including tests 
such as transgene elements, RCR, presence of common cancer-drivers/mutations and inse1iional 
mutagenesis. Samples will be submitted to the central laborato1y for evaluation. Refer to the 
central laborato1y manual for fmi her details. 
6.4. 
Disease Assessments 
Subjects will be evaluated for disease response by the site investigator as specified in Section 6 
of the substudy protocols and at the time points specified in the respective substudy protocol 
SOAs. 
6.5. 
Bone Marrow Aspirate / Biopsy requirements for Subjects With Unexplained 
Cytopenias or Suspicion of Hemophagocytic Lymphohistiocytosis 
A bone maiTow aspirate and biopsy should be considered for any subject with unexplained 
cytopenias or where there is suspicion of hemophagocytic lymphohistiocytosis (HLH). The 
samples should be reviewed at the local laborato1y, and a po1iion of the sample should be sent to 
the central laborato1y for explorato1y analyses. 
6.6. 
Pharmacokinetic Assessments 
PBMC samples for phaim acokinetic assessments will be drawn according to the schedule 
presented in the respective substudy protocol SOAs. Samples on Day 3 may be collected± 1 day. 
Phaim acokinetic assessments include monitoring of levels of brexucabtagene autoleucel 
CAR T cells in blood over time. 
6.7. 
Pharmacodynamic Assessments 
Sernm (and plasma) samples for phaimacodynainic assessments will be drawn according to the 
schedule presented in the substudy protocol SOAs. 
Phaim acod ainic assessments will include monitorin levels of analytes in sernm over time. 
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6.8.
Other Assessments
Samples for the assessments described in the following sections will be drawn according to the 
schedule presented in the substudy SOAs.
6.8.1.
Central Confirmation of Diagnosis
Local assessments for diagnosis and determination of study eligibility will be made by the 
primary investigator at each site. Diagnosis will be confirmed retrospectively by a centralized 
specialty laboratory (see central laboratory manual) using peripheral blood, bone marrow 
aspirate, bone marrow core biopsy, and/or tumor tissue in the form of formalin-fixed, 
paraffin-embedded block, unstained pre-cut slides along with a pathology report, as appropriate 
for each indication and described in the subprotocols.
6.8.2.
Exploratory Assessments
Indication-specific exploratory assessments are described in Section 6 of the respective substudy 
protocols.
6.8.2.1.
Other Exploratory Assessments
CSF may be harvested from subjects who develop ICANS or CRS to enable evaluation of 
inflammatory cytokines and chemokine levels. As applicable, lymphocyte and myeloid 
populations residing in the CSF, or other subject samples, may also be monitored for the purpose 
of understanding the safety profile of brexucabtagene autoleucel.
Additional exploratory analyses are described in each indication-specific substudy protocols.
6.8.3.
Survival Data
At the time points identified in the substudy SOAs, as well as additional time points outside of 
the SOA at the sponsor’s discretion, subjects and/or the subject’s referring healthcare 
provider (HCP) and/or general practitioner (GP) may be contacted directly by telephone or email 
or a search of public records per local regulations to assess survival status.

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7.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the respective substudies at 
each study period/visit, and that are common to all indications, are described in the following 
sections and will be performed at the time points presented in the respective SOA for each 
substudy. Study procedures that are unique to a specific indication are described in the respective 
substudy protocol.
Note: Substudies in WM and HCL were terminated early by the Sponsor, effective 21 June 
2023
The investigator must document any deviation from the protocol procedures and notify Kite or 
the contract research organization (CRO).
7.1.
Subject Informed Consent
Before a prospective subject can participate in the clinical study, the investigator must obtain 
written informed consent from the subject after adequate explanation of the study design, 
anticipated benefits, and potential risks. Subjects should sign the most current IRB/IEC-approved 
ICF before any study-specific activity or procedure is performed. Refer to Section 10.1.3 for 
more information about the informed consent process.
All subjects who are enrolled in the study should be reconsented with any updated version of the 
IRB/IEC-approved ICF if relevant to their participation in the study. Subjects who partially 
withdraw consent should be reconsented with the revised ICF.
7.1.1.
Informed Consent for Optional Research
In addition to the study-specific informed consent form (ICF) to be signed by each subject 
participating in the study, additional, optional consent will be sought from subjects for 
permission to use the remainder of study biospecimens for optional future research and/or 
genetic research in accordance with applicable regulations.
7.2.
Subject ID Assignment
Each subject who enters the screening period will receive a unique subject ID number before any 
study-specific procedure or activity is initiated. This number will be used to identify the subject 
throughout the study and must be used on all study documentation related to the subject. 
Furthermore, the subject ID number must remain constant throughout the entire clinical study; it 
must not be changed after enrollment or if the subject is rescreened or enrolled in the 
KT-US-982-5968 LTFU study.

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7.3.
Screening
The up to 28-day screening period begins on the date the subject signs the IRB/IEC-approved 
ICF and continues through confirmation of enrollment (ie, commencement of leukapheresis 
[Section 7.5.1]), or until the subject withdraws consent before enrollment, or it is determined that 
the subject is a screen failure (ie, does not meet the eligibility criteria per Section 4.2). Study 
sites will maintain a log of all screened subjects who were reviewed and evaluated for study 
participation. Information collected on the screening log should include limited information such 
as the date of screening, date the subject was enrolled, or the reason why the subject failed 
screening. These data will be entered in the eCRF.
Informed consent must be obtained before completion of any nonstandard of care, study-specific 
procedures. Procedures that are part of the standard of care such as blood samples or disease 
stabilizing prior therapy, are not considered study-specific procedures and may be performed 
before obtaining consent and if relevant used to confirm eligibility. Confirmation of these data 
must occur within the time allowance as outlined below and in the SOA for each substudy.
The procedures to be completed during the screening period are detailed in the SOA for each 
substudy.
7.3.1.
Rescreening
Subjects who are unable to complete or meet the eligibility criteria during the up to 28-day 
screening period will be permitted to rescreen once. The investigator should consult with the 
medical monitor about rescreening cases. Subjects will retain the same subject ID number 
assigned at the original screening. If rescreening occurs within 28 days after signing of the 
original ICF, the assessment or procedure that initially resulted in the subject failing screening 
will be performed, including any other procedures that fell outside of the designated screening 
window (eg, laboratory assessments); all other initial screening procedures/assessments do not 
need to be repeated. If rescreening occurs or leukapheresis is delayed more than 28 days after the 
signing of the original ICF, the subject must be reconsented and all screening 
procedures/assessments must be repeated.
7.4.
Enrollment
A subject is considered enrolled in the study at commencement of leukapheresis. Subjects must 
have undergone screening procedures and their results must have been confirmed by the 
investigator to meet the study eligibility criteria (Section 4.2) at screening. For laboratory tests 
performed after screening and before initiation of leukapheresis, allowance will be made for 
expected normal variation of within 5% of laboratory test value cutoffs noted in the inclusion 
criteria. A subject may not proceed to enrollment if they do not meet the eligibility criteria as 
indicated during screening and by laboratory tests performed after screening and before the 
initiation of leukapheresis. If there is a need for a subject to have leukapheresis repeated, they 
must continue to meet the study eligibility criteria (or within 5% of the laboratory test value 
cutoffs noted in the inclusion criteria) before the leukapheresis procedure is performed. (The 
±5% cutoffs do not apply to the hematological parameters listed in the common inclusion criteria 
#4 if lower values are attributable to underlying disease).

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7.5.
Pretreatment Period
7.5.1.
Leukapheresis
Leukapheresis is to be performed within approximately 5 days after eligibility confirmation. 
Refer to Section 3.2.1 for a description and definition of leukapheresis. Before leukapheresis 
commences, the following criteria must be met:
•
In general, all criteria that were confirmed during screening for eligibility must not be known 
to be violated before leukapheresis, except that allowance will be made for expected normal 
variation of within 5% of laboratory test value cutoffs noted in the inclusion criteria. 
Additionally, the investigator must review and confirm that the last CBC with differential 
and chemistry panel results from the blood draw before the start of leukapheresis meet the 
criteria detailed in inclusion criterion ±5%. If any screening assessments or procedures are 
repeated between confirmation of eligibility and the start of leukapheresis and the results are 
outside the criteria listed in Section 4.2 (or outside ±5% of the laboratory test value cutoffs 
noted in the inclusion criteria), the subject should not be leukapheresed, and the Kite medical 
monitor must be consulted (The ±5% cutoffs do not apply to the hematological parameters 
listed in the common inclusion criteria #4 if lower values are attributable to underlying 
disease).
•
Subjects must have no evidence of clinically significant infection before leukapheresis. 
Should a subject have clinically significant infection immediately before leukapheresis, cell 
collection must be delayed until the event resolves.
•
If leukapheresis is delayed > 5 days after eligibility confirmation, a CBC with differential 
and chemistry panel must be repeated.
•
If the WBC count from a sample collected at the time of leukapheresis is ≥ 20,000 cells/µL, 
the Kite medical monitor must be consulted before proceeding with leukapheresis.
•
Corticosteroid therapy at a pharmacologic dose (> 5 mg/day of prednisone or equivalent 
doses of other corticosteroids) and other immunosuppressive drugs must be avoided for 
7 days before leukapheresis (refer to Section 5.5).
Refer to Section 5.5.1 for medications that are not allowed before leukapheresis occurs.
The procedures/requirements that will occur on the leukapheresis collection day are detailed in 
the substudy SOAs.
In the event of a manufacturing failure of the CAR T-cell product (eg, the planned number of 
CAR T cells is not reached or there are observations affecting product safety), the leukapheresis 
procedure may be repeated.

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7.5.2.
Bridging Therapy (Optional; for RT and BL Subjects Only)
Bridging therapy (if deemed necessary for disease control) is applicable at the discretion of the 
investigator to RT and BL subjects only. Please refer to Section 7.2 of the respective substudy 
protocols for details.
7.5.3.
Baseline Disease Assessment Post Bridging (Optional; for RT and BL 
Subjects Only) and Post-Ibrutinib (Optional; for WM Subjects Only)
For subjects requiring bridging therapy (optional for RT and BL subjects only) or ibrutinib to 
reduce the risk of BTK inhibitor withdrawal symptoms (optional for WM subjects only), a 
disease assessment must be performed prior to initiating lymphodepleting chemotherapy to 
establish a new baseline. This disease assessment will not affect whether to initiate 
lymphodepleting chemotherapy and infusion of brexucabtagene autoleucel.
7.5.4.
Lymphodepleting Chemotherapy
On Day −5 through Day −3 before the administration of brexucabtagene autoleucel, subjects will 
receive a nonmyeloablative lymphodepleting regimen consisting of cyclophosphamide and 
fludarabine to induce lymphocyte depletion and create an optimal environment for expansion of 
brexucabtagene autoleucel CAR T cells in vivo.
Subjects will receive the following 3-day chemotherapy regimen per the schedule detailed 
below:
1) IV hydration with 1 L of 0.9% NaCl given before cyclophosphamide or fludarabine on all 
3 days of infusion
2) Cyclophosphamide (500 mg/m2/day; IV) over approximately 60 minutes on Day −5, Day −4, 
and Day −3
3) Fludarabine (30 mg/m2/day; IV) over approximately 30 minutes on Day −5, Day −4, and 
Day −3
4) An additional 1 L of 0.9% NaCl at completion of the cyclophosphamide or fludarabine 
infusion on all 3 days of infusion
5) Mesna together with cyclophosphamide (sodium 2-mercaptoethanesulfonate; a detoxifying 
agent used to inhibit cyclophosphamide induced hemorrhagic cystitis) per institutional 
guidelines
If, after the start of the lymphodepletion regimen, the creatinine clearance falls below 
70 mL/min, subsequent doses of fludarabine will be adjusted according to institutional 
guidelines.

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Lymphodepleting chemotherapy will be supplied by the study site unless otherwise noted. Refer 
to the current product label for guidance on packaging, storage, preparation, administration, and 
toxicity management associated with the administration of described chemotherapy agents.
Subjects should be instructed to drink plenty of liquids both during and for 24 hours following 
the chemotherapy. In general, subjects should be kept well hydrated but closely monitored to 
prevent fluid overload.
Brexucabtagene autoleucel product must be available before initiation of lymphodepleting 
chemotherapy.
7.5.4.1.
Requirements for Initiating Lymphodepleting Chemotherapy and the 
Brexucabtagene Autoleucel Infusion
Administration of brexucabtagene autoleucel to subjects with ongoing infection or inflammation, 
even if subjects are asymptomatic, may increase the risk of high-grade and fatal toxicity. All 
efforts should be made to rule out such conditions before both lymphodepleting chemotherapy 
and brexucabtagene autoleucel infusion. If any of the following criteria are met before initiation 
of lymphodepleting chemotherapy or the brexucabtagene autoleucel infusion, the workup listed 
in Section 7.6.4 must be performed to determine the potential cause if there is no identified 
source of infection:
•
Temperature > 38 ⁰C within 72 hours before lymphodepleting chemotherapy or the 
brexucabtagene autoleucel infusion
•
CRP ≥ 100 mg/L any time between enrollment to the start of lymphodepleting chemotherapy 
or the start of the brexucabtagene autoleucel infusion
•
WBC count or differential concerning for infectious process between enrollment to the start 
of lymphodepleting chemotherapy or start of the brexucabtagene autoleucel infusion (eg, 
WBC ≥ 20,000, rapidly increasing WBC, or differential with a high percentage of 
segments/bands)
Additionally:
•
All eligibility criteria listed in Section 4.2 of the master protocol and substudy protocols must 
continue to be met before the start of both the lymphodepleting chemotherapy and the start of 
the brexucabtagene autoleucel infusion. If any screening assessments or procedures are 
repeated after enrollment (initial confirmation of eligibility) and the results are outside the 
eligibility criteria listed in Section 4.2 (or within 5% of the laboratory test value cutoffs noted 
in the inclusion criteria), then the condition must resolve before proceeding with 
lymphodepleting chemotherapy or the brexucabtagene autoleucel infusion (the ±5% cutoffs 
do not apply to the hematological parameters listed in the common inclusion criteria #4, if 
lower values are attributable to underlying disease or have been impacted by the 
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•
Complete history and physical examination, including head, eyes, ears, nose, and throat and 
cardiac, vascular, respiratory, gastrointestinal, integumentary, and neurological systems must 
not reveal evidence of infection/inflammation
•
The subject must not have received systemic antimicrobials for the treatment of a known or 
suspected infection within 48 hours before lymphodepleting chemotherapy or the 
brexucabtagene autoleucel infusion (prophylactic use of antimicrobials is allowed)
•
Treatment course of any antimicrobials given for known or suspected antecedent infection 
should be complete as per an infectious disease consult (if applicable) recommendation 
before stopping or switching to prophylactic antimicrobials
•
If a subject is confirmed to have an infectious process for which antimicrobials are not 
available (eg, viral pneumonia), the infection must be clinically resolved as determined by 
the investigator in consultation with the infectious disease service (if applicable)
•
The most recently collected blood, urine, or other body fluid cultures must show no growth 
for at least 48 hours, and any other infectious workup performed (eg, bacterial, polymerase 
chain reaction [PCR], stool studies, imaging studies) must be negative. If clinical suspicion is 
for an infection for which cultures are unlikely to be positive within 48 hours (eg, fungal 
infection), adequate time must be allowed for cultures to become positive
•
Once the above criteria are met the subject can proceed with lymphodepleting chemotherapy, 
following the procedures described in Section 7.5.4, and the brexucabtagene autoleucel 
infusion, following the procedures described in Section 7.6.2 and Section 7.6.3.
7.5.4.2.
Lymphodepleting Chemotherapy
The procedures to be completed during Day −5, Day −4 and Day −3 are detailed in the 
respective substudy SOAs.
7.6.
Treatment Period (Day 0 to Day 7)
Assessments and procedures to be performed during the treatment period will be according to the 
schedule presented in the respective substudy SOAs.
All subjects will be hospitalized during the treatment period from before the brexucabtagene 
autoleucel infusion (Day 0) until a minimum of 7 days after treatment (Day 7) unless otherwise 
required by country regulatory agencies (refer to Section 12.4).
All subjects will receive the brexucabtagene autoleucel infusion at a healthcare facility and be 
monitored daily for a minimum of 7 days after treatment unless otherwise required by country 
regulatory agencies (refer to Section 12.4).
Central venous access, such as a port or peripherally inserted central catheter, is required for 
administration of brexucabtagene autoleucel infusion. Catheter care, per institutional guidelines, 
should be followed.

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Brexucabtagene autoleucel infusion is a subject-specific product, and the product must not be 
infused if the information on the subject-specific label does not match the intended subject’s 
information (eg, subject ID number). The volume of brexucabtagene autoleucel infusion infused, 
thaw start/stop time, and brexucabtagene autoleucel infusion administration start/stop time must 
all be noted in the subject’s medical record. The product must not be thawed until the subject is 
ready for the infusion.
Materials and instructions for the thawing, timing, and administering of brexucabtagene 
autoleucel infusion are outlined in the IPM. The IPM must be reviewed before administration of 
brexucabtagene autoleucel infusion. Study sites should follow institutional guidelines for the 
infusion of cell products.
Requirements that need to be met before the initiation of the brexucabtagene autoleucel infusion 
are described in Section 7.5.4.1.
If the brexucabtagene autoleucel infusion is delayed > 2 weeks, protocol guidelines should be 
followed regarding the need for repeat lymphodepleting chemotherapy (refer to Section 7.5.4).
7.6.1.
Brexucabtagene Autoleucel Premedications (Day 0)
The following pre-brexucabtagene autoleucel infusion medications should be administered 
approximately 1 hour before infusion of brexucabtagene autoleucel.
•
Acetaminophen/paracetamol 500 to 1,000 mg orally (PO) or equivalent
•
Diphenhydramine 12.5 to 25 mg IV or 25 mg PO or equivalent
7.6.2.
Infusion of Brexucabtagene Autoleucel (Day 0) and Assessments/Procedures 
to be Performed Before (Days −1 or 0) and After (Days 1 to 7) Infusion
The assessments and procedures performed on the day of administration of brexucabtagene 
autoleucel, and on additional days during the treatment period, are detailed in the respective 
substudy SOAs.
7.6.3.
Monitoring After Brexucabtagene Autoleucel Infusion
Subjects will remain hospitalized for at least 7 days after the brexucabtagene autoleucel infusion, 
unless otherwise required by country regulatory agencies (refer to Section 12.4) and will be 
closely monitored for signs and symptoms of CRS and neurologic events. In addition, the 
assessments described in the respective substudy SOAs will be performed during this period.
Subjects should not be discharged from the hospital until all brexucabtagene autoleucel-related 
nonhematologic toxicities resolve to Grade 1 or return to baseline. Subjects may be discharged 
with noncritical and clinically stable or improving toxicities (eg, renal insufficiency) even if 
higher than Grade 1, if deemed appropriate by the investigator.

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Subjects should remain hospitalized for ongoing brexucabtagene autoleucel-related fever, 
hypotension, hypoxia, or ongoing neurologic events higher than Grade 1 or if deemed necessary 
by the investigator.
Subjects should be instructed to remain within proximity of the study site for at least 4 weeks 
after the brexucabtagene autoleucel infusion. Subjects and their family members/caregivers 
should be educated on potential CRS and neurologic symptoms, such as fever, dyspnea, 
confusion, aphasia, dysphagia, somnolence, encephalopathy, ataxia, or tremor. Subjects or their 
family members/caregivers should be instructed to immediately contact the treating investigator 
or seek immediate medical attention if any of these symptoms develop.
Refer to Section 5.4 and Section 5.5 for descriptions of medications that should not be taken 
before and after the brexucabtagene autoleucel infusion.
7.6.4.
Requirements for Workup for Potential Infectious and/or Inflammatory 
States
For subjects with symptoms and/or clinical findings indicating a potential infectious or 
inflammatory state, and in the absence of an identified source of infection (eg, line infection or 
pneumonia on chest x-ray), the minimum workup to be performed before administration of 
lymphodepleting chemotherapy and/or brexucabtagene autoleucel consists of the following:
•
Consult the Kite medical monitor
•
Infectious disease service consult (if available)
•
Perform computed tomography (CT) imaging of the chest with IV contrast. CT imaging of 
the abdomen and pelvis with IV contrast should also be considered as clinically indicated. If 
there is a medical contraindication to contrast, then a non-contrast CT is allowed
•
The following must be performed (before initiation of antimicrobials if clinically feasible):
Blood cultures (aerobic and anaerobic × 2 bottles each), urinalysis, and urine culture. 
Deep/induced sputum culture if clinically indicated
All indwelling lines, such as central venous catheters, should be examined for any signs 
of infection, and additional cultures should be drawn from the line
Nasopharyngeal-throat swab or equivalent assay for viral infection such as influenza A/B 
(including H1N1), parainfluenza 1/2/3, adenovirus, respiratory syncytial virus, 
coronavirus, or metapneumovirus
Collection of fungal cultures and markers as appropriate (eg, galactomannan or 
Fungitell®)
Collection of appropriate serum viral studies (eg, cytomegalovirus)

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•
If a CNS process is suspected, appropriate brain imaging and subsequent lumbar puncture 
with cytology, culture, Gram stain, and viral PCR should be performed
•
Any additional sign- or symptom-directed investigation should be performed as clinically 
indicated
Before proceeding with lymphodepleting chemotherapy and/or the brexucabtagene autoleucel 
infusion, the above workup must not suggest the presence of an active infection, and all 
requirements for lymphodepleting chemotherapy and/or the brexucabtagene autoleucel infusion 
must be satisfied. If the brexucabtagene autoleucel infusion is delayed > 2 weeks following 
lymphodepleting chemotherapy, the protocol guidelines should be followed regarding the need 
for repeat lymphodepleting chemotherapy (refer to Section 7.5.4).
If the above workup was triggered due to CRP ≥ 100 mg/L, CRP should be repeated. If CRP 
continues to increase significantly, an evaluation should be performed for any other potential 
infectious or inflammatory condition that was not previously evaluated.
7.7.
Post-treatment Follow-Up Period
7.7.1.
Post-treatment Assessment Visits
Assessments and procedures to be performed during the post-treatment assessment period will be 
according to the schedule presented in the respective substudy SOAs.
After completing the brexucabtagene autoleucel infusion and being discharged from the hospital, 
all subjects will be followed during the post-treatment assessment period. Counting from Day 0 
(the day of brexucabtagene autoleucel infusion), subjects will return to the clinic for evaluation 
at the following intervals:
•
Day 14 (± 2 days)
•
Day 28 (± 3 days)
•
Week 8 (± 1 week)
•
Month 3 / 6 / 9 / 12 (± 2 weeks)
•
Month 18 / 24 (± 1 month)
•
Month 30 / 36 / 48 / 60 (± 1 month); WM and HCL substudies only
The procedures to be completed are outlined in the respective substudy SOA.
If the subject is readmitted to the hospital with any brexucabtagene autoleucel-related AE after 
the initial hospitalization for the brexucabtagene autoleucel infusion, the following samples will 
be collected on the day of admission, then weekly, and on the day of discharge; samples will be 
sent to the central laboratory:

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•
Analytes including cytokines (serum/plasma)
•
brexucabtagene autoleucel T cells (PBMCs)
Should the subject fail to return to the clinic for a scheduled protocol-specific visit, study sites 
will need to make at least 2 attempts by a combination of telephone and (e)mail to contact the 
subject. Sites must document both attempts to contact the subject. If a subject does not respond 
within 1 month after the second contact, the subject will be considered lost to follow-up and no 
additional contact will be required.
7.7.2.
Evaluation Visit After Disease Progression
If a subject’s disease progresses, the assessments/procedures listed in the respective substudy 
SOAs should be followed.
If disease progression is identified at a scheduled visit, the assessments scheduled for that visit 
will be performed in addition to any additional assessments or procedures listed in the SOA as 
required for disease progression. If necessary, some of these procedures can be performed at an 
additional unscheduled visit. If disease progression is identified between scheduled visits, the 
subject will be asked to attend an unscheduled visit for disease assessment and the procedures 
listed in the SOA.
Refer to Section 7.7.3 for information on follow-up for subjects whose disease progresses after 
receiving brexucabtagene autoleucel.
7.7.3.
Follow-up Assessments and Procedures for Enrolled Subjects Who Did Not 
Receive Brexucabtagene Autoleucel or Whose Disease Progressed After 
Brexucabtagene Autoleucel Treatment
For subjects who are enrolled, but who did not receive brexucabtagene autoleucel or those where 
progressive disease (PD) has been identified after brexucabtagene autoleucel treatment, the 
following assessments/procedures will be completed at the time points outlined in the respective 
substudy SOAs.
•
Survival status: Subjects and/or the subject’s referring HCP and/or GP may be contacted 
directly by telephone or email to assess survival status
•
Subsequent anticancer therapy (refer to Section 7.11)
•
AE/SAE reporting until 30 days after the last study-related procedure (refer to Section 8.6 for 
safety reporting guidelines)
•
Concomitant medication documentation until 30 days after the last study-specific procedure 
has occurred or until the initiation of new anticancer therapy, whichever occurs first (refer to 
Section 6.3.12)

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•
For subjects whose disease progressed after brexucabtagene autoleucel treatment, the 
following additional procedures are to be completed:
SAE reporting for all new malignancies (refer to Section 8.6.1.2)
RCR testing (refer to Section 6.3.16.2)
If applicable, anti-brexucabtagene antibody testing
•
Subjects who were enrolled but did not receive brexucabtagene autoleucel will be followed 
only until the end of this study (defined in Section 3.4).
7.8.
Assessments and Procedures for Subjects with Disease Progression
Subjects with disease progression will undergo the following assessments/procedures, as 
described in the ‘suspected disease progression’ section of the respective substudy SOAs.
•
Physical examination
•
Vital signs
•
Disease response assessments
•
Local and central laboratory assessments
•
Concomitant medications
•
AEs and SAEs
7.9.
Follow-up Assessments and Procedures for Subjects who Undergo an 
Allogeneic Stem Cell Transplant after Brexucabtagene Autoleucel Treatment
Subjects who undergo an allogeneic stem cell transplantation will continue in the study and will 
undergo the following assessments/procedures at the time points outlined in the respective 
substudy SOAs.
•
Disease assessment
•
Survival status
•
Subsequent anticancer therapy (refer to Section 7.11)
•
AE/SAE reporting (refer to Section 8.6 for safety reporting guidelines)
•
Concomitant medication documentation (refer to Section 6.3.12)
•
RCR testing (refer to Section 6.3.16.2 for details)
•
Anti-brexucabtagene antibodies testing, if applicable

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7.10.
Care After Completion of Participation in the Study
After completion of this study subjects who are infused with brexucabtagene autoleucel will 
continue in the LTFU study for continued monitoring as described in Section 3.5. Kite will not 
provide additional care for study subjects after their participation in the study has ended.
7.11.
Subsequent Anticancer Therapy
Subsequent anticancer therapy should not be administered unless a subject’s disease progression 
has been documented and confirmed. Subsequent anticancer therapy refers to treatment 
administered after the brexucabtagene autoleucel infusion that is necessary to treat a subject’s 
disease, such as non-study-specified chemotherapy, immunotherapy, targeted agents, stem cell 
transplant, radiation therapy, high-dose corticosteroids (other than those defined/allowed in this 
protocol), and other investigational agents.
Allogeneic transplant therapy (and associated conditioning treatment) will not be counted as a 
subsequent anticancer therapy.
All anticancer therapy administered to subjects who are enrolled in the study will be recorded in 
the study eCRF until the end of study (defined in Section 3.4) or, while still a participant in this 
study, the subject is considered lost to follow up, withdraws consent, or dies.
Any anticancer therapy administered for a new or secondary malignancy should be documented 
as a concomitant medication and not a subsequent therapy.
After confirmed disease progression and start of subsequent anticancer therapy, no further 
on-study disease response assessments are required.
7.12.
Instructions for Follow-up and Data to be Collected for Subjects Withdrawn 
From Treatment/Study
If partial withdrawal of consent occurs (defined in Section 4.3), the investigator must discuss 
with the subject the appropriate process for discontinuation from study treatment or other 
study-specific procedures and must discuss options for continued participation, completion of 
procedures, and the associated data collection as outlined in the respective substudy SOA, 
including the following:
•
Survival status, including the cause of death
•
Safety reporting, including new malignancies; SAEs related to brexucabtagene autoleucel 
including, but not limited to, neurologic events, infections, blood or immune disorders, and 
pregnancies
•
Targeted concomitant medications (refer to Table 5, Section 6.3.12)
•
Subsequent therapies
•
Central laboratory samples (per the respective substudy SOA)

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The level of follow-up and method of communication should also be discussed between the 
research staff and subject and documented in the source documents.
If withdrawal of full consent occurs (defined in Section 4.3), the investigator is to discuss with 
the subject appropriate procedures for withdrawal from the study. In such cases, the subject data 
collected up to withdrawal of consent will be retained and included in the analysis of the study 
and, where permitted by local regulations, publicly available data (eg, death records) can be 
included after withdrawal of consent.
Please refer to Section 4.3 for additional details.
7.13.
Sample Storage
Subject biospecimens, as well as any derivatives from these samples, will be stored for 15 years 
from the date that the last subject was treated with brexucabtagene autoleucel, in case any 
protocol-required analyses need repeating. In addition, Kite may conduct analyses on remaining 
samples to address exploratory research questions related to the mechanism of action of the 
treatment or disease-related features, for which subjects will be asked to provide consent. Each 
subject will have the right to have their sample material destroyed at any time by contacting the 
investigator who in turn can contact the sponsor. The investigator should provide the sponsor the 
study and subject ID number so that the sample can be located and destroyed. For subjects who 
withdraw consent, any samples that were not requested to be returned or destroyed will remain 
with the sponsor and any data that may be generated will be entered in the study database.

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8.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
8.1.
Definitions of AEs and SAEs
8.1.1.
Adverse Events
An AE is defined as any untoward medical occurrence in a clinical trial subject. The event does 
not necessarily have a relationship with study treatment. The investigator is responsible for 
ensuring that any AEs observed by the investigator or reported by the subject are recorded in the 
subject’s medical record.
The definition of AEs includes worsening of a pre-existing medical condition. Worsening 
indicates that the pre-existing medical condition has increased in severity, frequency, and/or 
duration or has an association with a worse outcome. When recording such events, descriptions 
that the pre-existing condition has changed (eg, more frequent headaches for a subject with 
pre-existing headaches or increased blood pressure in a subject with pre-existing hypertension) 
must be provided.
An AE does not include the following:
•
A pre-existing condition that has not worsened during the study or involves an intervention 
(such as elective cosmetic surgery or a medical procedure) while on study is not considered 
an AE. Interventions for pretreatment conditions (such as elective cosmetic surgery) or 
medical procedures that were planned before study participation are not considered AEs.
•
Hospitalization for study treatment infusions or study-mandated procedures, or as a 
precautionary measure per institutional policy are not considered AEs (refer also to 
Section 8.5).
•
The term “disease progression” as assessed by measurement of malignant lesions on 
radiographs or other methods is not considered to be an AE. Worsening of signs and 
symptoms of the malignancy under study are considered AEs.
Refer to Section 8.6.1 for information and instructions for recording and reporting AEs. Refer to 
Section 8.6.3 for information and instructions for recording and reporting AEs due to disease 
progression.
8.1.2.
Dose Limiting Toxicities
Dose limiting toxicities are defined as shown in Table 6 and Table 7 with onset within the first 
28 days after the brexucabtagene autoleucel infusion. Dose limiting toxicities requiring a pause 
in enrollment are described in Section 8.10.3

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Table 6.
Dose-limiting Toxicities
Dose-limiting Toxicities
Exceptions
Any brexucabtagene autoleucel related 
Grade 5 event
•
Grade 5 disease progression
Hematologic toxicity Grade 4 does not 
recover to Grade ≤ 2 by Day 28
•
Any hematologic toxicity Grade 4 attributable to underlying 
disease
•
Lymphopenia
Grade 3 or 4 thrombocytopenia lasting of 
any duration if accompanied by Grade 2 or 
higher bleeding
•
None
All brexucabtagene autoleucel related 
Grade 4 nonhematologic toxicities 
including opportunistic infections and 
complications associated with HIVa
•
None
Any brexucabtagene autoleucel related 
Grade 3 neurotoxicity including ICANS, 
regardless of duration
•
None
All brexucabtagene autoleucel related 
Grade 3 nonhematological toxicities 
lasting ≥ 7 days including opportunistic 
infections and complications associated 
with HIVa
•
Grade 3 fever
•
Grade 3 aspartate aminotransferase, alanine aminotransferase, 
alkaline phosphatase, bilirubin, or other liver function test 
elevation, provided there is resolution to Grade 2 or lower 
within 14 days
•
Grade 3 nausea and/or anorexia
•
Grade 3 febrile neutropenia returning to baseline within 
2 weeks
•
Grade 3 insomnia, fatigue, and malaise
•
Grade 3 infection that improves to Grade 2 or lower within 
2 weeks
•
Grade 3 TLS including associated manifestations attributable 
to TLS (eg, electrolyte abnormalities, renal function, or 
hyperuricemia)
All brexucabtagene autoleucel related 
Grade 3 cardiac and/or pulmonary events 
of any duration
•
Grade 3 cardiac and/or pulmonary events if related to CRS and 
improves to Grade 2 or lower within 72 hours
Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy, CRS, cytokine release syndrome; DLT, 
dose limiting toxicity; ICANS, immune effector cell-associated neurotoxicity syndrome; ICE, immune effector cell-associated 
encephalopathy; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; TLS, tumor lysis 
syndrome
Notes: Adverse events are graded using the NCI CTCAE v5.0. CRS and ICANS is graded according to the ASTCT consensus 
grading {Lee 2019}. The severity of individual signs/symptoms of CRS and neurological events will be graded according to NCI 
CTCAE v5.0 for those signs/symptoms that are not part of the grading scale.
a
Infections associated with HIV and AIDS such as (but not exclusive to): Candidiasis of bronchi, trachea, or lungs, 
extrapulmonary Cryptococcosis, Cytomegalovirus disease (other than liver, spleen or nodes), Histoplasmosis, disseminated 
or extrapulmonary, Mycobacterium avium complex, kansasii or other species (disseminated or extrapulmonary), 
Pneumocystis jirovecii pneumonia or complications such as HIV-associated Encephalopathy

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Table 7.
Recommendations Based on Dose Limiting Toxicities
Number of Subjects With a Dose Limiting Toxicity 
in a Cohort
Potential Recommendation
0 of 3 subjects or if 1 DLT occurred in the initial 
3 subjects and no DLT occurs in the subsequent 
3 subjects
If the dose is determined tolerable, then this will be the 
recommended dose
1 of 3 subjects
Enroll 3 more subjects at the same dose level.
≥ 2 of 3 subjects or if 1 DLT occurred in the initial 
3 subjects and ≥ 1 DLT occurs in the subsequent 
3 subjects
The lower dose level will be established as the 
recommended dose (if assessed to be tolerable and 
recommended by the SRT)
Abbreviations: DLT, dose limiting toxicity; SRT, safety review team
8.1.3.
SAEs
An SAE is defined as an AE that meets at least 1 of the following serious criteria:
•
Is fatal
•
Is life-threatening (ie, an event that places the subject at immediate risk of death; it does not 
refer to an event that hypothetically might have caused death if it were more severe)
•
Requires inpatient hospitalization or prolongation of planned hospitalization (refer to 
Section 8.5 for definition of prolongation of planned hospitalization for this study)
An AE would meet the criterion of “requires hospitalization” if the event necessitated 
admission to a healthcare facility
Events that require an escalation of care when the subject is already hospitalized should 
be recorded as an SAE. Examples of such events include movement from routine care in 
the hospital to the intensive care unit or if that event resulted in a prolongation of the 
planned hospitalization
Refer to Section 8.5 for hospitalizations that are not considered to be SAEs.
•
Results in persistent or significant disability/incapacity
•
Results in a congenital anomaly/birth defect
•
Is another medically important serious event. If an investigator considers an event to be 
clinically important, but it does not meet any of the serious criteria, the event could be 
classified as an SAE with the criterion of “other medically important serious event.”
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an AE 
according to the NCI CTCAE v5.0; the event itself may be of relatively minor medical 
significance and, therefore, may not meet the seriousness criteria. Severity and seriousness need 
to be independently assessed for each AE recorded in the eCRF.

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Progression of the malignancy during the study is not considered to be an SAE; signs and 
symptoms of disease progression can be considered as SAEs (and documented as being due to 
disease progression).
Refer to Section 8.6.1.2 for information and instructions for recording and reporting SAEs. Refer 
to Section 8.6.3 for information and instructions for recording and reporting SAEs due to disease 
progression.
8.1.4.
Targeted Adverse Events and Serious Adverse Events
Targeted AEs/SAEs include neurologic events, hematologic events, infections, graft versus host 
disease (GVHD) or aggravation of GVHD, autoimmune disorders, and secondary malignancies. 
Concomitant medications used to treat targeted AEs should be recorded throughout the study.
Although only secondary malignancies are considered as targeted AEs/SAEs, all new 
malignancies will be reported. New malignancies are defined as the development of any new 
malignancies occurring after the brexucabtagene autoleucel infusion. A secondary malignancy is 
defined as a new malignancy suspected to be possibly related to brexucabtagene autoleucel (ie, 
temporally associated with brexucabtagene autoleucel and without compelling alternate 
etiologies).
Refer to Sections 8.6.1.1 and 8.6.1.2 for information and instructions for recording and reporting 
targeted AEs and targeted SAEs, respectively.
8.2.
Pregnancies
There is currently no relevant clinical experience with brexucabtagene autoleucel in pregnant or 
lactating females, and reproductive studies in animals have not been performed. Accordingly, 
brexucabtagene autoleucel must not be administered to either pregnant females or females who 
are breastfeeding. Females of childbearing potential must have a negative pregnancy test before 
enrollment due to the potential for dangerous effects of bridging and/or lymphodepleting 
chemotherapy on the fetus. Females of childbearing potential should be monitored according to 
local and country-specific regulations.
Female subjects are recommended to use highly effective contraception (ie, a method with an 
annual failure rate of < 1%) for at least 12 months after completing lymphodepleting 
chemotherapy dosing or brexucabtagene autoleucel administration, whichever is longer. Male 
subjects should not father a child for at least 12 months after completing lymphodepletion 
chemotherapy dosing or brexucabtagene autoleucel, whichever is longer. Male subjects are 
recommended to use a condom or practice sexual abstinence during this time, in addition to their 
female partner using a highly effective method of contraception.
Refer to Section 12.3.2 for a complete list of highly effective contraception methods. Refer to 
Section 8.9.2.1 for reporting instructions for any pregnancy or lactation cases.

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8.3.
Clinical Laboratory and Vital Sign Abnormalities
8.3.1.
Abnormal Clinical Laboratory Findings
The investigator is responsible for reviewing laboratory test results and determining whether an 
abnormal value in an individual study subject represents a clinically significant change from the 
subject’s baseline values. In general, abnormal laboratory findings without clinical significance 
(based on the investigator’s judgment) are not to be recorded as AEs. However, abnormal 
laboratory findings that result in new or worsening clinical sequelae or that require therapy or an 
adjustment in current therapy, are considered AEs. Where applicable, clinical sequelae (not the 
laboratory abnormality) are to be recorded as the AE.
An abnormal laboratory test result must be reported as an AE if it is a change from baseline and 
meets any of the following criteria:
•
Is associated with clinical symptoms
•
Results in a medical intervention (eg, potassium supplementation for hypokalemia or iron 
replacement therapy for anemia) or a change in concomitant therapy
•
Is clinically significant in the investigator’s judgment
8.3.2.
Abnormal Vital Sign Values
Not all vital sign abnormalities qualify as an AE. A vital sign result must be reported as an AE if 
it is a change from baseline and meets any of the following criteria:
•
Is accompanied by clinical symptoms
•
Results in a medical intervention or a change in concomitant therapy
•
Is clinically significant in the investigator’s judgment
It is the investigator’s responsibility to review all vital sign findings. Medical and scientific 
judgment should be exercised in deciding if an isolated vital sign abnormality should be 
classified as an AE. However, if a clinically significant vital sign abnormality is a sign of a 
disease or syndrome (eg, high blood pressure), only the diagnosis (ie, hypertension) should be 
recorded in the eCRF.
8.4.
Assessments of AE and SAE Severity and Causality
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity and for final review and confirmation of accuracy of event information and 
assessments.

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8.4.1.
Assessment of AE/SAE Severity
The severity of AEs will be graded according to the NCI CTCAE version v5.0. A copy of the 
grading scale can be downloaded from the Cancer Therapy Evaluation Program home page 
(http://ctep.cancer.gov). For events that are not listed in the CTCAE (eg, 
hypogammaglobulinemia), the investigator may grade the severity according to the guidance in 
Table 8.
Table 8.
Severity Grading of AEs
Grade
Clinical Description of Severity
1
Mild, or
Asymptomatic or mild symptoms, or
Clinical or diagnostic observations only, or
Intervention not indicated
2
Moderate, or
Minimal, local, or noninvasive intervention indicated, or
Limiting age-appropriate instrumental ADLa
3
Severe or medically significant but not immediately life-threatening, or
Hospitalization or prolongation of hospitalization indicated, or
Disabling, or
Limiting self-care ADLb
4
Life-threatening consequences, or
Urgent intervention indicated
5
Death related to AE
Abbreviations: ADL, activities of daily living; AE, adverse event.
a
Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.
b
Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not being 
bedridden.
8.4.1.1.
Grading of CRS and Neurologic Events
Severity of CRS and ICANS events will be graded according to the ASTCT consensus grading 
{Lee 2019}.
The severity of individual signs/symptoms of CRS and neurologic events will be graded 
according to the NCI CTCAE v5.0 for those signs/symptoms that are not part of the ASTCT 
grading scale.
Refer to Section 8.8 for details regarding the management of these toxicities.

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8.4.2.
Assessment of AE/SAE Relationship to Brexucabtagene Autoleucel and 
Study Procedures
In reviewing AEs, investigators must assess whether the AE is possibly related to 
1) brexucabtagene autoleucel, 2) leukapheresis, 3) bridging therapy, 4) lymphodepleting 
chemotherapy, or 5) any study-specific procedure. The relationship is indicated by a “related” or 
“not related” response and entered in the eCRF. In assessing causality, the investigator or 
qualified subinvestigator will use clinical judgment and the following considerations:
•
Not related: Evidence exists that the AE has an etiology other than the IP or study procedure. 
For SAEs, an alternative causality must be provided (eg, disease progression, concurrent 
disease[s], concomitant medications, or other)
•
Related: There is reasonable possibility that the event may have been caused by the IP or as a 
result of a study procedure
8.5.
Hospitalization and Prolonged Hospitalization
Any AE that results in hospitalization or prolonged hospitalization should be documented and 
reported as an SAE as described in Section 8.6.1.2. Hospitalization is considered as prolonged 
when a subject continues in the hospital beyond the study-specific hospitalization period after 
infusion of brexucabtagene autoleucel.
The following hospitalization scenarios are not considered to be SAEs:
•
Hospitalization for palliative or hospice care
•
Planned hospitalization required by the protocol (eg, for monitoring of the subject or to 
perform an efficacy measurement for the study)
•
Planned hospitalization for a pre-existing medical condition (diagnosed prior to study entry) 
which was scheduled prior to informed consent / study start
•
Hospitalization due to progression of the underlying malignancy (Refer to Section 8.6.3 for 
instructions on reporting underlying signs/symptoms of the underlying malignancy/disease 
progression as AEs/SAEs.)
8.6.
Investigator Requirements and Instructions for Reporting AEs, SAEs, and 
Deaths to the Sponsor
8.6.1.
Reporting Adverse Events and Serious Adverse Events
The investigator or a delegated and qualified subinvestigator must address the below for 
AEs/SAEs:
•
AE diagnosis or syndrome (if not known, signs or symptoms)
•
Dates of onset and resolution

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•
Severity (Section 8.4.1)
•
Assessment of relatedness to brexucabtagene autoleucel, lymphodepleting chemotherapy, or 
study procedures (Section 8.4.2)
•
Action taken
Additional relevant data with respect to describing the AE/SAE will be collected in the eCRFs. 
For AEs/SAEs, a diagnosis (if known) rather than individual signs and symptoms should be 
recorded on the eCRF AE form. The exception is for CRS where both the diagnosis and 
significant signs and symptoms will be captured on the eCRF AE form.
The investigator is expected to follow reported AEs/SAEs until stabilization or resolution. If a 
subject begins a new anticancer therapy, the AE reporting period for nonserious AEs ends at the 
time the new treatment is started.
Refer to Section 8.6.3 for instructions on reporting AEs/SAEs associated with disease 
progression.
The investigator’s clinical judgment is used to determine whether a subject is to be removed 
from treatment due to an AE/SAE. In the event a subject requests to withdraw from 
protocol-required therapies, study-specific procedures, or the study due to an AE/SAE, the 
subject should undergo the procedures outlined in the Month 3 visit of the respective substudy 
SOA.
Refer to Section 8.6.1.1 and Section 8.6.1.2 for additional information on reporting AEs and 
SAEs, respectively.
8.6.1.1.
Reporting AEs
The investigator is responsible for reporting all AEs observed by the investigator or reported by 
the subject during the AE-reporting period described in Table 9. Refer to Section 8.6.3 for 
instructions on reporting AEs associated with disease progression.

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Table 9.
Reporting Requirements for AEs
Subjects Who Are Enrolled:
But Did Not Receive the Brexucabtagene Autoleucel 
Infusion
And Received the Brexucabtagene Autoleucel 
Infusion
AEs that occur from enrollment (ie, commencement of 
leukapheresis) through 3 months after the 
brexucabtagene autoleucel infusion or until initiation of 
another anticancer therapy, whichever occurs first, are 
to be monitored and reported
After 3 months, only targeted AEs will be reported 
through 15 years after the initial brexucabtagene 
autoleucel infusion, until disease progression, and/or 
the start of subsequent anticancer therapy, whichever 
occurs first, and will be recorded in the eCRF
•
Targeted AEs include neurological events, 
hematological events, infections, GVHD or 
aggravation of GVHD, autoimmune disorders, and 
secondary malignanciesa

(Notea: All new malignancies are to be 
reported; however, only secondary 
malignancies are considered as targeted AEs)
AEs that occur from enrollment (ie, commencement of 
leukapheresis) through 30 days after the last 
study-specific procedure (eg, leukapheresis, bridging 
chemotherapy, or lymphodepleting chemotherapy) or 
until initiation of a new anticancer therapy, whichever 
occurs first, will be reported
All AEs deemed related to the brexucabtagene 
autoleucel infusion should be recorded in the eCRF and 
reported regardless of the study period
Abbreviations: AE, adverse event; eCRF, electronic case report form; GVHD, graft-versus-host disease.
a
A new malignancy is defined as the development of any new malignancy, occurring after the brexucabtagene autoleucel 
infusion. Secondary malignancies are defined as new malignancies that are suspected to be possibly related to 
brexucabtagene autoleucel (ie, temporally associated with brexucabtagene autoleucel and without compelling alternate 
etiologies).
8.6.1.2.
Reporting SAEs
The investigator is responsible for reporting all SAEs observed by the investigator or reported by 
the subject during the SAE reporting periods described in Table 10. Refer to Section 8.6.2for 
instructions on reporting deaths, and Section 8.6.3 for reporting SAEs associated with disease 
progression.

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Table 10.
Reporting Requirements for SAEs
Subjects Who Are:
•
Screen Failures
•
Enrolled but Did Not Receive the 
Brexucabtagene Autoleucel Infusion
•
Enrolled and Received the Brexucabtagene Autoleucel 
Infusion 
All SAEs that occur from signing of the screening ICF 
through 3 months after the brexucabtagene autoleucel 
infusion or until initiation of subsequent anticancer therapy, 
whichever occurs first, will be recorded in the eCRF and 
reported. 
After 3 months, only targeted SAEs will be reported 
through 15 years after the initial brexucabtagene autoleucel 
infusion (reporting will continue after the end of this study 
within the LTFU/ KT-US-982-5968 trial), until disease 
progression, or the start of subsequent anticancer therapy, 
whichever occurs first, and will be recorded in the eCRF.
•
Targeted SAEs include neurologic events, 
hematological events, infections, GVHD or 
aggravation of GVHD, autoimmune disorders, and 
secondary malignanciesa

Notea: All new malignancies are to be reported; 
however, only secondary malignancies are 
considered as targeted SAEs 
All SAEs deemed related to the brexucabtagene autoleucel 
infusion should be recorded in the eCRF and reported 
regardless of study period.
For subjects who are screen failures or enrolled 
but did not receive brexucabtagene autoleucel 
infusion:
All SAEs that occur from signing of the screening 
ICF through 30 days after the last study-specific 
procedure (eg, screening procedure, leukapheresis, 
bridging therapy, or lymphodepleting 
chemotherapy) or until initiation of subsequent 
anticancer therapy, whichever occurs first, will be 
recorded in the eCRF and reported.
All deaths that occur from signing of the screening ICF. 
Refer to Section 8.6.2 and Section 8.6.3 for instructions on 
reporting deaths.
Abbreviations: eCRF, electronic case report form; GVHD, graft-versus-host-disease; ICF, informed consent form; LTFU, 
long-term follow-up; SAE, serious adverse event.
a
A new malignancy is defined as the development of any new malignancy after the brexucabtagene autoleucel infusion; the 
investigator must assess causality against brexucabtagene autoleucel, lymphodepleting chemotherapy, bridging therapy, or 
study procedures. Secondary malignancies are defined as new malignancies that are suspected to be possibly related to 
brexucabtagene autoleucel (ie, plausibly associated with the brexucabtagene autoleucel infusion and without compelling 
alternate etiologies).
Unless otherwise indicated in Table 10:
•
The following must be submitted to Kite via the electronic SAE (eSAE) system within 
24 hours after the investigator’s knowledge of the event:
All SAEs

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•
The following events must be submitted as SAEs via the eSAE system within 24 hours after 
the investigator’s knowledge of the event:
CRS events Grade 3 or higher
Neurologic events Grade 3 or higher
All events of cerebral edema
All events of HLH/macrophage activation syndrome
If the eSAE system is unavailable (eg, system outage), then the SAE must be submitted using the 
paper SAE Report Form and sent via email to the SAE reporting mailbox: 
. Subsequently, SAEs will be entered into the eSAE system once it 
becomes available.
After completion of this study and database closure, any relevant information on ongoing SAEs 
must be submitted to Kite within 24 hours after the investigator’s knowledge of the event using 
the portable document format (PDF) version of the paper SAE Report Form and sent via e-mail 
to the SAE Reporting mailbox: 
.
All SAEs will be reported to the health authorities per local reporting guidelines.
8.6.2.
Reporting Deaths
Death must be recorded on the death eCRF if it occurs at any point during the entire duration of 
the study. Refer to Section 8.6.3 for instructions on reporting deaths associated with the 
underlying malignancy/disease progression.
All deaths must be recorded on the Death eCRF, but only deaths caused by an AE should be 
reported as an SAE. For example, in an event of fatal pneumonia, the event should be reported as 
an SAE of pneumonia and the outcome as fatal. The event or condition that caused or 
contributed to the fatal outcome should be recorded on the SAE eCRF with entries including the 
start date of the event and death date as the stop date of the event. Every effort should be made to 
capture the established cause of death, which may become available later on (eg, after autopsy). 
Although death is an outcome and not a distinct AE, death may be reported as an SAE (ie, 
PT = death) when the cause of death is unknown (eg, sudden or unwitnessed death with 
unknown cause).
Any death occurring after signing of the main study ICF and within 3 months after 
brexucabtagene autoleucel infusion, regardless of attribution to treatment, requires expedited 
reporting within 24 hours after the investigator’s knowledge of the event. Any death occurring 
after the 3-month SAE reporting period requires expedited reporting within 24 hours only if it is 
considered related to treatment, the brexucabtagene autoleucel infusion, and/or study-required 
treatments (eg, lymphodepleting chemotherapy).
PPD
PPD

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8.6.3.
Reporting Adverse Events, Serious Adverse Events, and Deaths Associated 
With Disease Progression
Progression of the malignancy (“disease progression”) as assessed by the measurement of 
malignant lesions on radiographs or other methods during the study should not be reported as an 
AE or SAE.
For situations when an AE or SAE is due to the malignancy under investigation, the sign(s) and 
symptom(s), including worsening of sign(s) and symptom(s), of the malignancy under study 
should be reported as an AE/SAE in the appropriate section of the eCRF and the investigator 
should check the appropriate data field to indicate these signs and symptoms are due to the 
underlying disease/disease progression.
If the malignancy has a fatal outcome within 3 months after the brexucabtagene autoleucel 
infusion, the event leading to death must be recorded as an SAE with CTCAE severity of 
Grade 5 and outcome of “fatal.” Within this 3-month period, the death that is due to the 
underlying disease/disease progression must be reported immediately to Kite as an SAE, as 
follows:
•
If there are no signs and symptoms of alternate underlying disease associated with the death 
(although the death has been determined to be due to disease progression), the death should 
be reported immediately to Kite as an SAE with the primary tumor type (eg, “hairy cell 
leukemia”) as the event term.
•
If the death is due to a sign or symptom of the underlying disease/disease progression and the 
sign or symptom is a targeted SAE, then the SAE will be reported as the event term. The 
investigator should check the appropriate eCRF data field to indicate that these signs and 
symptoms are due to the underlying disease/disease progression.
8.7.
Sponsor Reporting Requirements (Includes Reporting of SAEs and Deaths)
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations (CFR), EU Regulation (536/2014) and relevant updates, and other country-
specific legislation or regulations, Kite may be required to expedite to worldwide regulatory 
agencies reports of serious adverse drug reactions or suspected unexpected serious adverse 
reactions (SUSARs). In accordance with the EU Regulation (536/2014), Kite or a specified 
designee will notify worldwide regulatory agencies and the relevant IEC in concerned Member 
States of applicable SUSARs, as outlined in current regulations.
Assessment of expectedness for SAEs will be determined by Kite using reference safety 
information specified in the current IB or relevant local label as applicable.
All investigators will receive a safety notification of relevant SUSAR reports associated with any 
study drug. The investigator should notify the IRB or IEC of SUSAR reports as soon as is 
practical where this is required by local regulatory agencies and in accordance with the local 
institutional policy.

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8.8.
Toxicity Management
8.8.1.
Toxicities Associated With Brexucabtagene Autoleucel Treatment
To date, the following important identified risks have been associated with brexucabtagene 
autoleucel treatment: CRS, neurologic events, cytopenias, infections, and 
hypogammaglobulinemia. For grading of these toxicities, please refer to Section 8.4.1.1. A guide 
to the ICE score is presented in Section 12.5.
Management of these toxicities will be performed according to the American Society of Clinical 
Oncology 2021 guidelines for management {Santomasso 2021} or per the authorized 
brexucabtagene autoleucel product information in any given country. In accordance with these 
guidelines, tocilizumab is required to be available for the treatment of CRS.
In addition, the following are considered important potential risks associated with 
brexucabtagene autoleucel: secondary malignancy, immunogenicity, replication competent 
retrovirus, tumor lysis syndrome, and aggravation of GVHD. For grading of these toxicities, 
please refer to Section 8.4.1. Management recommendations of these toxicities can be found in 
the IB. Tumor lysis syndrome should be managed in accordance with the authorized Tecartus 
product information and/or institutional guidelines.
As the safety experience with brexucabtagene autoleucel increases, the management guidance 
may be updated. Therefore, it is important that you always refer to the most current version of 
the protocol for guidance regarding managing brexucabtagene autoleucel related toxicities.
8.9.
Special Situations Reports
8.9.1.
Definitions of Special Situations
Special situation reports include all reports of medication error (eg, actual or potential, misuse, 
overdose, occupational exposure, drug interactions, exposure via breastfeeding, unexpected 
benefit, transmission of infectious agents via the product, counterfeit or falsified medicine, and 
pregnancy reports [Maternal Pregnancy and Partner Pregnancy]) regardless of an associated AE.
Medication error (actual or potential) is any unintentional error in the prescribing, dispensing, or 
preparation for administration or administration of an IP while the medication is in the control of 
a healthcare professional, patient, or consumer. Medication errors may be classified as a 
medication error without an AE, which includes situations of missed dose, medication error with 
an AE, intercepted medication error, or potential medication error.
Misuse is defined as any intentional and inappropriate use of an IP that is not in accordance with 
the protocol instructions or local prescribing information.
An overdose is defined as accidental or intentional administration of a quantity of an IP (eg, 
lymphodepleting chemotherapy or other study-specified IP) given per administration or 
cumulatively that is above the maximum recommended dose as per the protocol or product 

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labeling (as it applies to the daily dose of the subject in question). In cases of a discrepancy in 
drug accountability, overdose will be established only when it is clear that the subject has taken 
the excess dose(s). Overdose cannot be established when the subject cannot account for the 
discrepancy except in cases in which the investigator has reason to suspect that the subject has 
taken the additional dose(s).
Occupational exposure is defined as exposure to an IP as a result of one’s professional or 
nonprofessional occupation.
Drug interaction is defined as any drug/drug, drug/food, or drug/device interaction.
Unexpected benefit is defined as an unintended therapeutic effect where the results are judged to 
be desirable and beneficial.
Transmission of infectious agents is defined as any suspected transmission of an infected agent 
through a Kite IP.
Counterfeit or falsified medicine is defined as any IP with a false representation of 1) its identity, 
2) its source, or 3) its history.
8.9.2.
Instructions for Reporting Special Situations
8.9.2.1.
Instructions for Reporting Pregnancies
Any pregnancy in a female subject enrolled in the study must be reported, regardless of the time 
after the brexucabtagene autoleucel infusion. If pregnancy occurs in a female partner of a male 
subject within 12 months after completing lymphodepleting chemotherapy or the brexucabtagene 
autoleucel infusion, whichever is longer, the pregnancy must be reported. All such pregnancies 
must be reported to Kite Patient Safety and Pharmacovigilance using the Pregnancy Report Form 
within 24 hours after becoming aware of the pregnancy. Information regarding the pregnancy 
and/or the outcome will be requested by Kite. Pregnancy Report Forms should be reported to 
Kite Patient Safety and Pharmacovigilance via email: 
 or fax:
 
.
The pregnancy itself or an induced elective abortion to terminate a pregnancy without medical 
reasons are not considered AEs. Any premature termination of a pregnancy (eg, spontaneous 
abortion, induced therapeutic abortion due to complications, or other medical reasons) must be 
reported within 24 hours as an SAE. The underlying medical reason for this procedure should be 
recorded as the AE term. Any SAE occurring as an adverse pregnancy outcome after the study 
has been completed must be reported to Kite Patient Safety and Pharmacovigilance.
The pregnant subject or subject partner should receive appropriate monitoring and care until 
conclusion of the pregnancy. The outcome should be reported to Kite Patient Safety and 
Pharmacovigilance using the Pregnancy Outcome Report Form. If the end of the pregnancy 
occurs after the study has been completed, the outcome should be reported directly to Kite 
Patient Safety and Pharmacovigilance.
PPD
PPD
-
-

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If a lactation case occurs in a female subject in the study, the lactation case must be reported to 
Kite Patient Safety and Pharmacovigilance within 24 hours after the investigator’s awareness of 
the event using the Special Situations Reporting Form. In addition to reporting a lactation case 
during the study, investigators should monitor for pregnancy and lactation cases throughout the 
LTFU period. Report the lactation case and Special Situations Reporting Forms to Kite Patient 
Safety and Pharmacovigilance via email: 
 or fax: 
.
8.9.2.2.
Reporting Other Special Situations
All other special situations must be reported on the Special Situations Reporting Form and 
forwarded to the Kite Patient Safety and Pharmacovigilance within 24 hours after the 
investigator becomes aware of the situation. These reports must consist of situations that involve 
study drug and/or Kite concomitant medications but do not apply to non-Kite concomitant 
medications.
Special situations involving non-Kite concomitant medications do not need to be reported on the 
Special Situations Reporting Form; however, special situations that result in AEs due to a 
non-Kite concomitant medication must be reported as an AE.
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse” but may be more appropriately documented as a protocol deviation.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE Report Form. Details of the symptoms and 
signs, clinical management, and outcome of the AEs or SAEs will be reported, when available. 
Refer to Section 8.6 and the eCRF completion guidelines for instructions on special situation 
reporting.
8.10.
Safety Review Team, Data Safety Monitoring Board, and Criteria to Pause 
Enrollment
8.10.1.
Safety Review Team
An SRT, comprising the study sponsor and at least 1 study investigator, will be specifically 
chartered to review the safety data and make recommendations on further study conduct, 
progression, and/or dose modification in each substudy after 3 to 6 subjects have been treated 
with the initial dose (2 x 106 anti-CD19 CAR T cells/kg of body weight or a maximum flat dose 
of 2 x 108 anti-CD19 CAR T cells for subjects weighing > 100 kg) and followed for 28 days. In 
accordance with the rules defined in Table 7, the SRT can recommend to i) proceed with the 
starting dose; ii) include an additional 3 subjects for evaluation prior to recommending dose; or 
iii) recommend the remaining patients to be dosed with 1 x 106 anti-CD19 CAR T cells/kg or a 
maximum flat dose of 1 x 108 anti-CD19 CAR T cells for subjects weighing > 100 kg (with a 
subsequent SRT to be held after at least 3 subjects have been treated and followed for 28 days). 
Enrollment will be paused to allow the SRT to review safety data that have been acquired for 
28 days post infusion in all treated subjects in a DLT cohort, prior to providing a 
recommendation on the continued dose selection. Enrollment will re-start once the dose 
recommendation is available. Only subjects treated with the selected target dose will be included 
in the evaluable subject population for the primary analysis.
PPD
PPD

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Initially, 1 subject will be enrolled and infused in each substudy. No additional subjects will be 
enrolled until the subject has been monitored for at least 28 days post-infusion. Subsequently, an 
additional 2 subjects in each substudy can be enrolled in parallel. After these initial 3 subjects in 
an individual substudy have been evaluated for at least 28 days, the Safety Review Team will 
make recommendations on further substudy conduct.
The SRT recommendations will be formally communicated to the participating study sites.
8.10.2.
Data Safety Monitoring Board
An independent DSMB will be chartered to review safety and futility data throughout the study 
duration to make study conduct recommendations based on an analysis of risk versus benefit 
after the target dose of 2 x 106 or 1 x 106 anti-CD19 CAR T cells/kg (or for subjects weighing 
> 100 kg, a maximum flat dose of 2 x 108 anti-CD19 CAR T cells or 1 x 108 anti-CD19 CAR 
T cells if dose reduction is required) for each substudy is confirmed by the SRT. The DSMB will 
review safety and efficacy data against the non-binding futility rules as described in each 
substudy protocol. The DSMB will review data accruing from each substudy and provide 
ongoing recommendations on study conduct to the Kite Head of Cell Therapy Clinical 
Development (or designee). Moreover, the DSMB will be provided with all available data on the 
serious adverse events (SAEs; listings or narratives) and suspected unexpected serious adverse 
reactions (SUSAR) from the global safety database for review prior to implementing the SRTs 
dose recommendations.
8.10.3.
Criteria to Pause Enrollment
As part of its oversight of the study, the DSMB will continuously assess whether to continue, 
pause or stop the study. Considering the biological heterogeneity of the indications under 
investigation, pausing enrollment to each substudy will occur independently.
In the SRT phase (that includes the treatment of the initial 3 or 6 subjects), any Grade 5 adverse 
event that is related to brexucabtagene autoleucel treatment will trigger a pause in enrollment.
Moreover, enrollment will be paused following the treatment of the 3 subjects constituting a 
DLT cohort, to assess the frequency of DLTs and to allow the SRT to review 28 days of data 
post infusion in all treated subjects prior to providing a recommendation on the target dose.
After the pivotal dose has been confirmed, enrollment within a substudy will be paused if:
A Grade 5 brexucabtagene autoleucel-related AE occurs
or
Subject incidence of the following Grade 4 brexucabtagene autoleucel-related AEs is ≥ 33%:
•
ICANS (graded according to the ASTCT consensus grading {Lee 2019})
•
CRS (graded according to the ASTCT consensus grading {Lee 2019})
•
Other non-hematological Grade 4 SAEs
•
Infection (treatment-related)

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Additionally, study enrollment will be paused when the required number of subjects have been 
enrolled in the planned interim analyses for each substudy, until the data from this interim 
analysis have been assessed.

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9.
STATISTICAL CONSIDERATIONS
9.1.
Statistical Analysis Plan
An overview of the statistical considerations is provided below, with additional details for each 
indication described in the corresponding substudy protocols. 
Details of the statistical analysis plan (SAP) are provided in the SAP document.
Note: Substudies in WM and HCL were terminated early by the Sponsor, effective 21 June 
2023. No analyses will be conducted on these 2 substudies. 
9.2.
Hypothesis
Brexucabtagene autoleucel will improve the disease response rates compared with pre-specified 
historical control data as described within each substudy.
9.3.
Definition of Study Endpoints
9.3.1.
Definitions of Primary Endpoints
Primary endpoints are substudy specific and are described in the respective substudy protocols.
9.3.2.
Definition of Secondary Endpoints
Definitions of secondary endpoints shared across the substudies are detailed in Table 11, 
additional substudy specific secondary endpoints are described in the respective substudy 
protocols.
Table 11.
Definitions of Secondary Endpoints
Secondary Endpoint
Definition
DOR
DOR is derived only among subjects who experience an 
objective response. It is defined as time from first 
objective response to disease progression per indication 
specific response criteria or death from any cause.
Subjects who do not meet the criteria for disease 
progression and who have not died will be censored at the 
last evaluable disease assessment. 
PFS
Time from enrollment (for FAS) or brexucabtagene 
autoleucel infusion (for mITT) to disease progression per 
indication specific response criteria or death from any 
cause.
Subjects not meeting the criteria for progression by the 
analysis data cutoff date will be censored at their last 
evaluable disease assessment date.
FAS and mITT are defined in Section 9.6.5.1 (Table 13)

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Secondary Endpoint
Definition
OS
Time from enrollment (for FAS) or brexucabtagene 
autoleucel infusion (for mITT) to death from any cause.
TTNT
Time from enrollment (for FAS) or brexucabtagene 
autoleucel infusion (for mITT) to initiation of next 
anticancer treatment
Time to first response 
Time from enrollment (for FAS) or brexucabtagene 
autoleucel infusion (for mITT) to first objective response
Complete Response (CR)
CR rate by central assessment as defined in each 
substudy
Time to best response
Time from enrollment (for FAS) or brexucabtagene 
autoleucel infusion (for mITT) to best objective response
Changes over time in the PRO assessment domains, 
EORTC-QLQ-C30 and ED-5D-5L
Changes in EORTC QLQ-C30 and EQ-5D-5L domains 
from baseline to post baseline
Incidence of AEs and CTCAE grade changes in 
safety laboratory values
Incidence of dose limiting toxicities
Incidence of AEs defined as dose limiting toxicities 
(Table 6)
Incidence of antibodies against brexucabtagene 
autoleucel (immunogenicity)
The presence of anti-FMC63 antibodies, where FMC63 is 
the parent antibody for the single-chain variable fragment 
that is used for production of brexucabtagene autoleucel.
The presence of antibodies against a properly folded-
FMC63 CAR protein will be assessed before and after 
infusion of brexucabtagene autoleucel. These antibodies 
are referred to as anti-brexucabtagene autoleucel 
antibodies.
Abbreviations: AE, adverse event; CAR, chimeric antigen receptor; CTCAE, common terminology criteria for adverse events; 
DOR, duration of response; EORTC-QLQ-C30, European organization for research and treatment of cancer quality of life 
questionnaire C30 version 3.0; EQ-5D-5L, European quality of life 5-dimension 5-level scale; =FAS, full analysis set; 
mITT, modified intent to treat; OS, overall survival; PFS, progression free survival; PRO, patient-reported outcome; TTNT, time 
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9.3.3.
Definition of Other Endpoints of Interest
Definitions of other endpoints of interest are detailed in Table 12.
Table 12.
Definitions of Other Endpoints of Interest
Other Endpoints of Interest
Definition
Incidence of RCR 
Incidence of RCR will be assessed before and after infusion of 
brexucabtagene autoleucel. Frequency and percentage will be 
presented.
Levels of anti-CD19 CAR T cells in blood 
and relationship with clinical outcomes 
(efficacy and toxicity)
Presence, expansion and persistence of CAR T cells in blood will 
be monitored following infusion with brexucabtagene autoleucel at 
time points detailed in the substudy SOAs. 
Serum analytes (including cytokines and 
chemokines) 
Concentration of serum analytes (including those listed in 
Section 6.7) before and after infusion of brexucabtagene autoleucel. 
Possible associations with clinical outcome will be investigated and 
summarized.
Circulating B-cell levels
Circulating levels of B cells before and after infusion of 
brexucabtagene autoleucel and the association with 
pharmacokinetics will be investigated and summarized. 
T-cell product characteristics 
T-cell phenotypes and relationship with clinical outcome. Possible 
association with efficacy and toxicity readouts of interest (eg, 
response rates, CRS and Neurotoxicity) will be investigated and 
summarized.
Incidence of T-cell reactivity against 
brexucabtagene autoleucel CAR (T-cell 
Immunogenicity)
Presence of endogenous T-cell reactivity against the FMC63 CAR 
will be assessed before and after infusion of brexucabtagene 
autoleucel as detailed in the substudy SOAs; results will be 
tabulated.
Abbreviations: CAR, chimeric antigen receptor; CRS, cytokine release syndrome; RCR, replication competent retrovirus; 
SOA, schedule of assessments
9.4.
Determination of Sample Size
Sample size determinations are substudy specific and are described in the respective substudy 
protocols.
The power estimation and statistical inference are based on the mITT population as defined in 
Section 9.6.5.1 (ie, the subjects who are enrolled and treated with brexucabtagene autoleucel, 
with measurable disease at baseline (or post-bridging therapy, if applicable)).
9.5.
Access to Individual Subject Treatment Assignments and Minimization of 
Bias
This is an open-label study, and subjects and investigators will be aware of the treatment 
received. Data handling procedures for the study will be devised to reduce potential sources of 
bias and maintain the validity and credibility of the study. These procedures will be outlined in 
the SAP, SRT charter, DSMB charter, and Trial Integrity Document.

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9.6.
Planned Analyses
9.6.1.
Interim Analysis and Early Stopping Guidelines
An interim analysis and futility assessment will be conducted in each substudy and is described 
in the substudy protocols. The interim analysis data will be reviewed by the DSMB taking into 
account the complete benefit/risk profile of brexucabtagene autoleucel. The sponsor will decide 
if the substudies should be stopped early based on DSMB recommendation and the overall 
assessment of risk and benefit. Study enrollment will be paused to allow time for the interim 
analyses.
Details regarding the planned interim analysis and the non-binding futility rule for each of the 
substudies are provided in the respective substudy protocols.
9.6.2.
Primary Analysis
Details regarding the primary analyses for the substudies are provided in the respective substudy 
protocols.
9.6.3.
Final Analysis
The final analysis will occur when all subjects have completed the study. Details regarding the 
final analyses for the substudies are provided in the respective substudy protocols.
9.6.4.
Long-term Data Analysis
All subjects receiving the brexucabtagene autoleucel infusion will be followed for survival for up 
to approximately 15 years after the brexucabtagene autoleucel infusion (refer to Section 3.4 and 
Section 3.5).
After the primary analysis, additional follow-up analyses of efficacy and safety may be 
performed as needed to satisfy regulatory requirements.
9.6.5.
Analysis Conventions
9.6.5.1.
Analysis Sets
The analysis sets that will be used to analyze study data within each substudy are detailed in 
Table 13.

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Table 13.
Analysis Sets
Analysis Set
Definition
ITT (Full analysis) set
•
Consists of all enrolled subjects (ie, the subjects who had 
leukapheresis). The full analysis set will be used for summaries of 
subject disposition, as well as analyses on the key efficacy endpoints 
(disease response rate, DOR, PFS, and OS).
mITT analysis set
•
Consists of all subjects enrolled and treated with the pivotal dose of 
brexucabtagene autoleucel, with measurable disease at baseline (or post-
bridging therapy, if applicable). The mITT analysis set will be used for 
all efficacy analyses unless otherwise specified.
DLT-evaluable set
•
Consists of first 3 subjects treated. If 1 of these subjects experience a 
DLT within 28 day of brexucabtagene autoleucel infusion, an additional 
3 subjects will be included in the DLT-evaluable set. 
Safety analysis set
•
Consists of all subjects treated with any dose of brexucabtagene 
autoleucel. This analysis set will be used for all analyses of safety.
Abbreviations: DLT, dose-limiting toxicity; DOR, duration of response; mITT, modified intent-to-treat; OS, overall survival; 
PFS, progression-free survival.
9.6.5.2.
Data Handling Convention
Every effort will be made to obtain complete data for all important endpoints. In the case of 
missing data, missing values will be imputed or censored using appropriate statistical approaches 
with sensitivity analysis. More detail will be provided in the SAP.
9.7.
Demographic Data and Baseline Characteristics
Demographic and baseline measurements will be summarized using standard descriptive 
methods. Demographic summaries will include sex, race/ethnicity, and age.
9.8.
Efficacy Analysis
The efficacy analysis using disease assessment data (eg, disease response rates, DOR and 
progression-free survival [PFS]) will be conducted based on central assessment; the disease 
response rate and key secondary endpoints such as DOR, PFS, and overall survival (OS) analysis 
will also be conducted based on investigator assessment.
9.8.1.
Disease Response Rate
The primary endpoint on incidence of disease response and exact 2-sided 95% confidence 
intervals (CIs) will be generated for mITT and full analysis set (FAS) subjects. An exact 
binomial test will be used to compare the observed response rates per central assessment to the 
historical response rate as described in each substudy. The statistical inference on the efficacy 
evaluation of brexucabtagene autoleucel will be based on the mITT set. The disease response 
rate analysis will also be conducted using investigator assessment.

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9.8.2.
Best Objective Response
The incidence of subjects with CR, very good PR (for WM only), PR, table disease, PD, and not 
evaluable as the best response to treatment and exact 2-sided 95% CIs about the incidence will 
be generated for mITT and FAS subjects.
9.8.3.
Duration of Response
Kaplan-Meier (KM) estimates and 2-sided 95% CIs will be generated for the DOR for the 
subjects who responded to brexucabtagene autoleucel. The DOR will be derived using disease 
assessments obtained on study before initiation of a new anticancer therapy (including stem cell 
transplant). Subjects who do not meet the criteria for disease progression and who have not died 
will be censored at the last evaluable disease assessment. Disease assessments obtained after new 
anticancer therapies (including stem cell transplant) will not contribute to the derivation of DOR. 
Such subjects will have DOR censored at the last evaluable disease assessment prior to the 
commencement of the anticancer therapy or stem cell transplant. For subjects who undergo stem 
cell transplant while in remission, a supplementary analysis will be conducted in which disease 
assessments obtained after stem cell transplant are included in the derivation of DOR.
9.8.4.
Progression-free Survival
KM estimates and 2-sided 95% CIs will be generated for PFS time for both mITT and FAS 
subjects. Estimates of the proportion of subjects alive and progression free at 3-month intervals 
will be provided. PFS will be derived using disease assessments obtained on study prior to 
initiation of new anticancer therapy (including stem cell transplant). Subjects not meeting the 
criteria for progression by the analysis data cutoff date will be censored at their last evaluable 
disease assessment date. For subjects who undergo stem cell transplant while in remission, a 
supplementary analysis will be conducted in which disease assessments obtained after stem cell 
transplant are included in the derivation of PFS.
9.8.5.
Overall Survival
KM estimates and 2-sided 95% CIs will be generated for OS for both mITT and FAS subjects. 
Estimates of the proportion of subjects alive at 3-month intervals will be provided. Subjects who 
have not died by the analysis data cutoff date will be censored at their last known alive date.
9.9.
Safety Analysis
Subject incidence rates of treatment-emergent AEs (TEAEs), defined as AEs with an onset on or 
after the brexucabtagene autoleucel infusion, will be summarized. TEAEs including all, serious, 
fatal, Grade 3 or higher (per CTCAE v5.0) will be tabulated by preferred term and/or system 
organ class. CTCAE grade changes in safety laboratory values will be summarized with 
descriptive statistics. The incidence of concomitant medications will be summarized 
descriptively. Clinical and laboratory AEs will be coded using the Medical Dictionary for 
Regulatory Activities.

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Tables and/or narratives of deaths through the post-treatment follow-up and treatment-related 
SAEs will be provided.
9.10.
Multiplicity Adjustment
No multiplicity adjustments will be made.
9.11.
Pharmacokinetics Analysis
Results and summary statistics (eg, peak and area under the curve from Day 0 to Day 28) will be 
tabulated. Possible association with efficacy and toxicity readout of interest (eg, ORR, CRS and 
Neurotoxicity) will be investigated and summarized. The relationship with levels of CAR T cells 
(pharmacokinetics) and efficacy readouts (eg, disease response rate, CR rate and Ongoing 
Response Rate) will be summarized and tabulated.
9.12.
Pharmacodynamics Analysis
Results and summary statistics will be tabulated. Possible association with toxicity readouts of 
interest (eg, CRS and neurotoxicity) will be investigated and summarized.
9.13.
Patient-reported Outcome Analysis
Changes in EORTC QLQ-C30 domains, EQ-5D-5L index, and visual analog scale (VAS) scores 
from screening will be summarized with descriptive statistics. In addition, the mean/median 
changes in EORTC QLQ-C30 domains, EQ-5D-5L index, and VAS scores from screening over 
time will be presented with plots.

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10.
RESPONSIBILITIES
10.1.
Investigator Responsibilities
10.1.1.
Financial Disclosure
The investigator and subinvestigators will provide prompt and accurate documentation of their 
financial interest or arrangements with the sponsor or proprietary interests in the IP during the 
course of a clinical study. This documentation must be provided before the investigator’s (and 
any subinvestigator’s) participation in the study. The investigator and subinvestigator agree to 
notify Kite of any change in reportable interests during the study and for 1 year after completion 
of the study. Study completion is defined as the date when the last subject completes the 
protocol-defined activities.
10.1.2.
IRB/IEC Approvals
A copy of the protocol, ICF, and any additional subject or trial information, such as subject 
recruitment materials, must be submitted to each study site’s respective IRB/IEC for approval. 
After approval is obtained from the IRB/IEC, all documents must be provided to the key sponsor 
contact before subject recruitment can begin.
The investigator must also receive IRB/IEC approval for all protocol and ICF changes or 
amendments. Investigators must ensure that ongoing/continuous IRB/IEC approval (ie, annual 
approval) is provided throughout the conduct of the study. Copies of IRB/IEC approval are to be 
forwarded to the key sponsor contact for archiving.
During the study, investigators are to submit site-specific and study SAEs (provided to the study 
site by the key sponsor contact) along with any protocol deviations to their IRB/IEC in 
accordance with their respective IRB/IEC policies.
10.1.3.
Informed Consent
Before a subject can participate in the clinical study, the investigator is responsible for obtaining 
written informed consent from the subject after adequate explanation of the study design, 
anticipated benefits, and potential risks. The consent process and subject’s agreement or refusal 
to participate in the study is to be documented in the subject’s medical records. If the subject 
agrees to participate, the most current IRB/IEC-approved ICF is to be signed and personally 
dated by the subject and person who conducted the informed consent discussion. The original 
signed ICF will be retained in accordance with the institution’s policy and IRB/IEC 
requirements, and a copy of the ICF will be provided to the subject.
All subjects who are enrolled into the study should be reconsented with any updated version of 
the IRB/IEC-approved ICF if relevant to their participation in the study.

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The ICF will inform subjects about genomic testing and/or planned sample retention. In addition 
to the study-specific ICF to be signed by each subject participating in the study, subjects will be 
required to document agreement to provide additional samples or allow the use of the remainder 
of their already collected specimens for optional future genomic research, in accordance with 
applicable regulations. The results of the tests done on the samples will not be given to the 
subject or investigator, given that the results do not inform clinical decision making.
10.1.4.
Confidentiality
The investigator must assure that the subjects’ anonymity will be strictly maintained and that 
their identities are protected from unauthorized parties. Only an ID code and any other unique 
identifier(s) as allowed by local law (such as year of birth) will be recorded on any form or 
biological sample submitted to Kite or the laboratory. Laboratory specimens must be labeled in 
such a way as to protect subject identity while allowing the results to be recorded for the proper 
subject (refer to specific laboratory instructions for further information). Subject data will be 
processed in accordance with all applicable regulations.
Kite has established processes in place to ensure the security and confidentiality of data records 
and personal information. This includes: restricting access, via secure login information for 
individual authorized users, to electronic personal data and study data systems; 
pseudonymization of trial subject data; encryption of all personal data in transit and at rest; and a 
robust data privacy and security due diligence process with third party vendors, which includes a 
written contract with each vendor to abide by privacy and security obligations. Processes are also 
in place to avoid loss of information. Should a data security breach occur, Kite will follow their 
relevant SOPs to mitigate the impact. Kite will abide by all available National and International 
data protection legislation. Further details on what personal data are collected, where they are 
stored, how they are processed and who will have access is described in the study country 
specific patient information sheets.
The investigator agrees that all information received from Kite, including but not limited to the 
IB, this protocol, eCRFs, the study drug, and any other study information, remain the sole and 
exclusive property of Kite during the conduct of the study and thereafter. This information is not 
to be disclosed to any third party (except employees or agents directly involved in the conduct of 
the study or as required by law) without prior written consent from Kite. The investigator further 
agrees to take all reasonable precautions to prevent the disclosure by any employee or agent of 
the study site to any third party or otherwise into the public domain.
Per federal regulations and International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use (ICH)/GCP guidelines, investigators and institutions are 
required to permit direct access to the sponsor, CRO, IRB/IEC, and regulatory agencies to a 
subject’s original source documents for verification of study data. The investigator is responsible 
for informing potential subjects that such individuals will have access to their medical records, 
which include personal information.

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Subject confidentiality must be maintained on all material submitted to the key sponsor contact. 
The following rules are to be applied.
•
Subjects will be identified by a unique ID number.
•
Year of birth/age at time of enrollment will be reported according to local laws and 
regulations.
For the reporting of SAEs, subjects will be identified by their respective subject ID number and 
year of birth (as per their local reporting requirements).
10.1.5.
Study Files and Retention of Records
The investigator will maintain a list of qualified staff to whom study responsibilities have been 
delegated. These individuals authorized to fulfill these responsibilities should be outlined and 
included in the delegation of authority form.
Source documents are original documents, data, and records for which the study data are 
collected and verified. Example of such source documents may include, but are not limited to, 
hospital records and patient charts, laboratory, pharmacy, radiology and records, subject diaries, 
microfiches, correspondence, and death registries.
The investigator and study staff are responsible for maintaining a comprehensive filing system of 
all subject records that are readily retrieved to be monitored and/or audited at any time by the 
key sponsor contact (or delegate), regulatory authorities, and IRB/IECs. The filing system will 
include at minimum:
•
Subject content including ICFs and subject ID lists
•
Essential documents for the conduct of this clinical study
•
Proof of receipt, experimental treatment flow records, and experimental product-related 
correspondence.
Original source documents supporting entries into eCRFs must be maintained at the study site 
and readily available upon request. No study documents should be discarded without prior 
written agreement between Kite and the investigator. Should storage no longer be available to 
archive source documents or need to be moved to an alternative location, the research staff 
should notify the key sponsor contact before shipping the documents.
The required source data should include sequential notes containing at least the following 
information for each subject:
•
Subject ID
•
Documentation that the subject meets eligibility criteria (ie, medical history, physical 
examination, and confirmation of diagnosis [to support inclusion and exclusion criteria])

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•
Documentation of the reason(s) a consented subject is not enrolled
•
Participation in the study (including study number/name)
•
Study discussed and date of informed consent
•
Dates of all visits
•
Documentation that protocol-specific procedures were performed
•
Results of efficacy parameters, as required by the protocol
•
Start and end date (including dose regimen) of the IP, including the start and stop times of the 
brexucabtagene autoleucel infusion
•
Record of all AEs and other safety parameters (start and end date, and including causality 
and severity), and documentation that adequate medical care has been provided for any AE
•
Concomitant medications (including the start and end dates, dose [if relevant], and dose 
changes)
•
Date of study completion and reason for early discontinuation, if it occurs
Traceability records for the product, from procurement through manufacture to administration of 
the product, should be kept by each relevant party (eg, the sponsor and investigator/institution) 
for a minimum of 30 years after the expiry date of the product, or longer if required by the terms 
of the clinical trial authorization or by agreement with Kite. Before, during, and after completion 
or termination of the trial, each party should hold the necessary information available at all times 
to ensure bidirectional traceability, linking the subject information at the procurement site to the 
product and subject information at the study site to the product, while ensuring the data 
protection legally required for the subject.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Kite to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
If a subject transfers to another study site, the investigator must notify Kite in advance before 
assigning the subject’s study records to another party or moving them to another location.
10.1.6.
Electronic Case Report Forms
All data will be collected in an eCRF system. All entries must be completed in English and 
concomitant medications should be identified by trade names. For further details surrounding the 
completion of eCRFs, refer to the eCRF completion guidelines.

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For each subject consented, an eCRF casebook will be completed by an authorized study staff 
member whose training for this function is completed in the electronic data capture (EDC) 
system. The eCRF casebook will only capture the data required per the respective substudy SOA 
and procedures. The eligibility criteria and enrollment eCRFs should be completed only after all 
data related to eligibility have been received. Data entry should be performed in accordance with 
the eCRF completion guidelines provided by the sponsor.
Subsequent to data entry, a study monitor will perform source data verification within the EDC 
system. System-generated or manual queries will be issued in the EDC system as data 
discrepancies are identified by the monitor or Kite staff who routinely review the data for 
completeness, correctness, and consistency. The study site investigator or coordinator or other 
designee is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry and providing the reason 
for the update (eg, data entry error). Original entries, as well as any changes to data fields, will 
be stored in the audit trail of the system. At a minimum, before any interim time points or 
database lock (as instructed by Kite), the investigator will use his/her log-in credentials to 
confirm that the forms have been reviewed and that the entries accurately reflect the information 
in the source documents.
At the conclusion of the study, Kite will provide the study site investigator with a read-only 
archive copy of the data entered by that site. This archive must be stored in accordance with the 
records retention requirements outlined in Section 10.1.5.
10.1.7.
Access to Study Information
The investigator will make available all source documents and other records for this study to 
Kite’s appointed study monitors, IRBs/IECs, or regulatory or health authority inspectors. By 
signing the investigator statement, the investigator agrees to cooperate with the monitor to 
address and resolve issues identified during monitoring visits, audits, and regulatory authority 
inspections.
10.1.8.
Protocol Compliance
The investigator is responsible for ensuring that the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
10.2.
Sponsor Responsibilities
10.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Kite. The investigator must submit all protocol modifications to the IRB/IEC in 
accordance with local requirements and receive documented approval before modifications can 
be implemented. Documentation acknowledging agreement with the protocol amendment from 
the investigator and approval from the IRB/IEC are to be submitted to the key sponsor contact.

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10.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(ies) when 
applicable and in accordance with local regulatory requirements. Kite will ensure that the report 
meets the standards set out in the ICH Guideline for Structure and Content of Clinical Study 
Reports (ICH E3). Note that an abbreviated report may be prepared in certain cases. For studies 
with sites in countries following EU Regulation No. 536/2014, a CSR will be submitted within 
1 year after the global end of study (defined in Section 3.4).
Investigators in this study may communicate, orally present, or publish study data in scientific 
journals or other scholarly media in accordance with the Kite clinical trial agreement. 
10.2.3.
Financing and Insurance
Kite has insurance that provides compensation for study-related illness or injury pursuant to the 
information outlined in the injury section of the ICF.
Investigators and their study staff may be asked to provide services performed under this 
protocol (eg, attendance at investigator meetings). If required under the applicable statutory and 
regulatory requirements, Kite will capture and disclose to federal and state agencies any 
expenses paid or reimbursed for such services, including any clinical study payments, meal, 
travel expenses or reimbursements, consulting fees, and any other transfer of value.
10.3.
Joint Investigator/Sponsor Responsibilities
10.3.1.
Good Clinical Practice
The investigator, sponsor, and sponsor delegates will ensure that this study is conducted in 
accordance with ICH GCP guidelines, including the E6(R2) addendum for GCP, and applicable 
laws and regulations.
10.3.2.
Quality Control and Quality Assurance
The key sponsor contact, monitors, auditors, or regulatory inspectors are responsible for 
contacting and visiting the investigator for the purpose of inspecting the facilities and verifying 
source documents and records to assure that subject confidentiality is respected.
The monitor is responsible for source document verification of eCRF data at regular intervals 
during the study. Protocol adherence and accuracy and consistency of study conduct and data 
collection with respect to local regulations will be confirmed.
In accordance with ICH GCP and the audit plan, a study site may be chosen for a Kite Quality 
Assurance site audit. A Kite Quality Assurance site audit would include, but is not limited to, an 
inspection of the facility(ies), review of subject and study-related records, and compliance with 
protocol requirements, as well as ICH GCP and applicable regulatory policies. Investigators will 
provide Kite Quality Assurance auditors access to subject records.

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Representatives of regulatory authorities may conduct inspections of the clinical study. If the 
investigator is notified of an inspection by a regulatory authority, the investigator agrees to notify 
the sponsor immediately. The investigator agrees to provide to representatives of a regulatory 
agency access to records, facilities, and personnel for the effective conduct of any inspection or 
audit.
10.3.3.
Ethics
Study KT-US-568-0138 will be conducted under a US Investigational New Drug application or 
equivalent and in accordance with recognized international scientific and ethical standards, 
including but not limited to the ICH guideline for GCP and original principles embodied in the 
Declaration of Helsinki. These standards are consistent with the requirements of the US CFR 
Title 21, Part 312, and EU Regulation (2001/2014), as well as other local legislation.
10.3.4.
Study Discontinuation
Both Kite and the investigator reserve the right to terminate the investigator’s participation in the 
study as per the terms of the agreement in the study contract. The investigator is to provide 
written communication to the IRB/IEC of the trial completion or early termination.

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11.
REFERENCES
Anderson KC, Bates MP, Slaughenhoupt BL, Pinkus GS, Schlossman SF, Nadler LM. 
Expression of human B cell-associated antigens on leukemias and lymphomas: a 
model of human B cell differentiation. Blood 1984;63 (6):1424-33.
Becnel MR, Nastoupil LJ, Samaniego F, Davis RE, You MJ, Green M, et al. Lenalidomide Plus 
Rituximab (R(2) ) in Previously Untreated Marginal Zone Lymphoma: Subgroup 
Analysis and Long-Term Follow-up of an Open-Label Phase 2 Trial. Br J 
Haematol 2019;185:874-82.
Berger F, Traverse-Glehen A, Felman P, Callet-Bauchu E, Baseggio L, Gazzo S, et al. 
Clinicopathologic features of Waldenstrom's macroglobulinemia and marginal 
zone lymphoma: are they distinct or the same entity? Clin Lymphoma 2005;5 
(4):220-4.
Chen B, Fend F, Campo E, Quintanilla-Martinez L. Aggressive B-cell lymphomas—from 
morphology to molecular pathogenesis. Annals of Lymphoma 2019;3 (1).
Clinical Trials Facilitation and Coordination Group (CTFG). Recommendations related to 
contraception and pregnancy testing in clinical trials.  September 21, 2020.
Davila ML, Sadelain M. Biology and clinical application of CAR T cells for B cell malignancies. 
International Journal of Hematology 2016.
Fallowfield LJ, Baum M, Maguire GP. Do psychological studies upset patients? Journal of the 
Royal Society of Medicine 1987;80 (1):59.
Finney HM, Lawson AD, Bebbington CR, Weir AN. Chimeric Receptors Providing Both 
Primary and Costimulatory Signaling in T Cells from a Single Gene Product. J 
Immunol 1998;161 (6):2791-7.
Fridericia LS. The Duration of Systole in an Electrocardiogram in Normal Humans and in 
Patients with Heart Disease. Ann Noninvasive Electrocardiol 2003;8 (4):343-51.
Gattinoni L, Klebanoff CA, Palmer DC, Wrzesinski C, Kerstann K, Yu Z, et al. Acquisition of 
full effector function in vitro paradoxically impairs the in vivo antitumor efficacy 
of adoptively transferred CD8+ T cells. J Clin Invest 2005;115 (6):1616-26.
Grunenberg A, Buske C. Treatment options for relapsed Waldenström’s Macroglobulinemia. 
HemaSphere 2019;3 (S2):65-7.
Jackson HJ, Rafiq S, Brentjens RJ. Driving CAR T-cells forward. Nat Rev Clin Oncol 2016;13 
(6):370-83.

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Jacobson C, Locke FL, Ghobadi A, Miklos DB, J. LL, Oluwole OO, et al. Long-Term (4-and 5-
Year) Overall Survival in ZUMA-1, the Pivotal Study of Axicabtagene Ciloleucel 
in Patients with Refractory Large B-Cell Lymphoma [Presentation]. 63rd 
American Society of Hematology (ASH) Annual Meeting and Exposition; 2021a 
December 11; Atlanta, GA & Online. 
Jacobson CA, Chavez JC, Sehgal AR, William BM, Munoz J, Salles G, et al. Axicabtagene 
ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): 
a single-arm, multicentre, phase 2 trial. Lancet Oncol 2021b.
Kochenderfer JN, Feldman SA, Zhao Y, Xu H, Black MA, Morgan RA, et al. Construction and 
Preclinical Evaluation of an Anti-CD19 Chimeric Antigen Receptor. J 
Immunother 2009;32 (7):689-702.
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT 
Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity 
Associated with Immune Effector Cells. Biol Blood Marrow Transplant 
2019;25:625-38.
Nadler LM, Anderson KC, Marti G, Bates M, Park E, Daley JF, et al. B4, a human B 
lymphocyte-associated antigen expressed on normal, mitogen-activated, and 
malignant B lymphocytes. J Immunol 1983;131 (1):244-50.
Neelapu S, Locke F, Bartlett N, Lekakis L, Miklos D, Jacobson C, et al. Axicabtagene ciloleucel 
(axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin 
lymphoma (NHL): primary results of the pivotal trial ZUMA-1. International 
Conference on Malignant Lymphoma (ICML) 2017a.
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene 
Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J 
Med 2017b;377 (26):2531-44.
Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T 
cell response. Nat Rev Immunol 2012;12 (4):269-81.
Rinaldi A, Mian M, Chigrinova E, Arcaini L, Bhagat G, Novak U, et al. Genome-wide DNA 
profiling of marginal zone lymphomas identifies subtype-specific lesions with an 
impact on the clinical outcome. Blood 2011;117 (5):1595-604.
Roberts KG. Genetics and Prognosis of ALL in Children vs Adults. Am Soc Hematol 2018;2018 
(1):137-45.
Rossi D, Spina V, Gaidano G. Biology and treatment of Richter syndrome. Blood 2018;131 
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Ruella M, Maus MV. Catch Me If You Can: Leukemia Escape after CD19-Directed T Cell 
Immunotherapies. Comput Struct Biotechnol J 2016;14:357-62.
Ruella M, Xu J, Barrett DM, Fraietta JA, Reich TJ, Ambrose DE, et al. Induction of Resistance 
to Chimeric Antigen Receptor T Cell Therapy by Transduction of a Single 
Leukemic B Cell. Nat Med 2018;24:1499-503.
Santomasso BD, Nastoupil LJ, Adkins S, Lacchetti C, Schneider BJ, Anadkat M, et al. 
Management of Immune-Related Adverse Events in Patients Treated With 
Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline. J Clin Oncol 
2021;39 (35):3978-92.
Short NJ, Kantarjian HM, Ko H, Khoury JD, Ravandi F, Thomas DA, et al. Outcomes of adults 
with relapsed or refractory Burkitt and high-grade B-cell leukemia/lymphoma. 
Am J Hematol 2017;92 (6):E114-E7.
Sun R, Medeiros LJ, Young KH. Diagnostic and predictive biomarkers for lymphoma diagnosis 
and treatment in the era of precision medicine. Mod Pathol 2016;29 (10):1118-42.
TECARTUS, Kite Pharma Inc. TECARTUS® (brexucabtagene autoleucel) suspension for 
intravenous infusion. U.S Prescribing Information. Santa Monica, CA. Revised 
October.  2021:
Tiacci E, Park JH, De Carolis L, Chung SS, Broccoli A, Scott S, et al. Targeting Mutant BRAF 
in Relapsed or Refractory Hairy-Cell Leukemia. N Engl J Med 2015;373 
(18):1733-47.
Uckun FM. Regulation of Human B-Cell Ontogeny. Blood 1990;76 (10):1908-23.
Uckun FM, Jaszcz W, Ambrus JL, Fauci AS, Gajl-Peczalska K, Song CW, et al. Detailed Studies 
on Expression and Function of CD19 Surface Determinant by Using B43 
Monoclonal Antibody and the Clinical Potential of Anti-CD19 Immunotoxins. 
Blood 1988;71 (1):13-29.
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intravenous infusion. U.S. Prescribing Information. Santa Monica, CA. Revised 
April.  2021:

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12.
APPENDICES
Section 12.1 
Sponsor and Investigator Signature Page
Section 12.2 
Schedules of Assessment
Section 12.3 
Childbearing Potential and Birth Control
Section 12.4 
Country-specific Regulatory Agency Requirements
Section 12.5 
Immune Effector Cell-associated Encephalopathy Score
Section 12.6 
Patient-reported Outcomes
Section 12.7 
Practical Body Weight Calculation for Subjects Whose BMI is > 35 kg/m2
Section 12.8 
Pandemic Risk Assessment and Mitigation Plan
Section 12.9
Tabulated List of Investigational Medicinal Products and Auxiliary 
Medicinal Products
Section 12.10 
Protocol Amendment History

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12.1.
Sponsor and Investigator Signature Page
KITE PHARMA, INC.
2400 BROADWAY
SANTA MONICA, CA 90404
STUDY ACKNOWLEDGMENT
A Phase 2, Open-Label, Multicenter, Basket Study Evaluating the Efficacy of Brexucabtagene 
Autoleucel in Adults with Rare B-cell Malignancies
Amendment 3.0, 17 AUGUST 2023
This protocol has been approved by Kite Pharma, Inc. The following signature documents this 
approval.
See appended electronic signature
See appended electronic signature
Kite Medical Monitor Name (Printed) 
Signature
See appended electronic signature
Date
INVESTIGATOR STATEMENT
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated.
I agree to comply with the International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use (ICH) Harmonised Tripartite Guideline on Good Clinical 
Practice and applicable national or regional regulations and guidelines. I will provide all study 
personnel under my supervision copies of the protocol and access to all information provided by 
Kite Pharma, Inc. I will discuss this material with them to ensure that they are fully informed 
about the investigational product and study.
I agree and will ensure that financial disclosure statements will be completed by:
•
Me (including, if applicable, my spouse, legal partner, and dependent children)
•
Subinvestigators (including, if applicable, their spouse, legal partner, and dependent children) 
at the start of the study and for up to 1 year after the study is completed.
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the conduct of the clinical investigation without prior written consent 
from Kite Pharma, Inc.
Principal Investigator Name (Printed)
Signature
Date
Study Site Number

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12.2.
Schedules of Assessment
The assessments and procedures to be performed during the treatment and post-treatment 
follow-up periods are presented in the schedule of assessments in Section 12 of each substudy 
protocol.

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12.3. 
Childbearing Potential and Birth Control 
Final 
Amendment 3.0 
This study will follow the recommendations from the Clinical Trial Facilitation Group (CTFG) 
{Clinical Trials Facilitation and Coordination Group (CTFG) 2020} together with requirements 
from Kite, as described in the following sections. 
12.3.1. 
Definition of Childbearing Potential 
A woman is considered of childbearing potential (ie, fe1iile) following menarche and until 
becoming postmenopausal unless pe1m anently sterile. Pe1m anent sterilization methods include 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. 
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. A high follicle stimulating honnone (FSH) level in the postmenopausal range may be used 
to confnm a postmenopausal state in females not using ho1m onal contraception or honnonal 
replacement therapy. However, in the absence of 12 months of amenonhea, a single FSH 
measurement is insufficient. 
For the purpose of this study, a male is considered fe1iile after pube1iy unless pe1manently sterile 
by bilateral orchidectomy. 
12.3.2. 
Birth Control Methods That May Be Considered as Highly Effective 
Methods that can achieve a failure rate of < 1 % per year when used consistently and con ectly are 
considered as highly effective biith control methods. Such methods include: 
• 
Combined ( estrogen- and progesterone-containing) honnonal contraception associated with 
inhibition of ovulationa when used together with baiTier contraceptives ( condoms or 
diaphragm with spennicide): 
-Oral 
-Intravaginal 
-Transdennal 
• 
Progestogen-only honnonal contraception associated with inhibition of ovulationa when used 
together with baiTier contraceptives (condoms or diaphragm with spe1micide): 
-Oral 
- Injectable 
• Ho1monal contraception may be susceptible to interaction with the investigational product, which may reduce the 
efficacy of the contraception method. Honnonal contraceptives are only assessed as an appropriate contraceptive 
measure if used simultruteously with ban-ier contraceptives (condoms or diaphragm with spe1micide). 
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Implantableb
•
Intrauterine deviceb
•
Intrauterine hormone-releasing systemb
•
Bilateral tubal occlusionb
•
Vasectomized partnerb,c
•
Sexual abstinenced
12.3.3.
Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (calendar, 
symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method. A female condom and a male condom should not be used 
together.
b  Contraception methods that in the context of this guidance are considered to have low user dependency.
c  A vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of 
the female of childbearing potential trial participant and that the vasectomized partner has received medical 
assessment of the surgical success.
d  In the context of this guidance sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and preferred 
and usual lifestyle of the subject.

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12.4.
Country-specific Regulatory Agency Requirements
12.4.1.
Requirement for a Multidisciplinary Consultation Meeting Before Subject 
Inclusion in France
In accordance with Agence nationale de sécurité du médicament et des produits de santé 
(ANSM) requirements, a multidisciplinary team is required to consult prior to inclusion of a 
subject in the trial.
12.4.2.
Post-infusion Monitoring 
12.4.2.1.
For All European Union Countries
The post-infusion monitoring of subjects, described in Section 7.6.3 of this protocol, will be 
extended by monitoring on Days 8, 9, and 10, according to the procedures outlined in the 
substudy schedule of assessments, “treatment period” column. The subject may remain 
hospitalized or return to the clinic daily for this extended monitoring at the discretion of the 
investigator. Daily monitoring will include vital signs (refer to Section 6.3.5), blood draw for 
chemistry panel with C-reactive protein, blood draw for complete blood count with differential, 
and neurological examination (refer to Section 6.3.6). Any observed toxicity will be managed 
according to instructions detailed in Section 8 of this protocol.
12.4.2.2.
For Switzerland
All subjects in Switzerland will be hospitalized during the treatment period from before the 
brexucabtagene autoleucel infusion (Day 0) until a minimum of 10 days after treatment 
(Day 10). Subjects will be monitored post-infusion as described in Section 7.6.3.
12.4.3.
Pregnancy testing
Females of childbearing potential should be monitored according to local and country-specific 
regulations.
For EU/CH study sites, a pregnancy test will be completed within 7 days before both 
leukapheresis and lymphodepleting chemotherapy for women of childbearing potential.

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12.5.
Immune Effector Cell-associated Encephalopathy Score
A guide to the immune effector cell-associated encephalopathy score is presented in Table 14.
Table 14.
Immune Effector Cell-associated Encephalopathy Scorea
Task
Score
Orientation:
Orientation to year, month, city, and 
hospital 
4 points
Naming:
Ability to name 3 objects (eg, point to 
clock, pen, or button) 
3 points
Following commands:
Ability to follow simple 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:
Ability to count backwards from 100 
by 10 
1 point
a
Immune effector cell-associated encephalopathy score as developed by the American Society for Transplantation and 
Cellular Therapy consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector 
cells {Lee 2019}.

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12.6.
Patient-reported Outcomes
All patient-reported outcomes described are expected to be completed by the subject before any 
procedures are performed, excluding blood draws, and at the time points noted in the respective 
substudy.
12.6.1.
European Organisation for Research and Treatment of Cancer Quality of 
Life Questionnaire C30 Version 3.0
This measure is a 30-item questionnaire designed to provide a multidimensional assessment of 
health-related quality of life (HRQoL), with a recall period of 1 week. The European 
Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients 
Questionnaire (EORTC QLQ-C30) version (v)3.0 includes the following scales:
•
5 multi-item functional scales (assessing physical, role, emotional, cognitive, and social
functioning) and 3 symptom scales (fatigue, nausea and vomiting, and pain)
•
6 single-item symptom scales (dyspnea, insomnia, appetite loss, constipation, diarrhea, and
financial difficulties)
•
2 global scales (Global Health Status and HRQoL)
No items are shared between the scales. The first 28 of 30 items have 4-level ordinal responses 
from 1 (“not at all”) to 4 (“very much”). The final 2 items, comprising the global health status 
and HRQoL scale, have 7-level ordinal responses from 1 (“very poor”) to 7 (“excellent”). Each 
scale is measured from 0 to 100 after a linear transformation. Higher scores for functional scales 
and the Global Health Status or Global HRQoL scales indicate a higher level of functioning and 
a better HRQoL, respectively, whereas higher scores in symptom scales represent a higher level 
of symptoms.
This instrument does not sum together all items, which can potentially group differences and 
allows an assessment of change across the 15 different domains. In its current version (v3.0), the 
questionnaire takes approximately 11 minutes to complete.
12.6.2.
European Quality of Life 5-dimension 5-level Questionnaire
The European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) is a generic measure of 
health status captured on the day of assessment. Two components comprise the EQ-5D-5L: the 
EQ-5D descriptive system and the EQ visual analog scale (VAS). The descriptive system 
comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression) and is divided into 5 levels of severity: “no problems”, “slight problems”, 
“moderate problems”, “severe problems”, and “extreme problems”.
The EQ-5D-5L VAS is a vertical VAS for recording self-rated current HRQoL state reported 
from 0, described as “the worst health you can imagine”, to 100, described as “the best health 
you can imagine”.
The EQ-5D-5L takes approximately 5 minutes to complete.

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12.7.
Practical Body Weight Calculation for Subjects Whose Body Mass Index 
(BMI) is > 35 kg/m2
Dose calculation based on actual or practical body weight is as follows:
•
Actual body weight at leukapheresis is to be used for brexucabtagene autoleucel. For subjects 
weighing > 100 kg, a maximum flat dose of 2 × 108 anti-CD19 CAR T cells will be 
administered. 
•
Actual body weight is to be used for lymphodepleting chemotherapy and mesna when the 
subject’s body mass index (BMI) is ≤ 35 kg/m2.
•
Practical body weight is to be used for lymphodepleting chemotherapy and mesna when the 
subject’s BMI is > 35 kg/m2. See formula below.
BMI determination:
•
BMI = weight (kg)/[height (m)]2 or
•
BMI = 703 × weight (lb)/[height (in)]2
Calculation of ideal body weight:
•
Male = 50 kg + 2.3 (number of inches over 60 inches)
Example: ideal body weight of 5’10” male
50 + 2.3 (10) = 73 kg
•
Female = 45.5 kg + 2.3 (number of inches over 60 inches)
Example: ideal body weight of a 5’3” female
45.5 + 2.3 (3) = 52.4 kg
•
Calculation of “practical weight”: Calculate the average of the actual and the ideal body 
weights.

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12.8.
Pandemic Risk Assessment and Mitigation Plan
During an ongoing pandemic, potential risks associated with subjects being unable to attend 
study visits have been identified for this study.
These risks can be summarized as follows:
1) Subject safety monitoring and follow-up:
a) Subjects may be unable or unwilling to come to the investigational site for their 
scheduled study visits as required per protocol.
Mitigation plan: For subjects who may be unable or unwilling to visit the investigational 
site for their scheduled study visits as required per protocol, the principal investigator or 
qualified delegate will conduct a remote study visit, via phone or video conferencing, to 
assess the subjects within the target visit window date whenever possible. During the 
remote study visit, the following information at minimum will be reviewed:
i)
Confirm if subject has experienced any adverse events (AEs)/serious adverse events 
(SAEs)/special situations (including pregnancy) and follow-up on any unresolved 
AEs/SAEs.
ii) Review the current list of concomitant medications and document any new 
concomitant medications.
iii) If applicable, confirm electronic/paper diary questionnaires and patient reported 
outcomes have been completed and transmitted.
b) Subjects may be unable or unwilling to travel to the site for planned assessments (eg, 
blood draws, imaging, physical exams).
Mitigation plan: Local laboratories or other vendors may be utilized as appropriate to 
monitor subject safety until the subject can return to the site for their regular follow-up 
per protocol. Any changes in the party conducting laboratory assessments for the study 
because of the pandemic will be documented accordingly. Pregnancy testing may be 
performed using a home urine pregnancy test if local laboratory pregnancy testing is not 
feasible. Central lab kits may be sent to subject’s local hospital lab for sample collection. 
Relevant imaging (e.g. PET-CT, CT) can be done at the subject’s local hospital and 
images transferred or sent to the investigative site. Physical exams can be completed by a 
local physician with results sent to investigative site.
c) Subjects may be unable or unwilling to attend the study visit to sign an updated informed 
consent form version.
Mitigation plan: The site staff will follow their approved informed consent process and 
remain in compliance with the local ethics committee/institutional review board and 
national laws and regulations. Remote consent will be allowed if has been approved by 

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the local ethics committee/institutional review board. The consent process will be 
documented and confirmed by normal consent procedure at the investigative site at the 
earliest opportunity.
2) Protocol and monitoring compliance:
a) Protocol deviations may occur in situations where scheduled visits or procedures cannot 
be conducted as planned per protocol.
Mitigation plan: If it is not possible to complete a required procedure at a protocol-
specified time point, an unscheduled visit should be conducted as soon as possible when 
conditions allow so that the required procedure can be performed. The situation should be 
recorded and explained as a protocol deviation. Any missed subject visits must be 
reported in the eCRF, if possible, and recorded as deviations to the protocol because of 
the pandemic, so that they can be appropriately documented and described in the clinical 
study report. Any remote study visits that are conducted in lieu of clinic visits because of 
the pandemic will be documented as a protocol deviation related to the pandemic.
b) Study monitors may be unable to carry out source data review or source data verification, 
or study drug accountability or assess protocol and Good Clinical Practice compliance. 
This may lead to delays in source data verification, an increase in protocol deviations, or 
underreporting of AEs.
Mitigation plan: The study monitor is to remain in close communication with the site to 
ensure ongoing data entry and query resolution. Remote source data verification may be 
arranged if allowed by local regulation and the Study Monitoring Plan. The study monitor 
is to reference the Study Monitoring Plan for guidance on how to conduct an off-site 
monitoring visit. The study staff is to save and document all relevant communication in 
the study files. The status of sites that cannot accept monitoring visits and/or subjects 
on-site, must be tracked centrally and updated on a regular basis.
3) Missing data and data integrity:
There may be an increased amount of missing data because of subject’s missing 
visits/assessments. This could have an impact on the analysis and the interpretation of 
clinical study data.
Mitigation plan: Implications of a pandemic on methodological aspects for the study will be 
thoroughly assessed and documented, and relevant actions will be taken as appropriate (eg, 
modification of the statistical analysis plan) and in compliance with regulatory authorities’ 
guidance. Overall, the clinical study report will describe the impact of the pandemic on the 
interpretability of study data.

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Risks will be assessed continuously, and temporary measures will be implemented to mitigate 
these risks as part of a mitigation plan, as described above. These measures will be 
communicated to the relevant stakeholders as appropriate and are intended to provide alternate 
methods that will ensure the evaluation and assessment of the safety of subjects who are enrolled 
in this study.
Since these potential risks are considered mitigated with the implementation of these measures, 
the expected benefit-risk assessment of brexucabtagene autoleucel in study subjects remains 
unchanged.

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12.9.
Tabulated List of Investigational Medicinal Products and Auxiliary 
Medicinal Products
A list of all investigational and auxiliary medicinal products which can be used in Protocol 
KT-US-568-0138 (Master and all Subprotocols) is provided in Table 15 and Table 16 in 
compliance with EU Reg. 536/2014 Annex I Section D No. 17 lit. f.
Table 15
List of Investigational Medicinal Products 
Investigational Medicinal Products
Further information on dosage, dose regimen, route 
of administration and treatment period
Brexucabtagene autoleucel
Please refer to Section 3.2.4 of the Master protocol.
Table 16.
List of Auxiliary Medicinal Products
Auxiliary Medicinal Products (AxMPs) a
Further information on dosage, dose regimen, route 
of administration and treatment period
Master Protocol (applicable to all substudies)
Acetaminophen (paracetamol) or equivalent
Diphenhydramine or equivalent
Please refer to Section 7.6.1. of the Master protocol
Cyclophosphamide (as lymphodepleting 
chemotherapy)
Fludarabine
Mesna
Please refer to Section 5.1.2 and Section 7.5.4 of the 
Master protocol.
Tocilizumab
Dexamethasone (as toxicity management)
Methylprednisolone
AxMPs are not all specified in the protocol, however, 
are suggested within the standard of care toxicity 
management guidelines referred to in Section 8.8
Substudy A – Additional AxMPs
Ibrutinib
Please refer to Section 5.2. of the Substudy A protocol.
Substudy B – Additional AxMPs
For use as treatment prior to lymphodepleting 
chemotherapy, please refer to Section 5.2. of the 
Substudy B protocol.
Ibrutinib
For use as bridging therapy, please refer to Section 7.2 
(Table 2) of the Substudy B protocol
Cyclophosphamide (as bridging therapy)
Rituximab
Doxorubicin
Vincristine
Please refer to Section 7.2 (Table 2) of the Substudy B 
protocol

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Auxiliary Medicinal Products (AxMPs) a
Further information on dosage, dose regimen, route 
of administration and treatment period
Prednisolone
Ifosfamide
Carboplatin
Etoposide
Gemcitabine
Oxaliplatin
Venetoclax
Prednisone
Dexamethasone
Substudy C – Additional AxMPs
Cyclophosphamide (as bridging therapy)
Dexamethasone
Rituximab
Doxorubicin
Vincristine
Prednisolone
Ifosfamide
Carboplatin
Etoposide
Gemcitabine
Oxaliplatin
Please refer to section 7.1 Optional Bridging Therapy 
(Table 2) of the Substudy C protocol 
Substudy D – no additional AxMPs
a
All auxiliary medicinal products listed have marketing authorisation in all countries participating in ZUMA-25 Substudy. 
No AxMP is classified as a narcotic, psychotropic, radiopharmaceutical, or orphan medicine.

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12.10.
Protocol Amendment History
A high-level summary of amendment changes are provided in tabular form in the subsection below. 
Minor changes such as the correction of typographic errors, grammar, or formatting are not detailed.
12.10.1.
Amendment 1.0 (dated 20 July 2022)
Changes from the original protocol (dated 23 May 2022) to Amendment 1.0 (dated 20 July 2022) 
are detailed below.
Section Number and Name
High-level Description of Change
Brief Rationale
Synopsis Number of subjects 
anticipated to be enrolled and 
treated
BL sample size increased from 20 to 
30 subjects 
BL sample size increased in 
consideration of EMA 
Scientific Advice 
recommendations 
Synopsis Statistical methods
Updated sample size of Burkitt Lymphoma to 
30 subjects.
BL sample size increased in 
consideration of EMA 
Scientific Advice 
recommendations
Synopsis Number of study 
sites planned
Number of study sites increased from 
approximately 40 to 50
Increased the number of study 
sites to optimize enrollment
Section 3.2.1 Leukapheresis
Correction that 12 to 15 liters of apheresis 
material will be processed
Correction. Detailed volume is 
processed but not obtained 
from the subject
Section 3.7 Number of 
participating sites
Number of study sites increased from 
approximately 40 to 50
Increased the number of study 
sites to optimize enrolment
Section 4.1 Number of 
subjects and subject selection
BL sample size increased from 20 to 
30 subjects and thus total subjects enrolled 
increased to 170.
BL sample size increased in 
consideration of EMA 
Scientific Advice 
recommendations
Section 7.7.3 Follow-up 
assessments and procedures 
for enrolled subjects who did 
not receive brexucabtagene 
autoleucel or whose disease 
progressed after 
brexucabtagene autoleucel 
treatment
Removal of text “For RT and BL subjects who 
sign the optional portion of the ICF, fresh 
tumor samples will need to be collected (refer 
to respective substudy protocols for details).”
Correction. Removed text as 
no longer applicable

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12.10.2.
Amendment 1.1- EU-specific Protocol Amendment (dated 12 January 2023)
Changes from Amendment 1 (dated 20 July 2022) to Amendment 1.1 (dated 12 January 2023) 
are detailed below. For changes from Amendment 1 to Amendment 2, please refer to 
Section 12.10.2 and Section 12.10.3. Amendment 2 incorporates all changes in Amendment 1.1 
together with the changes outlined in Section 12.10.3. 
Section Number and Name
High-level Description of Change
Brief Rationale
Title page and synopsis
Added EU CT and NCT numbers
EU CT and NCT numbers not 
previously available
Synopsis and Section 4.2.1 
Inclusion Criteria Common to 
all Indications
Inclusion criteria 1 language updated adding 
that subjects must have provided written 
informed consent
Requirement for informed 
consent described in body of 
protocol, for clarity also added 
to inclusion criteria
Table 1 (Synopsis) and 
Table 6 (Section 8.1.2) – Dose 
limiting toxicities
•
Exception removed regarding
brexucabtagene autoleucel related Grade 4
non hematological toxicities
•
Confirmed and updated text to clarify that
any brexucabtagene autoleucel related
Grade 3 neurotoxicity, including ICANS,
regardless of duration, will constitute a
DLT
•
Changed “Exception of any grade TLS
including manifestations attributable to
TLS” to “Exception of Grade 3 TLS
including associated manifestations
attributable to TLS (eg, electrolyte
abnormalities, renal function, or
hyperuricemia)” regarding brexucabtagene
autoleucel related Grade 3
nonhematological toxicities
All Grade 4 
non-hematological events to 
be considered as DLTs and 
TLS reconsidered so that 
Grade 4 and 5 events would 
be considered a DLT.
Language about ICANS added 
for clarity.
Table 2 (Synopsis) and 
Table 7 (Section 8.1.2) – 
Recommendations Based on 
Dose Limiting Toxicities
Criteria for numbers of subjects with a DLT in 
a cohort clarified
For clarification
Section 1.4 Study Rationale
Added additional language describing that all 
study indications no established standard of 
care exist
To clarify that only subjects 
who have exhausted all the 
available approved treatment 
options will be included in 
this study
Section 3.2.4 Brexucabtagene 
autoleucel
Added text to state that “brexucabtagene 
autoleucel is the Investigational Medicinal 
Product (IMP) being assessed in this study 
(Appendix 12.9). Brexucabtagene autoleucel 
has been granted marketing authorization in 
numerous regions, including the US, EU, 
Canada, Great Britain, and Switzerland, and 
will be used in this study for new indications”
For clarity

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Section Number and Name
High-level Description of Change
Brief Rationale
Section 3.2.5 Auxiliary 
Medicinal Products
New section added to define that all other 
medications described in the Master protocol 
and subprotocols are considered auxiliary 
medicinal products. These medications are 
used in accordance with their authorized 
product information. The identified and 
potential risks and the risk minimization should 
be managed as described within the authorized 
product information and/or in accordance with 
institutional guidelines 
Regulatory update to define 
the medications considered as 
auxiliary medications and to 
detail the use of these 
medications / 
Section 3.4 End-of-Study 
Definition
The end-of-study is defined for each substudy 
as the time when the last enrolled subject 
within the specific substudy has completed 
their last visit (last patient last visit; LPLV)
For clarity
Section 3.6 Study 
Discontinuation Criteria
Added details regarding the role of the DSMB 
in reviewing substudy data and providing 
recommendations on study conduct, including 
that the recommendations may include that a 
substudy should be stopped
For clarity
Section 4.3.1 Reasons for 
Removal From Treatment
Added further information regarding why AEs 
may lead to removal of a subject from 
treatment and why the IMP may not be 
available
For clarity
Section 8.2 Pregnancies
Revised the language to state that male subjects 
should not (previously recommended not to) 
father a child for at least 6 months after 
completing lymphodepletion chemotherapy 
dosing or brexucabtagene autoleucel, 
whichever is longer
Strengthened the language 
regarding male subjects and 
fathering a child
Section 8.5 Hospitalization 
and Prolonged Hospitalization
For hospitalization scenarios, not considered to 
be SAEs, added further definition for planned 
hospitalization ie, a planned hospitalization for 
a pre-existing medical condition (diagnosed 
prior to study entry) which was scheduled prior 
to informed consent/study start 
For clarity
Section 8.6.1.1. Reporting 
AEs Table 9
Table 9 updated to add missing information 
concerning reporting requirements for subjects 
who have received brexucabtagene autoleucel. 
AE reporting is required from enrollment 
through 3 months after the brexucabtagene 
autoleucel infusion or until initiation of 
another anticancer therapy, whichever occurs 
first.
Correction of missing 
information 
Section 8.7 Sponsor Reporting 
Requirements (Includes 
Reporting of SAEs and 
Deaths) 
References to EU Clinical Trials Directive 
2001/20/EC changed to EU Regulation 
536/2014
Regulatory update

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Section Number and Name
High-level Description of Change
Brief Rationale
Section 8.8.1 Toxicities 
Associated with 
Brexucabtagene Autoelucel 
Treatment
Added text to detail that toxicities associated 
with brexucabtagene autoleucel will be 
managed according to ASCO guidelines or per 
the authorized Tecartus product information 
and that tocilizumab is required to be available 
for the treatment of CRS. In addition, text was 
added clarifying that tumor lysis syndrome 
should be managed in accordance with the 
authorized brexucabtagene autoleucel product 
information and/or institutional guidelines
Added brexucabtagene 
autoleucel toxicities may also 
be managed according to 
authorized Tecartus product 
information 
8.10.1 Safety Review Team
Enrollment will be paused to allow the SRT 28 
days of data post infusion in all treated subjects 
in a DLT cohort prior to providing a 
recommendation on the continued dose 
selection, and re-starting enrollment.
Self-explanatory
8.10.2 Data Safety Monitoring 
Board
Added further language to clarify the data 
received by the DSMB.
The DSMB will review data accruing from 
each substudy and provide ongoing 
recommendations on study conduct to the Kite 
Head of Cell Therapy Clinical Development 
(or designee). Moreover, the DSMB will be 
provided with all data on the serious adverse 
events (SAEs; listings or narratives) and 
suspected unexpected serious adverse reactions 
(SUSAR) from the global safety database for 
review prior to implementing the SRTs dose 
recommendations.
For clarity
Section 8.10.3 Criteria to 
Pause Enrollment
Pausing rules updated. Specifically:
During the SRT phase
Enrollment will be paused following the 
treatment of 3 subjects in a DLT cohort, to 
assess the frequency of DLTs and to allow the 
SRT 28 days of data post infusion in all treated 
subjects prior to providing a recommendation 
on the target dose.
After the pivotal dose has been established
The study will be paused in response to any 
Grade 5 brexucabtagene autoleucel related AE, 
no matter when this occurs. The study will also 
be paused if the incidence of the following 
Grade 4 related brexucabtagene autoleucel 
related AEs is ≥ 33%: ICANS, CRS, other 
non-hematological Grade 4 SAEs and 
infections (treatment related). The previously 
described requirement of these AEs having a 
duration lasting more than 7 days has been 
removed.
Criteria strengthened for 
subject safety

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Section Number and Name
High-level Description of Change
Brief Rationale
Section 10.1.4 Confidentiality
Updated confidentiality information to include 
language regarding the processes Kite have in 
place to ensure the security and confidentiality 
of data records and personal information
Language previously missing
Section 10.3.3 Ethics
Changed “European Community Directive 
2001/20/EC” to “EU Regulation (2001/2014)”
Regulatory requirement
Section 12.3.2 Birth Control 
Methods That May Be 
Considered as Highly 
Effective
Added requirement for a barrier contraceptive 
method (condoms or diaphragm with 
spermicide) to be used together with hormonal 
contraceptive measures
Strengthen the pregnancy 
prevention methods
Appendix 12.9 Tabulated List 
of Investigational Medicinal 
Products and Auxiliary 
Medicinal Products 
Added Appendix 12.9 to define and provide 
information on the Investigational Medicinal 
Product IMP used in this study and the 
medications considered auxiliary medicinal 
products
Regulatory requirement
12.10.3.
Amendment 2.0 (dated 01 March 2023)
Changes from Amendment 1.1 (dated 12 January 2023) to Amendment 2 (dated 01 March 2023) 
are detailed below
Section Number and Name
High-level Description of Change
Brief Rationale
Entire document
Minor spelling corrections
Self-explanatory
Title Page
Study title updated to read “A Phase 2, Open-
Label, Multicenter, Basket Study Evaluating 
the Efficacy of Brexucabtagene Autoleucel in 
Adults with Rare B-cell Malignancies 
(ZUMA-25) – Master Protocol” The 
evaluation of safety removed from the study 
title.
Request during Part 1 
EU-CTR application to update 
the trial title to focus on the 
primary endpoint only.
Title Page
Amendment history added
Self-explanatory
Synopsis and Section 4.2.2 
Exclusion Criteria
Exclusion criterion #18 updated to include 
hypersensitivity to excipients
Request by Swiss Regulatory 
Authority
Section 3.2.2 Bridging 
Therapy
Clarification provided regarding reference to 
RT and BL study protocols regarding bridging 
therapy
Self-explanatory
Section 3.2.3 
Lymphodepleting 
Chemotherapy, Section 5.1.2.1 
Fludarabine and Section 7.5.4 
Lymphodepleting 
Chemotherapy
Added clarifying text that if, after the start of 
the lymphodepletion regimen, the creatinine 
clearance falls below 60 mL/min, subsequent 
doses of fludarabine will be adjusted according 
to institutional guidelines
For clarification

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Section Number and Name
High-level Description of Change
Brief Rationale
Section 3.4 End-of-study 
Definition
End of study definition clarified to also include 
if a subject transitions to a separate LTFU 
study 
For clarification
Section 5.5.1 Washout Periods 
Prior to Leukapheresis 
/Enrollment
Added additional text regarding systemic 
corticosteroids “Systemic corticosteroids must 
be avoided as premedication in subjects for 
whom CT scans with contrast are 
contraindicated (eg, subjects with contrast 
allergy or impaired renal clearance) if the 
administration is within 7 days before 
leukapheresis or 5 days before brexucabtagene 
autoleucel administration (washout period)”
Additional requirement for the 
avoidance of steroids 
described. 
Section 5.5.2 Excluded 
Medications or Medications to 
be used with Caution After 
Leukapheresis/Enrollment
Section title updated to also refer to 
medications to be used with caution.
Text surrounding use of live vaccines aligned 
with exclusion criteria 19 “Vaccination with 
live viral vaccines is not recommended for at 
least 6 weeks prior to the start of 
lymphodepleting chemotherapy, during 
brexucabtagene autoleucel treatment, and for 
12 months after treatment with 
brexucabtagene autoleucel”. 
Added text referring investigators to the current 
IB for additional information about 
vaccination, including COVID-19 vaccines.
Alignment of protocol text as 
described and added reference 
to current IB added for further 
information on vaccination, 
for clarity
Section 6.3.2.1 Laboratory 
Tests for Safety and 
Pharmacokinetics 
/Pharmacodynamics 
Assessments, Table 4 Clinical 
Laboratory Tests for Safety 
Assessments Common Across 
all Substudies
Added requirement for serology anti HIV+2 
test at screening only for all patients
Testing for HIV status 
required in all subjects at 
screening
Section 6.3.2.1 Laboratory 
Tests for Safety and 
Pharmacokinetic/Pharmacody
namic Assessments
Added additional information that if the blood 
urea nitrogen test cannot be performed by the 
local laboratory, urea should be analyzed
Switzerland added to the requirements for 
serology testing at European study sites
Self-explanatory
Request by Swiss Regulatory 
Authority 
Section 6.3.11 Patient-
reported Outcomes
Additional detail added that PROs are expected 
to be completed by all subjects who remain 
on-study at the scheduled assessments, up to 
and until disease progression
Added that “the sponsor will provide training 
for relevant site personnel for the 
administration of the questionnaires, so that 
subjects fill in the questionnaires as completely 
and accurately as possible”.
For clarification

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Section Number and Name
High-level Description of Change
Brief Rationale
Section 6.3.14 Serology 
Testing
New section added to provide guidance on 
serology testing 
For clarification
Section 6.3.16.2 Replication-
Competent Retrovirus
Clarifying language added that after month 12, 
samples will only be collected and tested if an 
RCR event is clinically suspected and/or a 
subject tests positive for RCR at any time point 
within the first year. If the latter, 
samples/testing for RCR will continue per 
clinical discretion.
If a subject dies of a suspected retrovirus-
associated disease or develops a new 
malignancy suspected to be associated with 
brexucabtagene autoleucel during the study or 
long-term follow-up, a blood sample and tumor 
biopsy may be obtained and sent to the central 
laboratory to assay for brexucabtagene 
autoleucel CAR T cells and/or RCR
Self-explanatory
Section 6.6 Pharmacokinetic 
Assessments
Clarification that samples on Day 3 may be 
collected ± 1 day
Provides flexibility regarding 
central laboratory sample 
collection when the Day 3 
visit fall over a weekend
Section 7.1.1 Informed 
Consent for Optional Research
New section added describing the seeking of 
the subject’s permission to use the remainder of 
study biospecimens for optional future research 
and/or genetic research in accordance with 
applicable regulations.
For clarification
Section 7.4 Enrollment
Added clarifying text that “a subject may not 
proceed to enrollment if they do not meet the 
eligibility criteria as indicated during screening 
and by laboratory tests performed after 
screening and before the initiation of 
leukapheresis”.
For clarification
Section 7.6.4 Requirements 
for Workup for Potential 
and/or Inflammatory States
Added clarifying text that “for subjects with 
symptoms and/or clinical findings indicating a 
potential infectious or inflammatory state, and 
in the absence of an identified source of 
infection (eg, line infection or pneumonia on 
chest X-ray), the minimum workup to be 
performed before administration of 
lymphodepleting chemotherapy and/or 
brexucabtagene autoleucel consists of the 
following:”
For clarification
Section 7.13 Sample Storage
Text updated to indicate that subject 
biospecimens ‘will’ rather than ‘may’, be 
stored for 15 years after brexucabtagene 
autoleucel infusion, in case any protocol-
required analyses need repeating. 
For clarification added that 
subject specimens will be 
stored for 15 years in case any 
protocol-required analyses 
need repeating and described 

Brexucabtagene Autoleucel
Protocol KT-US-568-0138 (ZUMA-25) – Master Protocol
Final
Kite Pharma, Inc.
Amendment 3.0
CONFIDENTIAL
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17 August 2023
Section Number and Name
High-level Description of Change
Brief Rationale
In addition, Kite may conduct analyses on 
remaining samples to address exploratory 
research questions related to the mechanism of 
action of the treatment or disease related 
features, for which subjects will be asked to 
provide consent.
use of remaining samples with 
the subjects consent
Section 8.2 Pregnancies
Updated time for recommended use of 
contraception in female subjects and time 
period that male subjects should not father a 
child from 6 to 12 months.
Updated following requests 
from regulatory authorities  
Section 8.6.1.2 Reporting 
SAEs, Table 10 Reporting 
Requirements for SAEs 
Footnote for Table 10 regarding new 
malignancies updated to describe that the 
investigator must assess causality against 
brexucabtagene autoleucel, lymphodepleting 
chemotherapy, bridging therapy, or study 
procedures. 
In addition, for secondary malignancies, 
language updated to indicate rather than a 
temporal association, there should be a 
plausible association with the brexucabtagene 
autoleucel infusion and without compelling 
alternate etiologies.
For clarification regarding the 
Investigator assessment of 
etiology for new malignancies
Section 8.6.1.2 Reporting 
SAEs
Added text that reads “After completion of this 
study and database closure, any relevant 
information on ongoing SAEs must be 
submitted to Kite within 24 hours after the 
investigator’s knowledge of the event using the 
portable document format (PDF) version of the 
paper SAE Report Form and sent via e-mail to 
the SAE Reporting mailbox: 
”
Language added regarding 
continued SAE reporting 
requirements and methods 
after study closure
Section 8.6.2 Reporting 
Deaths
Added text that reads” All deaths must be 
recorded on the Death eCRF, but only deaths 
caused by an AE should be reported as an SAE. 
For example, in an event of fatal pneumonia, 
the event should be reported as an SAE of 
pneumonia and the outcome as fatal. The event 
or condition that caused or contributed to the 
fatal outcome should be recorded on the SAE 
eCRF with entries including the start date of 
the event and death date as the stop date of the 
event. Every effort should be made to capture 
the established cause of death, which may 
become available later on (eg, after autopsy). 
Although death is an outcome and not a distinct 
AE, death may be reported as an SAE (ie, 
PT = death) when the cause of death is 
unknown (eg, sudden or unwitnessed death 
with unknown cause).
For clarification
PPD

Brexucabtagene Autoleucel
Protocol KT-US-568-0138 (ZUMA-25) – Master Protocol
Final
Kite Pharma, Inc.
Amendment 3.0
CONFIDENTIAL
Page 127
17 August 2023
Section Number and Name
High-level Description of Change
Brief Rationale
Section 8.8.1 Toxicities 
Associated with 
Brexucabtagene Autoelucel 
Treatment
Added clarification that a guide to the ICE 
score is presented in Section 12.5
For clarification
Section 8.9.2.1 Instructions for 
Reporting Pregnancies
Added language on the timeframe for reporting 
requirements for pregnancies in female partners 
of male subjects i.e required within 12 months 
after completing lymphodepleting 
chemotherapy or the brexucabtagene infusion  
Timeframe for reporting 
pregnancy in a female partner 
of a male subject added
Section 10.1.3 Informed 
Consent
Added language to provide a reason why 
optional future genomic research test results 
will not be shared i.e. the results do not inform 
clinical decision making 
For clarification
Section 10.2.2 Study Report 
and Publications
Minor edits to guidance regarding study report 
and publications and updated language 
surrounding Investigators and publication rules 
which should be in accordance with the Kite 
clinical trial agreement.
Self-explanatory
Section 12.4 Country-specific 
Regulatory Agency 
Requirements, 12.4 Post-
Infusion Monitoring, 12.4.2.2 
For Switzerland
New section added regarding post-infusion 
monitoring in Switzerland i.e. subjects should 
remain in hospital for 10 days after 
brexucabtagene autoleucel for monitoring
Request from Swiss 
Regulatory Authority and 
Ethics Committee
Section 12.4 Country-specific 
Regulatory Agency 
Requirements, 12.4.3 
Pregnancy Testing
Switzerland added to the list of European 
countries requiring pregnancy testing 7 days 
prior to leukapheresis and lymphodepleting 
chemotherapy 
Request from Swiss 
Regulatory Authority and 
Ethics Committee
Section 12.7 Practical Body 
Weight Calculation for 
Subjects Whose Body Mass 
Index (BMI) is > 35 kg/m2
Clarified that for dose calculations, body 
weight at time of leukapheresis is to be used 
for brexucabtagene autoleucel 
For clarification
Section 12.7 Practical Body 
Weight Calculation for 
Subjects Whose Body Mass 
Index (BMI) is > 35 kg/m2
Removed text related to IL-2 dose
Text was originally added in 
error

Brexucabtagene Autoleucel
Protocol KT-US-568-0138 (ZUMA-25) – Master Protocol
Final
Kite Pharma, Inc.
Amendment 3.0
CONFIDENTIAL
Page 128
17 August 2023
12.10.4.
Amendment 3.0 (dated 17 August 2023)
Changes from Amendment 2.0 (dated 01 March 2023) to Amendment 3.0 are tabulated below.
Section Number and Name
High-level Description of Change
Brief Rationale
General
Correction of typographical errors
Self-explanatory
Title page and throughout the 
document
Added text to detail that substudies A and D 
were terminated early by the Sponsor, effective 
21 June 2023
Removed references to sites in the United 
Kingdom
Sponsor decision to terminate 
substudies A and D
No sites in the United 
Kingdom will be participating 
in the study
Synopsis
Added statements that substudies A and D were 
terminated early by the Sponsor, effective 21 
June 2023
Sponsor decision to terminate 
substudies A and D
Synopsis – Number of Study 
Sites Planned
Number of study sites reduced from 
approximately 50 to approximately 25
Number of sites reduced due 
to early termination of 
substudies A and D
Synopsis – Study Design
Clarifying language added to indicate that, 
following the early termination of substudies A 
and D, subjects are only to be enrolled in 
substudies B and C (effective 21 June 2023)
Sponsor decision to terminate 
substudies A and D
Section 1.3 Study Design
Edit text to indicate that studies focus on 
efficacy and not safety
To reflect that focus of study 
is on efficacy
Section 3.2.3 – 
Lymphodepleting 
Chemotherapy
Creatinine clearance threshold change from 
60 to 70 mL/min
To align with fludarabine 
product information
Section 3.7 Number of 
Participating Study Sites
Number of sites reduced from approximately 
50 to approximately 25. Reference to sites in 
Canada removed 
Number of sites reduced due 
to early termination of 
substudies A and D.
No sites in Canada recruiting 
subjects 
Section 4.1 Subjects and 
Subject Selection
Edited to indicate that approximately 90 
subjects will be enrolled in the 2 active 
substudies (RT and BL)
Numbers adjusted to reflect 
early termination of substudies 
A and D
Section 5.1.2.1 Fludarabine
Creatinine clearance threshold change from 
60 to 70 mL/min
To align with fludarabine 
product information
Section 6.3.16.2 Replication-
Competent Retrovirus
Edited to indicate that samples/testing for RCR 
will be per physician/investigator discretion
To specify that the testing 
must be undertaken by 
physician/investigator
Section 7.5.4 
Lymphodepleting 
Chemotherapy
Creatinine clearance threshold change from 
60 to 70 mL/min
To align with fludarabine 
product information

Brexucabtagene Autoleucel
Protocol KT-US-568-0138 (ZUMA-25) – Master Protocol
Final
Kite Pharma, Inc.
Amendment 3.0
CONFIDENTIAL
Page 129
17 August 2023
Section Number and Name
High-level Description of Change
Brief Rationale
Section 8.10.3 Criteria to 
Pause Enrollment
Added text to indicate that study enrollment 
will be paused when the required number of 
subjects have been enrolled in the planned 
interim analyses for each substudy, until the 
data from this interim analysis have been 
assessed
To allow the Sponsor to 
review for futility prior to 
exposing additional subjects to 
study treatment 
Section 9.6.1 Interim Analysis 
and Early Stopping Guidelines
Added text to indicate that study enrollment 
will be paused while allowing time for the 
interim analyses to be assessed
To allow the Sponsor to 
review for futility prior to 
exposing additional subjects to 
study treatment

ZUMA-25 Master protocol Amendment 3
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Clinical Development
eSigned
21-Aug-2023
12:54:09
PPD