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 A – Relapsed/Refractory Waldenstrom 
Macroglobulinemia
Note:
This subprotocol should be used in conjunction with the 
KT-US-568-0138 master protocol 
Protocol Number:
KT-US-568-0138-A (ZUMA-25A)
Indication:
Relapsed/refractory Waldenstrom macroglobulinemia 
Kite Investigational Product 
Brexucabtagene Autoleucel 
Kite IND Number:
028542
EU CT Number:
2022-501259-10-00
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
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, the United Kingdom, 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
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.
WM Substudy-specific Inclusion Criteria.............................................................................16
4.2.2.
WM Substudy-specific Exclusion Criteria............................................................................17
5.
STUDY TREATMENT........................................................................................................................................18
5.1.
Description of Study Treatment ..............................................................................................................18
5.2.
Prior and Concomitant Medications and Permitted Treatments..............................................................18
6.
STUDY ASSESSMENTS UNIQUE TO WALDENSTROM MACROGLOBULINEMIA...............................19
6.1.
Clinical Laboratory Tests ........................................................................................................................19
6.2.
Brain Magnetic Resonance Imaging .......................................................................................................20
6.3.
Lumbar Puncture .....................................................................................................................................21
6.4.
Disease Assessments ...............................................................................................................................21
6.4.1.
Assessment of Quantitative Monoclonal IgM, IgA, and IgG................................................22
6.4.2.
Assessment of Serum Protein Electrophoresis......................................................................22
6.4.3.
Serum Immunofixation..........................................................................................................22
6.4.4.
Imaging Requirements...........................................................................................................23
6.4.5.
Bone Marrow Biopsy/Aspirate..............................................................................................24
6.5.
Disease-specific Exploratory Assessments .............................................................................................25
7.
STUDY PROCEDURES UNIQUE TO WALDENSTROM MACROGLOBULINEMIA.................................26
7.1.
Screening .................................................................................................................................................26
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

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9.2.1.
Definition of Substudy Primary Endpoint.............................................................................28
9.2.2.
Definition of Substudy Secondary Endpoints .......................................................................28
9.3.
Determination of Sample Size.................................................................................................................29
9.4.
Planned Analyses.....................................................................................................................................29
9.4.1.
Interim Analysis and Early Stopping Guidelines ..................................................................29
9.4.2.
Primary Analysis ...................................................................................................................29
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 .......................................................................................................................47
12.3.1.
Definitions of Response for Waldenstrom Macroglobulinemia............................................47
12.3.2.
Waldenstrom Macroglobulinemia International Workshop Diagnosis 
Criteria...................................................................................................................................47
12.4.
Protocol Amendment History..................................................................................................................48
12.4.1.
Amendment 1.0 (dated 20 July 2022) ...................................................................................48
12.4.2.
Amendment 1.1 EU-specific Amendment (dated 12 January 2023).....................................48
12.4.3.
Amendment 2.0 (dated 01 March 2023)................................................................................49
LIST OF IN-TEXT TABLES
Table 1.
Substudy-specific Objectives and Endpoints ..........................................................................13
Table 2.
Clinical Laboratory Tests for Disease-specific Assessments..................................................19
Table 3.
Definitions of Substudy Secondary Endpoints........................................................................29
Table 4.
Schedule of Assessments: Screening, Pretreatment, Treatment, and Post-treatment 
Period.......................................................................................................................................36
Table 5.
Schedule of Assessments: Post-treatment Follow-up Period ..................................................44

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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 A – Relapsed/Refractory Waldenstrom Macroglobulinemia 
Indication: Adult subjects with relapsed/refractory (r/r) Waldenstrom macroglobulinemia 
(WM)
Kite IND Number: 028542
EU CT Number: 2022-501259-10-00
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 50 
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 WM by determining the combined 
rate of complete response (CR) and very good 
partial response (VGPR) by central assessment 
per the Sixth International Workshop in WM 

Combined rate of CR and VGPR rate by central 
assessment defined as the proportion of subjects 
who achieve either CR or VGPR 
Secondary Objectives
Secondary Endpoints

To determine the efficacy of brexucabtagene 
autoleucel in subjects with WM, by determining 
the Objective Response Rate (ORR) by central 
assessment

ORR, defined as the proportion of subjects who 
achieve a best response of CR, VGPR, or partial 
response (PR)

To determine the combined rate of CR and 
VGPR by investigator assessment 

Combined CR and VGPR rate by investigator 
assessment defined as the proportion of subjects 
who achieve either CR or VGPR

To determine the rates of individual responses 
by central assessment

Rate of VGPR and PR, separately
   

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Study Design: This substudy protocol contains details regarding all elements of the study that 
are unique to subjects with WM. 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 safety and efficacy of 
brexucabtagene autoleucel in subjects with r/r WM. 
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 chimeric 
antigen receptor (CAR) T cells/kg body weight. Following review by the SRT, the dose may 
be lowered to 1 × 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 36, and then annually out to Month 60.
Additional study details are provided in the KT-US-568-0138 master protocol. 
Subjects enrolled in this substudy, if already receiving a Bruton’s tyrosine kinase (BTK) 
inhibitor, may receive ibrutinib through screening and leukapheresis at the discretion of the 
investigator, as described in Section 5.2 and 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 60 subjects 
with r/r WM will be enrolled 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 WM
Duration of Treatment and Study Participation: The treatment period will be 1 week 
following infusion, and the duration of the study is 60 months.
Eligibility Criteria Unique to the WM 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 be met.
WM Substudy-specific Inclusion Criteria:
1) Confirmed clinicopathological diagnosis of WM in accordance with the consensus panel 
of the Second International Workshop on WM (see Section 12.3.2)

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2) Relapsed or refractory disease after 2 or more lines of therapy. Subjects will be eligible 
regardless of the duration of remission prior to relapse. 

Prior therapy must have included a BTK inhibitor. Also, chemotherapy and/or a 
proteasome inhibitor must have been attempted, with either subsequent documented 
disease progression or no response (stable disease) 
3) Requiring treatment as defined in the recommendations from the Second International 
Workshop on WM
4) Measurable disease, defined as presence of serum immunoglobulin (Ig) M with a 
minimum IgM level of > 2 times the upper limit of normal of each institution is required
5) The inclusion criteria concerning washout periods prior to leukapheresis in the 
KT-US-568-0138 master protocol must be met, with the exception that ibrutinib may be 
continued through leukapheresis and up to 5 half-lives (30 hours) prior to the start of 
lymphodepletion
WM Substudy-specific Exclusion Criteria:
1) History of allogeneic stem cell transplantation. A prior autologous stem cell 
transplantation is allowed, but at least 6 months should have elapsed 
2) Plasmapheresis for symptomatic hyperviscosity or serum IgM > 5,000 mg/dL < 35 days 
prior to the screening IgM assessment
3) Exclusion of IgM monoclonal gammopathy of undetermined significance or IgM multiple 
myeloma
4) Presence of a central nervous system involvement (Bing-Neel syndrome). Subjects with a 
prior history of Bing-Neel syndrome are eligible if they show a negative cerebrospinal 
fluid 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 to 6 subjects in this substudy have been treated with the initial dose 
(2 × 106 anti-CD19 CAR T cells/kg body weight) and followed for 28 days, as detailed in the 
KT-US-568-0138 master protocol.

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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.
Statistical Methods: 
Hypothesis: An alternative hypothesis is proposed with a target 20% combined CR and VGPR 
rate per central assessment against a null hypothesis that the combined CR and VGPR rate is 
≤ 6%. The hypothesis is that the combined CR and VGPR to brexucabtagene autoleucel per 
central assessment is > 6%. 
Sample Size Calculation: This single-arm, open-label substudy will enroll and treat 
60 subjects with the SRT-recommended dose of brexucabtagene autoleucel. This sample size 
will achieve a statistical power of 88% if there is at least a 14% improvement in combined CR 
and VGPR rate (brexucabtagene autoleucel: 20% versus historical control: 6%) at an alpha 
level of 0.025 (1-sided). 
Analyses: An interim analysis will be conducted after 20 subjects (33%) have had the 
opportunity to be evaluated for response 6 months after treatment with brexucabtagene 
autoleucel. In this interim analysis, the DSMB will review investigator-reported data for both 
safety and efficacy (futility only). The non-binding futility boundary of an overall response 
rate of 7.5% is based on the beta spending function of rho family (parameter = 0.35), with a 
crossing probability of 61% under the null hypothesis (overall response rate ≤ 6%). A decision 
will be made by the sponsor based on DSMB recommendation, with the complete benefit/risk 
profile of brexucabtagene autoleucel being taken into account. If a decision is made to 
discontinue this substudy, then this analysis will be considered the primary analysis of this 
substudy. 
If the decision based on the interim analysis is to continue the substudy, a primary analysis 
will be conducted after 60 subjects have been enrolled and treated with the SRT-
recommended dose of brexucabtagene autoleucel and have had the opportunity to be assessed 
for response at least 12 months after the brexucabtagene autoleucel infusion.
Hypothesis testing will be based on the number of responders observed among the 60 subjects, 
as described above. The point estimate of the combined CR and VGPR rate will be calculated, 
together with its 95% confidence interval using the Clopper-Pearson method. The p-value will 
be calculated based on an exact test. If more than 60 subjects are treated with the 
SRT-recommended dose in the substudy by the time of data cutoff, all treated subjects will be 
included in the primary analysis. 

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A follow-up analysis may be performed after all treated subjects have had the opportunity to 
be assessed for response at least 30 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.
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
BTK 
Bruton’s tyrosine kinase
CAR
chimeric antigen receptor 
CNS
central nervous system
CR
complete response/remission 
CRS
cytokine release syndrome
CSF
cerebrospinal fluid
CT 
computed tomography
DSMB
Data Safety Monitoring Board
eCRF
electronic case report form
EMD
extramedullary disease
ICANS
immune effector cell-associated neurotoxicity syndrome
Ig
immunoglobulin
IP
investigational product
MRI
magnetic resonance imaging
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
SPEP
serum protein electrophoresis
SRT
safety review team
SUSAR
suspected unexpected serious adverse reaction
VGPR
very good partial response
WBC
white blood cell
WM
Waldenstrom macroglobulinemia

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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
Waldenstrom macroglobulinemia (WM) is a B-cell disorder characterized by immunoglobulin M 
monoclonal gammopathy and lymphoplasmacytic cell infiltration of the bone marrow and other 
organs. WM is a rare disorder with approximately 1,000 to 1,500 new cases diagnosed every 
year in the United States, and is predominantly observed in older adults (median age at the time 
of diagnosis is 60 to 75 years) .
1.1.2.
Diagnosis
To establish a diagnosis of WM, it is mandatory to demonstrate both an IgM monoclonal 
gammopathy and bone marrow infiltration by a lymphoplasmacytic cell population manifested 
by small lymphocytes with evidence of plasmacytoid/plasma cell differentiation . The bone 
marrow infiltration should be supported by immunophenotypic studies (flow cytometry and/or 
immunohistochemistry) showing the following profile: slgM+, CD19+, CD20+, and CD22+. The 
lymphocytes in WM are typically negative for CD5, CD10, or CD23. However, this should not 
exclude diagnosis as exceptions occur and about 10% to 20% of cases may express CD5, CD10, 
or CD23. MYD88 (L265P) mutations are present in > 90% of patients with WM and can help 
differentiate WM/lymphoplasmacytic lymphoma from IgM myeloma or marginal zone 
lymphoma .
1.1.3.
Frontline Treatment
Similar to other indolent lymphomas, a ‘watch and wait’ approach is a standard paradigm for 
asymptomatic patients, and current guidelines advise that treatment should only be initiated for 
WM patients who have hyperviscosity or additional symptoms such as neuropathy, symptomatic 
adenopathy, organomegaly, amyloidosis, cryoglobulinemia, cold agglutin disease, anemia, or 
presence of cytopenia . While treatment options have improved over recent years, no currently 
approved therapies have curative potential, and all patients with WM ultimately relapse . 
Accordingly, treatment strategies must consider patient age and comorbidities, and balance 
disease control with compromising quality of life, risk of long-term toxicities, and the 
development of secondary malignancies. In general, therapeutic agents that are potentially 
limiting to future treatment options should be avoided during the initial therapy (eg, continuous 
oral alkylating agents or nucleoside analogs, especially if an autologous stem cell transplantation 
is being considered). The reasons for this approach is an increased risk for disease transformation 
or development of myelodysplastic syndromes or secondary acute myeloid leukemia . 

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The recommended frontline therapies currently include combinations of bendamustine and 
rituximab with and without dexamethasone. In addition, targeted therapy with a Bruton’s 
tyrosine kinase (BTK) inhibitor is currently recommended either with or without rituximab . 
Various other drugs and combinations exist both as preferred but also as alternative primary 
therapy depending on the comorbidities and frailty of the patients. These include proteasome 
inhibitors such as ixazomib or carfilzomib and nucleoside analogues such as cladribine or 
fludarabine .
1.1.4.
Second-line Treatment
Upon relapse, administering the same regimen used for primary treatment is reasonable if the 
regimen was well tolerated and induced prolonged response . While the introduction of BTK 
inhibitors has substantially improved outcomes in the relapsed/refractory (r/r) setting, the 
efficacy of BTK inhibitors can be negatively impacted by mutations in CXCR4 and MYD88 that 
are observed in a substantial number of patients . 
While another treatment option is allogeneic stem cell transplant, which has been shown to be 
efficacious in patients with WM, it is associated with substantial treatment-related morbidity and 
mortality, thereby limiting its utility .
Few studies have investigated the third-line setting for WM, and such studies often include 
subjects who have been exposed to various previous therapies. However, when specifically 
evaluating third-line subjects and applying the response rate definition of complete response and 
very good partial response (CR+VGPR), response rates ranging between 0% and 37% have been 
reported . These data underscore the fact that current therapies remain unsatisfactory and 
highlight the need for new therapeutic options.

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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 WM by determining the combined 
rate of CR and VGPR by central assessment per 
the Sixth International Workshop in WM 

Combined rate of CR and VGPR rate by central 
assessment defined as the proportion of subjects 
who achieve either CR or VGPR 
Secondary Objectives
Secondary Endpoints

To determine the efficacy of brexucabtagene 
autoleucel in subjects with WM by determining 
the Objective Response Rate (ORR) by central 
assessment

ORR, defined as the proportion of subjects who 
achieve a best response of CR, VGPR, or PR

To determine the combined rate of CR and 
VGPR by investigator assessment

Combined CR and VGPR rate by investigator 
assessment defined as the proportion of subjects 
who achieve either CR or VGPR

To determine the rates of individual responses by 
central assessment

Rate of VGPR and PR, separately
Abbreviations: CR, complete response; PR, partial response; VGPR, very good partial response; WM, Waldenstrom 
macroglobulinemia.

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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 WM. 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 safety and efficacy of 
brexucabtagene autoleucel in subjects with r/r WM who have received at least 2 lines of prior 
therapy.
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 chimeric 
antigen receptor (CAR) T cells/kg body weight. Following review by the SRT, the dose may be 
lowered to 1 × 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 36, and then annually out to Month 60.
Additional details of the study design are provided in Section 3 of the KT-US-568-0138 master 
protocol.
The study schema is detailed in Figure 1 of the KT-US-568-0138 master protocol.
Subjects enrolled in this substudy, if already receiving a BTK inhibitor, may receive ibrutinib 
through screening and leukapheresis at the discretion of the investigator, as described in 
Section 5.2 and Section 7.1. 
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 20 subjects (33%) in this substudy have been treated with the SRT-recommended dose 
of brexucabtagene autoleucel and have had the opportunity to be followed for 6 months after the 
brexucabtagene autoleucel infusion. 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 Allowance of Ibrutinib
If required, and per investigator discretion, ibrutinib treatment will be a non-mandatory treatment 
option through screening and leukapheresis and up to 5 half-lives (30 hours) prior to the start of 
lymphodepletion for subjects already receiving a BTK inhibitor, as described in Section 5.2 and 
Section 7.1. Allowing continued ibrutinib treatment (including initiation of ibrutinib in subjects 
receiving another BTK inhibitor) will minimize the risk of BTK inhibitor withdrawal symptoms  
and IgM flares . Only ibrutinib (and not acalabrutinib or zanubrutinib) is allowed due to 
differences in the impact on T-cell function between these drugs . 
3.1.1.2.
Assessment of IgM Levels
As it is anticipated that a significant number of eligible subjects will be receiving BTK inhibitor 
treatment, and since such treatment is known to lower IgM levels both while receiving treatment 
and for several months following withdrawal , a true baseline value and subsequent IgM 
response assessments at Day 28 and Month 3 will be difficult to obtain. To account for this, the 
following will apply:

To closely monitor and document IgM levels, serum IgM will be assessed at screening, prior 
to receiving lymphodepleting chemotherapy (for those subjects continuing ibrutinib therapy 
only), prior to dosing on Day 0, Day 7, and Day 14 and then per the schedule of assessments 
(SOA) (Table 4). 

The screening assessment will serve as the baseline value for subjects not receiving ibrutinib 
at screening, whereas the pre-lymphodepleting IgM assessment will serve as the baseline 
value for subjects who are receiving ibrutinib through screening to Day -7. For subjects who 
stop BTK inhibitor or ibrutinib therapy, a 30-hour washout period must be observed prior to 
collection of the screening IgM level. 

IgM levels obtained within 5 half-lives (ie, ≤ 35 days) after plasmapheresis will not be 
considered as nadir for the screening assessment or for response evaluation. Only IgM levels 
obtained more than 35 days after plasmapheresis can be used for the screening assessment 
and in response determination. 

Treatment failure will not be established at the Day 28 and Month 3 evaluation if only 
elevated IgM levels disqualify a subject from achieving a CR, VGPR, or partial response 
(PR). In such cases, a repeat disease response assessment should be performed to confirm the 
disease response (at the investigator’s discretion or at the next scheduled visit). 

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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 60 subjects with r/r WM who have received at least 2 lines of prior therapy will 
be enrolled and treated. Three to 6 additional subjects may be enrolled if the SRT recommend 
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.
WM Substudy-specific Inclusion Criteria
1) Confirmed clinicopathological diagnosis of WM in accordance with the consensus panel of 
the Second International Workshop on WM (see Section 12.3.2)
2) Relapsed or refractory disease after 2 or more lines of therapy. Subjects will be eligible 
regardless of the duration of remission prior to relapse. 

Prior therapy must have included a BTK inhibitor. Also, chemotherapy and/or a proteasome 
inhibitor must have been attempted, with either subsequent documented disease progression 
or no response (stable disease). 
3) Requiring treatment as defined in the recommendations from the Second International 
Workshop on WM
4) Measurable disease, defined as presence of serum IgM with a minimum IgM level of 
> 2 times the upper limit of normal of each institution is required
5) The inclusion criteria concerning washout periods prior to leukapheresis in the 
KT-US-568-0138 master protocol must be met, with the exception that ibrutinib may be 
continued through leukapheresis and up to 5 half-lives (30 hours) prior to the start of 
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4.2.2.
WM Substudy-specific Exclusion Criteria
1) History of allogeneic stem cell transplantation. A prior autologous stem cell transplantation is 
allowed, but at least 6 months should have elapsed 
2) Plasmapheresis for symptomatic hyperviscosity or serum IgM > 5,000 mg/dL < 35 days prior 
to the screening IgM assessment
3) Exclusion of IgM monoclonal gammopathy of undetermined significance or IgM multiple 
myeloma
4) Presence of central nervous system (CNS) involvement (Bing-Neel syndrome). Subjects with 
a prior history of Bing-Neel syndrome are eligible if they show a negative cerebrospinal fluid 
(CSF) and no involvement by imaging

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5.
STUDY TREATMENT
5.1.
Description of 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.
Bridging therapy is not applicable for subjects participating in this substudy.
Prior and concomitant medications that are either unique to WM or that are managed differently 
for subjects with WM are described below. Refer to Section 5 of the KT-US-568-0138 master 
protocol for additional details regarding brexucabtagene autoleucel treatment, prior and 
concomitant medications, and excluded medications.
5.2.
Prior and Concomitant Medications and Permitted Treatments
Subjects who were receiving ibrutinib prior to study entry, and for whom investigators deem it to 
be required, are permitted to continue this therapy through leukapheresis and up to 5 half-lives 
(30 hours) prior to the start of lymphodepletion, at the investigator’s discretion. Subjects 
receiving another BTK inhibitor and who require continued BTK inhibitor treatment should 
switch to ibrutinib at the discretion of the investigator at the start of screening. 
If subjects continue ibrutinib through the screening period and leukapheresis, a re-assessment of 
baseline eligibility must be performed at least 5 half-lives (30 hours) after cessation of ibrutinib 
treatment and before initiating lymphodepleting chemotherapy.
Plasmapheresis is not allowed between screening and infusion with brexucabtagene autoleucel in 
order to obtain a true baseline IgM value but may be used to prevent and/or treat IgM flares and 
symptomatic hyperviscosity postinfusion. Where possible, plasmapheresis should be avoided 
within 35 days of a scheduled disease response evaluation. Subjects who have undergone 
plasmapheresis within 35 days of a scheduled disease response will be considered non-evaluable. 

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6.
STUDY ASSESSMENTS UNIQUE TO WALDENSTROM 
MACROGLOBULINEMIA
The study assessments that are either unique to WM or that are managed differently for subjects 
with WM 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 SOA presented in Section 12.2 
(Table 4 and Table 5) of this substudy protocol. 
6.1.
Clinical Laboratory Tests 
Clinical laboratory tests for disease-specific assessments are presented in Table 2. Quantitative 
serum Igs (IgA, IgG and IgM), serum protein electrophoresis (SPEP) and serum immunofixation 
will be assessed at both the central and local laboratory (refer to the central laboratory manual for 
details). Whereas coagulation (prothrombin time, in vivo recovery, and activated prothrombin 
time), serum free light chain assay, B2-microglobulin and the bone marrow aspirate and biopsy 
are assessed at the local laboratory only.
Table 2.
Clinical Laboratory Tests for Disease-specific Assessments
Serum Chemistries (Serum)
Hematology (Blood)
Other 
Quantitative serum IGs (IgA, IgG, 
and IgM) 
Serum protein electrophoresis 
(SPEP) 
Serum immunofixation 
Coagulation (PT, INR and aPTT)
Serum free light chain assay 
Β2-microglobulin
No additional WM-specific 
hematology tests are required for 
this substudy
Bone marrow aspirate and 
trephine biopsy to assess bone 
marrow involvement (see 
Section 6.4.5)
Abbreviations: aPTT, activated partial thromboplastin time; Ig, immunoglobulin; IgG, immunoglobulin G; INR, International 
Normalized Ratio; PT, prothrombin time; SOA, schedule of assessments; SPEP, serum protein electrophoresis; WM, 
Waldenstrom macroglobulinemia.
Notes: Refer to the SOA in Section 12.2 for timing of assessments.

Coagulation assessments to be repeated at investigator discretion and in the case of suspicion 
of pathological findings or progressive disease

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6.2.
Brain Magnetic Resonance Imaging
If required, brain magnetic resonance imaging (MRI) will be performed with contrast whenever 
possible or without contrast in case of contraindication.
Screening:

Subjects with a prior history of CNS involvement (Bing-Neel syndrome) must have a brain 
MRI at screening to confirm absence of CNS involvement in order to be eligible for the 
study. 

Subjects with current symptoms or clinical signs of CNS malignancy, such as severe 
headaches, neck stiffness, seizures, encephalopathy, cranial nerve deficits, or any focal 
neurological findings on physical examination must undergo a brain MRI to rule out current 
CNS metastasis, in which case such subjects are not eligible for the study.

If required, the MRI should be performed as close to enrollment/leukapheresis as possible but 
within 28 days before leukapheresis for eligibility. An MRI collected as 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 with new-onset symptoms or clinical signs of CNS disease, as described above, are 
recommended to have a brain MRI. 

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 . 
In summary: i) a brain MRI can be considered for all grades of CRS; ii) a 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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6.3.
Lumbar Puncture
Opening pressures should be measured with each lumbar puncture when possible and recorded in 
the subject’s site chart. 
Screening:

Subjects with a history of CNS malignancy, or leptomeningeal carcinomatosis, or 
symptoms/clinical findings associated with CNS malignancy (eg, new-onset severe 
headaches, neck stiffness, or focal neurologic findings) will have a lumbar puncture 
performed at screening for examination of CSF to determine presence of CNS malignancy. 
There must be no evidence of CNS involvement to be eligible for this study.

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 6.2).

In the case of CRS and ICANS refer to the ASCO management guidelines for guidance for 
requirements for lumbar puncture examination . 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.
6.4.
Disease Assessments
Disease response will be assessed in accordance with recommendations from the Sixth 
International Workshop on WM; see Section 12.3.1. 
Disease assessments will be performed according to the schedule presented in the SOA (see 
Section 12.2) 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.

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6.4.1.
Assessment of Quantitative Monoclonal IgM, IgA, and IgG
Quantitative monoclonal IgM, IgA, and IgG assessments will be performed both locally and 
centrally at the timepoints specified in the SOA (see Section 12.2). The local laboratory 
assessment of IgM will be used to determine subject eligibility and disease response per 
investigator assessment. The serum samples submitted to a central laboratory will be used for 
evaluation of the primary endpoint (refer to the central laboratory manual for details). Local 
laboratory results will be recorded in the electronic case report form (eCRF). Central laboratory 
results will be provided to the vendor performing the central disease response assessment. 
In order to characterize IgM levels reflecting BTK inhibitor truncation and infusion of 
brexucabtagene autoleucel, IgM will be assessed during screening, prior to receiving 
lymphodepleting chemotherapy (for those continuing ibrutinib therapy), prior to dosing on 
Day 0, Day 7, and Day 14, and then as per scheduled visits (see Section 12.2).
A CR requires reconfirmation, demonstrating normal serum IgM levels (and absence of IgM 
paraprotein by immunofixation) by a measurement repeated at least 2 weeks later. Both a local 
and central evaluation should be made. Note: In the case of CR, the disease response reported 
should be based on the repeated IgM levels. 
Treatment failure cannot be established at the Day 28 and Month 3 evaluation if only elevated 
IgM levels disqualify from achieving a CR, VGPR, or PR. In this event, a repeat disease 
response assessment should be performed to confirm the disease response (at the investigator’s 
discretion or at the next scheduled visit). 
Where possible, plasmapheresis should be avoided within 35 days of a scheduled disease 
response evaluation. Subjects who have undergone plasmapheresis within 4 weeks of a 
scheduled disease response will be considered non-evaluable. 
6.4.2.
Assessment of Serum Protein Electrophoresis
Assessment of SPEP, for evaluation of serum-M protein, will be performed both locally and 
centrally at the timepoints specified in the SOAs (see Section 12.2). The samples submitted to 
the central laboratory will be used for assessment of the primary endpoint (refer to the central 
laboratory manual for details). Local laboratory results will be recorded in the eCRF. Central 
laboratory results will be provided to the vendor performing the central disease response 
assessment.
6.4.3.
Serum Immunofixation
The assessment of serum immunofixation will be performed both locally and centrally, at the 
timepoints specified in the SOAs (see Section 12.2). The samples submitted to the central 
laboratory will be used for assessment of the primary endpoint (refer to the central laboratory 
manual for details). Local laboratory results will be recorded in the eCRF. Central laboratory 
results will be provided to the vendor performing the central disease response assessment.

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Note: Repetitive serum immunofixation on study is only required to confirm a CR (required 
whenever the subject has no detectable monoclonal protein). A CR requires reconfirmation 
demonstrating normal serum IgM levels and absence of IgM paraprotein by immunofixation by a 
measurement repeated at least 2 weeks later. Both a local and central evaluation should be made. 
6.4.4.
Imaging Requirements 
Computed tomography (CT) imaging of diagnostic quality is required in all subjects at screening 
to assess for presence of extramedullary disease (EMD). Follow-up CT scans will be required in 
subjects with confirmed EMD by local radiology review at screening and prior to 
lymphodepleting chemotherapy (only in subjects receiving ibrutinib), as described below.
For all imaging, the following requirements should be met: 

The CT must be of diagnostic quality with IV-iodinated contrast, performed by either of the 
following modalities, depending on the site’s capability: 
as part of a combined positron emission tomography (PET)-diagnostic CT (if performed 
as SOC); 
or 
as a separate diagnostic quality CT (with IV-iodinated contrast) 

The CT scan must include the neck, chest, abdomen, and pelvis, along with the 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 the case where CT with contrast is contraindicated, an alternative would be MRI of the 
abdomen and pelvis and CT of the chest without contrast.

For subjects where the local radiology review has confirmed presence of EMD at screening, 
the screening and rebaseline scans, if applicable (i.e post ibrutinib if continued, see Section 
5.2) and all subsequent disease assessment CT scans will be submitted to and reviewed by an 
independent central reviewer.

Technical and shipping requirements for the 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.

A categorical response (ie, determination of completion resolution, reduction, no progression 
of EMD for subjects with confirmed presence of EMD) will be assessed by central 
radiological review in accordance with the Sixth International Workshop on WM disease 
response criteria for the primary endpoint. A local investigator assessment will also be made 
and reported in the eCRF. 

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Screening/Baseline: 

Diagnostic CT scans are required at screening for all subjects, which should be performed 
within 28 days of enrollment/leukapheresis and as close as possible to 
enrollment/leukapheresis. 
A CT scan performed at the trial site, after the subject’s last line of therapy and before 
signing of the informed consent form may be used (if relevant requirements described 
above are fulfilled) if within 28 days before enrollment/leukapheresis and no other 
anticancer treatment has been administered. For referred subjects a screening image is 
required. 
In subjects with EMD, as confirmed per local radiology review, who continue to receive 
ibrutinib through apheresis and up to Day -7, the CT scan must be repeated before 
initiating lymphodepleting chemotherapy to establish a new baseline.
Disease Assessment: 

For all subjects with confirmed EMD by local radiology review at screening/baseline, 
diagnostic CT scans will be performed at the time points outlined in the SOA (Table 4 and 
Table 5) through Month 60 or until disease progression, whichever comes first. 

Additional assessments may be performed, if clinically indicated, during the course of the 
study at any time disease progression is suspected. 

For subjects with or without EMD, imaging should be performed per SOC any time the 
subject presents with symptoms suggestive of disease progression. 
6.4.5.
Bone Marrow Biopsy/Aspirate
Bone marrow aspirate and biopsies will be analyzed by the investigator at the local laboratory. At 
screening only, bone marrow samples should be sent to the central laboratory for confirmation of 
diagnosis (refer to the central laboratory manual for details).
The following requirements for the bone marrow assessment must be met: 

SOC testing should be performed. The assessment methods, immunohistochemistry, flow 
cytometry or other will be reported in the eCRF.

Attempts should be made to characterize residual infiltrates with respect to their B-cell and 
plasma cell content.

The morphological status of the bone marrow will be reported in the eCRF (ie, 
morphologically normal bone marrow aspirate and trephine biopsy or morphologically 
abnormal bone marrow aspirate and trephine biopsy).

Bone marrow data extracted from the eCRF will be provided to the vendor performing the 
independent central primary endpoint assessment.

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Screening/Baseline:

A bone marrow aspirate and biopsy will be required in all subjects at screening. 

For subjects who continue to receive ibrutinib, a bone marrow aspirate and trephine biopsy 
will need to be repeated prior to initiating lymphodepleting chemotherapy to establish a new 
baseline.
Disease/Response Assessment:

At the time of the disease response assessments specified in the SOAs (see Section 12.2), 
bone marrow aspiration and trephine biopsy are required to confirm a CR (ie, if there is an 
absence of serum monoclonal IgM protein by immunofixation, normal serum IgM and 
complete resolution of EMD, if present at baseline). 

Bone marrow assessments may also be performed at the investigator’s discretion and if 
clinically indicated at disease progression. 
6.5.
Disease-specific Exploratory Assessments
Screening bone marrow aspirate and biopsies will be collected for central laboratory assessment 
of somatic mutations of MYD88 and CXCR4 and presence of CD138 via immunohistochemistry 
to confirm the WM diagnosis and for use as prognostic markers in exploratory analyses. Details 
for sample collection and processing are described in the central laboratory manual.

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7.
STUDY PROCEDURES UNIQUE TO WALDENSTROM 
MACROGLOBULINEMIA
Refer to Section 7 of the KT-US-568-0138 master protocol for the list of procedures for this 
study. Additional procedures for this WM subprotocol are listed below and presented in 
Section 12.2, Table 4 and Table 5 of this substudy protocol. 
7.1.
Screening
Due to the risk of BTK inhibitor withdrawal symptoms and IgM flares , subjects currently on a 
BTK inhibitor when entering the screening period may continue (if on ibrutinib) or should be 
switched to ibrutinib (if on other BTK inhibitor treatment), which may be used through 
leukapheresis and up to 5 half-lives (30 hours) prior to the start of lymphodepletion (refer to 
Section 5.2). 

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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 × 106 anti-CD19 CAR T cells/kg of body weight) and followed for 
28 days, as detailed in the KT-US-568-1038 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 20 subjects (33%) in 
this substudy have been treated with the SRT-recommended dose of brexucabtagene autoleucel 
and have had the opportunity to be followed for 6 months after the brexucabtagene autoleucel 
infusion. 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 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 will be tested with a target 20% combined CR and VGPR rate per 
central assessment against a null hypothesis that the combined CR and VGPR rate is ≤ 6%. The 
reference rate of 6% was based on a systematic literature review and meta-analysis . The 
hypothesis is that the combined CR and VGPR to brexucabtagene autoleucel per central 
assessment is greater than 6%. 
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 as outlined below also apply to this substudy.
9.2.1.
Definition of Substudy Primary Endpoint
The primary endpoint for this substudy is the combined CR and VGPR response rate, defined as 
the proportion of subjects who achieve either CR or VGPR by central assessment per the Sixth 
International Workshop in WM  (see Section 12.3.1).
9.2.2.
Definition of Substudy Secondary Endpoints
Secondary endpoints for this substudy are defined in Table 3.

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Table 3.
Definitions of Substudy Secondary Endpoints
Secondary Endpoints
Definition
Objective Response Rate (ORR) by central assessment
The proportion of subjects who achieve a best response 
of CR, VGPR, or PR by investigator assessment
Combined CR and VGPR rate by investigator 
assessment 
The proportion of subjects who achieve either CR or 
VGPR by investigator assessment per the Sixth 
International Workshop in WM 
Rates of VGPR and PR, separately
The proportion of subjects who achieve a best response 
of VGPR or PR by central assessment, respectively, 
per the Sixth International Workshop in WM 
Abbreviations: CR, complete response; PR, partial response; VGPR, very good partial response; WM, Waldenstrom 
macroglobulinemia.
9.3.
Determination of Sample Size 
This single-arm, open-label substudy will enroll and treat 60 subjects with the 
SRT-recommended dose of brexucabtagene autoleucel. This sample size will achieve statistical 
power of 88% if there is at least a 14% improvement in combined CR and VGPR 
(brexucabtagene autoleucel: 20% versus historical control: 6%) at an alpha level 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 89% 
per simulation based on binomial distribution without normal approximation. Statistically 
significant treatment effect can be claimed in this substudy if ≥ 8 responders (≥ 13.3%) are 
observed among the 60 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 20 subjects (33%) have had the opportunity to be 
evaluated for response 6 months after treatment with brexucabtagene autoleucel. In this interim 
analysis, the DSMB will review investigator-reported data for both safety and efficacy (futility 
only). The non-binding futility boundary of a combined CR and VGPR rate of 7.5% is based on 
the beta spending function of rho family (parameter = 0.35), with a crossing probability of 61% 
under the null hypothesis (combined CR and VGPR rate ≤ 6%). The futility boundary is crossed 
if 1 or no responder is observed among the 20 subjects. A decision 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 this substudy, then 
this analysis will be considered the primary analysis of this substudy. 
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 60 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 12 months after the brexucabtagene 
autoleucel infusion.

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Hypothesis testing will be based on the number of responders observed among the 60 subjects, as 
described above. The point estimate of the combined CR and VGPR rate will be calculated, 
together with its 95% confidence interval using the Clopper-Pearson method. The p-value will be 
calculated based on an exact test. In the event that more than 60 subjects are treated with the 
SRT-recommended dose in the 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 30 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 60 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
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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.

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11.
REFERENCES
Buske C, Leblond V, Dimopoulos M, Kimby E, Jager U, Dreyling M, et al. Waldenstrom's 
macroglobulinaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment 
and follow-up. Ann Oncol 2013;24 Suppl 6:vi155-9.
Castillo JJ, Allan JN, Siddiqi T, Advani RH, Meid K, Leventoff C, et al. Venetoclax in 
Previously Treated Waldenstrom Macroglobulinemia. J Clin Oncol 2022;40 
(1):63-71.
Castillo JJ, Gustine JN, Meid K, Dubeau T, Severns P, Treon SP. Ibrutinib withdrawal symptoms 
in patients with Waldenstrom macroglobulinemia. Haematologica 2018;103 
(7):e307-e10.
Davis J. E, Sharpe C, Mason K, Tam C. S, Koldej R. M, Ritchie D. S. Ibrutinib protects T cells 
in patients with CLL from proliferation‑induced senescence. Journal of 
Translational Medicine 2021;473 (19):1-13.
Dimopoulos MA, Kastritis E. How I treat Waldenstrom macroglobulinemia. Blood 2019;134 
(23):2022-35.
Dimopoulos MA, Zervas C, Zomas A, Kiamouris C, Viniou NA, Grigoraki V, et al. Treatment of 
Waldenstrom's macroglobulinemia with rituximab. J Clin Oncol 2002;20 
(9):2327-33.
Ghobadi A, Locke F, Neelapu S, Siddiqi T, Chavez J, Hosing C, et al. Updated Phase 1 Results 
from ZUMA-1: A Phase 1-2 Multi-Center Study Evaluating the Safety and 
Efficacy of KTE-C19 (Anti-CD19 CAR T Cells) in Subjects with Refractory 
Aggressive Non-Hodgkin Lymphoma (NHL). American Association for Cancer 
Research (AACR) Annual Meeting 2016;Abstract #CT135.
Ghobrial I M, Witzig T E, Gertz M, LaPlant B, Hayman S, Camoriano J, et al. Long-term results 
of the phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed 
or refractory Waldenstrom Macroglobulinemia. American Journal of Hematology 
2014;89 (3):237-42.
Ghobrial IM, Redd R, Armand P, Banwait R, Boswell E, Chuma S, et al. Phase I/II trial of 
everolimus in combination with bortezomib and rituximab (RVR) in 
relapsed/refractory Waldenstrom macroglobulinemia. Leukemia 2015;29 
(12):2338-46.
Hampel P. J, Ding W, Call T. G, Rabe K. G, Kenderian S. S, Witzig T. E, et al. Rapid disease 
progression following discontinuation of ibrutinib in patients with chronic 
lymphocytic leukemia treated in routine clinical practice. Leukemia & Lymphoma 
2019;60 (11):2712–9.

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-A (ZUMA-25A) - Waldenstrom Macroglobulinemia
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Kyriakou C, Canals C, Sibon D, Cahn JY, Kazmi M, Arcese W, et al. High-dose therapy and 
autologous stem-cell transplantation in Waldenstrom macroglobulinemia: the 
Lymphoma Working Party of the European Group for Blood and Marrow 
Transplantation. J Clin Oncol 2010;28 (13):2227-32.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology 
(NCCN Guidelines®). Hairy Cell Leukemia. Version 1.2022 - September 8, 
2021.  2021:
National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in 
Oncology (NCCN Guidelines®). Waldenström 
Macroglobulinemia/Lymphoplasmacytic Lymphoma. Version 1.2022 — June 24.  
2021:
Owen RG, Kyle RA, Stone MJ, Rawstron AC, Leblond V, Merlini G, et al. Response assessment 
in Waldenstrom macroglobulinaemia: update from the VIth International 
Workshop. Br J Haematol 2013;160 (2):170 - 6.
Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML, et al. 
Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus 
panel recommendations from the Second International Workshop on 
Waldenstrom's Macroglobulinemia. Semin Oncol 2003;30 (2):110-5.
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.
Souchet L, Levy V, Ouzegdouh M, Tamburini J, Delmer A, Dupuis J, et al. Efficacy and long-
term toxicity of the rituximab-fludarabinecyclophosphamide combination therapy 
in Waldenstrom’s macroglobulinemia. American Journal of Hematology 2016;91 
(8):782-6.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of 
Tumours of Haematopoietic and Lymphoid Tissues, Fourth Edition. Fourth ed. 
International Agency for Research on Cancer; 2008. vol 2).
Treon SP, Tripsas CK, Meid K, Warren D, Varma G, Green R, et al. Ibrutinib in Previously 
Treated Ibrutinib in Previously Treated. N Engl J Med 2015;372 (15):1430-40.
Treon SP, Xu L, Yang G, Zhou Y, Liu X, Cao Y, et al. MYD88 L265P somatic mutation in 
Waldenstrom's macroglobulinemia. N Engl J Med 2012;367 (9):826-33.

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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
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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 A – Relapsed/Refractory Waldenstrom 
Macroglobulinemia
Amendment 2.0, 01 MARCH 2023
This protocol has been approved by Kite Pharma, Inc. The following signature documents this approval.
See appended electronic signature
See appended electronic signature
Kite Medical Monitor Name (Printed) 
Signature
See appended electronic signature
Date
INVESTIGATOR STATEMENT
I have read the protocol, including all appendices, and I agree that it contains all necessary details for me 
and my staff to conduct this study as described. I will conduct this study as outlined herein and will make 
a reasonable effort to complete the study within the time designated.
I agree to comply with the International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) Harmonised Tripartite Guideline on Good Clinical Practice and 
applicable national or regional regulations and guidelines. I will provide all study personnel under my 
supervision copies of the protocol and access to all information provided by Kite Pharma, Inc. I will 
discuss this material with them to ensure that they are fully informed about the investigational product 
and study.
I agree and will ensure that financial disclosure statements will be completed by:

Me (including, if applicable, my spouse, legal partner, and dependent children)

Subinvestigators (including, if applicable, their spouse, legal partner, and dependent children) at the 
start of the study and for up to 1 year after the study is completed.
I agree to ensure that the confidential information contained in this document will not be used for any 
purpose other than the conduct of the clinical investigation without prior written consent from Kite 
Pharma, Inc.
Principal Investigator Name (Printed)
Signature
Date
Study Site Number

Brexucabtagene Autoleucel
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12.2.
Schedule of Assessments
Table 4.
Schedule of Assessments: Screening, Pretreatment, Treatment, and Post-treatment Period
Timeframe:
Screening
Pretreatment Period
Treatment
Period
Post-treatment Follow-up Period
Enrollment/
Leukapheresis
Optional Ibrutinib 
Therapy
Note: ibrutinib is 
optional and these 
procedures only 
apply if ibrutinib 
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
Post-ibrutinib 
disease assessment
(if applicable)
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
Daily
X
X
X
X
X
Neurologic 
examinatione
X
X
QOD
X
X
X
X
ECOG performance 
status 
X
X

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Timeframe:
Screening
Pretreatment Period
Treatment
Period
Post-treatment Follow-up Period
Enrollment/
Leukapheresis
Optional Ibrutinib 
Therapy
Note: ibrutinib is 
optional and these 
procedures only 
apply if ibrutinib 
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
Post-ibrutinib 
disease assessment
(if applicable)
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
LVEF (ECHO or 
MUGA)
X
ECG
X
Brain MRI (if 
applicable)f
Xf
Lumbar puncture (if 
applicable)g
Xf
PROs: EORTC-
QLQ-C30 and EQ-
5D-5Lh
X
X
X
X
X
Disease response assessments (please also refer to the imaging manual and central laboratory manual for guidance)
CT scani
X
X
X
X
X
Bone marrow 
aspirate and biopsyj
X
X
X
X
X
Quantitative serum 
immunoglobulins 
IgA, IgG and IgMk
X
X
X
D7
X
X
X
X
X

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Timeframe:
Screening
Pretreatment Period
Treatment
Period
Post-treatment Follow-up Period
Enrollment/
Leukapheresis
Optional Ibrutinib 
Therapy
Note: ibrutinib is 
optional and these 
procedures only 
apply if ibrutinib 
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
Post-ibrutinib 
disease assessment
(if applicable)
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
Serum protein 
electrophoresis 
(SPEP)
X
X
X
X
X
Serum 
immunofixationl,m
X
X
X
X
X
Overall response 
assessmentl
X
X
X
Local laboratory assessments 
Chemistry panel 
(CrCl at screening) 
(serum)
X
X
X
X
X
Xn
Daily
X
X
X
X
X
CBC with 
differential (blood)o
X
X
X
X
X
Xn
Daily
X
X
X
X
X
LDHp, CRP, ferritin 
(serum)
X
X
Xn
Daily
X
X
X
Coagulation (PT, 
INR and aPTT)q
X
X
X
Serum free light 
chain assay
X
X
X
X
X

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Timeframe:
Screening
Pretreatment Period
Treatment
Period
Post-treatment Follow-up Period
Enrollment/
Leukapheresis
Optional Ibrutinib 
Therapy
Note: ibrutinib is 
optional and these 
procedures only 
apply if ibrutinib 
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
Post-ibrutinib 
disease assessment
(if applicable)
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
β2-microglobulin
X
X
β-hCG pregnancy 
test ([WOCBP] 
serum or urine)
X
Xr
Xr
X
X
X
Serology for 
EU/CH/UK sites 
(serum)s
Xs
Xs
HIV positive 
subjects only: HIV 
viral load and CD4 
count
Xt
X
X
X
Central laboratory assessments (please refer to the central laboratory manual for guidance)
CBC with 
differential (blood)
X
Xn
D3, D7
X
X
X
X
X
Anti-
brexucabtagene 
autoleucel 
antibodies (serum)
Xu
X
X
X
Analytes, including 
cytokines 
(serum/plasma)v
Xu
Xn
D1, D2, 
D3, D5, D7
X
X
X
X
X

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Timeframe:
Screening
Pretreatment Period
Treatment
Period
Post-treatment Follow-up Period
Enrollment/
Leukapheresis
Optional Ibrutinib 
Therapy
Note: ibrutinib is 
optional and these 
procedures only 
apply if ibrutinib 
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
Post-ibrutinib 
disease assessment
(if applicable)
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 CAR 
T-cell levels and 
exploratory analyses 
(PBMCs)v 
Xu
Xn
D3, D7
X
X
X
X
X
RCR (PBMCs)w
Xn
X
Leukapheresis 
X
 
Fludarabine and 
Cyclophosphamidex 
X
X
X
Brexucabtagene 
Autoleucel infusion 
(IV) and 
premedications
X
Concomitant 
medications
X
X
X
X
X
X
Daily
X
X
X
X
X
Adverse events and 
serious adverse 
eventsy 
X
X
X
X
Daily
X
X
X
X
X
Abbreviations: approx., approximately; ASCO, American Society of Clinical Oncology; BTK, Bruton’s tyrosine kinase; 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; EMD, extramedullary disease; 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 

Brexucabtagene Autoleucel
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Union; hCG, human chorionic gonadotropin; ICANS, immune effector cell-associated neurotoxicity syndrome; ICE, immune effector cell-associated encephalopathy; ICF, 
informed consent form; Ig, immunoglobulin; IV, intravenous; LDH, lactate dehydrogenase; LVEF, left ventricular ejection fraction; M, month; MRI, magnetic resonance imaging; 
MUGA, multigated acquisition scan; PBMCs, peripheral blood mononuclear cell; PD, progressive disease, PR, partial response; PRO, patient reported outcome; QOD, every other 
day; RCR, replication-competent retrovirus; SOA, schedule of assessments; UK, United Kingdom; VGPR, very good partial response; W/w, week; WOCBP, women of child 
bearing 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, CH and UK, 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 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.
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 (may also include the mini-mental status exam), should be performed on Day 0 
before the brexucabtagene autoleucel infusion and can be performed QOD 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. 
f
Brain MRI: 

Screening through start of lymphodepletion: Subjects with a prior history of CNS involvement (Bing-Neel syndrome) must have a brain MRI at screening to confirm 
absence of CNS involvement in order to be eligible for the study. Subjects with current symptoms or clinical signs of CNS malignancy, such as severe headaches, neck 
stiffness, seizures, encephalopathy, cranial nerve deficits, or any focal neurological findings on physical examination must undergo brain MRI to rule out current CNS 
metastasis, in which case such subjects are not eligible for the study. 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 6.2).

Post-infusion: Subjects with new-onset symptoms of CNS malignancy/disease, as described above, are recommended to have a brain MRI. In addition, in the case of 
CRS and ICANS refer to the ASCO management guidelines for guidance of requirements for brain imaging . 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: Subjects with a history of CNS malignancy, or leptomeningeal carcinomatosis, or symptoms/clinical findings associated with CNS malignancy (eg, new-onset 
severe headaches, neck stiffness, or focal neurologic findings) will have a lumbar puncture performed at screening for examination of cerebrospinal fluid (CSF) to 
determine the presence of CNS malignancy.

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 . In summary: i) a 
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 6.3). 
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
CT scan: 

Screening/baseline: CT scans should be obtained during screening and within 28 days before enrollment/leukapheresis to assess for presence of EMD. In subjects with 
confirmed EMD at screening, if the subject receives ibrutinib therapy between the last CT scan and lymphodepleting chemotherapy, the CT scan must be repeated for 

Brexucabtagene Autoleucel
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disease re-evaluation. For subjects where the local radiology review has confirmed presence of EMD at screening, the screening and  post ibrutinib (baseline), if 
applicable, CT scans will be submitted to and reviewed by an independent central reviewer.

Disease assessment: Follow-up CT scans will be required in subjects with confirmed EMD by local radiology review at screening.  Additional assessments may be 
performed, if clinically indicated, at any time disease progression is suspected. 
j
Bone marrow aspirate and biopsy: 

Screening/baseline: A bone marrow aspirate and biopsy are required at screening and within 28 days prior to enrollment. These samples are required to be sent to the 
central laboratory for post-enrolment central confirmation of eligibility (refer to the central laboratory manual for details). For subjects who continue to receive ibrutinib, 
a bone marrow aspirate and trephine biopsy will need to be repeated prior to initiating lymphodepleting chemotherapy to establish a new baseline.

Disease assessment: A bone marrow aspiration and trephine biopsy are required to confirm a CR (ie, if there is an absence of serum monoclonal IgM protein by 
immunofixation, normal serum IgM and complete resolution of EMD, if present at baseline). Bone marrow assessments may also be performed at the investigator’s 
discretion and if clinically indicated at disease progression. 
k
Quantitative IgM, IgA, and IgG: In order to establish a baseline IgM assessment, IgM will be assessed during screening and after cessation of ibrutinib treatment and prior to 
start of lymphodepletion (if the subject received ibrutinib therapy at screening), as well as prior to dosing on D0, on D7 and D14 and then as per the SOA. 
l
Serum immunofixation: Required at screening and after cessation of ibrutinib treatment and prior to start of lymphodepletion (if the subject received ibrutinib therapy at 
screening). Repetitive serum immunofixation on study is only required to confirm CR (conducted on the first observation that the subject has no detectable monoclonal 
protein) and then repeated to continue to confirm CR or until disease progression.
m
Overall disease response assessment: A CR requires reconfirmation demonstrating normal serum IgM levels and absence of IgM paraprotein by immunofixation by a 
measurement repeated at least 2 weeks later. For initial disease response assessments at D28 and M3, due to the possibility of BTK inhibitor withdrawal symptoms and 
delayed IgM flare, if the response criteria for CR/VGPR or PR are met, with the exception of IgM criteria, then this would not qualify as treatment failure and a repeat disease 
response assessment should be performed at the investigator’s discretion or the next scheduled visit. Where possible, plasmapheresis should be avoided within 4 weeks of a 
scheduled disease response evaluation. Subjects who have undergone plasmapheresis within 4 weeks of a scheduled disease response will be considered non-evaluable. 
n
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.
o
CBC with differential (blood): At the timepoints at which PBMC samples are collected for analysis of brexucabtagene autoleucel T-cell levels, blood samples will also be 
collected and sent to the central laboratory for assessment of CBC with differential (note: these samples are in addition to those sent to the local laboratory for assessment of 
CBC with differential for clinical/safety evaluation). 
p
LDH should continue to be monitored after the baseline assessment as clinically indicated.
q
Coagulation assessments to be repeated at investigator discretion and in case of suspicion of pathological findings or progressive disease.
r
Pregnancy test (serum or urine): For EU/CH/UK study sites, the test will be completed within 7 days before both leukapheresis and lymphodepleting chemotherapy for 
WOCBP.
s
Serology tests for EU/CH/UK study sites (serum): Serology tests (ie, HIV, hepatitis B virus, hepatitis C virus, and syphilis) will be done per institutional guidelines and 
EU/CH/UK regulations. Testing may be done within the 30 days before leukapheresis/enrollment and/or on the day of leukapheresis/enrollment.
t
Hepatitis B and C testing is also required at screening.
u
Baseline for assessments of brexucabtagene autoleucel CAR T cells, analytes, and anti-brexucabtagene autoleucel antibodies: A sample will be collected at enrollment/before 
the leukapheresis procedure. 
v
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). 

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
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.
w
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.
x
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).
y
Collection of serious adverse events starts from signing of the screening ICF, and collection of adverse events starts from commencement of the leukapheresis procedure.

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Table 5.
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)
M30
(± 1 M)
M36
(± 1 M)
M48
(± 3 M)
M60
(± 3 M)
Suspected 
Disease 
Progressiona
Physical examinationb
X
X
X
X
X
X
X
X
X
X
Vital signs
X
PROs: EORTC-QLQ-C30 and
EQ-5D-5Lc
X
X
X
X
X
Disease assessments (please also refer to the imaging manual and central laboratory manual for guidance)
CT scand
X
X
Bone marrow aspirate and biopsye
X
X
Quantitative serum IgA, IgG, and IgM
X
X
X
X
X
X
X
X
X
X
Serum protein electrophoresis (SPEP)
X
X
X
X
X
X
X
X
X
X
Serum immunofixationf
X
X
X
X
X
X
X
X
X
X
Overall response assessmentg
X
X
X
X
X
X
X
X
X
X
Local laboratory assessments
CBC with differential (blood)h
X
X
X
X
X
X
X
X
X
X
Chemistry panel (serum)
X
LDHi
X
X
Serum free light chain assay
X
X
X
X
X
X
X
X
X
X
Coagulation (PT, INR and aPTT)j
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
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)
M30
(± 1 M)
M36
(± 1 M)
M48
(± 3 M)
M60
(± 3 M)
Suspected 
Disease 
Progressiona
Central laboratory assessments (please refer to the central laboratory manual for guidance)
CBC with differential (blood)h
X
X
X
X
X
X
Analytes, including cytokines 
(serum/plasma)k
X
Anti-brexucabtagene autoleucel 
antibodies (serum)
X
X
X
X
Brexucabtagene autoleucel CAR T-cell 
levels and exploratory analyses 
(PBMCs)k
X
X
X
X
X
X
RCR (PBMCs)l
X
X
All brexucabtagene autoleucel-related 
SAEs and any deaths regardless of 
causality
X
X
X
X
X
X
X
X
X
X
Targeted AE/SAEsm
X
X
X
X
X
X
X
X
X
X
Targeted concomitant medicationsn 
X
X
X
X
X
X
X
X
X
X
Subsequent therapy for WMo
X
X
X
X
X
X
X
X
X
X
Survival statusp
X
X
X
X
X
X
X
X
X
X
Abbreviations: AE, adverse event; CAR, chimeric antigen receptor; CBC, complete blood count; CR, complete response; CRS, cytokine release syndrome; CT, computed 
tomography; EMD, extramedullary disease; 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; GP, general practitioner; hCG, human chorionic gonadotrophin; HCP, healthcare provider; IG, immunoglobulin; LDH, 
lactate dehydrogenase; LTFU, long-term follow-up; M, month; PBMC, peripheral blood mononuclear cell; PD, progressive disease; PRO, patient-reported outcome; RCR, 
replication-competent retrovirus; SAE, serious adverse event; SOA, schedule of assessment; w, weeks; WM, Waldenstrom macroglobulinemia; WOCBP, women of child bearing 
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
Follow-up CT scans will be required in subjects with confirmed EMD by local radiology review at screening. Additional assessments may be performed, if clinically 
indicated, at any time disease progression is suspected.
e
Bone marrow aspiration and biopsy may also be done at the investigator’s discretion and are required at any time to confirm a CR (ie, if absence of serum monoclonal IgM 
protein by immunofixation, normal serum IgM and complete resolution of EMD if present at baseline) and if clinically indicated at disease progression.

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f
Repetitive serum immunofixation on study is only required to confirm CR (conducted on the first observation that the subject has no detectable monoclonal protein) and then 
repeated every time until disease progression.
g
Overall disease response assessment: A CR requires reconfirmation demonstrating normal serum IgM levels, and absence of IgM paraprotein by immunofixation by a 
measurement repeated at least 2 weeks later.
h
CBC with differential (blood): 

Local laboratory assessments: Blood will be collected at the time points specified through Month 60 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).
i
LDH should continue to be monitored after the baseline assessment as clinically indicated.
j
Coagulation assessments to be repeated at investigator discretion and in case of suspicion of pathological findings or PD 
k
Analytes (including cytokines) (serum) 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.
l
RCR (PBMCs): 

Samples will be collected at Months 6 and 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 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).
m
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 60 after the initial brexucabtagene autoleucel infusion or until disease progression 
and/or the start of subsequent anticancer therapy, whichever occurs first. After Month 60, 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. 
n
Targeted concomitant medications will be collected up to 60 months after the brexucabtagene autoleucel infusion or until disease progression or the start of subsequent 
anticancer therapy, whichever occurs first.
o
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.
p
Subjects 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.
Definitions of Response for Waldenstrom Macroglobulinemia
Definitions of Response for Waldenstrom Macroglobulinemia as per the Sixth 
International Workshop .

Complete response (CR): Absence of serum monoclonal IgM protein by immunofixation; 
normal serum IgM level and complete resolution of extramedullary disease (EMD), ie, 
lymphadenopathy and splenomegaly if present at baseline; morphologically normal bone 
marrow/aspirate and trephine biopsy. A CR requires reconfirmation demonstrating normal 
serum IgM levels, and absence of IgM paraprotein by immunofixation by a measurement 
repeated at least 2 weeks later.

Very good partial response (VGPR): Monoclonal IgM protein is detectable; ≥ 90% 
reduction in serum IgM level from baseline; complete resolution of EMD, ie, 
lymphadenopathy and splenomegaly if present at baseline; no new signs or symptoms of 
active disease. 

Partial response (PR): Monoclonal IgM protein is detectable; ≥ 50% but < 90% reduction in 
serum IgM level from baseline; reduction of EMD (ie, lymphadenopathy and splenomegaly 
if present at baseline; no new signs or symptoms of active disease). 

Minor response: Monoclonal IgM protein is detectable; ≥ 25% but < 50% reduction in 
serum IgM level from baseline; no progression in extramedullary disease (ie, 
lymphadenopathy/splenomegaly if present at baseline; no new signs or symptoms of active 
disease). 

Stable disease: Monoclonal IgM protein is detectable; < 25% reduction and < 25% increase 
in serum IgM level from baseline; no new signs or symptoms of active disease. 

Progressive disease: ≥ 25% increase in serum IgM level from lowest nadir (requires 
confirmation) and/or progression in clinical features attributable to the disease.
12.3.2.
Waldenstrom Macroglobulinemia International Workshop Diagnosis 
Criteria
Proposed Criteria for the Diagnosis of Waldenstrom Macroglobulinemia 

IgM monoclonal gammopathy of any concentration

Bone marrow infiltration by small lymphocytes, plasmacytoid cells, and plasma cells

Diffuse, interstitial, or nodular pattern of bone marrow infiltration

CD19+, CD20+, sIgM+. Note that CD5, CD10, CD23 can be expressed in some cases of 
Waldenstrom macroglobulinemia but does not exclude diagnosis

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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
To optimize enrollment
Section 12.2 Schedule of 
assessments, Table 4 Schedule 
of Assessments: Screening, 
Pretreatment, Treatment, and 
Post-treatment Period
Removed schedule of PROs: EORTC-QLQ-
C30 and EQ-5D-5L at Post-Ibrutinib disease 
assessment (if applicable)
Correction. Removed PROs 
assessment timepoint no 
longer applicable
Section 12.2 Schedule of 
assessments Table 4 Schedule 
of Assessments: Screening, 
Pretreatment, Treatment, and 
Post-treatment Period
Footnote u: Baseline for assessments of 
brexucabtagene autoleucel CAR T cells, 
analytes, and anti-brexucabtagene autoleucel 
antibodies: A sample will be collected at 
enrollment/before the leukapheresis procedure
Correction. A repeated blood 
sample collection for subjects 
who received ibrutinib therapy 
is no longer applicable
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
EU CT and NCT numbers provided
EU CT and NCT numbers 
previously unavailable
Synopsis (Statistical Methods) 
and Sections 9.1 Hypothesis 
and 9.4.2 Primary Analysis

“significantly” removed from statement 
that “The hypothesis is that the combined 
CR and VGPR to brexucabtagene 
autoleucel per central assessment is 
significantly > 6%.”

Text edited to now state that the p-value 
‘will be’ calculated based on an exact test, 
rather than ‘may be’ tested. 
For clarity

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Section Number and Name
High-level Description of Change
Brief Rationale
Section 3.1 Study Design
Added 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 (Eligibility Criteria 
Unique to the WM Substudy) 
and Section 4.2.1 WM 
Substudy-specific Inclusion 
Criteria
Inclusion criterion 2 amended to include that 
subjects will be eligible regardless of the 
duration of remission prior to relapse
For clarity 
Section 12.2 Schedule of 
Assessments, Table 4 Schedule 
of Assessments: Screening, 
Pretreatment, Treatment, and 
Post-treatment Period
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
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 A – Relapsed/Refractory 
Waldenstrom Macroglobulinemia”. The 
evaluation of safety (secondary endpoint) was 
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
Section 6.2 Brain Magnetic 
Resonance Imaging
At screening CNS involvement will be 
assessed by local review, and images will not 
be sent for central review
Post-infusion, a brain MRI only needs to be 
submitted to the independent central reviewer 
when there is evidence of disease progression
For clarification
Section 6.4.4 Imaging 
Requirements
For assessment of EMD, the term ‘measurable’ 
has been replaced with ‘presence of’ or simply 
‘EMD’ throughout this section, to align with 
the disease response criteria, which assesses 
presence or absence of EMD. 
Added text to clarify when scans should be 
submitted for central review (ie, required for 
subjects where the local radiology review has 
confirmed presence of EMD at screening)
Language regarding EMD 
updated to align with the 
disease response criteria.
Correction to previous 
language which indicated all 
screening / baseline scans 
were to be submitted for 
central review

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Section Number and Name
High-level Description of Change
Brief Rationale
Section 12.2 Schedule of 
Assessments, Table 4 
Schedule of Assessments: 
Screening, Pretreatment, 
Treatment, and 
Post-Treatment Period
PROs: EORTC-QLQ-C30 and EQ-5D-5L, 
removed from post-ibrutinib disease 
assessment column
Timepoint is captured in the 
schedule of assessments at 
Day -5
Section 12.2 Schedule of 
Assessments, Table 4 
Schedule of Assessments: 
Screening, Pretreatment, 
Treatment, and Post-
Treatment Period
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 4 
Schedule of Assessments: 
Screening, Pretreatment, 
Treatment, and Post-
Treatment Period
Footnote i: Screening: For subjects where the 
local radiology review has confirmed 
presence of EMD at screening, the screening 
and post ibrutinib (baseline), if applicable, CT 
scans will be submitted to and reviewed by an 
independent central reviewer
Disease assessment: Follow-up CT scans will 
be required in subjects with confirmed EMD 
by local radiology review at screening 
Footnote i and j: EMD language updated to 
remove the term ‘measurable’ 
Footnotes updated to align 
with Section 6.4.4 Imaging 
requirements and changes 
described above
Section 12.2 Schedule of 
Assessments, Table 4 
Schedule of Assessments: 
Screening, Pretreatment, 
Treatment, and 
Post-Treatment Period
Footnotes ‘r’ pregnancy testing and ‘s’ 
serology testing updated to include Switzerland
Request by Swiss Regulatory 
Authority and alignment with 
Master protocol Section 6
Section 12.2 Schedule of 
Assessments, Table 4 
Schedule of Assessments: 
Screening, Pretreatment, 
Treatment, and 
Post-Treatment Period
Footnote v: 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 5 
Schedule of assessments: 
Post-treatment Follow-up 
Period
Window M18 changed from ±2 weeks to ±1 
month
Provides added flexibility
Section 12.2 Schedule of 
Assessments, Table 5 
Schedule of assessments: 
Post-Treatment Follow-up 
Period
Footnote d: Follow-up CT scans will be 
required in subjects with confirmed EMD by 
local radiology review at screening 
For clarification