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 SUBPROTOCOL
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) – Substudy C – 
Relapsed/Refractory Burkitt Lymphoma
Note:
This subprotocol should be used in conjunction with the 
KT-US-568-0138 master protocol
Protocol Number:
KT-US-568-0138-C (ZUMA-25C)
Indication:
Relapsed/refractory Burkitt lymphoma
Kite Investigational Product: 
Brexucabtagene autoleucel
Kite IND Number:
028542
EU CT Number:
2022-501261-46-00
Clinical Trials.gov Identifier:
NCT05537766
Sponsor:
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
United States of America
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 1.0: 20 July 2022
Amendment 1.1: 12 January 2023
Amendment 2.0: 01 March 2023
Amendment 3.0: 17 August 2023
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.

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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 SUBPROTOCOL..........................................................................................................................1
TABLE OF CONTENTS................................................................................................................................................3
LIST OF IN-TEXT TABLES .........................................................................................................................................4
LIST OF IN-TEXT FIGURES........................................................................................................................................4
PROTOCOL SYNOPSIS................................................................................................................................................5
LIST OF ABBREVIATIONS.......................................................................................................................................10
1.
INTRODUCTION................................................................................................................................................11
1.1.
Disease Background ................................................................................................................................11
1.1.1.
Epidemiology ........................................................................................................................11
1.1.2.
Diagnosis ...............................................................................................................................11
1.1.3.
Frontline Treatment...............................................................................................................11
1.1.4.
Second-line Treatment...........................................................................................................12
2.
OBJECTIVES AND ENDPOINTS......................................................................................................................13
3.
STUDY DESIGN.................................................................................................................................................14
3.1.
Study Design ...........................................................................................................................................14
3.1.1.
Rationale for Study Design Elements....................................................................................15
4.
SUBJECT POPULATION...................................................................................................................................16
4.1.
Number of Subjects and Subject Selection .............................................................................................16
4.2.
Eligibility Criteria....................................................................................................................................16
4.2.1.
BL Substudy-specific Inclusion Criteria ...............................................................................16
4.2.2.
BL Substudy-specific Exclusion Criteria ..............................................................................16
5.
STUDY TREATMENT........................................................................................................................................17
6.
STUDY ASSESSMENTS UNIQUE TO BURKITT LYMPHOMA...................................................................18
6.1.
Brain Magnetic Resonance Imaging .......................................................................................................18
6.1.1.
Lumbar Puncture ...................................................................................................................19
6.2.
Disease Assessments ...............................................................................................................................19
6.2.1.
Imaging Requirements...........................................................................................................19
6.2.2.
Bone Marrow Aspirate/Biopsy..............................................................................................21
6.3.
Tumor Biopsy..........................................................................................................................................22
6.4.
Disease-specific Exploratory Assessments .............................................................................................23
7.
STUDY PROCEDURES UNIQUE TO BURKITT LYMPHOMA ....................................................................24
7.1.
Optional Bridging Therapy......................................................................................................................24
8.
ADVERSE EVENTS AND TOXICITY MANAGEMENT................................................................................27
8.1.
Safety Review Team and Data Safety Monitoring Board.......................................................................27
9.
STATISTICAL CONSIDERATIONS.................................................................................................................28
9.1.
Hypothesis ...............................................................................................................................................28
9.2.
Definition of Substudy Endpoints ...........................................................................................................28
9.2.1.
Definition of Substudy Primary Endpoints ...........................................................................28
9.2.2.
Definition of Substudy Secondary Endpoints .......................................................................28
9.2.3.
Definition of Other Substudy Endpoints of Interest..............................................................29
9.3.
Determination of Sample Size.................................................................................................................29

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9.4.
Planned Analyses.....................................................................................................................................29
9.4.1.
Interim Analysis and Early Stopping Guidelines ..................................................................29
9.4.2.
Primary Analysis ...................................................................................................................30
9.4.3.
Follow-Up Analysis...............................................................................................................30
9.4.4.
Final Analysis........................................................................................................................30
10.
RESPONSIBILITIES...........................................................................................................................................31
11.
REFERENCES.....................................................................................................................................................32
12.
APPENDICES......................................................................................................................................................34
12.1.
Sponsor and Investigator Signature Page................................................................................................35
12.2.
Schedule of Assessments.........................................................................................................................36
12.3.
Disease Response Criteria .......................................................................................................................45
12.3.1.
International Working Group Lugano Classification............................................................45
12.4.
Protocol Amendment History..................................................................................................................50
12.4.1.
Amendment 1.0 (dated 20 July 2022) ...................................................................................50
12.4.2.
Amendment 1.1 EU-specific Amendment (dated 12 January 2023).....................................51
12.4.3.
Amendment 2.0 (dated 01 March 2023)................................................................................52
12.4.4.
Amendment 3.0 (dated 17 August 2023) ..............................................................................54
LIST OF IN-TEXT TABLES
Table 1.
Substudy-specific Objectives and Endpoints ..........................................................................13
Table 2.
Bridging Therapy Regimens....................................................................................................25
Table 3.
Definition of Substudy Secondary Endpoint...........................................................................28
Table 4.
Definition of Substudy Exploratory Endpoint.........................................................................29
Table 5.
Schedule of Assessments: Screening, Pretreatment, Treatment, and Post-treatment 
Periods .....................................................................................................................................36
Table 6.
Schedule of Assessments: Post-treatment Follow-up Period ..................................................42
Table 7.
Deauville 5-point Scale for Positron Emission Tomography Scoring ....................................45
LIST OF IN-TEXT FIGURES
Figure 1.
Bone Marrow Assessment Schema .........................................................................................22

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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)
Substudy C – Relapsed/Refractory Burkitt Lymphoma
Indication: Adult subjects with relapsed/refractory (r/r) Burkitt lymphoma (BL)
Kite IND Number: 028542
EU CT Number: 2022-501261-46-00
Clinical Trials.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: Objectives and endpoints that are common to all indications are 
detailed in the KT-US-568-0138 master protocol.
Additional objectives and endpoints that are specific to this substudy are detailed below.
Primary Objective
Primary Endpoint
•
To evaluate the efficacy of brexucabtagene 
autoleucel in subjects with BL, by determining 
the objective response rate (ORR) by central 
assessment
•
ORR, defined as the proportion of subjects who 
achieve a best response of either complete 
response (CR) or partial response (PR). Response 
will be determined by central assessment per the 
Lugano Classification {Cheson 2014}
Secondary Objective
Secondary Endpoint
•
To evaluate the efficacy of brexucabtagene 
autoleucel in subjects with BL, by determining 
the ORR by investigator assessment
•
ORR, defined as the proportion of subjects who 
achieve a best response of either CR or PR. 
Response will be determined by investigator 
assessment per the Lugano Classification 
{Cheson 2014}
Exploratory Objective
Exploratory Endpoint
•
To evaluate the efficacy of brexucabtagene 
autoleucel in subjects with BL based on receipt 
of bridging therapy
•
ORR, defined as the proportion of subjects who 
achieve a best response of either CR or PR, in 
subgroups by receipt of bridging therapy (yes/no)

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Study Design: This substudy protocol contains details regarding all elements of the study that 
are unique to subjects with BL. In contrast, the KT-US-568-0138 master protocol contains 
additional information that is common for all indications in this basket study. Both the 
KT-US-568-0138 master protocol and this substudy protocol should be referenced in parallel.
This is a Phase 2, open-label, multicenter study evaluating the efficacy of brexucabtagene 
autoleucel in subjects with r/r BL.
Initially, 1 subject will be enrolled and infused. No additional subjects will be enrolled until 
the subject has been monitored for at least 28 days post-infusion. Subsequently, an additional 
2 subjects can be enrolled in parallel. After these initial 3 subjects have been evaluated for at 
least 28 days, the safety review team (SRT) will make recommendations on the further 
conduct of this substudy.
Following enrollment, eligible subjects will be treated with cyclophosphamide and fludarabine 
lymphodepleting chemotherapy, followed by an initial dose of 2 x 106 anti-CD19 chimeric 
antigen receptor (CAR) T cells/kg body weight. Following review by the SRT, the dose may 
be lowered to 1 x 106 anti-CD19 CAR T cells/kg body weight.
Disease response will be assessed at Day 28, Month 3, and then every 3 months up to 
Month 12, followed by every 6 months up to Month 24.
Additional study details are provided in the KT-US-568-0138 master protocol.
Subjects enrolled in this substudy may receive optional bridging therapy as described in 
Section 7.1.
The study schema is detailed in Figure 1 of the KT-US-568-0138 master protocol.
Number of Subjects Anticipated to be Enrolled and Treated: Approximately 30 subjects 
with r/r BL will be enrolled and treated in this substudy. Three to 6 additional subjects may be 
enrolled if the SRT recommends proceeding at the lower dose level.
Target Population: Male or female adults ≥ 18 years of age diagnosed with r/r BL
Duration of Treatment and of Study Participation: The treatment period will be 1 week 
following infusion, and the duration of the study is 24 months.
Eligibility Criteria Unique to the BL Substudy:
In addition to the common eligibility criteria specified in the KT-US-568-0138 master 
protocol, all of the following additional substudy-specific eligibility criteria must also be met.
BL Substudy-specific Inclusion Criteria:
1) Histologically confirmed mature B-cell non-Hodgkin lymphoma Burkitt 
lymphoma/leukemia
2) Relapsed or refractory disease after any first-line chemoimmunotherapy, defined as 1 of 
the following:
a) Refractory disease, defined as progressive disease or stable disease as best response to 
first-line therapy; subjects who are intolerant to first-line therapy are excluded

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b) Relapsed disease, defined as complete remission to first-line therapy followed by 
biopsy-proven disease relapse. Subjects will be eligible regardless of the duration of 
remission prior to relapse.
At least 1 measurable lesion based on the Lugano Classification {Cheson 2014}. Lesions that 
have been previously irradiated will be considered measurable only if progression has been 
documented following completion of radiation therapy
BL Substudy-specific Exclusion Criteria:
1) Burkitt-like lymphoma with 11q aberration, high-grade B-cell lymphoma with MYC and 
BCL2 and/or BCL6 rearrangement, or high-grade B-cell lymphoma not otherwise specified
2) Prior allogeneic stem cell transplant < 3 months prior to screening and/or < 4 months prior 
to planned infusion of brexucabtagene autoleucel
3) Presence of active graft-versus-host disease following prior allogeneic stem cell transplant
4) Presence of central nervous system (CNS) involvement. Subjects with a prior history of 
CNS involvement are eligible if they show a negative cerebrospinal fluid (CSF) and no 
involvement by imaging 
Study Procedures: Subjects will undergo procedures and assessments as detailed in the 
schedule of assessments (see Section 12.2).
Investigational Product and Study Treatments, Dose, and Mode of Administration:
Treatment consists of a lymphodepleting chemotherapy regimen, followed by a single infusion 
of brexucabtagene autoleucel. Additional details are provided in the KT-US-568-0138 master 
protocol.
Safety Review Team and Data Safety Monitoring Board: 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 after 3 or 6 subjects in this substudy have been treated with the initial dose 
(2 x 106 anti-CD19 CAR T cells/kg of body weight) and followed for 28 days, as detailed in 
the KT-US-568-0138 master protocol.
An independent Data Safety Monitoring Board (DSMB) will be chartered to review safety and 
efficacy data to make study conduct recommendations based on an analysis of risk versus 
benefit. The DSMB will review serious adverse event (SAE) information (listings or 
narratives) and suspected unexpected serious adverse reactions (SUSARs) on a regular basis 
throughout subject treatment in the study and per the DSMB charter or DSMB discretion. The 
DSMB may request additional safety or efficacy data or recommend modifying the study 
conduct. The sponsor may request additional reviews by the DSMB. Data submitted to the 
DSMB may or may not be source data verified to facilitate timely DSMB review.
SUSARs and SAE listings or narratives may be submitted to the DSMB chair as described in 
the DSMB charter.
Additional details regarding the SRT, DSMB, and dose-limiting toxicities are provided in the 
KT-US-568-0138 master protocol.

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Statistical Methods:
Hypothesis: An alternative hypothesis is proposed with a target 70% ORR per central 
assessment against a null hypothesis that the ORR is ≤ 39%. The hypothesis is that the ORR to 
brexucabtagene autoleucel per central assessment is greater than 39%.
Sample Size Calculation: This single-arm, open-label substudy will enroll and treat 30 subjects 
with the SRT-recommended dose of brexucabtagene autoleucel. This sample size will achieve 
a statistical power of 92% if there is at least a 31% improvement in ORR (brexucabtagene 
autoleucel: 70% versus historical control: 39%) with a type 1 error rate of 0.025 (1-sided).
Analyses: An interim analysis will be conducted after 10 subjects (33%) have had the 
opportunity to be evaluated for response 3 months after treatment with brexucabtagene 
autoleucel. In this interim analysis, the DSMB will review investigator-reported data for 
2 purposes: 
•
Futility (efficacy): The non-binding futility boundary is ORR of 43.8% based on the beta 
spending function of rho family (parameter = 0.7), with a crossing probability of 62.2% 
under the null hypothesis (ORR ≤ 39%). A decision on futility will be made by the sponsor 
based on DSMB recommendation, with the complete benefit/risk profile of 
brexucabtagene autoleucel being taken into account. The futility boundary is crossed if 
≤ 4 responders are observed among the 10 subjects. If the decision is made to discontinue 
the substudy, then this analysis will be considered the primary analysis of this substudy. 
Study enrollment will be paused following treatment of the 10th subject with 
brexucabtagene autoleucel and until results from the interim analysis have been assessed.
•
If the decision based on the interim analysis is to continue the substudy, a primary analysis 
will be conducted after 30 subjects have been enrolled and treated with the 
SRT-recommended dose of brexucabtagene autoleucel and the last subject has had the 
opportunity to be assessed for response at least 6 months after the brexucabtagene 
autoleucel infusion.
Hypothesis testing will be based on the number of objective responders observed among the 
30 subjects, as described above. The point estimate of the ORR will be calculated, together 
with its 95% confidence interval using the Clopper-Pearson method. The p-value will be 
calculated based on exact test. If more than 30 subjects are treated with the SRT-recommended 
dose in this substudy by the time of data cutoff, all treated subjects will be included in the 
primary analysis.
A follow-up analysis may be performed after all treated subjects have had the opportunity to 
be assessed for response at least 18 months after the brexucabtagene autoleucel infusion to 
further evaluate the risk-benefit profile of brexucabtagene autoleucel, including the durability 
of response. This analysis will be descriptive.
Additional descriptive analyses may occur after the primary analysis and follow-up analysis 
described above have been completed.
The final analysis will be performed after all subjects have completed the study, outstanding 
data queries have been resolved or adjudicated as unresolvable, and the data have been cleaned 
and finalized.

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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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LIST OF ABBREVIATIONS 
ASCO
American Society of Clinical Oncology
BL
Burkitt lymphoma
CAR
chimeric antigen receptor 
CNS
central nervous system
CR
complete response
CRS
cytokine release syndrome
CSF
cerebrospinal fluid
CT 
computed tomography
DSMB
Data Safety Monitoring Board
EBV
Epstein-Barr virus
FDG
fluorodeoxyglucose
ICANS
immune effector cell-associated neurotoxicity syndrome
IHC
immunohistochemistry
IV
intravenous
MRI
magnetic resonance imaging
NHL
non-Hodgkin lymphoma
ORR
objective response rate
OS
overall survival
PET
positron emission tomography
PR
partial response
r/r
relapsed/refractory
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

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1.
INTRODUCTION
Refer to the KT-US-568-0138 master protocol for information related to brexucabtagene 
autoleucel (KT-US-568-0138 master protocol – Section 1.1), previous clinical studies 
(KT-US-568-0138 master protocol – Section 1.2.2), and the study rationale (KT-US-568-0138 
master protocol – Section 1.4).
1.1.
Disease Background
1.1.1.
Epidemiology
Burkitt lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma (NHL) which 
manifests in the subtypes of sporadic, endemic (Epstein-Barr virus [EBV]-associated), and 
immunodeficiency-associated BL. The sporadic subtype of BL is the most frequent outside of 
Africa and is EBV-associated in 10% to 20% of patients. BL is observed in the United States and 
Europe with an overall incidence of 3 cases per million persons per year in the general 
population, and thus accounts for < 1% of adult NHLs {Morton 2006}. BL is more common in 
children, where it represents 30% of NHLs and has a peak incidence at 11 years of age, whereas 
the peak incidence is at 30 years in adults. Whites have a higher incidence of the disease, and the 
incidence in males is 3 to 4 times that observed in females {Jacobson 2014}.
1.1.2.
Diagnosis
Due to the aggressive nature of BL, patients often present with rapidly enlarging masses and 
evidence of spontaneous tumor lysis and high serum lactate dehydrogenase levels. Moreover, 
sporadic BL has a propensity for involving the abdomen and involves the bone marrow and 
central nervous system (CNS) {Jacobson 2014}.
BL is of germinal center B-cell origin with tumor cells expressing CD10, BCL6, CD19, CD20, 
CD79a, and CD45 and is characterized by a chromosomal translocation most commonly 
involving the MYC gene locus on chromosome 8 and the immunoglobulin heavy chain locus on 
chromosome 14 (t(8;14)). Furthermore, up to 70% of patients harbor TCF3 or ID3 mutations 
{Dunleavy 2018a, Jacobson 2014, Schmitz 2012}. 
1.1.3.
Frontline Treatment
BL is currently treated with high-intensity, multi-drug chemotherapy regimens including 
doxorubicin, alkylators, vincristine, and etoposide (CODOX-M/IVAC, HyperCVAD, and 
DA-REPOCH). Due to the significant tumor burden in BL, many regimens include a steroid 
preface with a focus on avoiding tumor lysis syndrome. Therapy directed at the eradication 
and/or prevention of CNS disease is also applied. Survival outcomes using such frontline 
approaches generally exceed 70% {Jacobson 2014}. 

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1.1.4.
Second-line Treatment
Treatment options for patients with relapsed/refractory (r/r) BL are limited and outcomes are 
poor {Dunleavy 2018a}. Second-line therapies include chemotherapy such as etoposide, 
prednisolone, vincristine, cyclophosphamide, doxorubicin, and regular- or double-dose rituximab 
(DA-EPOCH-R or -RR), as well as hematopoietic stem cell transplant. Recently, Short and 
colleagues evaluated such regimens in a retrospective cohort of 35 r/r patients with Burkitt 
leukemia (n = 21), BL (n = 7), high-grade B-cell leukemia (n = 6), and high-grade B-cell 
lymphoma (n = 1) treated with varying chemotherapeutic regimens and found an objective 
response rate (ORR) of 39% {Short 2017}. Meanwhile, Pineda and colleagues found a median 
overall survival (OS) after relapse between 3 and 4 months in a Spanish population including BL 
patients across 40 sites from 1997 to 2014 {Pineda 2015}. Accordingly, patients with 
chemotherapy-sensitive disease can obtain deep remissions, while the overall outcome for 
patients with r/r disease remains dismal {Short 2017, Sweetenham 1996}. 
Recently, chimeric antigen receptor (CAR) T-cell therapy has been investigated in subjects with 
r/r BL. In a study of 6 adults who received a CAR19/22 T-cell therapy, 3 achieved an objective 
response, including 2 partial responses (PRs) and 1 complete response (CR). The subject who 
achieved a CR subsequently received allogeneic stem cell transplant, and 1 subject who achieved 
a PR had received CAR19/22 T cells following autologous stem cell transplant; both were in 
remission at 37 and 22 months of follow-up, respectively {Zhou 2021}. 
Nonetheless, r/r BL remains a largely incurable disease, and patients have very poor outcomes, 
with an ORR to salvage therapy of 39% and a median OS of 2.8 months {Short 2017}. Thus, 
new treatment options are needed to achieve durable responses in a significant fraction of 
patients.

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2.
OBJECTIVES AND ENDPOINTS
Refer to Section 2 of the KT-US-568-0138 master protocol for a summary of common objectives 
and endpoints for this study.
Additional objectives and endpoints that are specific for this substudy are detailed in Table 1.
Table 1.
Substudy-specific Objectives and Endpoints
Primary Objective
Primary Endpoint
•
To evaluate the efficacy of brexucabtagene 
autoleucel in subjects with BL, by determining the 
ORR by central assessment
•
ORR, defined as the proportion of subjects who 
achieve a best response of either CR or PR. 
Response will be determined by central 
assessment per the Lugano Classification {Cheson 
2014}
Secondary Objective
Secondary Endpoint
•
To evaluate the efficacy of brexucabtagene 
autoleucel in subjects with BL, by determining the 
ORR by investigator assessment
•
ORR, defined as the proportion of subjects who 
achieve a best response of either CR or PR. 
Response will be determined by investigator 
assessment per the Lugano Classification {Cheson 
2014}
Exploratory Objective
Exploratory Endpoint
•
To evaluate the efficacy of brexucabtagene 
autoleucel in subjects with BL based on receipt of 
bridging therapy 
•
ORR, defined as the proportion of subjects who 
achieve a best response of either CR or PR, in 
subgroups by receipt of bridging therapy (yes/no)
Abbreviations: BL, Burkitt lymphoma; CR, complete response; ORR, objective response rate; PR, partial response.

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3.
STUDY DESIGN
3.1.
Study Design
This substudy protocol contains details regarding all elements of the study that are unique to 
subjects with BL. In contrast, the KT-US-568-0138 master protocol contains additional 
information that is common for all indications in this basket study. Both the KT-US-568-0138 
master protocol and this substudy protocol should be referenced in parallel.
This is a Phase 2, open-label, multicenter study evaluating the efficacy of brexucabtagene 
autoleucel in subjects with r/r BL. 
Initially, 1 subject will be enrolled and infused. No additional subjects will be enrolled until the 
subject has been monitored for at least 28 days post-infusion. Subsequently, an additional 
2 subjects can be enrolled in parallel. After these initial 3 subjects have been evaluated for at 
least 28 days, the safety review team (SRT) will make recommendations on the further conduct 
of this substudy.
Following enrollment, eligible subjects will be treated with cyclophosphamide and fludarabine 
lymphodepleting chemotherapy, followed by an initial dose of 2 × 106 anti-CD19 CAR 
T cells/kg body weight. Following review by the SRT, the dose may be lowered to 1 × 106 CAR 
T cells/kg body weight.
Disease response will be assessed at Day 28, Month 3, and then every 3 months up to Month 12, 
followed by every 6 months up to Month 24.
Additional details of the study design are provided in Section 3 of the KT-US-568-0138 master 
protocol.
Subjects enrolled in this substudy may receive optional bridging therapy as described in 
Section 7.1.
The study schema is detailed in Figure 1 of the KT-US-568-0138 master protocol.
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. Additional details of the SRT are provided in Section 8.1.
An independent Data Safety Monitoring Board (DSMB) will be chartered to review safety and 
efficacy data to make study conduct recommendations based on an analysis of risk versus 
benefit. The DSMB will review investigator-reported safety and efficacy data against the futility 
rules after 10 subjects (50%) in this substudy have been treated with the SRT-recommended dose 
of brexucabtagene autoleucel and have had the opportunity to be followed for 3 months after the 
brexucabtagene autoleucel infusion. Study enrollment will be paused following treatment of the 
10th subject with brexucabtagene autoleucel and until results from the interim analysis have been 
assessed. Additional details of the DSMB are provided in Section 8.1.

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The end-of-study is defined in the Master protocol (refer to Section 3.4 of the Master protocol).
3.1.1.
Rationale for Study Design Elements
3.1.1.1.
Rationale for Bridging Therapy
Due to the aggressive nature of BL, bridging therapy may be administered at the discretion of the 
investigator, if deemed necessary for disease control between leukapheresis and availability of 
brexucabtagene autoleucel. Bridging therapy regimens and timing requirements are described in 
Section 7.1.

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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 30 subjects with r/r BL who have received at least 1 line of prior therapy will be 
enrolled and treated. Three to 6 additional subjects may be enrolled if the SRT recommends 
proceeding at the lower dose level (refer to Section 8.10.1 of the KT-US-568-0138 master 
protocol for additional details).
4.2.
Eligibility Criteria
To be enrolled in the study, subjects must meet the common eligibility criteria detailed in 
Section 4.2 of the KT-US-568-0138 master protocol. In addition, subjects must also meet all of 
the additional substudy-specific eligibility criteria detailed in Section 4.2.1 and Section 4.2.2.
4.2.1.
BL Substudy-specific Inclusion Criteria
1) Histologically confirmed mature B-cell NHL Burkitt lymphoma/leukemia
Relapsed or refractory disease after any first-line chemoimmunotherapy, defined as 1 of the 
following:
a) Refractory disease, defined as progressive disease or stable disease as best response to 
first-line therapy; subjects who are intolerant to first-line therapy are excluded
b) Relapsed disease, defined as complete remission to first-line therapy followed by 
biopsy-proven disease relapse. Subjects will be eligible regardless of the duration of 
remission prior to relapse. 
At least 1 measurable lesion based on the Lugano Classification {Cheson 2014}. Lesions that 
have been previously irradiated will be considered measurable only if progression has been 
documented following completion of radiation therapy 
4.2.2.
BL Substudy-specific Exclusion Criteria
1) Burkitt-like lymphoma with 11q aberration, high-grade B-cell lymphoma with MYC and 
BCL2 and/or BCL6 rearrangement, or high-grade B-cell lymphoma not otherwise specified
2) Prior allogeneic stem cell transplant < 3 months prior to screening and/or < 4 months prior to 
planned infusion of brexucabtagene autoleucel
3) Presence of active graft-versus-host disease following prior allogeneic stem cell transplant
4) Presence of central nervous system (CNS) involvement. Subjects with a prior history of CNS 
involvement are eligible if they show a negative cerebrospinal fluid (CSF) and no 
involvement by imaging.

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5.
STUDY TREATMENT
Study treatment consists of lymphodepleting chemotherapy and a single infusion of 
brexucabtagene autoleucel, as described in Section 3.2 of the KT-US-568-0138 master protocol.
Subjects enrolled in this substudy may receive optional bridging therapy as described in 
Section 7.1. Permitted bridging therapy regimens are detailed in Table 2.
Refer to Section 5 of the KT-US-568-0138 master protocol for additional details of the 
brexucabtagene autoleucel treatment, prior and concomitant medications, and excluded 
medications.

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6.
STUDY ASSESSMENTS UNIQUE TO BURKITT LYMPHOMA
The study assessments that are either unique to BL or that are managed differently for subjects 
with BL are described here. Please refer to Section 6 of the KT-US-568-0138 master protocol for 
details of all other study assessments. Study assessments described in the KT-US-568-0138 
master protocol and herein are to be performed according to the schedule of assessments (SOA) 
presented in Section 12.2 (Table 5 and Table 6) of this substudy protocol.
6.1.
Brain Magnetic Resonance Imaging
Brain magnetic resonance imaging (MRI) will be performed with contrast whenever possible or 
without contrast in case of contraindication.
Screening:
•
All subjects are required to have a brain MRI at screening to confirm the absence of CNS 
involvement and study eligibility.
•
The MRI should be performed as close to enrollment/leukapheresis as possible and within 
28 days before leukapheresis for eligibility. An MRI collected as standard of care (SOC) 
within this timeframe is acceptable.
•
After the initial screening and eligibility confirmation, if the subject presents with new-onset 
symptoms or clinical signs of CNS malignancy/disease, a repeat MRI is required to reassess 
eligibility prior to the start of lymphodepleting chemotherapy.
•
CNS involvement will be assessed by local review, and images will not be sent for central 
review.
Post-infusion:
•
Subjects are recommended to have a brain MRI if presenting with new-onset symptoms or 
clinical signs of CNS malignancy/disease, such as severe headaches, neck stiffness, seizures, 
encephalopathy, cranial nerve deficits, or any focal neurological findings on physical 
examination.
•
In addition, in the case of cytokine release syndrome (CRS) and immune effector 
cell-associated neurotoxicity syndrome (ICANS), refer to the American Society of Clinical 
Oncology (ASCO) management guidelines for guidance of requirements for brain imaging 
{Santomasso 2021}. In summary: i) brain MRI can be considered for all grades of CRS; 
ii) brain MRI or other neuroimaging can be considered for ICANS Grade 2 or higher, as 
supported by the ASCO management guidelines.
•
A brain MRI only needs to be submitted to the independent central reviewer when there is 
evidence of disease progression.

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6.1.1.
Lumbar Puncture
Opening pressures should be measured with each lumbar puncture when possible and recorded in 
the subject’s site chart. 
Screening: 
•
All subjects are required to have a new lumbar puncture performed at screening and as close 
as possible to leukapheresis to assess cerebrospinal fluid (CSF) for possible CNS 
involvement and to determine the presence of CNS malignancy.
•
After the initial screening and eligibility confirmation, if the subject presents with new-onset 
symptoms or clinical signs of CNS malignancy/disease, a repeat lumbar puncture is required 
to reassess eligibility prior to the start of lymphodepleting chemotherapy.
Post-infusion: 
•
Subjects with symptoms or clinical signs of CNS malignancy, such as new-onset severe 
headaches, neck stiffness, seizures, encephalopathy, cranial nerve deficits, or any focal 
neurologic findings on physical examination, will have a lumbar puncture for examination of 
CSF (and brain MRI as described in Section 6.1).
•
In the case of CRS and ICANS, refer to the ASCO management guidelines for guidance for 
requirements for lumbar puncture examination {Santomasso 2021}. In summary: i) lumbar 
puncture is recommended for consideration in cases of CRS; ii) for ICANS, a lumbar 
puncture is recommended for Grade 3 or higher neurotoxicity and may be considered for 
Grade 2.
CSF samples will be analyzed at the local laboratory. An aliquot will be sent to the central 
laboratory for assessment of analytes (including cytokines) and immune cell subsets.
6.2.
Disease Assessments
Disease assessments will be performed according to the schedule presented in the SOA (Table 5 
and Table 6) and as described below. In addition, subjects with symptoms suggestive of disease 
progression should be evaluated for progression at the time symptoms occur, even if this requires 
an unscheduled visit.
6.2.1.
Imaging Requirements
Positron emission tomography (PET)-diagnostic computed tomography (CT) scans are required 
in all subjects at screening, after bridging therapy (if applicable), and at the disease response 
assessment time points specified in the SOA (Table 5 and Table 6).

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For all PET-CT scans, the following requirements should be met:
•
The CT must be of diagnostic quality with intravenous (IV)-iodinated contrast, performed by 
either of the following modalities, depending on the site’s capability:
as part of a combined PET-diagnostic CT; or
as a separate diagnostic-quality CT (with IV-iodinated contrast)
•
The PET-diagnostic CT scan must include the neck, chest, abdomen, and pelvis, along with 
appropriate imaging of all other sites of disease.
•
If IV-iodinated contrast is contraindicated per the investigator, then the diagnostic CT scan 
can use non-iodinated contrast. If non-iodinated contrast is not available or not recommended 
by the investigator, then the diagnostic CT can be nonenhanced.
•
In cases where CT with contrast is contraindicated, MRI of the abdomen and pelvis and CT 
of the chest without contrast is an acceptable alternative.
•
All screening/baseline and disease assessment PET-diagnostic CT scans will be submitted to 
and reviewed by an independent central reviewer.
•
Technical and shipping requirements for the PET-diagnostic CT scans will be outlined in the 
study imaging manual.
•
On-study images will be performed with the same imaging modality and anatomical location 
as imaged at baseline.
•
The PET portion of the PET-diagnostic CT scan will be scored per the Deauville 5-point 
scale. Both the PET and CT portions of the scan will be interpreted according to the Lugano 
Classification {Cheson 2014}. Refer to Section 12.3.1 for additional details.
Screening/Baseline:
•
To confirm eligibility and/or to establish baseline (if bridging therapy is administered), 
PET-diagnostic CT scans are required at screening.
•
PET-diagnostic CT scans should be performed as close to enrollment/leukapheresis as 
possible and within 28 days before leukapheresis for eligibility (unless imaging is available 
from SOC assessment within 28 days before enrollment), with the following clarifications:
A PET-diagnostic CT scan performed at the study site after the subject’s last line of 
therapy and before signing of the informed consent form may be used for confirmation of 
eligibility, if relevant requirements described above are fulfilled and if it was performed 
within 28 days before enrollment/leukapheresis and no other anticancer treatment has 
been administered. (For subjects who are referred, a screening image is required.)

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If a PET-diagnostic CT scan is performed > 28 days before the initiation of 
lymphodepleting chemotherapy or if the subject receives any anticancer therapy (bridging 
therapy) between the last PET-diagnostic CT scan and initiation of lymphodepleting 
chemotherapy, the PET-diagnostic CT scan must be repeated before lymphodepleting 
chemotherapy to establish a new baseline.
Disease Assessment:
•
The PET-diagnostic CT scans will be performed at the time points outlined in the SOA 
(Table 5 and Table 6) through Month 24 or until disease progression, whichever comes first. 
•
A PET-diagnostic CT scan can be performed at any time disease progression is suspected.
•
To limit radiation exposure, investigators are encouraged to leave at least 4 weeks between 
consecutive scans
6.2.2.
Bone Marrow Aspirate/Biopsy
Refer to Section 12.3.1 for treatment response assessment requirements per the Lugano 
Classification {Cheson 2014}. Bone marrow aspirate and biopsies will be analyzed by the 
investigator at the local laboratory.
Screening/Baseline: 
•
For fluorodeoxyglucose (FDG)-avid lymphoma, a subject’s bone marrow involvement 
should be assessed by PET-diagnostic CT (refer to Section 6.2.1).
•
If the lymphoma is not FDG-avid, a bone marrow aspirate and biopsy is required at 
screening. If the screening bone marrow assessment shows infiltration, bone marrow aspirate 
and biopsy will be required after bridging therapy (if applicable) (Figure 1).
Disease/Response Assessment: 
•
If there is evidence of baseline bone marrow involvement, the PET-diagnostic CT is not 
available, the lymphoma is not FDG-avid, or there are unexplained cytopenias or suspicion 
of bone marrow involvement, a bone marrow aspirate and biopsy will be performed in 
subjects who are being assessed for CR in order to confirm CR {Cheson 2014} (also refer to 
Figure 1). 
•
To confirm a CR, the bone marrow aspirate and biopsy must show no evidence of disease by 
morphology or, if indeterminate by morphology, must be negative by immunohistochemistry 
(IHC).

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Figure 1.
Bone Marrow Assessment Schema
Abbreviations: CR, complete response; FDG, fluorodeoxyglucose; PET-CT, positron emission tomography-computed 
tomography.
6.3.
Tumor Biopsy
Screening: 
To retrospectively confirm the BL diagnosis, the most recently available archived or newly 
acquired tumor biopsy sample will be collected and submitted to the central laboratory. A new 
biopsy is only to be acquired if the location is easily accessible, and if appropriate taking into 
account subject safety. Archived tumor biopsy samples will consist of either 1 formalin-fixed 
paraffin-embedded tumor block or at least 20 unstained slides. Should an archived tumor sample 
be unavailable or insufficient, a fresh tumor sample is required to be obtained before initiation of 
lymphodepleting chemotherapy.
Screening PET-CT
Screening PET-CT is positive 
(tumor is FDG-avid)
Screening PET-CT is negative 
(tumor is not FDG-avid)
No bone marrow assessment 
required at screening or 
post-bridging (if applicable) or 
at later disease assessments
Bone marrow assessment 
required at screening
Bone marrow assessment 
negative at screening
No further bone marrow 
assessments required 
post-bridging (if 
applicable) or at later 
disease assessments
Bone marrow assessment 
positive at screening
Bone marrow 
assessments required 
post-bridging (if 
applicable) and to 
confirm CR
I 
I 
I 
! 
! 
! 
! 
I 

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Disease Progression: 
If a tumor biopsy that is clinically indicated in the management of a study-treated subject is 
acquired, a portion of the biopsy should be sent to the central laboratory for additional 
exploratory analyses.
6.4.
Disease-specific Exploratory Assessments
Tumor biopsy at screening will be collected for central laboratory assessment in order to perform 
genetic testing for the evaluation of somatic mutations of MYC by fluorescence in situ 
hybridization (FISH) analysis and IHC staining with a B-cell lymphoma panel to confirm the BL 
diagnosis and for investigation of prognostic markers in exploratory analyses.

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7.
STUDY PROCEDURES UNIQUE TO BURKITT LYMPHOMA
Refer to Section 7 of the KT-US-568-0138 master protocol for the list of procedures for this 
study. Additional procedures for this BL subprotocol are listed below.
For short-term disease control, optional bridging therapy is allowed per investigator discretion. 
To exclude any impact of bridging therapy, a new baseline for subjects receiving bridging 
therapy is required as outlined in the SOA.
7.1.
Optional Bridging Therapy
Bridging therapy will be permitted at the discretion of the investigator, if deemed required to 
control disease after leukapheresis. Bridging therapy is recommended for subjects with high 
disease burden. Bridging therapy may be administered after leukapheresis, and the last dose of 
any bridging therapy regimen must be completed at least 7 days or 5 half-lives, whichever is 
shorter, before initiating lymphodepleting chemotherapy.
If a subject receives any bridging therapy between leukapheresis and lymphodepleting 
chemotherapy, then the baseline imaging and any additional assessments to confirm measurable 
disease must be repeated after the bridging therapy and before lymphodepleting chemotherapy 
commences to establish a new baseline. For subjects who receive irradiation as bridging therapy, 
irradiated lesions can no longer serve as target lesions, and other target lesions must be present to 
allow for response assessment.
Permitted bridging therapy regimens are outlined in Table 2. Doses listed are recommendations 
only and should be adjusted for age, comorbidities, or per local or institutional guidelines.

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Table 2.
Bridging Therapy Regimens
Type
Therapy Regimen
Timing and Washout 
Requirements
R-ICE
{Kewalramani 2004}
Rituximab 375 mg/m2 IV on Day 1
Ifosfamide 5,000 mg/m2 IV on Day 4
Carboplatin area under the curve 5, 
dose = 5 × (25 + CrCl), capped at 800 mg, IV 
on Day 4
Etoposide 100 mg/m2/day IV on Days 3 to 5
DA-EPOCH-R
{Dunleavy 2018b}
Etoposide 50 mg/m2/day IV on Days 1 to 4
Doxorubicin 10 mg/m2/day IV on Days 1 to 4
Vincristine 0.4 mg/m2/day IV on Days 1 to 4
Cyclophosphamide 750 mg/m2/day IV on 
Day 5
Prednisone 60 mg/m2/BID PO on Days 1 to 5
Rituximab 375 mg/m2 IV on Day 1
R-GEMOX
{Collignon 2019}
Rituximab 375 mg/m2 IV on Days 1 and 15 
Gemcitabine 1,000 mg/m2 IV on Day 1
Oxaliplatin 100 mg/m2 IV on Day 1
Hyper-CVAD
{Thomas 2006}
Hyperfractionated cyclophosphamide 
300 mg/m2 IV every 12 hours for 6 doses on 
Days 1 to 3, with sodium 
mercaptoethanesulfonate 600 mg/m2 daily via 
continuous infusion on Days 1 to 3
Vincristine 2 mg IV on Days 4 and 11
Doxorubicin 50 mg/m2 IV over 24 hours on 
Day 4
Dexamethasone 40 mg PO or IV daily on 
Days 1 to 4 and Days 11 to 14
Dexamethasone
40 mg daily for 4 days
May be administered after 
leukapheresis/enrollment
Last dose must be completed at 
least 7 days or 5 half-lives, 
whichever is shorter, before the 
start of lymphodepleting 
chemotherapy
Irradiation
As per local guidelines
May be administered after 
leukapheresis/enrollment
Last irradiation dose must be 
completed at least 7 days before the 
start of lymphodepleting 
chemotherapy
Abbreviations: BID, twice a day; CrCl, creatinine clearance; DA-EPOCH-R, dose-adjusted etoposide, prednisone, vincristine, 
cyclophosphamide, doxorubicin, and rituximab; hyper-CVAD, hyperfractionated cyclophosphamide, vincristine, doxorubicin, 
and dexamethasone; IV, intravenous; PO, oral; R-GEMOX, rituximab with gemcitabine and oxaliplatin; R-ICE, rituximab with 
ifosfamide, carboplatin, and etoposide.

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Bridging therapy will be supplied by the study site. Sites should refer to the current product label 
for guidance on packaging, storage, preparation, administration, and toxicity management of 
bridging therapy.
Regardless of the choice of bridging regimen, all organ and marrow functional parameters listed 
in the KT-US-568-0138 master protocol common inclusion criteria must be met before initiation 
of lymphodepleting chemotherapy, and all toxicities related to bridging therapy must return to 
Grade 1 or lower or baseline levels before initiation of lymphodepleting chemotherapy. 
The procedures to be performed during the period in which bridging therapy is administered are 
detailed in the SOA (Section 12.2).

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8.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
Refer to Section 8 of the KT-US-568-0138 master protocol for adverse events and toxicity 
management. The SRT and independent DSMB for this subprotocol are described below.
8.1.
Safety Review Team and Data Safety Monitoring Board
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 after 3 to 6 subjects in this substudy have been treated 
with the initial dose (2 x 106 anti-CD19 CAR T cells/kg of body weight) and followed for 
28 days, as detailed in the KT-US-568-0138 master protocol.
An independent DSMB will be chartered to review safety and efficacy data to make study 
conduct recommendations based on an analysis of risk versus benefit. The DSMB will review 
investigator-reported safety and efficacy data against the futility rules after 10 subjects (50%) in 
this substudy have been treated with the SRT-recommended dose of brexucabtagene autoleucel 
and have had the opportunity to be followed for 3 months after the brexucabtagene autoleucel 
infusion. Study enrollment will be paused following treatment of the 10th subject with 
brexucabtagene autoleucel and until results from this interim analysis have been assessed. The 
DSMB will also review serious adverse event (SAE) information (listings or narratives) and 
suspected unexpected serious adverse reactions (SUSARs) on a regular basis throughout subject 
treatment in the study and per the DSMB charter or DSMB discretion. The DSMB may request 
additional safety or efficacy data or recommend modifying the study conduct. The sponsor may 
request additional reviews by the DSMB. Data submitted to the DSMB may or may not be 
source data verified to facilitate timely DSMB review.
SUSARs and SAE listings or narratives may be submitted to the DSMB chair as described in the 
DSMB charter.
Additional details regarding the SRT, DSMB, and dose-limiting toxicities are provided in 
Section 8.10.1, Section 8.10.2, and Section 8.1.2 of the KT-US-568-0138 master protocol, 
respectively.

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9.
STATISTICAL CONSIDERATIONS 
An overview of the statistical considerations that are specific to this subprotocol are provided 
below. Refer to Section 9 of the KT-US-568-0138 master protocol for an overview of the 
statistical considerations that are common across indications.
Details of the statistical analysis plan (SAP) will be provided in the SAP document.
9.1.
Hypothesis
An alternative hypothesis is proposed with a target 70% ORR per central assessment against a 
null hypothesis that the ORR is ≤ 39%. The reference rate of 39% was based on Short and 
colleagues {Short 2017}, as an outcome of a systemic literature review. The hypothesis is that 
the ORR to brexucabtagene autoleucel per central assessment is greater than 39%. 
The hypothesis testing will be conducted at a significance level of 0.025 (1-sided). The responses 
from subjects in the study population are assumed to be independent and follow a binomial 
distribution.
9.2.
Definition of Substudy Endpoints
In addition to the secondary and exploratory endpoints outlined in the KT-US-568-0138 master 
protocol, the endpoints outlined below also apply to this substudy.
9.2.1.
Definition of Substudy Primary Endpoints
The primary endpoint for this substudy is the ORR, defined as the proportion of subjects who 
achieve a best response of either CR or PR, by central assessment per the Lugano Classification 
{Cheson 2014}.
9.2.2.
Definition of Substudy Secondary Endpoints
The secondary endpoint for this substudy is defined in Table 3. 
Table 3.
Definition of Substudy Secondary Endpoint
Secondary Endpoint
Definition
ORR by investigator assessment
Proportion of subjects who achieve a best response of 
either CR or PR by investigator assessment per the 
Lugano Classification {Cheson 2014}
Abbreviations: CR, complete response; ORR, objective response rate; PR, partial response.

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9.2.3.
Definition of Other Substudy Endpoints of Interest
The exploratory endpoint for this substudy is defined in Table 4.
Table 4.
Definition of Substudy Exploratory Endpoint
Exploratory Endpoint
Definition
ORR based on receipt of bridging therapy
Proportion of subjects who achieve a best response of 
either CR or PR, in subgroups by receipt of bridging 
therapy (yes/no)
Abbreviations: CR, complete response; ORR, objective response rate; PR, partial response.
9.3.
Determination of Sample Size
This single-arm, open-label substudy will enroll and treat 30 subjects with the 
SRT-recommended dose of brexucabtagene autoleucel. This sample size will achieve a statistical 
power of 92% if there is at least a 31% improvement in ORR (brexucabtagene autoleucel: 70% 
versus historical control: 39%) with a type 1 error rate of 0.025 (1-sided) under the 2-look design 
based on normal approximation, with variance of standardized test statistic under null hypothesis 
(H0) using EAST (Version 6.5). The empirical power is 93% per simulation based on binomial 
distribution without normal approximation. Statistically significant treatment effect can be 
claimed in this substudy if ≥ 17 responders (≥ 56.5%) are observed among the 30 subjects at the 
primary analysis.
9.4.
Planned Analyses
9.4.1.
Interim Analysis and Early Stopping Guidelines
An interim analysis will be conducted after 10 subjects (33%) have had the opportunity to be 
evaluated for response 3 months after treatment with brexucabtagene autoleucel. Study 
enrollment will be paused following treatment of the 10th subject with brexucabtagene autoleucel 
and until results from this interim analysis have been assessed. In this interim analysis, the 
DSMB will review investigator-reported data for both safety and efficacy (futility only). The 
non-binding futility boundary is ORR of 43.8% based on the beta spending function of rho 
family (parameter = 0.7), with a crossing probability of 62.2% under the null hypothesis 
(ORR ≤ 39%). The futility boundary is crossed if ≤ 4 responders are observed among the 
10 subjects. A decision on futility will be made by the sponsor based on DSMB 
recommendation, with the complete benefit/risk profile of brexucabtagene autoleucel being taken 
into account. If the decision is made to discontinue the substudy, then this analysis will be 
considered the primary analysis of this substudy.

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9.4.2.
Primary Analysis
If the decision based on the interim analysis is to continue the substudy, a primary analysis will 
be conducted after 30 subjects have been enrolled and treated with the SRT-recommended dose 
of brexucabtagene autoleucel (modified intent-to-treat [mITT] analysis set) and the last subject 
has had the opportunity to be assessed for response at least 6 months after the brexucabtagene 
autoleucel infusion.
Hypothesis testing will be based on the number of objective responders observed among the 
30 subjects, as described above. The point estimate of the ORR will be calculated, together with 
its 95% confidence interval using the Clopper-Pearson method. The p-value will be calculated 
based on exact test. If more than 30 subjects are treated with the SRT-recommended dose in this 
substudy by the time of data cutoff, all treated subjects will be included in the primary analysis.
9.4.3.
Follow-Up Analysis
A follow-up analysis may be performed after all treated subjects have had the opportunity to be 
assessed for response at least 18 months after the brexucabtagene autoleucel infusion to further 
evaluate the risk-benefit profile of brexucabtagene autoleucel, including the durability of 
response. This analysis will be descriptive.
Additional descriptive analyses may occur after the primary analysis and follow-up analysis 
described above have been completed.
9.4.4.
Final Analysis
The duration of the study is 24 months. The final analysis will be performed after all subjects 
have completed the study, outstanding data queries have been resolved or adjudicated as 
unresolvable, and the data have been cleaned and finalized.

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-C (ZUMA-25C) – Burkitt Lymphoma
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10.
RESPONSIBILITIES
Please refer to Section 10 of the KT-US-568-0138 master protocol for details regarding 
investigator and sponsor responsibilities.

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-C (ZUMA-25C) – Burkitt Lymphoma
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11.
REFERENCES
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. 
Recommendations for initial evaluation, staging, and response assessment of 
Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 
2014;32 (27):3059-68.
Collignon A, Houillier C, Ahle G, Chinot O, Choquet S, Schmitt A, et al. (R)-GEMOX 
chemotherapy for unfit patients with refractory or recurrent primary central 
nervous system lymphoma: a LOC study. Annals of hematology 2019;98 (4):915-
22.
Dunleavy K. Approach to the Diagnosis and Treatment of Adult Burkitt's Lymphoma. J Oncol 
Pract 2018a;14 (11):665-71.
Dunleavy K, Fanale MA, Abramson JS, Noy A, Caimi PF, Pittaluga S, et al. Dose-adjusted 
EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, 
and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC 
rearrangement: a prospective, multicentre, single-arm phase 2 study. Lancet 
Haematol 2018b;5 (12):e609-e17.
Jacobson C, LaCasce A. How I treat Burkitt lymphoma in adults. Blood 2014;124 (19):2913-20.
Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A, et al. Rituximab and ICE 
as second-line therapy before autologous stem cell transplantation for relapsed or 
primary refractory diffuse large B-cell lymphoma. Blood 2004;103 (10):3684-8.
Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma 
incidence patterns by WHO subtype in the United States, 1992-2001. Blood 
2006;107 (1):265-76.
Pineda A, Sancho JM, Garcia O, Esteve J, Tormo M, Martinez P, et al. Incidence, Treatment and 
Prognosis of Patients with Relapsed Burkitt Lymphoma/Leukemia Treated with 
Specific Chemotherapy or Immunochemotherapy in Spain. Blood (ASH Annual 
Meeting Abstracts) 2015;126 (23):2723.
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.
Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M, et al. Burkitt lymphoma 
pathogenesis and therapeutic targets from structural and functional genomics. 
Nature 2012;490 (7418):116-20.

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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.
Sweetenham JW, Pearce R, Taghipour G, Blaise D, Gisselbrecht C, Goldstone AH. Adult 
Burkitt's and Burkitt-like non-Hodgkin's lymphoma--outcome for patients treated 
with high-dose therapy and autologous stem-cell transplantation in first remission 
or at relapse: results from the European Group for Blood and Marrow 
Transplantation. J Clin Oncol 1996;14 (9):2465-72.
Thomas DA, Faderl S, O'Brien S, Bueso-Ramos C, Cortes J, Garcia-Manero G, et al. 
Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of 
adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. 
Cancer 2006;106 (7):1569-80.
Zhou X, Ge T, Li T, Huang L, Cao Y, Xiao Y, et al. CAR19/22 T cell therapy in adult refractory 
Burkitt's lymphoma. Cancer Immunol Immunother 2021;70 (8):2379-84.

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12.
APPENDICES
Section 12.1.
Sponsor and Investigator Signature Page 
Section 12.2.
Schedule of Assessments 
Section 12.3.
Disease Response Criteria
Section 12.4.
Protocol Amendment History

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-C (ZUMA-25C) – Burkitt Lymphoma
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Amendment 3.0
CONFIDENTIAL
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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 (ZUMA-25) – Substudy C – Relapsed/Refractory Burkitt 
Lymphoma
Amendment 3.0, 17 AUGUST 2023
This protocol has been approved by Kite Pharma, Inc. The following signature documents this approval.
See appended signature page
See appended signature page
Kite Medical Monitor Name (Printed) 
Signature
See appended signature page
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.
Schedule of Assessments
Table 5.
Schedule of Assessments: Screening, Pretreatment, Treatment, and Post-treatment Periods
Timeframe:
Screening
Pretreatment Period
Treatment Period
Post-treatment Follow-up Period
Enrollment/ 
Leukapheresis
Optional Bridging Therapy 
Note: bridging therapy is 
optional, and these 
procedures only apply if 
bridging therapy has been 
administered
Lymphodepleting 
Chemotherapy
Infusion of 
Brexucabtagene 
Autoleucel and 
Monitoring
(Each visit calculated from D0)
Procedure
Within 
28 days 
before 
enrollment
Within approx. 
5 days after 
eligibility 
confirmation
Dosing of 
bridging 
therapy and 
monitoring
Post-bridging 
therapy disease 
assessment
D−5
D−4
D−3
D0
D1 to D7a
D14
(±2 d)
D28
(±3 d)
W8
(±1 w)
M3
(±2 w)
Suspected Disease Progressionb
Informed consent
X
Demographic data
X
Medical history
X
Previous cancer 
treatment history
X
Physical examinationc
X
X
X
X
X
X
X
Daily
X
X
X
X
X
Weight (height at 
screening only) 
X
X
Vital signsd
X
X
X
X
X
X
X
X
Daily
X
X
X
X
X
Neurologic examinatione
X
X
QOD
X
X
X
X
ECOG performance 
status
X
X
LVEF (ECHO or 
MUGA)
X
ECG
X
Brain MRIf
X
Lumbar punctureg
X

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Timeframe:
Screening
Pretreatment Period
Treatment Period
Post-treatment Follow-up Period
Enrollment/ 
Leukapheresis
Optional Bridging Therapy 
Note: bridging therapy is 
optional, and these 
procedures only apply if 
bridging therapy has been 
administered
Lymphodepleting 
Chemotherapy
Infusion of 
Brexucabtagene 
Autoleucel and 
Monitoring
(Each visit calculated from D0)
Procedure
Within 
28 days 
before 
enrollment
Within approx. 
5 days after 
eligibility 
confirmation
Dosing of 
bridging 
therapy and 
monitoring
Post-bridging 
therapy disease 
assessment
D−5
D−4
D−3
D0
D1 to D7a
D14
(±2 d)
D28
(±3 d)
W8
(±1 w)
M3
(±2 w)
Suspected Disease Progressionb
PROs: 
EORTC-QLQ-C30 and 
EQ-5D-5Lh
X
X
X
X
X
Disease response assessments (please refer to the imaging manual and central laboratory manual for guidance)
PET-diagnostic CTi
X
X
X
X
X
Bone marrow aspirate 
and biopsyj
X
X
X
X
X
Archived/fresh tumor 
samplek
X
X
Overall response 
assessment
X
X
X
Local laboratory assessments
Chemistry panel (CrCl 
at screening) (serum)
X
X
X
X
X
X
Xl
Daily
X
X
X
X
X
CBC with differential 
(blood)
X
X
X
X
X
X
Xl
Daily
X
X
X
X
X
LDHm, CRP, ferritin 
(serum)
X
X
Xl
Daily
X
X
X
β-hCG pregnancy test 
([WOCBP] serum or 
urine)
X
Xn
Xn
X
X
X
Serology for EU/CH 
sites (serum)o
Xo
Xo

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Timeframe:
Screening
Pretreatment Period
Treatment Period
Post-treatment Follow-up Period
Enrollment/ 
Leukapheresis
Optional Bridging Therapy 
Note: bridging therapy is 
optional, and these 
procedures only apply if 
bridging therapy has been 
administered
Lymphodepleting 
Chemotherapy
Infusion of 
Brexucabtagene 
Autoleucel and 
Monitoring
(Each visit calculated from D0)
Procedure
Within 
28 days 
before 
enrollment
Within approx. 
5 days after 
eligibility 
confirmation
Dosing of 
bridging 
therapy and 
monitoring
Post-bridging 
therapy disease 
assessment
D−5
D−4
D−3
D0
D1 to D7a
D14
(±2 d)
D28
(±3 d)
W8
(±1 w)
M3
(±2 w)
Suspected Disease Progressionb
HIV positive subjects 
only: HIV viral load 
and CD4 count
Xp
X
X
X
Central laboratory assessments (please refer to the central laboratory manual for guidance)
CBC with differential 
(blood)q
X
Xr
Xl
D3, D7
X
X
X
X
X
Anti-brexucabtagene 
autoleucel antibodies 
(serum)
X
X
X
X
Analytes, including 
cytokines 
(serum/plasma)s
Xr
Xr
Xl
D1, D2, D3, 
D5, D7
X
X
X
X
X
Brexucabtagene 
autoleucel CAR T-cell 
levels and exploratory 
analyses (PBMCs)s
Xr
Xr
Xl
D3, D7
X
X
X
X
X
RCR (PBMCs)t
Xl
X
Leukapheresis 
X
Bridging therapy 
(optional)u
X
Fludarabine/ 
cyclophosphamidev
X
X
X

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Amendment 3.0
CONFIDENTIAL
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Timeframe:
Screening
Pretreatment Period
Treatment Period
Post-treatment Follow-up Period
Enrollment/ 
Leukapheresis
Optional Bridging Therapy 
Note: bridging therapy is 
optional, and these 
procedures only apply if 
bridging therapy has been 
administered
Lymphodepleting 
Chemotherapy
Infusion of 
Brexucabtagene 
Autoleucel and 
Monitoring
(Each visit calculated from D0)
Procedure
Within 
28 days 
before 
enrollment
Within approx. 
5 days after 
eligibility 
confirmation
Dosing of 
bridging 
therapy and 
monitoring
Post-bridging 
therapy disease 
assessment
D−5
D−4
D−3
D0
D1 to D7a
D14
(±2 d)
D28
(±3 d)
W8
(±1 w)
M3
(±2 w)
Suspected Disease Progressionb
Brexucabtagene 
autoleucel infusion (IV) 
and premedications
X
Concomitant 
medications
X
X
X
X
X
X
X
X
Daily
X
X
X
X
X
Adverse events and 
serious adverse eventsw
X
X
X
X
X
X
X
X
Daily
X
X
X
X
X
Abbreviations: approx., approximately; ASCO, American Society of Clinical Oncology; CAR, chimeric antigen receptor; CBC, complete blood count; CNS, central nervous 
system; CR, complete response; CrCl, creatinine clearance; CRP, C-reactive protein; CRS, cytokine release syndrome; CSF, cerebrospinal fluid; CT, computed tomography; 
D/d, day; ECG, electrocardiogram; ECHO, echocardiogram; ECOG, Eastern Cooperative Oncology Group; EORTC-QLQ-C30, European Organisation for Research and 
Treatment of Cancer Quality of Life Questionnaire; EQ-5D-5L, European Quality of Life 5-Dimension 5-Level scale; EU, European Union; FDG, fluorodeoxyglucose; 
hCG, human chorionic gonadotropin; ICANS, immune effector cell-associated neurotoxicity syndrome; ICE, immune effector cell-associated encephalopathy; ICF, informed 
consent form; IV, intravenous; LDH, lactate dehydrogenase; LVEF, left ventricular ejection fraction; M, month; MRI, magnetic resonance imaging; MUGA, multigated acquisition 
scan; PBMC, peripheral blood mononuclear cell; PET, positron emission tomography; PRO, patient-reported outcome; QOD, every other day; RCR, replication-competent 
retrovirus; SOA, schedule of assessments; SOC, standard of care;  W/w, week; WOCBP, women of childbearing potential.
Note: Please refer to the footnotes listed below in parallel with Section 6 of this protocol and the KT-US-568-0138 master protocol.
a
For EU and CH, post-infusion monitoring extended by monitoring on Days 8, 9, and 10 (vital signs, blood draw for chemistry panel with CRP and CBC and neurological 
examination). For EU, the subject may remain hospitalized or return to the clinic daily for this extended monitoring, at the discretion of the investigator.  For CH, patients 
must remain hospitalized.
b
Subjects with symptoms suggestive of disease progression should be evaluated for progression at the time symptoms occur, even if this requires an unscheduled visit.
c
Physical examination will include assessment of splenomegaly and lymphadenopathy. Subjects with symptoms or clinical signs related to CRS should undergo physical 
examination at least daily until symptoms resolve to baseline. 
d
Vital signs will include blood pressure, heart rate, respiration rate, oxygen saturation, and temperature. It is recommended that vital signs are monitored during and after study 
treatment and then routinely per institutional guidelines. Vital signs may be monitored more frequently as clinically indicated.
e
Neurologic examination: A neurologic examination, including an ICE cognition assessment, should be performed on Day 0 before the brexucabtagene autoleucel infusion and 
should be performed every other day during the hospitalization period. If a subject hospitalization is extended beyond Day 7, a neurologic examination including a cognition 
assessment will continue to be performed as clinically indicated.

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f
Brain MRI:
•
Screening through start of lymphodepletion: All subjects are required to have a brain MRI at screening to confirm the absence of CNS involvement and study eligibility. 
After the initial screening and eligibility confirmation, if the subject presents with new-onset symptoms or clinical signs of CNS malignancy/disease, a repeat MRI is 
required to reassess eligibility prior to the start of lymphodepleting chemotherapy (see Section 6.1).
•
Post-infusion: Subjects are recommended to have a brain MRI if presenting with new-onset symptoms or clinical signs of CNS malignancy/disease, such as severe 
headaches, neck stiffness, seizures, encephalopathy, cranial nerve deficits, or any focal neurological findings on physical examination. In addition, in the case of CRS 
and ICANS, refer to the ASCO management guidelines for guidance of requirements for brain imaging {Santomasso 2021}. In summary: i) brain MRI can be considered 
for all grades of CRS; ii) brain MRI or other neuroimaging can be considered for ICANS Grade 2 or higher, as supported by the ASCO management guidelines.
g
Lumbar puncture: Opening pressures should be measured with each lumbar puncture when possible and recorded in the subject’s site chart.
•
Screening: All subjects will undergo a new lumbar puncture at screening as close as possible to leukapheresis to assess for CNS disease. After the initial screening and 
eligibility confirmation, if the subject presents with new-onset symptoms or clinical signs of CNS malignancy/disease, a repeat lumbar puncture is required to reassess 
eligibility prior to the start of lymphodepleting chemotherapy. Subjects with a prior history of CNS involvement are eligible if they show a negative cerebrospinal fluid 
(CSF) at screening and no involvement by imaging.
•
Post-infusion: Subjects with symptoms or clinical signs of CNS malignancy, such as new-onset severe headaches, neck stiffness, seizures, encephalopathy, cranial nerve 
deficits, or any focal neurologic findings on physical examination, will have a lumbar puncture for examination of CSF, including sending a sample to the central 
laboratory. In the case of CRS and ICANS, refer to the ASCO management guidelines for guidance for requirements for lumbar puncture examination {Santomasso 
2021}. In summary: i) lumbar puncture is recommended for consideration in cases of CRS; ii) for ICANS, a lumbar puncture is recommended for Grade 3 or higher 
neurotoxicity and may be considered for Grade 2 (see Section 6.1.1).
h
PROs are to be completed by the subject before any study-specific assessments or procedures are performed (excluding blood draws) and before the subject receives any 
disease status information or the brexucabtagene autoleucel infusion on Day 0.
i
PET-diagnostic CT:
•
Screening/baseline: PET-CT scan should be performed as close to enrollment/leukapheresis as possible and within 28 days before leukapheresis for eligibility (unless 
imaging is available from SOC assessment within 28 days before enrollment). If a PET-CT scan is performed > 28 days before the initiation of lymphodepleting 
chemotherapy or if the subject receives any anticancer therapy (bridging therapy) between the last PET-CT scan and initiation of lymphodepleting chemotherapy, a new 
baseline PET-CT scan must be performed before lymphodepleting chemotherapy.
•
Disease assessment: PET-CT is required for each disease response assessment per the SOA and at any time disease progression is suspected.To limit radiation exposure, 
investigators are encouraged to leave at least 4 weeks between consecutive scans
j
Bone marrow aspirate and biopsy (only relevant for non-FDG-avid lymphoma):
•
Screening/baseline: For FDG-avid lymphoma, a subject’s bone marrow involvement should be assessed by PET-diagnostic CT. If the lymphoma is not FDG-avid, a bone 
marrow aspirate and biopsy is required at screening. If the screening bone marrow assessment shows infiltration, bone marrow aspirate and biopsy will be required after 
bridging therapy (if applicable).
•
Disease/response assessment: If there is evidence of baseline bone marrow involvement, the PET-diagnostic CT is not available, the lymphoma is not FDG-avid, or there 
are unexplained cytopenias or suspicion of bone marrow involvement, a bone marrow aspirate and biopsy will be performed in subjects who are being assessed for CR in 
order to confirm CR (see Section 6.2.2). To confirm a CR, the bone marrow aspirate and biopsy must show no evidence of disease by morphology or, if indeterminate by 
morphology, must be negative by immunohistochemistry.
k
Archived/fresh tumor sample(s):
•
Screening: The most recently available archived or newly acquired tumor biopsy sample will be collected and submitted to the central laboratory. Archived tumor biopsy 
samples will consist of either 1 formalin-fixed paraffin-embedded tumor block or at least 20 unstained slides. Should an archived tumor sample be unavailable or 
insufficient, a fresh tumor sample is required to be obtained before initiation of lymphodepleting chemotherapy.
•
Disease progression: If a tumor biopsy that is clinically indicated in the management of a study-treated subject is acquired, a portion of the biopsy should be sent to the 
central laboratory for additional exploratory analyses.

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l
Assessments may be performed on the day before administration of brexucabtagene autoleucel (ie, on Day −1). For tests performed at the central laboratory, this decision will 
be driven by the availability of the central laboratory to process samples on the day they are collected from the subject (refer to the laboratory manual for holidays). For 
samples collected on Day 0, collection will occur before the start of the brexucabtagene autoleucel infusion.
m
LDH should continue to be monitored after the baseline assessment as clinically indicated.
n
Pregnancy test (serum or urine): For EU/CH study sites, the test will be completed within 7 days before both leukapheresis and lymphodepleting chemotherapy for females of 
childbearing potential.
o
Serology tests for EU/CH study sites (serum): Serology 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 the 30 days before leukapheresis/enrollment and/or on the day of leukapheresis/enrollment.
p
Hepatitis B and C testing is also required at screening.
q
CBC with differential (blood): At the time points at which PBMC samples are collected for analysis of brexucabtagene autoleucel CAR T-cell levels, blood samples will also 
be collected and sent to the central laboratory for assessment of CBC with differential (these samples are in addition to samples collected at the specified time points and that 
are sent to the local laboratory for assessment of CBC with differential for clinical/safety evaluation).
r
Baseline for assessments of brexucabtagene autoleucel CAR T cells and analytes: A sample will be collected at enrollment/before the leukapheresis procedure. Subjects who 
receive bridging therapy will also have a blood sample collected before receiving the first dose of lymphodepleting chemotherapy.
s
Analytes (including cytokines) (serum/plasma) and brexucabtagene autoleucel CAR T cells (PBMCs):
•
Samples on Day 3 may be collected ± 1 day.
•
If a subject is re-admitted to the hospital after the initial hospitalization observation period with any brexucabtagene autoleucel-related adverse events, blood samples for 
assessment of brexucabtagene autoleucel CAR T cells and serum analytes will be collected on the day of hospital re-admission and then weekly through, and including, 
the day of discharge, if the samples were not already collected on the same days as per the SOA (ie, 2 identical collections on the same day are not needed).
•
If the subject experiences a Grade 3 or higher brexucabtagene autoleucel-related toxicity, such as Grade 3 CRS or neurologic event, 1 additional blood draw for 
brexucabtagene autoleucel CAR T cells (PBMCs) and serum analytes will be collected at the time of the Grade 3 or higher brexucabtagene autoleucel-related toxicity 
and upon resolution of the event, if the samples were not already collected on the same days as per the SOA (ie, 2 identical collections on the same day are not needed).
•
Blood samples for assessment of brexucabtagene autoleucel CAR T cells and serum analytes should be collected at the time of disease progression prior to starting 
subsequent anticancer therapy.
•
Exploratory T-cell immunogenicity will be performed with PBMCs at leukapheresis and Month 3. Extra blood collection is required for such testing.
•
Exploratory analyses will include lymphocyte subsets.
t
RCR (PBMCs):
•
Samples will be collected at baseline (before CAR T-cell infusion) and at Month 3.
•
If a subject develops a secondary malignancy during the study, every effort should be made to obtain a blood sample to assay for RCR and vector elements. In the case of 
a secondary malignancy, every effort will be made to obtain a blood sample (PBMC) and biopsy sample of the neoplastic tissue or the pertinent autopsy tissue to start a 
testing workflow, including tests such as transgene elements, RCR, presence of common cancer-drivers/mutations and insertional mutagenesis (see Section 6.3.15.3 of 
the KT-US-568-0138 master protocol).
u
Bridging therapy may be administered per investigator discretion if deemed required for disease control. Refer to Section 7.1 for details.
v
Mesna will be administered around the time of the cyclophosphamide dose according to institutional standards (refer to Section 5.1.2.3 and Section 7.5.3 of the 
KT-US-568-0138 master protocol).
w
Collection of serious adverse events starts from signing of the screening ICF, and collection of adverse events starts from commencement of the leukapheresis procedure.

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-C (ZUMA-25C) – Burkitt Lymphoma
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Amendment 3.0
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Table 6.
Schedule of Assessments: Post-treatment Follow-up Period
Timeframe: 
Long-term Follow-up Period (Each visit calculated from Day 0)
Procedure
M6
(± 2 w)
M9
(± 2 w)
M12
(± 2 w)
M18
(± 1 M)
M24
(± 1 M)
Suspected 
Disease 
Progressiona
Physical examinationb
X
X
X
X
X
X
Vital signs
X
Lumbar puncture
PROs: EORTC-QLQ-C30 and EQ-5D-5Lc
X
X
X
X
X
Disease response assessments (please refer to the imaging manual and central laboratory manual for guidance)
PET-diagnostic CTd
X
X
X
X
X
X
Bone marrow aspirate and biopsye
Xe
X
Overall response assessment
X
X
X
X
X
X
Local/central laboratory assessments
CBC with differential (blood)f
X
X
X
X
X
X
Local laboratory assessments
Chemistry panel (serum)
X
LDHg
X
X
β-hCG pregnancy test ([WOCBP] serum or urine)
X
HIV positive subjects only: HIV viral load and 
CD4 count
X
X
X
X
X
Central laboratory assessments (please refer to the central laboratory manual for guidance)
Analytes, including cytokines (serum/plasma)h
X
Anti-brexucabtagene autoleucel antibodies (serum)
X
X
X
X
Brexucabtagene autoleucel CAR T-cell levels and 
exploratory analyses (PBMCs)h
X
X
X
X
X
X

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Timeframe: 
Long-term Follow-up Period (Each visit calculated from Day 0)
Procedure
M6
(± 2 w)
M9
(± 2 w)
M12
(± 2 w)
M18
(± 1 M)
M24
(± 1 M)
Suspected 
Disease 
Progressiona
RCR (PBMCs)i
X
X
Tumor biopsyj
X
All brexucabtagene autoleucel-related SAEs and any 
deaths regardless of causality
X
X
X
X
X
X
Targeted AE/SAEsk
X
X
X
X
Xk
X
Targeted concomitant medicationsl
X
X
X
X
X
X
Subsequent therapy for BLm
X
X
X
X
X
X
Survival statusn
X
X
X
X
X
X
Abbreviations: AE, adverse event; BL, Burkitt lymphoma; CAR, chimeric antigen receptor; CBC, complete blood count; CR, complete response; CRS, cytokine release syndrome; 
CT, computed tomography; EORTC-QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EQ-5D-5L, European Quality of Life 
5-Dimension 5-Level scale; FDG, fluorodeoxyglucose; GP, general practitioner; hCG, human chorionic gonadotropin; HCP, healthcare provider; LDH, lactate dehydrogenase; 
LTFU, long-term follow-up; M, month; PBMC, peripheral blood mononuclear cell; PET, positron emission tomography; PRO, patient-reported outcome; RCR, replication-
competent retrovirus; SAE, serious adverse event; SOA, schedule of assessments; w, week; WOCBP, women of childbearing potential.
Note: Please refer to the footnotes listed below in parallel with Section 6 of this protocol and the KT-US-568-0138 master protocol.
a
Subjects with symptoms suggestive of disease progression should be evaluated for progression at the time symptoms occur, even if this requires an unscheduled visit.
b
Physical examination will include assessment of splenomegaly and lymphadenopathy.
c
PROs are to be completed before any assessments or procedures are performed (excluding blood draws) and before the subject receives any disease status information.
d
PET-diagnostic CT: PET-CT is required for each disease response assessment per the SOAs and at any time disease progression is suspected. To limit radiation exposure, 
investigators are encouraged to leave at least 4 weeks between consecutive scans.
e
If there is evidence of baseline bone marrow involvement, the PET-diagnostic CT is not available, the lymphoma is not FDG-avid, or there are unexplained cytopenias or 
suspicion of bone marrow involvement, a bone marrow aspirate and biopsy will be performed in subjects who are being assessed for CR in order to confirm CR (see 
Section 6.2.2). To confirm a CR, the bone marrow aspirate and biopsy must show no evidence of disease by morphology or, if indeterminate by morphology, must be negative 
by immunohistochemistry.
f
CBC with differential (blood):
•
Local laboratory assessments: Blood will be collected at the time points specified through Month 24 or until disease progression, whichever occurs first, and sent to the 
local laboratory for clinical/safety evaluation.
•
Central laboratory assessments: Blood will be collected at the time points specified through Month 24 and sent to the central laboratory for assessment of CBC with 
differential (these samples are in addition to samples collected at the specified time points that are sent to the local laboratory for assessment of CBC with differential for 
clinical/safety evaluation).
g
LDH should continue to be monitored after the baseline assessment as clinically indicated.

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h
Analytes (including cytokines) (serum/plasma) and brexucabtagene autoleucel CAR T cells (PBMCs):
•
If a subject is re-admitted to the hospital after the initial hospitalization observation period with any brexucabtagene autoleucel-related AEs, blood samples for 
assessment of brexucabtagene autoleucel CAR T cells and serum analytes will be collected on the day of hospital re-admission and then weekly through, and including, 
the day of discharge, if the samples were not already collected on the same days as per the SOA (ie, 2 identical collections on the same day are not needed).
•
If the subject experiences a Grade 3 or higher brexucabtagene autoleucel-related toxicity, such as Grade 3 CRS or neurologic event, 1 additional blood draw for 
brexucabtagene autoleucel CAR T cells (PBMCs) and serum analytes will be collected at the time of the Grade 3 or higher brexucabtagene autoleucel-related toxicity 
and upon resolution of the event, if the samples were not already collected on the same days as per the SOA (ie, 2 identical collections on the same day are not needed).
•
Blood samples for assessment of brexucabtagene autoleucel CAR T cells and serum analytes should be collected at the time of disease progression prior to starting 
subsequent anticancer therapy.
•
Exploratory analyses will include lymphocyte subsets.
i
RCR (PBMCs):
•
Samples will be collected at Month 6 and Month 12 and analyzed. Additional samples will be collected and analyzed only if an RCR event is clinically suspected and/or 
a subject’s PBMC sample tests positive for RCR at any time point within the first 12 months following brexucabtagene autoleucel infusion.
•
If a subject develops a secondary malignancy during the study or follow-up and RCR is suspected, every effort should be made to obtain a blood sample to assay for 
RCR and vector elements. In the case of a secondary malignancy, every effort will be made to obtain a blood sample (PBMC) and biopsy sample of the neoplastic tissue 
or the pertinent autopsy tissue to start a testing workflow, including tests such as transgene elements, RCR, presence of common cancer-drivers/mutations and insertional 
mutagenesis (see Section 6.3.15.3 of the KT-US-568-0138 master protocol).
j
If a tumor biopsy that is clinically indicated in the management of a study-treated subject is acquired, a portion of the biopsy should be sent to the central laboratory for 
additional exploratory analyses.
k
Targeted AEs/SAEs include neurologic events, hematologic events, serious infections, autoimmune disorders, and secondary malignancies. From 3 months after the 
brexucabtagene autoleucel infusion, targeted AEs/SAEs will be reported through Month 24 after the initial brexucabtagene autoleucel infusion or until disease progression 
and/or the start of subsequent anticancer therapy, whichever occurs first. After Month 24, the subject will transition to the LTFU study where targeted AEs/SAEs will be 
reported through 15 years. All new malignancies (defined as the development of any new malignancies occurring after the administration of brexucabtagene autoleucel) are to 
be reported; however, only secondary malignancies (defined as the development of any new malignancy suspected to be possibly related to brexucabtagene autoleucel) are 
considered to be targeted AEs/SAEs.
l
Targeted concomitant medications will be collected up to 24 months after the brexucabtagene autoleucel infusion or until disease progression or the start of subsequent 
anticancer therapy, whichever occurs first. (Reporting will continue through 60 months as part of the LTFU study.)
m
Subsequent anticancer therapy administered after brexucabtagene autoleucel infusion for a subject’s disease will be collected until 1 of the following occurs: subject 
completes the post-treatment follow-up period, is considered lost to follow-up, withdraws consent, or dies. The subject and/or the referring HCP and/or GP may be contacted 
directly by telephone or email to collect information about subsequent therapy.
n
Subject and/or referring HCP and/or GP may be contacted directly by telephone or email to assess survival status.

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12.3.
Disease Response Criteria
12.3.1.
International Working Group Lugano Classification
Disease assessments are to be performed according to the International Working Group Lugano 
Response Criteria for Malignant Lymphoma {Cheson 2014}; refer also to instructions provided 
in the study imaging manual. 
The Deauville 5-point scale (5PS) is used for positron emission tomography (PET) scoring; the 
scores and their descriptions are presented in Table 7.
Table 7.
Deauville 5-point Scale for Positron Emission Tomography Scoring
Score
Description
1
No uptake above background
2
Uptake ≤ mediastinum
3
Uptake > mediastinum but ≤ liver
4
Uptake moderately higher than liver
5
Uptake markedly higher than liver and/or new lesions
X
New areas of uptake unlikely to be related to lymphoma
Source: {Cheson 2014}.
12.3.1.1.
Complete Remission 
12.3.1.1.1.
Complete Metabolic Response for PET−Computed Tomography-based Response
The designation of complete metabolic response requires all of the following:
•
A 5PS score of 1, 2, or 3, with or without a residual mass:
In Waldeyer’s ring or extranodal sites with high physiologic uptake or activation within 
the spleen or marrow, uptake may be greater than normal in the mediastinum and/or liver. 
In this circumstance, complete metabolic response may be inferred if uptake at sites of 
initial involvement is no greater than surrounding normal tissue even if the tissue has 
high physiologic uptake.
•
No new sites of disease should be observed
•
No evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow 

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12.3.1.1.2.
Complete Radiologic Response for Computed Tomography-based Response 
The designation of complete radiologic response requires all of the following:
•
Target nodes/nodal masses must regress to ≤ 1.5 cm in longest transverse diameter (LDi) of a 
lesion
•
No extra lymphatic sites of disease
•
Absent nonmeasured lesion
•
Organ enlargement regress to normal
•
No new sites of disease should be observed
•
Bone marrow normal by morphology; if indeterminate, immunohistochemistry negative
12.3.1.2.
Partial Remission
12.3.1.2.1.
Partial Metabolic Response for PET–Computed Tomography-based Response
The designation of partial metabolic response requires all of the following:
•
A 5PS score of 4 or 5, with reduced uptake compared to baseline (screening), and residual 
mass(es) of any size.
Note:
At the interim, these findings suggest responding disease
At the end of treatment, these findings suggest residual disease
•
No new sites of disease should be observed
•
Residual uptake is higher than uptake in normal bone marrow but reduced compared with 
baseline (diffuse uptake is compatible with reactive changes from chemotherapy allowed)
If there are persistent focal changes in the marrow in the context of a nodal response, 
consideration should be given to further evaluation with magnetic resonance imaging or biopsy 
or an interval scan.

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12.3.1.2.2.
Partial Radiologic Response for Computed Tomography-based Response 
The designation of partial radiologic response requires all of the following:
•
≥ 50% decrease in the sum of the product of the perpendicular diameters of up to 6 target 
measurable nodes and extranodal sites.
When a lesion is too small to measure on a computed tomography (CT) scan, assign 
5 mm × 5 mm as the default value
When the lesion is no longer visible, assign 0 x 0 mm
For a node > 5 mm × 5 mm, but smaller than normal, use the actual measurement for 
calculation
•
Absent/normal, regressed, but no increase of nonmeasured lesions
•
Spleen must have regressed by > 50% in length beyond normal
•
No new sites of disease should be observed
12.3.1.3.
Stable Disease
12.3.1.3.1.
No Metabolic Response for PET–CT-based Response
The designation of no metabolic response requires all of the following:
•
A 5PS score of 4 or 5, with no significant change in FDG uptake compared with baseline 
(screening) at an interim time point or the end of treatment
•
No new sites of disease should be observed
•
No change from baseline in bone marrow
12.3.1.3.2.
Stable Radiologic Disease for CT-based Response 
The designation of stable radiologic disease requires all of the following:
•
< 50% decrease from baseline in the sum of the product of the perpendicular diameters of up 
to 6 dominant, measurable nodes and extranodal sites; no criteria for progressive disease 
(PD) are met
•
No increase consistent with progression in nonmeasured lesion and organ enlargement
•
No new sites of disease should be observed 

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12.3.1.4.
Progressive Disease
12.3.1.4.1.
Progressive Metabolic Disease for PET–CT-based Response
The designation of progressive metabolic disease requires at least 1 of the following:
•
A 5PS score 4 or 5 with an increase in intensity of uptake from baseline nadir and/or
•
New FDG-avid foci consistent with lymphoma at an interim time point or the end of 
treatment assessment
•
New FDG-avid foci consistent with lymphoma rather than another etiology (eg, infection or 
inflammation). If uncertain regarding the etiology of new lesions, a biopsy or interval scan 
may be considered
•
New or recurrent FDG-avid foci in bone marrow
12.3.1.4.2.
Progressive Radiologic Disease for CT-based Response
The designation of progressive radiologic disease requires at least 1 of the following:
•
An individual node/lesion must be abnormal with:
LDi > 1.5 cm, and
An increase by ≥ 50% from the cross product of LDi and perpendicular diameter nadir, 
and
An increase in LDi or shortest transverse diameter, shortest axis perpendicular to the LDi, 
(shortest transverse diameter) from nadir
■
0.5 cm for lesions ≤ 2 cm
■
1.0 cm for lesions > 2 cm
In the setting of splenomegaly, the splenic length must increase by > 50% of the extent of 
its prior increase beyond baseline (eg, a 15-cm spleen must increase to > 16 cm). If there 
is no prior splenomegaly, the spleen must increase by ≥ 2 cm from baseline
New or recurrent splenomegaly
•
New or clear progression of preexisting nonmeasured lesions

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•
New lesion:
Regrowth of previously resolved lesions
A new node > 1.5 cm in any axis
A new extranodal site > 1.0 cm in any axis; if < 1.0 cm in any axis, its presence must be 
unequivocal and attributable to lymphoma
Assessable disease of any size unequivocally attributable to lymphoma
•
New or recurrent bone marrow involvement

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12.4.
Protocol Amendment History
12.4.1.
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 study 
sites planned
Number of study sites increased from 
approximately 40 to 50
Increased the number of study 
sites to optimize enrolment
Synopsis Number of 
subjects enrolled and 
treated and Section 4.1 
Number of subjects and 
subject selection
Updated sample size of Burkitt Lymphoma to 30 
subjects.
BL sample size increased in 
consideration of EMA 
Scientific Advice 
recommendations
Synopsis Statistical 
methods
Updated statistical methods to reflect the 
updated number of BL subjects that will be 
enrolled in substudy C. 
Updates to statistical methods 
due to increase in number of 
subjects planned to be treated 
in Burkitt Lymphoma substudy.
Section 6.4 Tumor biopsy
Disease Progression: 
If a tumor biopsy that is clinically indicated in 
the management of a study-treated subject is 
acquired, a portion of the biopsy should be sent 
to the central laboratory for additional 
exploratory analyses.
Addition to clarify samples are 
applicable only for study 
treated subjects
Section 9.3 Determination 
of sample size
Updates to indicate this single-arm, open-label 
substudy will enroll and treat 30 subjects with 
the SRT recommended dose of brexucabtagene 
autoleucel. 
Additional edits to indicate this sample size will 
achieve a statistical power of 92%  and that 
statistically significant treatment effect can be 
claimed in this substudy if ≥ 17 responders (≥ 
56.5%) are observed among the 30 subjects at 
the primary analysis.
Updated statistical rationale for 
increased sample size 
calculations
Section 9.4.1 Interim 
analysis and early stopping 
guidelines
Updates to indicate that the non-binding futility 
boundary is ORR of 43.8% based on the beta 
spending function of rho family 
(parameter = 0.7), with a crossing probability of 
62.2% under the null hypothesis (ORR ≤ 39%). 
Updates to statistical methods 
for planned analyses due to 
increase in number of subjects 
planned to be treated in Burkitt 
Lymphoma substudy following 
EMA scientific feedback
Section 9.4.2 Primary 
analysis
Subject number for primary analysis increased 
from 20 to 30. In addition, text is amended to 
indicate that hypothesis testing will be based on 
the number of objective responders observed 
among the 30 subjects 
Updates to statistical methods 
for planned analyses due to 
increase in number of subjects 
planned to be treated in Burkitt 
Lymphoma substudy following 
EMA scientific feedback

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Section Number and 
Name
High-level Description of Change
Brief Rationale
Section 12.2 Schedule of 
assessments, Table 5 
Schedule of Assessments: 
Screening, Pretreatment, 
Treatment, and Post-
treatment Periods
Added schedule of PROs: EORTC-QLQ-C30 
and EQ-5D-5L at Post-bridging therapy 
assessment (if applicable)
Correction. Added an 
applicable PROs assessment 
timepoint
Section 12.2 Schedule of 
assessments, Table 5 
Schedule of Assessments: 
Screening, Pretreatment, 
Treatment, and Post-
treatment Periods
Footnote k Disease progression: If a tumor 
biopsy that is clinically indicated in the 
management of a study-treated subject is 
acquired, a portion of the biopsy should be sent 
to the central laboratory for additional 
exploratory analyses
Addition to clarify samples are 
applicable only for study 
treated subjects
Section 12.2 Schedule of 
assessments, Table 6 
Schedule of Assessments: 
Post-treatment Follow-up 
Period
Footnote j: If a tumor biopsy that is clinically 
indicated in the management of a study-treated 
subject is acquired, a portion of the biopsy 
should be sent to the central laboratory for 
additional exploratory analyses
Addition to clarify samples are 
applicable only for study 
treated subjects
12.4.2.
Amendment 1.1 EU-specific Amendment (dated 12 January 2023)
A high-level summary of this amendment is provided in tabular form in the subsection below. 
Minor changes such as the correction of typographic errors, grammar, or formatting are not 
detailed.
For changes from Amendment 1 to Amendment 2, please refer to Section 12.4.2 and 
Section 12.4.3. Amendment 2 incorporates all changes in Amendment 1.1 together with the 
changes outlined in Section 12.4.3.
Protocol changes that are common across all substudies are detailed in the Master protocol 
(Appendix 12.10).
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
Section 3.1 Study Design
Add text to detail that the end of study is 
defined in the Master protocol (Section 3.4). 
(Defined as the LPLV within each specific 
substudy)
For clarity
Synopsis Statistical Methods 
and Sections 9.1 Hypothesis 
and 9.4.2 Primary Analysis
•
“significantly” removed from statement 
that “The hypothesis is that the ORR to 
brexucabtagene autoleucel per central 
assessment is significantly greater than 
39%.”
For clarity

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Section Number and Name
High-level Description of Change
Brief Rationale
•
Text edited to now state that the p-value 
‘will be’ calculated based on an exact test, 
rather than ‘may be’ tested. 
Synopsis Eligibility Criteria 
Unique to the BL Substudy 
and Section 4.2.1 BL 
Substudy-Specific Inclusion 
Criteria
Inclusion criterion 2 updated to (i) allow any 
first line chemoimmunotherapy, and (ii) 
Subjects will be eligible regardless of the 
duration of remission prior to relapse
For clarity 
Section 6.4 Tumor Biopsy
Added text to detail that a new biopsy will be 
acquired only if the location is easily 
accessible, and if appropriate taking into 
account subject safety
Self-explanatory
Section 12.2 Schedule of 
Assessments Table 5
Pregnancy test added at Day 28
Alignment with CTFG 
guidelines for pregnancy 
testing following 
administration of fludarabine 
and cyclophosphamide 
12.4.3.
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
Correction of minor typographical errors
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) – Substudy C – 
Relapsed/Refractory Burkitt Lymphoma”. The 
evaluation of safety (secondary endpoint) 
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 # 4 added “presence of 
central nervous system (CNS) involvement. 
Subjects with a prior history of CNS 
involvement are eligible if they show a 
negative cerebrospinal fluid (CSF) and no 
involvement by imaging”
Self-explanatory
Section 6.1 Brain Magnetic 
Resonance Imaging
At screening, CNS involvement will be 
assessed by local review, and images will not 
be sent for central review.
For clarification

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Section Number and Name
High-level Description of Change
Brief Rationale
Section 12.2 Schedule of 
Assessments, Table 5 
Schedule of Assessments: 
Screening, Pretreatment, 
Treatment, and Post-
Treatment Periods
Requirement for PRO assessment at post-
bridging therapy disease assessment removed
Typo. PRO assessments will 
be done at Day -5 in all 
subjects, regardless of whether 
the subject received bridging 
therapy 
Section 12.2 Schedule of 
assessments, Table 5 Schedule 
of Assessments: Screening, 
Pretreatment, Treatment, and 
Post-Treatment Periods
Added text to Footnote ‘a’: “For EU and UK, 
the subject may remain hospitalized or return 
to the clinic daily for this extended monitoring, 
at the discretion of the investigator.  For CH, 
patients must remain hospitalized for 10 days 
after brexucabtagene autoleucel”
Request by Swiss Regulatory 
Authority
Section 12.2 Schedule of 
Assessments, Table 5 
Schedule of assessments: 
Screening, Pretreatment, 
Treatment, and Post-
Treatment Periods
Added text to Footnote ‘g’: “Subjects with a 
prior history of CNS involvement are eligible if 
they show a negative cerebrospinal fluid (CSF) 
at screening and no involvement by imaging”.
Self-explanatory
Section 12.2 Schedule of 
assessments, Table 5 Schedule 
of assessments: Screening, 
Pretreatment, Treatment, and 
Post-Treatment Periods
 Footnotes ‘n’ pregnancy testing and ‘o’ 
serology testing updated to include Switzerland 
(CH) 
Request by Swiss Regulatory 
Authority and alignment with 
Master protocol Section 6
Section 12.2 Schedule of 
assessments, Table 5 Schedule 
of assessments: Screening, 
Pretreatment, Treatment, and 
Post-Treatment Periods
Footnote ‘s’: Samples on Day 3 may be 
collected ± 1 day
Provides flexibility regarding 
central laboratory sample 
collection when the Day 3 
visit falls over a weekend
Section 12.2 Schedule of 
Assessments, Table 6 
Schedule of Assessments: 
Post-Treatment period
Visit window for M18 changed from ± 2 weeks 
to ± 1 month
Provides added flexibility

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12.4.4.
Amendment 3.0 (dated 17 August 2023)
Changes from Amendment 2.0 (dated 01 March 2023) to Amendment 3 (dated 17 August 2023) 
are detailed below
Section Number and Name
High-level Description of Change
Brief Rationale
General
Correction of typographical errors 
Removed references to study sites in the UK as 
UK is no longer participating.
Self-explanatory
Synopsis- Study Design
Removed to indicate that the study will focus 
on efficacy and not safety
Request from EMA reviewer 
during Part 1 EU-CTR 
application to update the trial 
title to focus on the primary 
endpoint only
Synopsis - Number of Study 
Sites Planned
Number of participating sites amended to 
approximately 25
 Number of sites reduced due 
to early termination of 
substudies A and D
Synopsis- Statistical Methods
Added language to indicate study enrollment 
will be paused following treatment of the 10th 
subject with brexucabtagene autoleucel and 
until results from the interim analysis have 
been assessed
To allow the Sponsor to 
review for futility prior to 
exposing additional subjects 
to study treatment
Section 3.1 Study Design
Text removed to indicate that the study will 
focus on efficacy and not safety
Request during Part 1 
EU-CTR application to update 
the trial title to focus on the 
primary endpoint only
Section 3.1 Study Design
Added language to indicate study enrollment 
will be paused following treatment of the 10th 
subject with brexucabtagene autoleucel and 
until results from the interim analysis have 
been assessed
To allow the Sponsor to 
review for futility prior to 
exposing additional subjects 
to study treatment
Study 6.1.1 Lumbar Puncture
Added text to indicate a screening lumbar 
puncture should be performed  as close as 
possible to leukapheresis
To specify timing of the 
lumbar puncture
Section 6.2.1 Imaging 
Requirements
Added language to indicate that to limit 
radiation exposure, investigators are 
encouraged to leave at least 4 weeks between 
consecutive scans
To limit radiation exposure of 
subjects
Section 8.1 SRT and DSMB
Added language to indicate study enrollment 
will be paused following treatment of the 10th 
subject with brexucabtagene autoleucel and 
until results from the interim analysis have 
been assessed
To allow the Sponsor to 
review for futility prior to 
exposing additional subjects 
to study treatment

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Section Number and Name
High-level Description of Change
Brief Rationale
Section 9.4.1 Interim Analysis 
and Early Stopping Guidelines
Added language to indicate study enrollment 
will be paused following treatment of the 10th 
subject with brexucabtagene autoleucel and 
until results from the interim analysis have 
been assessed
To allow the Sponsor to 
review for futility prior to 
exposing additional subjects 
to study treatment
Section 12.2 Schedule of 
assessments, Table 5 Schedule 
of assessments: Screening, 
Pretreatment, Treatment, and 
Post-Treatment Periods
Footnote e- added clarifying text that 
neurological should be performed every other 
day during the hospitalization period
To clarify requirements for 
neurological assessments
Section 12.2 Schedule of 
assessments, Table 5 Schedule 
of assessments: Screening, 
Pretreatment, Treatment, and 
Post-Treatment Periods
Added text to indicate a screening lumbar 
puncture should be performed as close as 
possible to leukapheresis
To specify timing of the 
lumbar puncture
Section 12.2 Schedule of 
assessments, Table 5 Schedule 
of assessments: Screening, 
Pretreatment, Treatment, and 
Post-Treatment Periods
Footnote i: added that “To limit radiation 
exposure, investigators are encouraged to leave 
at least 4 weeks between consecutive scans”
To limit radiation exposure of 
subjects
Section 12.2 Schedule of 
Assessments, Table 6 
Schedule of Assessments: 
Post-Treatment period
Footnote d: added that “To limit radiation 
exposure, investigators are encouraged to leave 
at least 4 weeks between consecutive scans”
To limit radiation exposure of 
subjects

ZUMA-25_BL Amendment 3
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Clinical Development
eSigned
31-Aug-2023
14:20:52
PPD