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 D – Relapsed/Refractory Hairy Cell Leukemia
Note:
This subprotocol should be used in conjunction with the 
KT-US-568-0138 master protocol 
Protocol Number:
KT-US-568-0138-D (ZUMA-25D)
Indication:
Relapsed/refractory hairy cell leukemia
Kite Investigational Product 
Brexucabtagene Autoleucel
Kite IND Number:
028542
EU CT Number:
2022-501262-21-00
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...........................................................................................................11
2.
OBJECTIVES AND ENDPOINTS......................................................................................................................13
3.
STUDY DESIGN.................................................................................................................................................14
3.1.
Study Design ...........................................................................................................................................14
4.
SUBJECT POPULATION...................................................................................................................................15
4.1.
Number of Subjects and Subject Selection .............................................................................................15
4.2.
Eligibility Criteria....................................................................................................................................15
4.2.1.
HCL Substudy-specific Inclusion Criteria ............................................................................15
4.2.2.
HCL Substudy-specific Exclusion Criteria ...........................................................................15
5.
STUDY TREATMENT........................................................................................................................................16
6.
STUDY ASSESSMENTS UNIQUE TO HAIRY CELL LEUKEMIA...............................................................17
6.1.
Clinical Laboratory Tests ........................................................................................................................17
6.2.
Brain Magnetic Resonance Imaging .......................................................................................................17
6.3.
Lumbar Puncture .....................................................................................................................................18
6.4.
Disease Assessments ...............................................................................................................................19
6.4.1.
Assessment of Leukemic Cells by Peripheral Blood Smear or Flow 
Cytometry..............................................................................................................................19
6.4.2.
Imaging Requirements...........................................................................................................20
6.4.3.
Bone Marrow Biopsy/Aspirate..............................................................................................21
6.5.
Hematology Assessments........................................................................................................................22
6.6.
Disease-specific Exploratory Assessments .............................................................................................22
6.6.1.
Measurable Residual Disease Analysis.................................................................................22
7.
STUDY PROCEDURES UNIQUE TO HAIRY CELL LEUKEMIA.................................................................23
8.
ADVERSE EVENTS AND TOXICITY MANAGEMENT................................................................................24
8.1.
Safety Review Team and Data Safety Monitoring Board.......................................................................24
9.
STATISTICAL CONSIDERATIONS.................................................................................................................25
9.1.
Hypothesis ...............................................................................................................................................25
9.2.
Definition of Substudy Endpoints ...........................................................................................................25
9.2.1.
Definition of Substudy Primary Endpoint.............................................................................25
9.2.2.
Definition of Substudy Secondary Endpoint.........................................................................25
9.2.3.
Definition of Other Substudy Endpoint of Interest ...............................................................26
9.3.
Determination of Sample Size.................................................................................................................26

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9.4.
Planned Analyses.....................................................................................................................................26
9.4.1.
Interim Analysis and Early Stopping Guidelines ..................................................................26
9.4.2.
Primary Analysis ...................................................................................................................26
9.4.3.
Follow-Up Analysis...............................................................................................................27
9.4.4.
Final Analysis........................................................................................................................27
10.
RESPONSIBILITIES...........................................................................................................................................28
11.
REFERENCES.....................................................................................................................................................29
12.
APPENDICES......................................................................................................................................................31
12.1.
Sponsor and Investigator Signature Page................................................................................................32
12.2.
Schedule of Assessments.........................................................................................................................33
12.3.
Disease Response Criteria .......................................................................................................................42
12.3.1.
Response Criteria in HCL .....................................................................................................42
12.4.
Protocol Amendment History..................................................................................................................43
12.4.1.
Amendment 1.0 (dated 20 July 2022) ...................................................................................43
12.4.2.
Amendment 1.1 EU-specific Amendment (dated 12 January 2023).....................................43
12.4.3.
Amendment 2.0 (dated 01 March 2023)................................................................................45
LIST OF IN-TEXT TABLES
Table 1.
Substudy-specific Objectives and Endpoints ..........................................................................13
Table 2.
Clinical Laboratory Tests for Disease-specific Assessments..................................................17
Table 3.
Definition of Substudy Secondary Endpoint...........................................................................25
Table 4.
Definition of Substudy Exploratory Endpoint.........................................................................26
Table 5.
Schedule of Assessments: Screening, Pretreatment, Treatment, and Post-treatment 
Periods .....................................................................................................................................33
Table 6.
Schedule of Assessments: Post-treatment Follow-up Period ..................................................38

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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 D – Relapsed/Refractory Hairy Cell Leukemia 
Indication: Adult subjects with relapsed/refractory (r/r) hairy cell leukemia (HCL)
Kite IND Number: 028542
EU CT Number: 2022-501262-21-00
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 subjects with HCL by determining 
the objective response rate (ORR) by central 
assessment

ORR by central assessment defined as the 
proportion of subjects who achieve either 
complete response (CR) or partial response (PR)
Secondary Objective
Secondary Endpoint

To evaluate the efficacy of brexucabtagene 
autoleucel in subjects with HCL by ORR by 
investigator assessment

ORR by investigator assessment defined as the 
proportion of subjects who achieve either CR or 
PR
Exploratory Objective
Exploratory Endpoint

To evaluate the measurable residual disease 
(MRD) negative response rate in subjects with 
HCL who have achieved a CR by central 
assessment

Rate of MRD negative response among subjects 
who have achieved a CR by central assessment

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Study Design: This substudy protocol contains details regarding all elements of the study that 
are unique to subjects with r/r HCL. 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 HCL. Subjects with r/r HCL must have received 
at least 2 lines of prior systemic therapy including a purine nucleoside analog (PNA) and 
moxetumomab pasudotox if eligible and commercially available.
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 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.
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 20 subjects 
with r/r HCL will be enrolled and treated in this substudy. Three to 6 additional subjects may 
be enrolled if the SRT recommends proceeding at the lower dose level.
Target Population: Male or female adults ≥ 18 years of age diagnosed with r/r HCL
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 HCL Substudy:
In addition to the common eligibility criteria specified in the KT-US-568-0138 master 
protocol, all the following additional substudy-specific eligibility criteria must also be met.
HCL Substudy-specific Inclusion Criteria:
1) Subjects will be eligible regardless of the duration of remission prior to relapse and must 
have confirmed HCL (r/r classic HCL or r/r HCL variant) by immunophenotyping and 
histology with a need for therapy based on at least 1 of the following criteria:

neutrophils < 1.0 × 109/L

platelets < 100 × 109/L

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
hemoglobin < 11 g/dL

symptomatic splenomegaly

symptomatic lymphadenopathy
2) Subjects must have received:

At least 2 prior therapies, including at least a PNA and moxetumomab pasudotox if 
eligible and available
HCL Substudy-specific Exclusion Criteria:
1) Prior history of allogeneic stem cell transplant
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 
brexucabtagene autoleucel. Additional details are provided in the KT-US-568-0138 master 
protocol.
Safety Review Team and Data Safety Monitoring Board: An SRT, comprising the study 
sponsor and at least 1 study investigator, will be specifically chartered to review the safety 
data and make recommendations on further study conduct, progression, and/or dose 
modification after 3 or 6 subjects in this substudy have been treated with the initial dose 
(2 ×106 anti-CD19 CAR T cells/kg of body weight) and followed for 28 days, as detailed in 
the KT-US-568-0138 master protocol.
An independent Data Safety Monitoring Board (DSMB) will be chartered to review safety and 
efficacy data to make study conduct recommendations based on an analysis of risk versus 
benefit. The DSMB will review serious adverse event (SAE) information (listings or 
narratives) and suspected unexpected serious adverse reactions (SUSARs) on a regular basis 
throughout subject treatment in the study and per the DSMB charter or DSMB discretion. The 
DSMB may request additional safety or efficacy data or recommend modifying the study 
conduct. The sponsor may request additional reviews by the DSMB. Data submitted to the 
DSMB may or may not be source data verified to facilitate timely DSMB review.
SUSARs and SAE listings or narratives may be submitted to the DSMB chair as described in 
the DSMB charter.
Additional details regarding the SRT, DSMB, and dose-limiting toxicities are provided in the 
KT-US-568-0138 master protocol.

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Statistical Methods:
Hypothesis: An alternative hypothesis is proposed with a target 60% ORR per central 
assessment against a null hypothesis that the ORR is ≤ 26%. The hypothesis is that the ORR to 
brexucabtagene autoleucel per central assessment is greater than 26%.
Sample Size Calculation: This single-arm, open-label substudy will enroll and treat 
20 subjects with the SRT-recommended dose of brexucabtagene autoleucel. This sample size 
will achieve a statistical power of 90% if there is at least a 34% improvement in ORR 
(brexucabtagene autoleucel: 60% versus historical control: 26%) with a type 1 error rate of 
0.025 (1-sided).
Analyses: An interim analysis will be conducted after 10 subjects (50%) have had the 
opportunity to be evaluated for response 3 months after treatment with brexucabtagene 
autoleucel. In this interim analysis, the DSMB will review investigator-reported data for both 
safety and efficacy (futility only). The non-binding futility boundary of an ORR of 29.4% is 
based on the beta spending function of rho family (parameter = 2), with a crossing probability 
of 60% under the null hypothesis (ORR ≤ 26%). 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, the primary analysis 
will be conducted after 20 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 objective responders observed among the 
20 subjects, as described above. The point estimate of the ORR will be calculated, together 
with its 95% confidence interval using the Clopper-Pearson method. The p-value will be 
calculated based on an exact test. If more than 20 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.
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 after the brexucabtagene autoleucel 
infusion to further evaluate the risk-benefit profile of brexucabtagene autoleucel, including the 
durability of response. This analysis will be descriptive.
Additional descriptive analyses may occur after the primary analysis and follow-up analysis 
described above have been completed.
The final analysis will be performed after all subjects have completed the study, outstanding 
data queries have been resolved or adjudicated as unresolvable, and the data have been 
cleaned and finalized.

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This study will be conducted in compliance with this protocol; the International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines of 
Good Clinical Practice, including archiving of essential documents; and all applicable regulatory 
and local requirements.
This study will be conducted under United States Code of Federal Regulations Title 21 Part 312 
or equivalent.

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LIST OF ABBREVIATIONS
ANC
absolute neutrophil count
ASCO
American Society of Clinical Oncology
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
HCL
hairy cell leukemia
ICANS
immune effector cell-associated neurotoxicity syndrome
IV
intravenous(ly)
MRD
measurable residual disease
MRI
magnetic resonance imaging
ORR
objective response rate
PET
positron emission tomography
PNA
purine nucleoside analog
PR
partial response/remission
r/r
relapsed/refractory
SAE
serious adverse event
SAP
statistical analysis plan
SOA
schedule of assessments
SOC
standard of care
SRT
safety review team
SUSAR
suspected unexpected serious adverse reaction

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1.
INTRODUCTION
Refer to the KT-US-568-0138 master protocol for information related to brexucabtagene 
autoleucel (KT-US-568-0138 master protocol - Section 1.1), previous clinical studies 
(KT-US-568-0138 master protocol – Section 1.2.2), and the study rationale (KT-US-568-0138 
master protocol - Section 1.4).
1.1.
Disease Background
1.1.1.
Epidemiology
Hairy cell leukemia (HCL) is an indolent and rare B-cell leukemia comprising 2% of all 
leukemias, corresponding to an estimated 1,200 cases annually in the US .
1.1.2.
Diagnosis
The normal B cell counterpart of HCL remains debated; however, expression signatures suggest 
that HCL is derived from the post-germinal center memory B cell . The World Health 
Organization classifies 2 separate forms of HCL: i) classic HCL in which the specific mutation, 
BRAF (V600E), is present in the majority of patients; and ii) HCL variant in which the BRAF 
(V600E) mutation is absent (Grever et al, 2017). By flow cytometry, both forms of HCL are 
characterized by the B-cell antigens FMC7, CD11c, CD19, CD20, CD22 and have strongly 
positive surface immunoglobulin expression; however, whereas classic HCL is positive for 
CD25 and CD123, HCL variant is most often negative .
Clinically, HCL is characterized by symptoms of fatigue, weakness and infections and some 
patients will present with splenomegaly . In addition, often patients present because of incidental 
findings of pancytopenia. In the initial work-up, leukemic cells are typically found infiltrating 
the bone marrow and spleen, and may also be found in the liver, lymph nodes, and rarely in the 
skin. Small numbers of circulating hairy cells may also be present .
1.1.3.
Frontline Treatment
The median survival of patients with HCL without effective treatment is about 4 years . 
However, HCL treatment was revolutionized with the advent of purine nucleoside analog (PNA) 
therapy in the late 1980s and the PNAs cladribine and pentostatin have shown durable CR rates 
of 72 to 89% in the frontline setting , with most patients remaining in CR after several years of 
follow-up. While the majority of patients with HCL will require treatment, a minority (about 
10%) may not require immediate therapy and may be closely observed until therapy is needed.
1.1.4.
Second-line Treatment
Despite the efficacy of PNA therapy, up to 40 to 50% of HCL patients relapse and for these 
patients second-line PNA therapy induces less durable remissions and is associated with a 
significant risk of side-effects, including bone marrow aplasia, persistent CD4 lymphopenia, 

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infections, and neurotoxicity . Accordingly, the current clinical guidelines  recommend 
alternative therapies in the relapsed/refractory (r/r) setting, depending on the duration of CR or 
relapse. For patients with a duration of response of less than 2 years, a clinical trial or alternative 
therapies or purines may be explored, including rituximab ± vemurafenib or peg-interferon-α.
In a study in subjects with r/r HCL, Nieva et al found an objective response rate (ORR) of only 
25% in subjects who relapsed after PNA treatment and received rituximab as second-line 
therapy. These findings underscore that novel therapies, beyond PNAs and rituximab, are needed 
to induce durable remissions for patients in need of third or more lines of therapy for HCL. 
While moxetumomab pasudotox (anti-CD22 immunotoxin) has been approved for the third line 
treatment of HCL, its use has been limited since the drug is only approved and available in the 
US. Also, the oral BRAF inhibitor vemurafenib in combination with rituximab has shown 
promising response rates, but whether this will lead to regulatory approval remains uncertain . As 
such, a significant unmet medical need remains for patients with treatment resistant HCL.

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2.
OBJECTIVES AND ENDPOINTS
Refer to the Section 2 of the KT-US-568-0138 master protocol for a summary of common 
objectives and endpoints for this study.
Additional objectives and endpoints that are specific for this substudy are detailed in Table 1.
Table 1.
Substudy-specific Objectives and Endpoints
Primary Objective
Primary Endpoint

To evaluate the efficacy of brexucabtagene 
autoleucel in subjects with HCL by determining 
the ORR by central assessment

ORR by central assessment defined as the 
proportion of subjects who achieve either CR or PR 
Secondary Objective
Secondary Endpoint

To evaluate the efficacy of brexucabtagene 
autoleucel in subjects with HCL by ORR by 
investigator assessment

ORR by investigator assessment defined as the 
proportion of subjects who achieve either CR or PR
Exploratory Objective
Exploratory Endpoint

To evaluate the MRD negative response rate in 
subjects with HCL who have achieved a CR by 
central assessment

Rate of MRD negative response among subjects 
who have achieved a CR by central assessment
Abbreviations: CR, complete response; HCL, hairy cell leukemia; MRD, measurable residual disease; ORR, objective response 
rate; PR, partial response.

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3.
STUDY DESIGN
3.1.
Study Design
This substudy protocol contains details regarding all elements of the study that are unique to 
subjects with HCL. 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 HCL. Subjects with r/r HCL must have received at 
least 2 lines of prior systemic therapy including a purine nucleoside analog (PNA) and 
moxetumomab pasudotox if eligible and commercially available.
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 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.
An SRT, comprising the study sponsor and at least 1 study investigator, will be specifically 
chartered to review the safety data and make recommendations on further study conduct, 
progression, and/or dose modification. Additional details of the SRT are provided in Section 8.1.
An independent Data Safety Monitoring Board (DSMB) will be chartered to review safety and 
efficacy data to make study conduct recommendations based on an analysis of risk versus 
benefit. The DSMB will review investigator-reported safety and efficacy data against the futility 
rules after 10 subjects (50%) in this substudy have been treated with the SRT-recommended dose 
of brexucabtagene autoleucel and have had the opportunity to be followed for 3 months after the 
brexucabtagene autoleucel infusion. Additional details of the DSMB are provided in Section 8.1.
The end-of-study is defined in the Master protocol (refer to Section 3.4 of the Master protocol).

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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 20 subjects with r/r HCL 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 recommends 
proceeding at the lower dose level (refer to Section 8.10.1 of the KT-US-568-0138 master 
protocol for additional details).
4.2.
Eligibility Criteria
To be enrolled in the study, subjects must meet the common eligibility criteria detailed in 
Section 4.2 of the KT-US-568-0138 master protocol. In addition, subjects must also meet all of 
the additional, substudy-specific eligibility criteria detailed in Section 4.2.1 and Section 4.2.2.
4.2.1.
HCL Substudy-specific Inclusion Criteria
1) Subjects will be eligible regardless of the duration of remission prior to relapse and must 
have confirmed HCL (r/r classic HCL or r/r HCL variant) by immunophenotyping and 
histology with a need for therapy based on at least one of the following criteria:

neutrophils < 1.0 × 109/L

platelets < 100 × 109/L

hemoglobin < 11 g/dL

symptomatic splenomegaly

symptomatic lymphadenopathy
2) Subjects must have received:

At least 2 prior therapies, including at least a PNA and moxetumomab pasudotox if 
eligible and available
4.2.2.
HCL Substudy-specific Exclusion Criteria
1)
Prior history of allogeneic stem cell transplant

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5.
STUDY TREATMENT
Study treatment consists of lymphodepleting chemotherapy and a single infusion of 
brexucabtagene autoleucel, as described in Section 3.2 of the KT-US-568-0138 master protocol.
Bridging therapy is not applicable for subjects participating in this substudy.
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.

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6.
STUDY ASSESSMENTS UNIQUE TO HAIRY CELL 
LEUKEMIA
The study assessments that are either unique to HCL or that are managed differently for subjects 
with HCL are described here. Please refer to the KT-US-568-0138 master protocol Section 6 for 
details of all other study assessments. Study assessments described in the KT-US-568-0138 
master protocol and herein are to be performed according to the schedule of assessments (SOA) 
presented in Section 12.2 (Table 5 and Table 6) of this substudy protocol.
6.1.
Clinical Laboratory Tests
Clinical laboratory tests for disease-specific assessments are presented in Table 2. The 
hematology assessments are performed at the local laboratory only, the bone marrow trephine 
biopsy will be assessed at both local and central laboratory assessment, and the bone marrow 
aspirate will be assessed at the central laboratory only.
Table 2.
Clinical Laboratory Tests for Disease-specific Assessments
Serum Chemistries (Serum)
Hematology (Blood)
Other 
No additional HCL-specific 
serum chemistry tests are 
required for this substudy
Peripheral blood assessment of 
circulating leukemic cells (see 
Section 6.4.1)
Hematologic disease response 
parameters (see Section 6.5):

Lymphocyte count

Absolute neutrophil count

Platelet count

Hemoglobin
Peripheral blood assessment of MRD, 
only in the case of a fibrotic bone 
marrow (see Section 6.6.1)
Bone marrow aspirate and trephine 
biopsy to assess bone marrow 
involvement and MRD (see 
Section 6.4.3)
Abbreviations: HCL, hairy cell leukemia; MRD, measurable residual disease; SOA, schedule of assessments.
Note: Refer to the SOA in Section 12.2 for timing of assessments.
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:

At screening, subjects with current symptoms or clinical signs of central nervous system 
(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.

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
If required, the MRI should be performed as close to enrollment/leukapheresis as possible 
and within 28 days before leukapheresis for eligibility. An MRI collected as standard of care 
(SOC) within this timeframe is acceptable.

After the initial screening and eligibility confirmation, if the subject presents with new-onset 
symptoms or clinical signs of CNS malignancy/disease, a repeat MRI is required to reassess 
eligibility prior to the start of lymphodepleting chemotherapy.

CNS involvement will be assessed by local review, and images will not be sent for central 
review.
Post-infusion:

Subjects 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.
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 symptoms or clinical signs of CNS malignancy (eg, new-onset severe 
headaches, neck stiffness, or focal neurologic findings), or leptomeningeal carcinomatosis, 
will have a lumbar puncture performed at screening for examination of cerebrospinal fluid 
(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.

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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, 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 Consensus 
Guidelines for the Diagnosis and Management of Patients with Classic Hairy Cell Leukemia ; 
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. Assessment of hemoglobin, platelets, or absolute 
neutrophil count (ANC) must be performed at least 4 weeks after the subject has received any 
transfusions or growth factors. If the need for transfusions or growth factors means that the 
disease response assessment cannot fall within the scheduled study visit window, an unscheduled 
disease response assessment should be performed as soon as possible thereafter (all other 
assessments should be performed at the visit per the SOA). Assessment of disease response will 
be considered non-evaluable if a blood transfusion was administered in the 4 weeks preceding 
the assessment.
In addition, subjects with symptoms suggestive of disease progression should be evaluated for 
progression at the time symptoms occur, even if this requires an unscheduled visit.
6.4.1.
Assessment of Leukemic Cells by Peripheral Blood Smear or Flow 
Cytometry
The assessment of leukemic cells in peripheral blood will be performed locally at the timepoints 
specified in the SOA (see Section 12.2). The assessment can be via routine smear 
(hematoxylin/eosin staining) or by other methodologies (eg, flow cytometry). The assessment is 
required to confirm a CR in accordance with the consensus guidelines and may also be done at 
the investigator’s discretion at any time and, in cases of disease progression, if clinically 
indicated.
The local laboratory assessment will be reported in the electronic case report form (eCRF). Data 
extracted from the eCRF will be provided to the vendor performing the independent central 
primary endpoint assessment.

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6.4.2.
Imaging Requirements
Computed tomography (CT) of diagnostic quality or MRI is required in all subjects to assess 
hepatomegaly, splenomegaly and lymphadenopathy in accordance with the consensus guidelines.
For all imaging, the following requirements should be met:

If CT is used it must be of diagnostic quality with intravenous (IV)-iodinated contrast, 
performed by either of the following modalities, depending on the site’s capability:
as part of a combined positron emission tomography-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.

All screening and disease assessment CT or MRI scans will be submitted to and reviewed by 
an independent central reviewer.

Technical and shipping requirements for the CT or MRI 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 central radiological review will be made in accordance with the response criteria outlined 
in Section 12.3 . Moreover, the median spleen diameter will be recorded. A local investigator 
assessment will also be made and reported in the eCRF.
Screening/Baseline:

Diagnostic CT or MRI 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 or MRI scan performed at the trial site, after the subject’s last line of therapy and 
before signing of the informed consent form (ICF) may be used (if relevant requirements 
described above are fulfilled) and if within 28 days before enrollment/leukapheresis and 
no other anticancer treatment has been administered. A screening image is required for 
referred subjects.

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Disease Assessment:

Follow-up CT or MRI imaging is required at the timepoints specified in the SOA and at any 
time disease progression is suspected.
6.4.3.
Bone Marrow Biopsy/Aspirate
Bone marrow aspirate and biopsies will be analyzed by the investigator at the local laboratory. 
All bone marrow samples should be sent to the central laboratory for confirmation of diagnosis 
(screening bone marrow only) and measurable residual disease (MRD) assessment (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.

The morphological status of the bone marrow will be reported in the eCRF (ie, presence or 
absence of morphological evidence of HCL, percentage improvement in bone marrow 
biopsy infiltration of HCL).

Bone marrow data extracted from the eCRF will be provided to the vendor performing the 
independent central primary endpoint assessment.
Screening/Baseline:

A bone marrow aspirate and biopsy will be required in all subjects 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.
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 or PR if there is 
normalization of peripheral blood counts, and must be performed if disease progression is 
suspected.

Bone marrow assessments may also be performed at the investigator’s discretion and if 
clinically indicated at disease progression.

Aspirate samples should be provided for central analysis of MRD (refer to Section 6.6.1), 
whenever possible at the time of CR.
Progression:
If a bone marrow biopsy is clinically indicated to confirm disease progression, a portion of this is 
required to be sent to the central laboratory for additional exploratory analysis.

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6.5.
Hematology Assessments
Local laboratory measurement of lymphocyte count, ANC, platelet count, and hemoglobin are 
required at screening and at all time points indicated in the SOA for disease assessments, per the 
consensus guidelines. As described in Section 6.4, assessment of ANC, platelets, or growth 
factors for disease response should be done at least 4 weeks after receiving any transfusion or 
growth factors.
6.6.
Disease-specific Exploratory Assessments
Screening bone marrow aspirate and biopsies will be collected for central laboratory assessment 
of somatic mutations of BRAF (V600E) and B-cell lymphoma characterization by an 
immunohistochemistry B-cell lymphoma panel to confirm the HCL diagnosis and for use as 
prognostic markers in exploratory analyses.
6.6.1.
Measurable Residual Disease Analysis
MRD assessments by evaluation of bone marrow aspirate samples or peripheral blood (if the 
bone marrow aspirate is fibrotic) will be performed by central analysis using allele-specific DNA 
polymerase chain reaction testing for BRAF (V600E) (sensitivity, ≥0.01% mutant copies). BRAF 
mutation MRD analysis will be performed by a centralized specialty laboratory (see the central 
laboratory manual) using bone marrow aspirate samples, when obtained in accordance with 
Section 6.4.3.
Further details are provided in the central laboratory manual.

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7.
STUDY PROCEDURES UNIQUE TO HAIRY CELL 
LEUKEMIA
Refer to Section 7 of the KT-US-568-0138 master protocol for the list of procedures for this 
study.

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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-568-0138 master protocol.
An independent DSMB will be chartered to review safety and efficacy data to make study 
conduct recommendations based on an analysis of risk versus benefit. The DSMB will review 
investigator-reported safety and efficacy data against the futility rules after 10 subjects (50%) in 
this substudy have been treated with the SRT-recommended dose of brexucabtagene autoleucel 
and have had the opportunity to be followed for 3 months after the brexucabtagene autoleucel 
infusion. 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 be monitored or unmonitored to facilitate timely DSMB review.
SUSARs and SAE listings or narratives may be submitted to the DSMB chair as described in the 
DSMB charter.
Additional details regarding the SRT, DSMB, and dose-limiting toxicities are provided in 
Section 8.10.1, Section 8.10.2, and Section 8.1.2 of the KT-US-568-0138 master protocol, 
respectively.

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9.
STATISTICAL CONSIDERATIONS
An overview of the statistical considerations that are specific to this subprotocol are provided 
below. Refer to Section 9 of the KT-US-568-0138 master protocol for an overview of the 
statistical considerations that are common across indications.
Details will be provided in the statistical analysis plan (SAP) at finalization.
9.1.
Hypothesis
An alternative hypothesis will be tested with a target 60% ORR per central assessment against a 
null hypothesis that the ORR is ≤ 26%. The reference rate of 26% was based on Nieva et al . The 
hypothesis is that the ORR to brexucabtagene autoleucel per central assessment is greater than 
26%.
The hypothesis testing will be conducted at a significance level of 0.025 (1-sided). The responses 
from subjects in the study population are assumed to be independent and follow a binomial 
distribution.
9.2.
Definition of Substudy Endpoints
In addition to the secondary and exploratory endpoints outlined in the KT-US-568-0138 master 
protocol, the endpoints outlined below also apply to this substudy.
9.2.1.
Definition of Substudy Primary Endpoint
The primary endpoint for this substudy is the ORR by central assessment defined as the 
proportion of subjects who achieve either CR or PR, per the response criteria described by 
Grever and colleagues (; see Section 12.3.1).
9.2.2.
Definition of Substudy Secondary Endpoint
The secondary endpoint for this substudy is defined in Table 3.
Table 3.
Definition of Substudy Secondary Endpoint
Secondary Endpoint
Definition
ORR by investigator assessment 
The proportion of subjects who achieve either CR or 
PR by investigator assessment
Abbreviations: CR, complete response; ORR, objective response rate; PR, partial response

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9.2.3.
Definition of Other Substudy Endpoint of Interest
The exploratory endpoint for this substudy is defined in Table 4.
Table 4.
Definition of Substudy Exploratory Endpoint
Exploratory Endpoint
Definition
Rate of MRD negative response among subjects who 
have achieved a CR by central assessment
Rate of MRD negative response in bone marrow 
among subjects who have achieved a CR by central 
assessment, where MRD negative is defined as 
MRD < 10-4 per the standard assessment
Abbreviations: CR, complete response; MRD, measurable residual disease.
9.3.
Determination of Sample Size
This single-arm, open-label substudy will enroll and treat 20 subjects with the 
SRT-recommended dose of brexucabtagene autoleucel. This sample size will achieve a statistical 
power of 90% if there is at least a 34% improvement in ORR (brexucabtagene autoleucel: 60% 
versus historical control: 26%) with a type 1 error rate of 0.025 (1-sided) under the 2-look design 
based on normal approximation, with variance of standardized test statistic under null hypothesis 
(H0) using EAST (Version 6.5). The empirical power is 87% per simulation based on binomial 
distribution without normal approximation. Statistically significant treatment effect can be 
claimed in this substudy if ≥ 10 responders (≥ 50.0%) are observed among the 20 subjects at the 
primary analysis.
9.4.
Planned Analyses
9.4.1.
Interim Analysis and Early Stopping Guidelines
An interim analysis will be conducted after 10 subjects (50%) have had the opportunity to be 
evaluated for response 3 months after treatment with brexucabtagene autoleucel. In this interim 
analysis, the DSMB will review investigator-reported data for both safety and efficacy (futility 
only). The non-binding futility boundary of an ORR of 29.4% is based on the beta spending 
function of rho family (parameter = 2), with a crossing probability of 60% under the null 
hypothesis (ORR ≤ 26%). The futility boundary is crossed if ≤ 2 responders are observed among 
the 10 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 20 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 objective responders observed among the 
20 subjects, as described above. The point estimate of the ORR will be calculated, together with 
its 95% confidence interval using the Clopper-Pearson method. The p-value will be calculated 
based on an exact test. In the event that more than 20 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.

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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
Betticher DC, Fey MF, von Rohr A, Tobler A, Jenzer H, Gratwohl A, et al. High incidence of 
infections after 2-chlorodeoxyadenosine (2-CDA) therapy in patients with 
malignant lymphomas and chronic and acute leukaemias. Ann Oncol 1994;5 
(1):57-64.
Bouroncle BA. Thirty-five years in the progress of hairy cell leukemia. Leuk Lymphoma 
1994;14 Suppl 1:1-12.
Cawley JC. The pathophysiology of the hairy cell. Hematol Oncol Clin North Am 2006;20 
(5):1011-21.
Cheson BD. Infectious and immunosuppressive complications of purine analog therapy. J Clin 
Oncol 1995;13 (9):2431-48.
Cheson BD, Sorensen JM, Vena DA, Montello MJ, Barrett JA, Damasio E, et al. Treatment of 
hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol 
mechanism of the National Cancer Institute: a report of 979 patients. J Clin Oncol 
1998;16 (9):3007-15.
Golomb HM, Catovsky D, Golde DW. Hairy cell leukemia: a clinical review based on 71 cases. 
Ann Intern Med 1978;89 (5 Pt 1):677-83.
Grever MR, Abdel-Wahab O, Andritsos LA, Banerji V, Barrientos J, Blachly JS, et al. 
Consensus guidelines for the diagnosis and management of patients with classic 
hairy cell leukemia. Blood 2017;129 (5):553-60.
Kreitman RJ, Cheson BD. Malignancy: Current Clinical Practice: Treatment of Hairy Cell 
Leukemia at the Close of the 20th Century. Hematology 1999;4 (4):283-303.
Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Karlin L, Robak T, et al. Moxetumomab 
pasudotox in relapsed/refractory hairy cell leukemia. Leukemia 2018;32 (8):1768-
77.
Legrand O, Vekhoff A, Marie JP, Zittoun R, Delmer A. Treatment of hairy cell leukaemia (HCL) 
with 2-chlorodeoxyadenosine (2-CdA): identification of parameters predictive of 
adverse effects. Br J Haematol 1997;99 (1):165-7.
Matutes E, Oscier D, Montalban C, Berger F, Callet-Bauchu E, Dogan A, et al. Splenic Marginal 
Zone Lymphoma Proposals for a Revision of Diagnostic, Staging and Therapeutic 
Criteria. Leukemia 2008;22:487-95.

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National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology 
(NCCN Guidelines®). Hairy Cell Leukemia. Version 1.2022 - September 8, 
2021.  2021:
Nieva J, Bethel K, Saven A. Phase 2 study of rituximab in the treatment of cladribine-failed 
patients with hairy cell leukemia. Blood 2003;102 (3):810-3.
Robbins BA, Ellison DJ, Spinosa JC, Carey CA, Lukes RJ, Poppema S, et al. Diagnostic 
application of two-color flow cytometry in 161 cases of hairy cell leukemia. 
Blood 1993;82 (4):1277-87.
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.
Seymour JF, Kurzrock R, Freireich EJ, Estey EH. 2-chlorodeoxyadenosine induces durable 
remissions and prolonged suppression of CD4+ lymphocyte counts in patients 
with hairy cell leukemia. Blood 1994;83 (10):2906-11.
Sharpe RW, Bethel KJ. Hairy cell leukemia: diagnostic pathology. Hematol Oncol Clin North 
Am 2006;20 (5):1023-49.
Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid 
malignancy statistics by World Health Organization subtypes. CA Cancer J Clin 
2016;66:443-59.
Tiacci E, De Carolis L, Simonetti E, Capponi M, Ambrosetti A, Lucia E, et al. Vemurafenib plus 
Rituximab in Refractory or Relapsed Hairy-Cell Leukemia. N Engl J Med 
2021;384 (19):1810-23.
Tiacci E, Liso A, Piris M, Falini B. Evolving concepts in the pathogenesis of hairy-cell 
leukaemia. Nat Rev Cancer 2006;6 (6):437-48.

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

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
Final
Kite Pharma, Inc.
Amendment 2.0
CONFIDENTIAL
Page 32
01 March 2023
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 D – Relapsed/Refractory Hairy Cell 
Leukemia
Amendment 2.0, 01 MARCH 2023
This protocol has been approved by Kite Pharma, Inc. The following signature documents this approval.
See appended signature page
See appended signature page
Kite Medical Monitor Name (Printed) 
Signature
See appended signature page
Date
INVESTIGATOR STATEMENT
I have read the protocol, including all appendices, and I agree that it contains all necessary details for me 
and my staff to conduct this study as described. I will conduct this study as outlined herein and will make 
a reasonable effort to complete the study within the time designated.
I agree to comply with the International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) Harmonised Tripartite Guideline on Good Clinical Practice and 
applicable national or regional regulations and guidelines. I will provide all study personnel under my 
supervision copies of the protocol and access to all information provided by Kite Pharma, Inc. I will 
discuss this material with them to ensure that they are fully informed about the investigational product 
and study.
I agree and will ensure that financial disclosure statements will be completed by:

Me (including, if applicable, my spouse, legal partner, and dependent children)

Subinvestigators (including, if applicable, their spouse, legal partner, and dependent children) at the 
start of the study and for up to 1 year after the study is completed.
I agree to ensure that the confidential information contained in this document will not be used for any 
purpose other than the conduct of the clinical investigation without prior written consent from 
Kite Pharma, Inc.
Principal Investigator Name (Printed)
Signature
Date
Study Site Number

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
Final
Kite Pharma, Inc.
Amendment 2.0
CONFIDENTIAL
Page 33
01 March 2023
12.2.
Schedule of Assessments
Table 5.
Schedule of Assessments: Screening, Pretreatment, Treatment, and Post-treatment Periods
Timeframe:
Screening
Pretreatment Period
Treatment Period
Post-treatment Follow-up Period
Enrollment/
Leukapheresis
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
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
Daily
X
X
X
X
X
Weight (height at screening only)
X
X
Vital signsd
X
X
X
X
X
X
Daily
X
X
X
X
X
Neurologic examinatione 
X
X
QOD
X
X
X
X
ECOG performance status 
X
X
LVEF (ECHO or MUGA)
X
ECG
X
Brain MRI (if applicable)f
Xf
Lumbar puncture (if applicable)g
Xg
PROs: EORTC-QLQ-C30 and 
EQ-5D-5h
X
X
X
X
X

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
Final
Kite Pharma, Inc.
Amendment 2.0
CONFIDENTIAL
Page 34
01 March 2023
Timeframe:
Screening
Pretreatment Period
Treatment Period
Post-treatment Follow-up Period
Enrollment/
Leukapheresis
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
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
Disease response assessments (hematology components captured within CBC under local labs, please also refer to the imaging manual and central laboratory manual for 
guidance)
Imaging CT/MRIi
X
X
X
X
Bone marrow aspirate and 
biopsyj
X
X
X
X
Assessment of leukemic cells 
in peripheral bloodk
X
X
X
X
Overall response assessment
X
X
X
Local laboratory assessment 
Chemistry panel (CrCl at 
screening) (serum)
X
X
X
X
X
Xl
Daily
X
X
X
X
X
CBC with differential (blood)
X
X
X
X
X
Xl
Daily
X
X
X
X
X
LDHm, CRP, ferritin (serum)
X
X
Xl
Daily
X
X
β-hCG pregnancy test 
([WOCBP] serum or urine)
X
Xn
Xn
X
X
X
Serology for EU/CH/UK sites 
(serum)o
Xo
Xo
HIV positive subjects only: 
HIV viral load and CD4 count
Xp
X
X
X

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
Final
Kite Pharma, Inc.
Amendment 2.0
CONFIDENTIAL
Page 35
01 March 2023
Timeframe:
Screening
Pretreatment Period
Treatment Period
Post-treatment Follow-up Period
Enrollment/
Leukapheresis
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
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
Central laboratory assessments (please refer to the central laboratory manual for guidance)
CBC with differential (blood)
X
Xl
D3, D7
X
X
X
X
X
Anti-brexucabtagene autoleucel 
antibodies (serum)
Xq
X
X
X
Analytes, including cytokines 
(serum/plasma)r
Xq
Xl
D1, D2, D3, 
D5, D7
X
X
X
X
X
Brexucabtagene autoleucel 
CAR T-cell levels and 
exploratory analyses (PBMCs)r
Xq
Xl
D3, D7
X
X
X
X
X
RCR (PBMCs)s
Xl
X
MRD assessment via peripheral 
blood (only in case of fibrotic 
bone marrow aspirate)
X
(Xj,k)
(Xj,k)
(Xj,k)
Leukapheresis 
X
Fludarabine/
cyclophosphamidet 
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 eventsu
X
X
X
X
Daily
X
X
X
X
X

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
Final
Kite Pharma, Inc.
Amendment 2.0
CONFIDENTIAL
Page 36
01 March 2023
Abbreviations: approx., approximately; ASCO, American Society of Clinical Oncology; CAR, chimeric antigen receptor; CBC, complete blood count; CNS, central nervous 
system; CR, complete response;CrCl, creatinine clearance; CRP, C-reactive protein; CRS, cytokine release syndrome; CSF, cerebospinal fluid; CT, computed tomography; 
D/d, day; ECG, electrocardiogram;ECHO, echocardiogram; ECOG, Eastern Cooperative Oncology Group; EORTCQLQ-C30, European Organization for Research and Treatment 
of Cancer Quality of Life Questionnaire; EQ-5D-5L, European Quality of Life 5-Dimension 5-Level scale; EU, European Union; hCG, human chorionic gonadotropin; 
ICANS, immune effector cell-associated neurotoxicity syndrome; ICE, immune effector cell-associated encephalopathy; ICF, informed consent form; IV, intravenous; 
LDH, lactate dehydrogenase; LVEF, left ventricular ejection fraction, M, month; MRD, measurable residual disease; MRI, magnetic resonance imaging; MUGA, multigated 
acquisition scan; PBMCs, peripheral blood mononuclear cells; PR, partial response; PRO, patient-reported outcome; QOD, every other day; RCR, replication-competent retrovirus; 
SOA, schedule of assessments; SOC, standard of care; UK, United Kingdom; 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, hepatomegaly, 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 every other day during the hospitalization period. If a subject hospitalization is extended beyond Day 7, a 
neurologic examination including a cognition assessment will continue to be performed as clinically indicated.
f
Brain MRI:

Screening through start of lymphodepletion: At screening, 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 and 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 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
Imaging CT/MRI:

Screening/baseline: CT or MRI (for assessment of liver, spleen and lymph nodes) should be performed as close to enrollment as possible and within 28 days before 
enrollment/leukapheresis for eligibility (unless imaging is available from SOC assessment within 28 days before enrollment).

Disease assessment: Follow-up imaging is required at the timepoints specified in the SOA and at any time disease progression is suspected.

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
Final
Kite Pharma, Inc.
Amendment 2.0
CONFIDENTIAL
Page 37
01 March 2023
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).

Disease assessment: Bone marrow aspiration and biopsy are required at Day 28 and Month 3, thereafter may also be done at the investigator’s discretion and at any time 
to confirm a CR or PR and must be performed if disease progression is suspected. Submission of bone marrow aspirate to the central lab is required at the time of CR for 
MRD assessment by BRAF mutation. If the bone marrow aspirate is fibrotic, a peripheral blood sample is required for central laboratory MRD assessment by BRAF 
mutation.
k
Assessment of circulating leukemic cells: The assessment of circulating leukemic cells in peripheral blood can be via routine smear Wright’s stain) or by other methodologies 
(eg, flow cytometry). The assessment may be done at the investigator’s discretion and at any time to confirm a CR. If the bone marrow aspirate is fibrotic, submission of 
circulating blood to the central lab is also required for MRD assessment by BRAF mutation.
l
Assessments may be performed on the day before administration of brexucabtagene autoleucel (ie, on Day −1). For tests performed at the central laboratory, this decision will 
be driven by the availability of the central laboratory to process samples on the day they are collected from the subject (refer to the laboratory manual for holidays). For 
samples collected on Day 0, collection will occur before the start of the brexucabtagene autoleucel infusion.
m
LDH should continue to be monitored after the baseline assessment as clinically indicated.
n
Pregnancy test (serum or urine): For EU/CH/UK study sites, the test will be completed within 7 days before both leukapheresis and lymphodepleting chemotherapy for 
women of childbearing potential.
o
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.
p
Hepatitis B and C testing is also required at screening.
q
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.
r
Analytes (including cytokines) (serum) and brexucabtagene autoleucel CAR T cells (PBMCs):

Samples on Day 3 may be collected ± 1 day.

If a subject is re-admitted to the hospital after the initial hospitalization observation period with any brexucabtagene autoleucel-related adverse events, blood samples for 
assessment of brexucabtagene autoleucel CAR T cells and serum analytes will be collected on the day of hospital re-admission and then weekly through, and including, 
the day of discharge, if the samples were not already collected on the same days as per the SOA (ie, 2 identical collections on the same day are not needed).

If the subject experiences a Grade 3 or higher brexucabtagene autoleucel-related toxicity, such as Grade 3 CRS or neurologic event, 1 additional blood draw for 
brexucabtagene autoleucel CAR T cells (PBMCs) and serum analytes will be collected at the time of the Grade 3 or higher brexucabtagene autoleucel-related toxicity 
and upon resolution of the event, if the samples were not already collected on the same days as per the SOA (ie, 2 identical collections on the same day are not needed).

Blood samples for assessment of brexucabtagene autoleucel CAR T cells and serum analytes should be collected at the time of disease progression prior to starting 
subsequent anticancer therapy.

Exploratory T-cell immunogenicity will be performed with PBMCs at leukapheresis and Month 3. Extra blood collection is required for such testing.

Exploratory analyses will include lymphocyte subsets.
s
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.
t
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-598-0138 
master protocol).
u
Collection of serious adverse events starts from signing of the screening ICF, and collection of adverse events starts from commencement of the leukapheresis procedure.

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
Final
Kite Pharma, Inc.
Amendment 2.0
CONFIDENTIAL
Page 38
01 March 2023
Table 6.
Schedule of Assessments: Post-treatment Follow-up Period
Timeframe:
Long-term Follow-up Period (Each visit calculated from Day 0)
Procedure
M6
(± 2 w)
M9
(± 2 w)
M12
(± 2 w)
M18
(± 1 M)
M24
(± 1 M)
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 response assessment (hematology components captured within CBC under local labs, please also refer to the imaging manual and central laboratory manual for 
guidance)
Imaging CT/MRId
X
X
X
X
X
X
X
X
X
X
Bone marrow aspirate and 
biopsye
X
X
Assessment of leukemic 
cells in peripheral bloodf
X
X
Overall response 
assessment,
X
X
X
X
X
X
X
X
X
X
Local laboratory assessments
CBC with differential 
(blood)g
X
X
X
X
X
X
X
X
X
X
Chemistry panel (serum)
X
LDHh
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
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 
I 

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
Final
Kite Pharma, Inc.
Amendment 2.0
CONFIDENTIAL
Page 39
01 March 2023
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)g
X
X
X
X
X
X
Analytes, including 
cytokines (serum/plasma)i
X
Anti-brexucabtagene 
autoleucel antibodies 
(serum)
X
X
X
X
Brexucabtagene autoleucel 
CAR T-cell levels and 
exploratory analyses 
(PBMCs)i
X
X
X
X
X
X
RCR (PBMCs)j
X
X
MRD assessment via 
peripheral blood (only in 
case of fibrotic bone marrow 
aspirate)e
(X)e
(X)e
All brexucabtagene 
autoleucel-related SAEs and 
any deaths regardless of 
causality
X
X
X
X
X
X
X
X
X
X
Targeted AE/SAEsk 
X
X
X
X
Xk
X
Xk
X
X
X
Targeted concomitant 
medicationsl
X
X
X
X
X
X
Xl
X
X
X
Subsequent therapy for 
HCLm 
X
X
X
X
X
X
X
X
X
X
Survival statusn
X
X
X
X
X
X
X
X
X
X

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
Final
Kite Pharma, Inc.
Amendment 2.0
CONFIDENTIAL
Page 40
01 March 2023
Abbreviations: AE, adverse event; CAR, chimeric antigen receptor; CBC, complete blood count; CR, complete response; CT, computed tomography; EORTC-QLQ-C30, 
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EQ-5D-5L, European Quality of Life 5-Dimension 5-Level scale; GP, general 
practitioner; HCL, hairy cell leukemia; HCP, healthcare provider; LDH, lactate dehydrogenase; LTFU, long-term follow-up; M, month; MRD, measurable residual disease; MRI, 
magnetic resonance imaging; PBMC, peripheral blood mononuclear cell; PR, partial response; PROs, patient-reported outcomes; RCR, replication-competent retrovirus; SAE, 
serious adverse event; SOA, schedule of assessments; w, weeks.
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, hepatomegaly, 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 imaging diagnostic CT or MRI is required at the timepoints specified. Additional assessments may be performed, if clinically indicated, during the course of the 
study at any time disease progression is suspected.
e
Bone marrow aspiration and biopsy may be done at the investigator’s discretion and at any time to confirm a CR or PR, and must be performed if disease progression is 
suspected. Submission of bone marrow aspirate to the central lab is required at the time of CR for MRD assessment by BRAF mutation. If the bone marrow aspirate is fibrotic, 
a peripheral blood sample is required for central laboratory MRD assessment by BRAF mutation.
f
Assessment of circulating leukemic cells in peripheral blood can be via routine smear (hematoxylin/eosin staining) or by other methodologies (eg, flow cytometry). The 
assessment may be done at the investigator’s discretion and at any time to confirm a CR and at disease progression, if clinically indicated.
g
CBC with differential (blood):

Local laboratory assessments: Blood will be collected at the timepoints 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 timepoints 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 timepoints that are sent to the local laboratory for assessment of CBC with differential for 
clinical/safety evaluation).
h
LDH should continue to be monitored after the baseline assessment as clinically indicated.
i
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.
j
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-598-0138 master protocol).

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
Final
Kite Pharma, Inc.
Amendment 2.0
CONFIDENTIAL
Page 41
01 March 2023
k
Targeted AEs/SAEs include neurologic events, hematologic events, serious infections, autoimmune disorders, and secondary malignancies. From 3 months after the 
brexucabtagene autoleucel infusion, targeted AEs/SAEs will be reported through Month 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.
l
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.
m
Subsequent anticancer therapy administered after brexucabtagene autoleucel infusion for a subject’s disease will be collected until 1 of the following occurs: subject 
completes the post-treatment follow-up period, is considered lost to follow-up, withdraws consent, or dies. The subject and/or the referring HCP and/or GP may be contacted 
directly by telephone or email to collect information about subsequent therapy.
n
Subject and/or referring HCP and/or GP may be contacted directly by telephone or email to assess survival status.

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
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Amendment 2.0
CONFIDENTIAL
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01 March 2023
12.3.
Disease Response Criteria
Response criteria in hairy cell leukemia based on Grever et al 2017 .
12.3.1.
Response Criteria in HCL
Complete Response (CR)

No evidence of leukemic cells in the peripheral blood and/or by routine 
H/E staining of bone marrow.

Resolution of any splenomegaly. by computed tomography (CT) or 
magnetic resonance imaging (MRI).

Normalization CDC as exhibited by:

absolute neutrophil count > 1.5 x 109/L,

platelets >100 x 109/L, and

hemoglobin > 11.0 g/dL without blood transfusions for at least 4 
weeks.
Partial Response (PR)
The subject must have the following (if abnormal prior to treatment):

≥50% reduction in organomegaly by CT or MRI, or resolution to size 
consistent with CR,

minimum of 50% improvement in bone marrow biopsy infiltration with 
hairy cell leukemia

Normalization CBC as exhibited by:

ANC > 1.5 x 109/L

Platelets ≥ 100 x 109/L

Hemoglobin ≥ 11.0 g/dL without blood transfusions for at least 
4 weeks.
Stable Disease (SD)
Stable disease will be characterized by not meeting the criteria for CR, partial 
response, or progressive disease (PD) as outlined below.
Progressive Disease (PD)
PD is defined by at least one of the following compared to pretreatment:

increase in symptoms related to disease

≥ 25% increase in organomegaly 

≥ 25% decline in hematologic parameters (ANC, Hgb, and/or platelets
Abbreviations: ANC; absolute neutrophil count; CR, complete response; CBC, complete blood count; CT, computed 
tomography; magnetic resonance imaging; PD, progressive disease; PR, partial response; SD, stable disease.

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
Final
Kite Pharma, Inc.
Amendment 2.0
CONFIDENTIAL
Page 43
01 March 2023
12.4.
Protocol Amendment History
12.4.1.
Amendment 1.0 (dated 20 July 2022)
Changes from the original protocol (dated 23 May 2022) to Amendment 1.0 (dated 20 July 2022) 
are detailed below.
Section Number and Name
High-level Description of Change
Brief Rationale
Synopsis Number of study 
sites planned
Number of study sites increased from 
approximately 40 to 50
Increased the number of study 
sites to optimize enrolment
Section 12.2 Schedule of 
assessments, Table 5 Schedule 
of Assessments: Screening, 
Pretreatment, Treatment, and 
Post-treatment Periods
Removal of EORTC-QLQ-C30 and EQ-5D 
PRO collection at enrollment/leukapheresis 
timepoint
Correction of typo. The PRO 
assessment will be at Day -5 
in all subjects
Section 6.4.3 Bone marrow 
biopsy/aspirate
Disease Response Assessment:

Added clarification that aspirate samples 
should be provided for central analysis of 
MRD (refer to Section 6.6.1), whenever 
possible, at the time of CR
Addition for clarification, 
since central analysis of MRD 
is applicable only at the time 
of CR
Section 12.2 Schedule of 
assessments, Table 5 Schedule 
of Assessments: Screening, 
Pretreatment, Treatment, and 
Post-treatment Periods
Footnote j: Bone marrow aspirate and biopsy: 
Added clarification that disease assessment: 
Bone marrow aspiration and biopsy are 
required at Day 28 and Month 3, thereafter 
may also be done at the investigator’s 
discretion and at any time to confirm a CR or 
PR and must be performed if disease 
progression is suspected. Submission of bone 
marrow aspirate to the central lab is required at 
the time of CR for MRD assessment by 
BRAF mutation
Addition for clarification, 
since central analysis of MRD 
is applicable only at the time 
of CR
Section 12.2 Schedule of 
assessments, Table 6 Schedule 
of Assessments: Post-
treatment Follow-up Period
Added clarifying text in Footnote e: Bone 
marrow aspiration and biopsy may be done at 
the investigator’s discretion and at any time to 
confirm a CR or PR and must be performed if 
disease progression is suspected. Submission 
of bone marrow aspirate to the central lab is 
required at the time of CR for MRD 
assessment by BRAF mutation. 
Addition for clarification, 
since central analysis of MRD 
is applicable only at the time 
of CR
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.

Brexucabtagene Autoleucel
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Amendment 2.0
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For changes from Amendment 1 to Amendment 2, please refer to Sections 12.4.2 and 
Section 12.4.3. Amendment 2 incorporates all changes in Amendment 1.1 together with the 
changes outlined in Section 12.4.3.
Protocol changes that are common across all substudies are detailed in the Master protocol 
(Appendix 12.10).
Section Number and Name
High-level Description of Change
Brief Rationale
Title page and Synopsis
Added EU CT and NCT numbers
EU CT and NCT numbers not 
previously available
Synopsis Statistical Methods 
and Sections 9.1 Hypothesis 
and 9.4.2 Primary Analysis

“significantly” removed from statement 
that “The hypothesis is that the ORR to 
brexucabtagene autoleucel per central 
assessment is greater than 26%.”

Text edited to now state that the p-value 
‘will be’ calculated based on an exact test, 
rather than ‘may be’ tested. 
For clarity
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 HCL Substudy 
and Section 4.2.1 HCL 
Substudy-specific Inclusion 
Criteria
Inclusion criterion 1 updated to state that 
“Subjects will be eligible regardless of the 
duration of remission prior to relapse and must 
have confirmed HCL by immunophenotyping 
and histology with a need for therapy based on 
at least one of the following criteria”
For clarity and to align with 
updated diagnostic 
methodology for HCL 
immunophenotyping
Section 12.2 Schedule of 
Assessments Table 5
Pregnancy test added at Day 28
Alignment with CTFG 
guidelines for pregnancy 
testing following 
administration of fludarabine 
and cyclophosphamide 

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
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Amendment 2.0
CONFIDENTIAL
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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 D – Relapsed/Refractory Hairy 
Cell Leukemia”. The evaluation of safety 
(secondary endpoint) removed from the study 
title.
Request during Part 1 
EU-CTR application to update 
the trial title to focus on the 
primary endpoint only
Title Page
Amendment history added
Self-explanatory
Synopsis and Section 4.2.1 
Inclusion Criteria
Inclusion criteria #1 edited to include subjects 
diagnosed with either r/r classic or r/r HCL 
variant
For clarification
Section 6.2 Brain Magnetic 
Resonance Imaging
Added clarification that 

at screening CNS involvement will be 
assessed by local review, and images 
will not be sent for central review

A brain MRI only needs to be 
submitted to the independent central 
reviewer when there is evidence of 
disease progression
For clarification
Section 12.2 Schedule of 
Assessments Table 5 Schedule 
of Assessments: Screening, 
Pretreatment, Treatment, and 
Post-Treatment Periods
Serology for EU, CH and EU
MRD assessment added at screening
Request by Swiss Regulatory 
Authority and correction for 
baseline MRD assessment
Section 12.2 Schedule of 
assessments Table 5 Schedule 
of assessments: Screening, 
Pretreatment, Treatment, and 
Post-Treatment Periods
Footnote ‘a’: ForEU 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 post 
brexucabtagene autoleucel infusion
Request by Swiss Regulatory 
Authority
Section 12.2 Schedule of 
assessments Table 5 Schedule 
of assessments: Screening, 
Pretreatment, Treatment, and 
Post-Treatment Periods
Footnote ‘j’ amended to include “if the bone 
marrow aspirate is fibrotic, a peripheral blood 
sample is required for central laboratory MRD 
assessment by BRAF mutation”.
For clarification and 
alignment with subprotocol 
Section 6.6.1
Section 12.2 Schedule of 
assessments Table 5 Schedule 
of assessments: Screening, 
Pretreatment, Treatment, and 
Post-Treatment Periods
Footnotes ‘n’ pregnancy testing and ‘o’ 
serology testing updated to include Switzerland
Request by Swiss Regulatory 
Authority and alignment with 
Master protocol Section 6

Brexucabtagene Autoleucel
Protocol KT-US-568-0138-D (ZUMA-25D) - Hairy Cell Leukemia
Final
Kite Pharma, Inc.
Amendment 2.0
CONFIDENTIAL
Page 46
01 March 2023
Section Number and Name
High-level Description of Change
Brief Rationale
Section 12.2 Schedule of 
assessments Table 5 Schedule 
of assessments: Screening, 
Pretreatment, Treatment, and 
Post-Treatment Periods
Footnote ‘r’: Clarification added that samples 
on Day 3 may be collected ± 1 day
 Provides flexibility regarding 
central laboratory sample 
collection when the Day 3 
visit falls over a weekend
Section 12.2 Schedule of 
assessments, Table 6 Schedule 
of Assessments: Post-
treatment Follow-up Period
Visit M18 window changed from ±1 week to 
±1 month
 Provides added flexibility
Section 12.3.1 Response 
Criteria in HCL
Progressive disease definition updated to 
include “increase in symptoms related to 
disease”; and “≥ 25% increase in 
organomegaly” 
Correction of missing criteria