Clinical trial NCT04789408
Conditions: Acute Myeloid Leukemia
Sponsor: Kite, A Gilead Company
Start date: 2021-07-19; Completion date: 2024-05-18
Enrollment: 15 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The goal of this clinical study is to learn more about the safety and dosing of the study drug, KITE-222, in participants with relapsed/refractory (r/r) acute myeloid leukemia (AML).

Detailed description:

Arms: arm 1: Participants with relapsed or refractory (r/r) acute myeloid leukemia (AML) will receive lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by a single infusion of KITE-222 chimeric antigen receptor (CAR) transduced autologous T cells administered intravenously (IV) at a low dose on Day 0 based on participants body weight. arm 2: Participants with r/r AML will receive lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by a single infusion of KITE-222 CAR transduced autologous T cells administered IV at a higher dose on Day 0 based on participants body weight. arm 3: Participants with r/r AML will receive lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by a single infusion of KITE-222 CAR transduced autologous T cells administered IV at the highest dose on Day 0 based on participants body weight. arm 4: Participants will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose \[at the maximum tolerated dose (MTD) determined\] of KITE-222.
Interventions: intervention 1: Cyclophosphamide intervention 2: Fludarabine intervention 3: KITE-222
Intervention descriptions: intervention 1: Administered intravenously intervention 2: Administered intravenously intervention 3: A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously

Protocol documents:
Prot_000.pdf: 
  
CLINICAL STUDY PROTOCOL
Protocol Title:
A Phase 1 Open-label, Multicenter Study Evaluating 
the Safety of KITE-222, an Autologous Anti-CLL-1 
CAR T-cell Therapy, in Subjects With 
Relapsed/Refractory Acute Myeloid Leukemia
Protocol Number:
KT-US-486-0201
Indication:
Relapsed/refractory acute myeloid leukemia
Kite Investigational Product:
KITE-222
Kite IND Number:
27115
EudraCT Number:
2020-000962-40
Clinical Trials.gov Identifier:
NCT04789408
Sponsor:
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
United States of America
Contact Information:
The medical monitor’s name and contact information 
will be provided on the Key Study Team Contact List
Protocol Version/Date:
Original:
20 April 2020
Amendment Number and Date:
Amendment 1.0:
24 September 2020
Amendment Number and Date:
Amendment 2.0:
04 February 2021
Amendment Number and Date:
Amendment 3.0:
02 May 2022
Amendment Number and Date:
Amendment 4.0:
17 January 2023
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 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.


KITE-222
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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................2
LIST OF IN-TEXT TABLES .........................................................................................................................................6
LIST OF IN-TEXT FIGURES........................................................................................................................................6
PROTOCOL SYNOPSIS................................................................................................................................................7
LIST OF ABBREVIATIONS.......................................................................................................................................16
1.
INTRODUCTION................................................................................................................................................19
1.1.
Disease Background ................................................................................................................................19
1.1.1.
Acute Myeloid Leukemia......................................................................................................19
1.1.2.
Current Treatment for Patients With AML and Unmet Need ...............................................20
1.2.
KITE-222.................................................................................................................................................22
1.3.
Summary of Relevant Nonclinical Studies With KITE-222 ...................................................................23
1.4.
Study Rationale .......................................................................................................................................23
1.4.1.
Rationale for Study................................................................................................................23
1.4.2.
Rationale for the Use of CLL-1 as a Target Antigen for AML.............................................24
1.4.3.
Rationale for KITE-222 Starting Dose..................................................................................26
1.4.4.
Rationale for Trial Design to Address KITE-222 Safety Risk..............................................27
1.4.5.
Rationale for Bridging Therapy.............................................................................................28
1.4.6.
Rationale for Lymphodepleting Chemotherapy ....................................................................28
1.5.
Benefit/Risk Assessment for the Study ...................................................................................................29
1.6.
Compliance..............................................................................................................................................29
2.
OBJECTIVES.......................................................................................................................................................30
2.1.
Primary Objective....................................................................................................................................30
2.2.
Secondary Objectives ..............................................................................................................................30
3.
STUDY DESIGN.................................................................................................................................................31
3.1.
Endpoints.................................................................................................................................................31
3.1.1.
Primary Endpoints.................................................................................................................31
3.1.2.
Secondary Endpoints.............................................................................................................31
3.2.
Study Design ...........................................................................................................................................32
3.3.
Study Treatments.....................................................................................................................................33
3.3.1.
Leukapheresis........................................................................................................................33
3.3.3.
Lymphodepleting Chemotherapy ..........................................................................................34
3.3.4.
KITE-222 Dose Cohorts........................................................................................................34
3.3.5.
Conditioning Chemotherapy and Allo-SCT..........................................................................35
3.4.
Duration of Treatment and Study............................................................................................................36
3.4.1.
Duration of Treatment ...........................................................................................................36
3.4.2.
Duration of Subject Participation ..........................................................................................36
3.4.3.
End of Study Definition.........................................................................................................36
3.5.
Long-term Follow-up Study....................................................................................................................36
3.6.
Study Discontinuation Criteria................................................................................................................36
3.7.
Number of Participating Sites .................................................................................................................37
3.8.
Source Data .............................................................................................................................................37
4.
SUBJECT POPULATION...................................................................................................................................38
4.1.
Number of Subjects and Subject Selection .............................................................................................38
4.2.
Eligibility Criteria....................................................................................................................................38
CCI
CCI
CCI--


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4.2.1.
Inclusion Criteria...................................................................................................................38
4.2.2.
Exclusion Criteria..................................................................................................................40
4.3.
Subject Withdrawal .................................................................................................................................43
4.3.1.
Reasons for Removal From Treatment..................................................................................43
4.3.2.
Reasons for Removal From Study.........................................................................................43
4.4.
Replacement of Subjects .........................................................................................................................44
4.5.
Pregnancy and Lactation .........................................................................................................................44
5.
INVESTIGATIONAL PRODUCT ......................................................................................................................45
5.1.
Randomization, Blinding, and Treatment Codes ....................................................................................45
5.2.
Description of Investigational Product....................................................................................................45
5.3.
Packaging, Labeling, Storage, and Handling of Investigational Product................................................45
5.4.
Dosage and Administration .....................................................................................................................45
5.5.
Prior and Concomitant Medications........................................................................................................46
5.6.
Excluded Medications .............................................................................................................................46
5.7.
Accountability and Return of Investigational Product ............................................................................47
6.
STUDY ASSESSMENTS....................................................................................................................................48
6.1.
Demographic Data...................................................................................................................................48
6.2.
Medical and Treatment History...............................................................................................................48
6.3.
Safety Assessments .................................................................................................................................48
6.3.1.
AEs ........................................................................................................................................48
6.3.2.
Clinical Laboratory Tests ......................................................................................................48
6.3.3.
Physical Examination ............................................................................................................50
6.3.4.
Weight ...................................................................................................................................50
6.3.5.
Vital Signs .............................................................................................................................50
6.3.6.
Cardiac Function ...................................................................................................................50
6.3.7.
Chest Imaging........................................................................................................................51
6.3.8.
Neurologic Examinations and Assessments..........................................................................51
6.3.9.
ECOG ....................................................................................................................................51
6.3.10.
Brain Magnetic Resonance Imaging .....................................................................................51
6.3.11.
Lumbar Puncture ...................................................................................................................51
6.3.12.
Concomitant Medications......................................................................................................52
6.3.13.
Other Safety Assessments .....................................................................................................53
6.4.
Disease Assessments ...............................................................................................................................53
6.4.1.
Bone Marrow Evaluation and Disease Assessment ..............................................................54
6.4.2.
Measurable Residual Disease................................................................................................55
6.4.4.
Imaging Requirements (for Subjects with Known Non-CNS 
Extramedullary Disease at Baseline).....................................................................................56
6.5.
Pharmacokinetic Assessments.................................................................................................................57
6.6.
Pharmacodynamic Assessments..............................................................................................................57
7.
STUDY PROCEDURES......................................................................................................................................59
7.1.
Subject Informed Consent .......................................................................................................................59
7.2.
Subject ID Assignment............................................................................................................................59
7.3.
Screening Period......................................................................................................................................59
7.3.1.
Antiproliferative Treatment Administered During the Screening Period .............................61
7.4.
Rescreening .............................................................................................................................................61
7.5.
Enrollment ...............................................................................................................................................62
7.6.
Pretreatment Period .................................................................................................................................62
7.6.1.
Leukapheresis/Enrollment.....................................................................................................62
7.6.3.
Lymphodepleting Chemotherapy ..........................................................................................65
CCI
CCI
CCI
-
-


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7.7.
Treatment Period .....................................................................................................................................68
7.7.1.
Requirements for KITE-222 Infusion ...................................................................................69
7.7.2.
KITE-222 Premedications (Day 0)........................................................................................70
7.7.3.
KITE-222 Infusion (Day 0) and After (Days 1 to 13, Day 14 [Week 2], 
Days 15 to 27, and Day 28 [Week 4])...................................................................................70
7.7.4.
Monitoring After KITE-222 Infusion....................................................................................71
7.7.5.
Requirements for Workup for Potential Infectious and/or Inflammatory 
States .....................................................................................................................................72
7.8.
Post-treatment Follow-up Period.............................................................................................................73
7.8.1.
Post-treatment Follow-up Assessment Visits........................................................................73
7.8.2.
Evaluation Visit at the Time of Disease Progression or Relapse ..........................................75
7.9.
Follow-up Period (After Month 3 Post-treatment Until Transition to LTFU Study)..............................76
7.9.1.
Follow-up Assessments and Procedures for Enrolled Subjects Who 
Received KITE-222...............................................................................................................77
7.9.2.
Follow-up Procedures for Enrolled Subjects Whose Disease Progressed 
After KITE-222 Treatment....................................................................................................78
7.9.3.
Procedures for Enrolled Subjects Who Were Not Treated With KITE-222 .........................78
7.10.
Retreatment..............................................................................................................................................79
7.11.
Poststudy Care.........................................................................................................................................79
7.12.
Subsequent Anticancer Therapy..............................................................................................................79
7.13.
Instructions for Follow-up and Data to Be Collected for Subjects Withdrawn From Study ..................79
7.14.
Sample Storage........................................................................................................................................80
8.
ADVERSE EVENTS AND TOXICITY MANAGEMENT................................................................................81
8.1.
Definitions of AEs and SAEs..................................................................................................................81
8.1.1.
AEs ........................................................................................................................................81
8.1.2.
DLTs......................................................................................................................................81
8.1.3.
SAEs......................................................................................................................................83
8.1.4.
Targeted AEs and SAEs ........................................................................................................84
8.2.
Clinical Laboratory and Vital Sign Abnormalities..................................................................................84
8.2.1.
Abnormal Clinical Laboratory Findings ...............................................................................84
8.2.2.
Abnormal Vital Sign Values .................................................................................................84
8.3.
Assessments of AE and SAE Severity and Causality .............................................................................85
8.3.1.
Assessment of AE/SAE Severity...........................................................................................85
8.3.2.
Assessment of AE/SAE Relationship to IP and Study Procedures .......................................85
8.4.
Hospitalization and Prolonged Hospitalization.......................................................................................86
8.5.
Investigator Requirements and Instructions for Reporting AEs, SAEs, and Deaths to the 
Sponsor....................................................................................................................................................86
8.5.1.
Reporting AEs and SAEs ......................................................................................................86
8.5.2.
Reporting Deaths...................................................................................................................89
8.5.3.
Reporting AEs, SAEs, and Deaths Associated With Disease Progression 
or Relapse..............................................................................................................................90
8.6.
Sponsor Reporting Requirements (Includes Reporting of SAEs and Deaths) ........................................90
8.7.
Toxicity Management..............................................................................................................................91
8.8.
Special Situations Reports.......................................................................................................................91
8.8.1.
Definitions of Special Situations...........................................................................................91
8.8.2.
Instructions for Reporting Special Situations........................................................................92
8.9.
Safety Review Team................................................................................................................................93
8.10.
Criteria to Pause or Stop Enrollment.......................................................................................................94
9.
STATISTICAL CONSIDERATIONS.................................................................................................................95
9.1.
Statistical Analysis Plan ..........................................................................................................................95
9.2.
Hypothesis ...............................................................................................................................................95
9.3.
Determination of Sample Size.................................................................................................................95
9.4.
Access to Individual Subject Treatment Assignments and Minimization of Bias ..................................95


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9.5.
Planned Analysis .....................................................................................................................................95
9.5.1.
Interim Analysis and Early Stopping Guidelines ..................................................................95
9.6.
Primary Analysis .....................................................................................................................................96
9.6.1.
Final Analysis........................................................................................................................96
9.6.2.
Long-term Data Analysis ......................................................................................................96
9.7.
Analysis Conventions..............................................................................................................................96
9.7.1.
Analysis Sets .........................................................................................................................96
9.8.
Demographic Data and Baseline Characteristics ....................................................................................97
9.9.
Efficacy Analysis.....................................................................................................................................97
9.9.1.
Composite Complete Remission Rate...................................................................................97
9.9.2.
Overall Remission Rate.........................................................................................................97
9.9.3.
Relapse-free Survival ............................................................................................................97
9.9.4.
Allo-SCT Rate.......................................................................................................................98
9.9.5.
Event-free Survival................................................................................................................98
9.9.6.
Overall Survival.....................................................................................................................98
9.9.7.
30- and 60-day All-cause Mortality ......................................................................................99
9.9.8.
MRD− Response Rate............................................................................................................99
9.10.
Safety Analysis........................................................................................................................................99
9.11.
Pharmacokinetics Analysis......................................................................................................................99
9.12.
Pharmacodynamics Analysis.................................................................................................................100
10.
RESPONSIBILITIES.........................................................................................................................................101
10.1.
Investigator Responsibilities .................................................................................................................101
10.1.1.
Financial Disclosure ............................................................................................................101
10.1.2.
IRB/IEC Approvals .............................................................................................................101
10.1.3.
Informed Consent ................................................................................................................101
10.1.4.
Confidentiality.....................................................................................................................102
10.1.5.
Study Files and Retention of Records .................................................................................103
10.1.6.
Electronic Case Report Forms.............................................................................................104
10.1.7.
Access to Study Information ...............................................................................................105
10.1.8.
Protocol Compliance ...........................................................................................................105
10.2.
Sponsor Responsibilities .......................................................................................................................105
10.2.1.
Protocol Modifications ........................................................................................................105
10.2.2.
Study Report and Publications ............................................................................................105
10.2.3.
Financing and Insurance......................................................................................................106
10.3.
Joint Investigator/Sponsor Responsibilities ..........................................................................................106
10.3.1.
Good Clinical Practice.........................................................................................................106
10.3.2.
Ethics ...................................................................................................................................106
10.3.3.
Quality Control and Quality Assurance ..............................................................................107
10.3.4.
Study Discontinuation .........................................................................................................107
11.
REFERENCES...................................................................................................................................................108
12.
APPENDICES....................................................................................................................................................118
12.1.
Sponsor and Investigator Signature Page..............................................................................................119
12.2.
Schedule of Assessments.......................................................................................................................120
12.3.
Childbearing Potential and Birth Control..............................................................................................131
12.3.1.
Definition of Childbearing Potential ...................................................................................131
12.3.2.
Birth Control Methods That May Be Considered as Highly Effective ...............................131
12.3.3.
Unacceptable Birth Control Methods..................................................................................132
12.4.
Country-specific Requirements.............................................................................................................133
12.5.
Response Criteria in AML (Based on European Leukemia Net 2017 Classification)..........................135
12.6.
Immune Effector Cell-associated Encephalopathy Score......................................................................137
12.7.
Pandemic Risk Assessment and Mitigation Plan ..................................................................................138


KITE-222
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LIST OF IN-TEXT TABLES
Table 1.
Approved Regimens for the Treatment of Adults With R/R AML.........................................21
Table 2.
Clinical Trials Evaluating Anti-CLL-1 CAR T-cell Therapies in AML.................................25
Table 3.
Dose Cohorts ...........................................................................................................................35
Table 4.
Clinical Laboratory Tests for Safety Assessments..................................................................49
Table 5.
Reporting Requirements for Concomitant Medications..........................................................52
Table 6.
Allowed Bridging Therapy Agents..........................................................................................64
Table 7.
Reporting Requirements for AEs ............................................................................................87
Table 8.
Reporting Requirements for SAEs ..........................................................................................88
Table 9.
Exact 95% Confidence Intervals Corresponding to Composite Complete Remission 
Rate..........................................................................................................................................95
Table 10.
Schedule of Assessments – Treatment Period and Post-treatment Follow-up Period...........121
Table 11.
Schedule of Assessments – Follow-up Period Without Allo-SCTA......................................127
Table 12.
Schedule of Assessments – Follow-up Period After Allo-SCTA...........................................128
Table 13.
Response Criteria in AML (Based on ELN 2017 Classification)..........................................135
Table 14.
Immune-effector Cell-associated Encephalopathy Score......................................................137
LIST OF IN-TEXT FIGURES
Figure 1.
Study Schema ..........................................................................................................................15


KITE-222
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PROTOCOL SYNOPSIS
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
Study Title:
A Phase 1 Open-label, Multicenter Study Evaluating the 
Safety of KITE-222, an Autologous Anti-CLL-1 CAR 
T-cell Therapy, in Subjects With Relapsed/Refractory 
Acute Myeloid Leukemia
Indication:
Relapsed/refractory (r/r) acute myeloid leukemia (AML)
Investigational Product:
KITE-222
IND Number:
EudraCT Number:
Clinical Trials.gov Identifier:
27115
2020-000962-40
NCT04789408
Number of Study Sites 
Planned:
Approximately 15 study sites in the United States and 
European Union
Objective:
Evaluate the feasibility, safety, maximum tolerated dose 
(MTD), and optimal dose of KITE-222 in the treatment of 
subjects with r/r AML
Endpoints:
Primary

Incidence of dose-limiting toxicities (DLTs) in 
subjects treated with KITE-222
Secondary

Incidence of adverse events (AEs)

Clinically significant changes in laboratory parameters

Time to neutrophil recovery

Time to platelet recovery

Composite complete remission (CCR) rate, defined as 
the proportion of subjects who achieve a complete 
remission (CR) plus the proportion of subjects who 
achieve a CR without measurable residual disease 
(CRMRD−) plus the proportion of subjects who 
achieve a CR with incomplete hematologic recovery 
(CRi) per the European Leukemia Net (ELN) 2017 
Classification {Dohner 2017}, as determined by the 
study investigators


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
Overall remission (OR) rate (CR + CRMRD− + CRi + 
morphologic leukemia-free state [MLFS] + partial 
remission [PR]) per the ELN 2017 Classification 
{Dohner 2017}, as determined by the study 
investigators.

Relapse-free survival (RFS)

Allogenic stem-cell transplant (allo-SCT) rate

Event-free survival (EFS)

Overall survival (OS)

30- and 60-day all-cause mortality

Pharmacokinetics: peak and area-under-the-curve 
(AUC) of KITE-222 chimeric antigen receptor (CAR) 
T cells in subjects with r/r AML treated with 
KITE-222

Pharmacodynamics: peak and AUC of selected 
biomarkers in subjects with r/r AML treated with 
KITE-222

Analysis of antibodies against the KITE-222 CAR
Study Design:
Number of Subjects Anticipated 
to Be Enrolled; Number of 
Subjects Anticipated to Be 
Enrolled and Treated:
Study KT-US-486-0201 is a Phase 1, open-label, 
multicenter study evaluating the feasibility, 
safety, and tolerability of KITE-222, an autologous CAR 
T-cell therapy targeting C-type lectin-like molecule-1 
(CLL-1), in subjects with r/r AML.
Initially, the study will enroll subjects to dose-escalation 
cohorts; approximately 18 subjects with r/r AML will be 
treated in a 3 + 3 study design to determine the MTD of 
KITE-222. For more details on the 3 + 3 study design and 
study conduct, please refer to Section 3.2 Study Design.
After the dose-escalation stage, the study will expand to 
open an expansion cohort and enroll and treat 
approximately 22 subjects at the MTD of KITE-222 
determined by the safety review team (SRT). The 
expansion cohort will refine the understanding of the 
safety, tolerability, and preliminary efficacy of KITE-222. 
There will be an additional SRT review after 
approximately the first 6 subjects are treated and followed 
for 28 days in the expansion cohort.
To be eligible for the study, subjects are required to be fit 
for allo-SCT and have an identified stem-cell donor prior 


KITE-222 
Protocol KT-US-486-0201 
CONFIDENTIAL 
Kite Pha1ma, Inc. 
Amendment 4.0 
to enrollment. Enrollment occurs at the commencement of 
leukapheresis for the manufacturing ofKITE-222. 
During the KITE-222 manufacturing window, subjects 
deemed by investigators to require bridging therapy may 
be treated with 
Upon successful manufacturing, subjects will receive non-
myeloablative lymphodepleting chemotherapy with 
cyclophosphamide and fludarabine from 
-
KITE-222 will be administered on Day 0. 
Subjects must be hospitalized from infusion (Day 0) until 
Day 14 at a minimum. From Day 14, subjects may be 
evaluated for discharge and considered for outpatient 
follow-up if toxicities have returned to Grade 1, have 
resolved, returned to baseline, or are deemed clinically 
insignificant by the investigator ( eg, renal insufficiency 
that is improving). Assessments detailed in the schedule 
of assessments (SOA) (Table 10, Table 11, and Table 12) 
can be obtained on an outpatient basis, including complete 
blood count (CBC), if KITE-222-related Grade 4 
neutropenia persists. 
Conditioning chemotherapy for allo-SCT may be initiated 
only after completion of the Day 28 disease response 
assessment at the discretion of the investigator and after 
consultation with the medical monitor. Allo-SCT may be 
used to rescue persistent KITE-222-related Grade 4 
neutropenia or thrombocytopenia (see DLT Section 8.1.2) 
or to consolidate response in subjects treated with 
KITE-222. 
For study requirements, refer to the SOA. 
Overall: Up to approximately 40 subjects will be treated 
in the study, of whom up to approximately 18 subjects 
will be treated in the dose-escalation coho1is and 
22 subjects in the expansion cohort. 
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KITE-222 
Protocol KT-US-486-0201 
Target Population: 
Duration of Treatment and 
Study Paiiicipation: 
Diagnosis and Main 
Eligibility Criteria: 
Study Procedures/ Frequency: 
CONFIDENTIAL 
Kite Pha1ma, Inc. 
Amendment 4.0 
Adults (:::: 18 years of age) with r/r de novo or seconda1y 
AML as defined by the ELN 2017 Classification {Dohner 
2017}, excluding acute promyelocytic leukemia. 
Subjects will receive 1 infusion of KITE-222. 
The duration of the study for individual subjects will vaiy 
depending on a subject's response to treatment, survival, 
and timing of the transition to a separate Kite Long-tenn 
Follow-up (L TFlJ) study. 
For a subject who completes paiticipation in this study 
and also completes the L TFU period in the sepai·ate L TFU 
study, the entire duration of a subject's paiiicipation in 
both studies will be up to approximately 15 yeai·s from the 
time of the initial infusion of KITE-222. 
The need for prolonged follow-up is based on the 
mitigate the potential risks o delayed onset AEs. 
Please refer to protocol Section 4.2 Eligibility Criteria for 
complete eligibility criteria. Subjects must have r/r AML 
with m01phological disease in the BM and/or peripheral 
blood prior to emollment (ie, commencement of 
leukapheresis for the manufacture of KITE-222). Subjects 
are required to be fit for allo-SCT and have an identified 
stem-cell donor prior to emollment. 
Emollment occurs upon leukapheresis of the subject's 
peripheral blood mononuclear cells (PBMCs) for the 
manufacturing ofKITE-222. 
During the KITE-222 manufacturing window, subjects 
deemed by investigators to require bridging therapy may 
be treated wit 
Upon successful manufacture of KITE-222, subjects will 
receive 1 
hode letin chemothera 
with 
c 
and fludai·abine 
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KITE-222 
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Amendment 4.0 
KITE-222 will be administered IV as a single infusion of 
CAR-trnnsduced autologous T cells at the assigned dose 
on Day 0. 
At the discretion of the investigator and after consultation 
with the medical monitor, subjects may proceed to 
conditioning chemotherapy for allo-SCT to rescue 
persistent Grade 4 neutrnpenia or thrombocytopenia 
toxicity (see DLT Section 8.1.2) and/or to consolidate 
response after the Week 4 disease response assessments 
are completed. 
At specific time points as outlined in the SOA, subjects 
will undergo the following assessments/procedures: 
collection of infonned consent, general medical histo1y 
including previous treatments for AML, physical 
examination including vital signs and perfonnance status, 
neurologic assessments, blood draws for CBC, cheinistiy 
panels, coagulation, cytokines, C-reactive protein, levels 
of KITE-222/phaimacokinetics, lymphocyte subsets, 
CLL-1 expression 
ana ys1s, an nnmunogemc1ty, me u mg monitoring 
antibodies against the KITE-222 CAR. Females of 
childbearing potential will undergo a urine or sernm 
pregnancy test. 
Subjects will also undergo a baseline electi·ocai·diogram 
(ECG), echocai·diogram (ECHO), brain computed 
tomography (CT) scan or magnetic resonance imaging 
(MRI) in cases with a prior histo1y of cenu-al nervous 
system [CNS] involvement by AML or clinical symptoms 
suggestive of neurological involvement, chest x-ray or CT 
or MRI scan, and BM aspirate and biopsy prior to 
emollment and associated leukapheresis. 
Subjects with a histo1y of CNS malignancy, 
leptomeningeal carcinomatosis, or symptoms of CNS 
malignancy will have lumbar punctures perfo1med for the 
collection of cerebrospinal fluid at screening and after 
KITE-222 infusion if they experience clinically 
significant Grade 2 or higher immune-effector cell-
associated neurotoxicity. 
Routinely throughout the conduct of the study, subjects 
will be asked to repo1i concoinitant medications and AEs 
and will have their disease assessed. 
Page 11 
17 Janua1y 2023 


KITE-222 
Protocol KT-US-486-0201 
Investigational Product and 
Study Treatments; 
Dose and Mode of 
Administration: 
Safety Review Team 
CONFIDENTIAL 
Kite Pha1ma, Inc. 
Amendment 4.0 
KITE-222 is an autologous CLL-1-targeted CART-cell 
therapy. The KITE-222 treatment regimen includes 
lymphodepleting chemotherapy followed by IV 
administration of KITE-222. 
Lymphodepleting chemotherapy consists of the following: 
KITE-222 will be administered on Day Oas a single IV 
infusion at one of the following assigned dose levels: 
Dose Cohort 
Dose-escalation 
Cohort 1 
Dose-escalation 
Cohort 2 
Dose-escalation 
Cohort 3 
Expansion Coho1t 
Number ofKITE-222 CART Cells•,b 
Subject Weight 
< SO kg 
Subject. Weight 
2'. 50 kg 
The optimal dose for the expansion 
coho1t will be detennined by the SRT 
after completion of the dose-escalation 
pa1t 
Abbreviations: CAR, chimeric antigen receptor; SRT, safety review 
team. 
a 
All doses are acceptable within 20% of the assigned dose. 
b 
A subject may receive the highest dose manufactured if less than 
the targeted dose after discussion with the Kite medical monitor. 
Out-of-specification product may be administered in line with the 
local regulation both during dose escalation and expansion phase. 
Additional doses beyond the cmTent schema may be 
explored at the discretion of the SRT as necessaiy for 
subject safety and to achieve a therapeutic window. 
The SRT, consisting of study sponsor representatives and 
including at least 1 active study investigator, will review 
safety data. and make recommendations on fiut her study 
conduct dming the study. 
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17 Janua1y 2023 


KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
CONFIDENTIAL
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The SRT will convene with a pause in treatment to 
confirm each dose escalation or de-escalation according to 
the 3 + 3 study design. The SRT will review safety data 
once the last treated subject of the 3 subject group has had 
the opportunity to be followed for 28 days and evaluated 
for the incidence of DLTs.
During the expansion cohort, the SRT will convene to 
review AEs and serious AEs after approximately the first 
6 subjects have had the opportunity to be followed for 
28 days after administration of the optimal dose of 
KITE-222. Additional SRT meetings will occur as 
necessary through the course of the study to address 
safety concerns or other matters affecting study conduct.
Criteria for Evaluation:
Subjects will undergo assessments listed below according 
to the schedule presented in the SOA (Section 12.2).
Safety:
Safety assessments will include collection of AEs, clinical 
laboratory tests, physical examination, weight, vital signs, 
neurologic examinations, Eastern Cooperative Oncology 
Group (ECOG) performance status, cardiac function, 
brain MRI or CT (if MRI is not feasible), lumbar 
puncture, collection of concomitant medications, and 
assessment of the presence of anti-KITE-222 antibodies 
Efficacy:
Efficacy will be assessed in all subjects as a secondary 
endpoint. Disease response assessment will be performed 
as per ELN 2017 Classification (Section 12.5) {Dohner 
2017}.
Pharmacokinetics/
Pharmacodynamics:
Pharmacokinetics and pharmacodynamics of KITE-222 
will be assessed through samples sent to the central 
laboratory as per SOA. KITE-222 pharmacokinetics and 
pharmacodynamics will be reported as secondary 
endpoints.
Statistical Methods:
No formal hypothesis will be tested in this study. The 
study is designed to evaluate the feasibility, safety, and 
tolerability of KITE-222, an autologous CLL-1 targeted 
CAR T-cell therapy, in subjects with r/r AML.
Demographic and baseline measurements as well as key 
safety and efficacy data will be summarized using 
standard descriptive methods.
CCI-


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Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
CONFIDENTIAL
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The primary analysis of the primary endpoint will be 
conducted when the last treated subject in the dose 
expansion cohort has had the opportunity to be evaluated 
for response 3 months after KITE-222 infusion or 
1 month after allo-SCT, whichever occurs first.
This study will be conducted in compliance with this protocol, 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.


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
Figure 1. 
Study Schema 
Enrollment 
/Leu kap heresis 
Lymphodepleting 
Chemotherapy 
Day-S 
DayO 
Ma n ufa ctu ri ng 
I 
Safety monitoring, 
correlatives and tumor 
assessments 
Day 7 
Dayl4 
Inpatient Hos pita I ization Period 
Conditioning 
and Allogeneic 
SCT 
Days 28-42 
) 
Subjects must be hospitalized from infusion (Day 0) until Day 14 at a minimum. From Day 14, subjects may be evaluated for 
discharge and considered for outpatient follow-up if toxicities have returned to Grade 1, have resolved, returned to baseline, or 
are deemed clinically insignificant by the investigator (eg, renal insufficiency that is improving). Assessments detailed in the 
SOA (Table 10, Table 11, and Table 12) can be obtained on an outpatient basis. including complete blood count (CBC), if 
KITE-222-related Grade 4 neutropenia persists. 
Lymphodepleting chemotherapy: cyclophos hamid 
udarabine 
Bridging thera 
as s ecified er rotocol i 
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Protocol KT-US-486-0201
Amendment 4.0
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LIST OF ABBREVIATIONS
AE
adverse event
ALC
absolute lymphocyte count
ALL
acute lymphoblastic leukemia 
Allo-SCT
allogeneic stem-cell transplant(ation)
AML
acute myeloid leukemia
ASTCT
American Society for Transplantation and Cellular Therapy
AUC
area-under-the-curve
Auto-SCT
autologous stem-cell transplant(ation)
BCL
B-cell lymphoma
BCMA
B-cell maturation antigen
β-hCG
beta-human chorionic gonadotropin
BM
bone marrow
CAR
chimeric antigen receptor 
CBC
complete blood count
CCR
composite complete remission
CFR
Code of Federal Regulations
CI
confidence interval
CIBMTR
Center for International Blood and Marrow Transplant Research
CLL-1
C-type lectin-like molecule-1
CNS
central nervous system
CPF
cell processing facility
CR
complete remission
CRi
complete remission with incomplete hematologic recovery
CRMRD−
complete remission without measurable residual disease
CRO
contract research organization
CRP
C-reactive protein
CRS
cytokine release syndrome
CSF
cerebrospinal fluid
CT 
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
CTFG
Clinical Trial Facilitation Group
DLBCL
diffuse large B-cell lymphoma 
DLI
donor lymphocyte infusions
DLT
dose-limiting toxicity
DVT
deep vein thrombosis
eACT
Engineered Autologous T-cell Therapy™
ECG
electrocardiogram
ECHO
echocardiogram
ECOG
Eastern Cooperative Oncology Group


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Protocol KT-US-486-0201
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eCRF
electronic case report form
EDC
electronic data capture
EFS
event-free survival
ELN
European Leukemia Net
eSAE
electronic serious adverse event
EU
European Union
FAS
full analysis set
FDA
Food and Drug Administration
FFPE
formalin-fixed paraffin-embedded
FLAG-Ida
fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor
FLT
fms-like tyrosine kinase
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
GM-CSF
granulocyte-macrophage colony-stimulating factor
GVHD
graft-versus-host disease
HCP
health care provider 
HEENT
head, eyes, ears, nose, and throat
HIV
human immunodeficiency virus
HLH
hemophagocytic lymphohistiocytosis
HMA
hypomethylating agent
HSC
hematopoietic stem cell 
IB
Investigator’s Brochure
ICANS
immune-effector cell-associated neurotoxicity syndrome
ICE
immune-effector cell-associated encephalopathy
ICF
informed consent form
ICH
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use
ID
identification
IDH
isocitrate dehydrogenase
IEC
Independent Ethics Committee
IFN-γ
interferon gamma 
IL
interleukin
IND
investigational new drug
IP
investigational product
IPM
Investigational Product Manual
IRB
Institutional Review Board
ITD
internal tandem duplication
IUD
intrauterine device
IV
intravenous(ly)
KM
Kaplan-Meier 
LDAC
low-dose cytarabine


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Protocol KT-US-486-0201
Amendment 4.0
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LDH
lactate dehydrogenase
MCP-1
monocyte chemotactic protein-1
MedDRA
Medical Dictionary for Regulatory Activities
MFC
multiparametric flow cytometry
mITT
modified intent-to-treat
MLFS
morphologic leukemia-free state 
MRD
measurable or minimal residual disease
MRI
magnetic resonance imaging
MTD
maximum tolerated dose
NCCN
National Comprehensive Cancer Network
NCI
National Cancer Institute
NPM
nucleophosmin
OR
overall remission
OS
overall survival
PBMC
peripheral blood mononuclear cell
PCR
polymerase chain reaction
PO
orally
PR
partial remission
PT
preferred term
qPCR
quantitative polymerase chain reaction
QTc
corrected QT interval
r/r
relapsed or refractory
RFS
relapse-free survival
SAE
serious adverse event
SAP
statistical analysis plan 
SCT
stem-cell transplantation
SD
stable disease
SOA
schedule of assessments
SOC
system organ class 
SRT
safety review team
SUSAR
suspected unexpected serious adverse reaction
TEAE
treatment-emergent adverse event
TLS
tumor lysis syndrome
TNF
tumor necrosis factor
US
United States
WBC
white blood cell
CCI-


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Protocol KT-US-486-0201
Amendment 4.0
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1.
INTRODUCTION
1.1.
Disease Background
1.1.1.
Acute Myeloid Leukemia
Acute myeloid leukemia (AML), also known as acute myelocytic leukemia or acute 
myelogenous leukemia, is a heterogeneous hematologic malignancy that originates in myeloid 
precursors in the bone marrow (BM). Myeloid cells develop into subsets of leukocytes 
(granulocytes or monocytes, but not lymphocytes), erythrocytes, and thrombocytes. In AML, 
a patient’s BM makes abnormal myeloblasts (blasts) that fail to differentiate. The accumulation 
of blasts and concomitant decrease in functional granulocytes, monocytes, erythrocytes, and 
thrombocytes leads to severe infections, anemia, and hemorrhage.
AML is the most common form of acute leukemia in adults, accounting for about a third of all 
leukemia diagnoses {National Cancer Institute (NIH) 2019, Sant 2014} and also represents the 
largest number of annual leukemia deaths in the United States (US) and Europe {National 
Cancer Institute (NIH) 2020, Sant 2014}. The National Cancer Institute (NCI) Surveillance, 
Epidemiology, and End Results (SEER) program estimates the occurrence of approximately 
19,940 new diagnoses and 11,180 deaths from AML in 2020 in the US {National Cancer 
Institute (NIH) 2020}. The incidence, 4.3 per 100,000, is roughly equal across races and is 
substantially higher in men than women {Howlader 2020}. AML is generally a disease of older 
adults with a median age at diagnosis of 68 years; approximately 75% of patients are aged 
≥ 55 years {Howlader 2019a, Howlader 2019b}. The 5-year overall survival (OS) rate for adults 
is 24% (67% for patients ≤ 19 years) in the most recently available analyses (2008 to 2014) in 
the US {American Cancer Society 2019}.
AML is a complex disease characterized by numerous somatically acquired mutations {Khwaja 
2016}. For example, the Cancer Genome Atlas AML sub-study identified 23 genes that were 
commonly mutated (ie, recurrent mutations) {The Cancer Genome Atlas Research Network 
2013}. The European Leukemia Net (ELN) recommendations for diagnosis and management of 
AML in adults classify AML into 3 major categories: AML with recurrent genetic abnormalities; 
AML with myelodysplasia-related changes; and AML, not otherwise specified {Dohner 2017}. 
The ELN category of AML with recurrent genetic abnormalities includes 11 categories, each 
with a defining genetic alteration. BM analysis with cytogenetics and/or fluorescent in-situ 
hybridization and molecular mutation analysis are typically performed to assess the risk and 
treatment options {O'Donnell 2017}.
Additional prognostic factors conferring an increased risk for poor outcome in AML include 
cigarette smoking and exposure to ionizing radiation {American Cancer Society 2019}. A large 
proportion of AML is secondary, arising from either chemotherapy (5% to 20%) or 
transformation of myelodysplastic syndromes and/or myeloproliferative neoplasms 
(10% to 20%) {Cheung 2019, O'Donnell 2017}. Patients diagnosed with secondary AML, 
regardless of the causative event, tend to exhibit worse clinical outcomes.


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Protocol KT-US-486-0201
Amendment 4.0
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1.1.2.
Current Treatment for Patients With AML and Unmet Need
Standard-of-care treatment for AML has evolved over the last decade with the advent of several 
targeted agents for specific AML subtypes and consideration of patient fitness for therapy over 
cutoffs by age. Broadly, subjects receive induction therapy to achieve remission, followed by 
consolidation therapy to deepen response {Dohner 2017}.
For eligible subjects, the backbone of therapy continues to comprise intensive chemotherapy to 
induce remission. Induction regimens have historically included a “7 + 3” regimen of cytarabine 
for 7 days plus an anthracycline (daunorubicin or idarubicin) or anthracenedione (mitoxantrone) 
for 3 days. Response rates to intensive induction chemotherapy are high, with 60% to 80% of 
younger adults and approximately 40% to 60% of older adults (> 60 years) achieving complete 
remission (CR) {Dohner 2017}. In recent years, some subjects with appropriate AML genetics 
may receive a tyrosine kinase inhibitor or anti-CD33 antibody-drug conjugate as part of their 
7 + 3-based induction regimen. Achievement of remission is followed by consolidative 
chemotherapy, (typically 2 to 4 cycles of standard to high-dose cytarabine) to eliminate residual 
cancerous blasts {O'Donnell 2017}. A subset of patients with intermediate- to adverse-risk 
genetic abnormalities of AML in first or second CR may complete consolidation with allogeneic 
stem-cell transplantation (allo-SCT), or more infrequently, autologous stem-cell transplantation 
(auto-SCT) {Cerrano 2019, National Comprehensive Cancer Network (NCCN) 2018, O'Donnell 
2017}. Approximately 3500 patients with AML annually receive an allo-SCT in US and almost 
8000 in Europe according to the Center for International Blood and Marrow Transplant Research 
(CIBMTR) and European Society for Blood and Marrow Transplantation (EBMT) respectively. 
AML is the most frequent indication for allo-SCT and the number of patients receiving an 
allo-SCT has doubled in the last decade {Passweg 2020}.
Notably, patients considered ineligible for standard intensive induction chemotherapy regimens 
(based on performance status, comorbidities, cytogenetic/molecular abnormalities) have poorer 
outcomes and constitute the majority of patients with AML {Klepin 2014, O'Donnell 2017}. 
Treatment alternatives for this group of patients include best supportive care, low-intensity 
treatment, or clinical trials with investigational drugs. Low-intensity options include either 
low-dose cytarabine (LDAC) or therapy with a hypomethylating agent (HMA). LDAC is 
generally well tolerated with CR achieved in approximately 15% to 25% of subjects, but the OS 
is short at a median of 5 to 6 months. HMA regimens such as azacitidine have demonstrated an 
increased median OS of 10.4 months versus LDAC, best supportive care, and 7 + 3-based 
regimens, which showed a median OS of 6.5 months {Dombret 2015}. Recent Food and Drug 
Administration (FDA) approvals for treatment of elderly patients or who have comorbidities 
precluded from intensive induction chemotherapy include venetoclax in combination with HMAs 
(azacitidine or decitabine) or LDAC, and glasdegib in combination with LDAC {Huang 2019}. 
However, these newer regimens have not overcome the low CR rates or shortened median 
survival seen in patients unfit for intensive induction.
Despite the high response rates to induction therapy for fit subjects, relapsed disease is common 
even in this subset of patients {Dohner 2017, Hofmann 2019}. Moreover, approximately 25% of 
patients are refractory to intensive induction therapy {Othus 2015}. Patients with 
relapsed/refractory (r/r) AML have a short median OS of 3 to 9 months {Huang 2019, Sarkozy 


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Protocol KT-US-486-0201
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2013, Short 2018, Stahl 2018}, and currently, no standard-of care-regimen exists for these 
patients (Table 1). Salvage therapies can include intermediate-dose cytarabine with or without 
anthracycline; fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor 
(FLAG-Ida); mitoxantrone, etoposide, and cytarabine. The aim of the treatment for fit subjects 
with r/r AML is to induce a complete response and consolidate with an allo-SCT {Dohner 2017, 
Jabbour 2014}. Several novel agents for the treatment of adult patients with r/r AML and 
targetable mutations have been approved by the FDA in the past few years, including enasidenib, 
ivosidenib, gemtuzumab ozogamicin, quizartinib, and gilteritinib {Cortes 2019, DiNardo 2018, 
Perl 2019, Stein 2019, Taksin 2007}. Despite the addition of these newly approved agents, 
clinical trial participation is still the first recommended option in r/r AML {Heuser 2020}, 
wherein additional novel therapies, including targeted immunotherapies, enzymatic inhibitors, 
and combination therapies, are currently being evaluated. However, much work is yet to be done 
for these to be translated into a substantial benefit for patients, as evidenced by the current 24% 
5-year survival rate for adults with AML {American Cancer Society 2019}.
Table 1.
Approved Regimens for the Treatment of Adults With R/R AML
Agent/
Reference
Description
Subjects
N
Median 
Age 
(Years)
CR/ 
CRi
(%)
Subsequent 
Allo-SCT 
(%)
Median 
OS
(Months)
Chemotherapy Regimens
Clofarabine+ 
cytarabine
1 gm/m2 
{Faderl 2012}
Deoxyadenosine 
analog
r/r AML with 
≤ 2 prior induction 
regimens
320
67
35/12
21
6.6
HDAC 
1.5 gm/m2
{Giles 2009}
Pyrimidine 
nucleoside 
r/r AML in 1st 
relapse after prior 
CR/CRi 
86
60
16/2
15
5.8
Investigator’s 
choice of 
7 cytarabine-
containing 
regimens (MEC, 
FLAG-Ida, etc)
{Roboz 2014}
Pyrimidine 
nucleoside
r/r AML after 2 or 
3 prior induction 
regimens
190
60
12/9
11
3.3
CLAG-M 
{Wierzbowska 
2008}
Purine analog, 
pyrimidine 
analog, and 
G-CSF 
r/r AML
114
45
58/7
30
of subjects 
with CR
9.0
Azacitidine or 
decitabine
{Stahl 2018}
Hypomethylating 
agents
r/r AML after ≥ 1 
course of intensive 
chemotherapy
655
65
11/5
5.6
6.7
{Cortes 2015}
Liposome-
encapsulated 
cytarabine and 
daunorubicin
First relapse after 
initial CR lasting 
≥ 1 month
81
52
30/10
46
8.5


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Agent/
Reference
Description
Subjects
N
Median 
Age 
(Years)
CR/ 
CRi
(%)
Subsequent 
Allo-SCT 
(%)
Median 
OS
(Months)
Targeted Agents
Quizartinib
{Cortes 2018}
FLT3 inhibitor
r/r AML with a 
FLT3-ITD 
activating 
mutation, after 
HSCT or one 
second-line salvage 
regimen
76
51 in 
cohort 2
4/40
35 in 
cohort 2
~5
Gilteritinib
{Perl 2019}
FLT3 inhibitor
r/r AML after ≥ 1 
induction
247
62
21/13
25
~6
Enasidenib
{Stein 2017}
Inhibitor of 
mutant IDH
r/r AML with an 
IDH2a mutation
176
67
20/9
10
9.3
Ivosidenib
{DiNardo 2018}
Inhibitor of 
mutant IDH
r/r AML with a 
susceptible IDH1a 
mutation
179
67
22/12
Not 
reported
8.8
Gemtuzumab 
ozogamicin
{Taksin 2007}
Anti-CD33 mAb 
conjugated with 
calicheamicin 
(an anthracycline)
r/r CD33+ AML
57
64
26/7
5
8.4
{DiNardo 2021}
BCL-2 inhibitor + 
FLAG-Ida
r/r AML
23
47
48/13
46
13
{Zappasodi 
2021}
BCL-2 inhibitor + 
Hypomethylating 
agent
r/r AML with an 
available SCT 
donor
10
52
40/10
70
9
Abbreviations: allo-SCT, allogeneic stem-cell transplantation; AML, acute myeloid leukemia; BCL, B-cell lymphoma; 
CD, cluster of differentiation; CLAG-M, cladribine, ara-C, G-CSF, and mitoxantrone; CR, complete remission; CRi, complete 
remission with incomplete hematologic recovery; FLAG-Ida, fludarabine, cytarabine, idarubicin, and G-CSF; FLT3, fms-like 
tyrosine kinase 3; G-CSF, granulocyte colony-stimulating factor; HDAC, high-dose cytarabine; HSCT, hematopoietic stem-cell 
transplantation; IDH, isocitrate dehydrogenase; ITD, internal tandem duplication; mAb, monoclonal antibody; MEC, 
mitoxantrone, etoposide, and cytarabine; OS, overall survival; r/r, relapsed/refractory; SCT, stem-cell transplantation 
a.
IDH1 and IDH2 are different isozymes of IDH. 
For patients relapsing after allo-SCT the prognosis is poor. An analysis of the CIBMTR showed 
that of 1788 AML patients relapsing after allografts, only 23% of patients were alive at 1 year 
after relapse {Bejanyan 2015}. The 3-year OS increased as time from stem-cell transplant (SCT) 
to relapse increased, with estimates of 4%, 12%, 26% and 38% for relapses within 1 to 6 months, 
6 months to 2 years, 2 to 3 years, and more than 3 years after allo-SCT, respectively {Dohner 
2017}. There are currently no drugs specifically approved for this patient population. There are 
no apparent differences in survival between patients who receive donor lymphocyte infusions 
(DLI) and those that receive a second allo-SCT, with a 2-year survival rate of approximately 
25% for both procedures. Non-relapse mortality is higher with the second allo-SCT than with 
DLI {Kharfan-Dabaja 2018}.
1.2.
KITE-222
Kite Pharma, Inc. (hereafter referred to as Kite) is developing KITE-222, an autologous chimeric 
antigen receptor (CAR) T-cell therapy, targeting C-type lectin-like molecule-1 (CLL-1)1. CLL-1 
1 CLL-1 is also known as C-type lectin domain family 12 member A, myeloid inhibitory C-type lectin-like receptor, 
and dendritic cell-associated lectin 2.


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Protocol KT-US-486-0201 
Amendment 4.0 
expression is restricted to the surface of myeloid cells in peripheral blood and BM and is 
upregulated in AML (refer to Section 1.4.2). 
. 
. 
. 
, 
expansion, production o cytokines, and targeted cytotoxicity. 
a lentiviral vector containing an anti-CLL-1 CAR gene. Trans uced Teel s are t en propagated 
in culture to generate sufficient engineered T cells for administration. 
1.3. 
Summary of Relevant Nonclinical Studies With KITE-222 
Nonclinical studies have demonstrated the in vitro and in vivo activity of KITE-222 against 
AML. Please refer to the cmTent Investigator's Brochure (IB) for a summaiy on nonclinical data 
for KITE-222. 
1.4. 
Study Rationale 
1.4.1. 
Rationale for Study 
As most advanced cancers eventually become refracto1y to conventional therapies, new treatment 
modalities are needed. Immunotherapy, which is based on enhancing an immune response 
against the tumor, is a promising approach to treating many cancer types. T cells play an 
impo1tant role in destroying diseased cells throughout the body. Engineered Autologous T-cell 
Therapy™ (eACTTM) is a process by which a patient's own T cells are collected and subsequently 
genetically altered to recognize and target antigens expressed on the cell surface of specific 
malignancies {Kochenderfer 2013}. The ability to genetically engineer human T cells and use 
them to mediate cancer regression in patients has been demonstrated in a number of studies and 
has opened possibilities for the treatment of patients with a wide variety of cancer types. 
Two recent CAR T-cell therapies developed by Kite Phaima, namely axicabtagene ciloleucel 
(axi-cel; YESCARTA ®) and brexucabtagene autoleucel (brexu-cel; TECARTUS®), which are 
directed against the B-cell specific cell smface mai·ker CD 19, have resulted in clinically 
meaningful response rates in vai·ious B-cell malignancies, including diffuse large B-cell 
lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL) and also B-cell 
acute lymphoblastic leukeinia (ALL) {Jacobson 2022, Locke 2019, Neelapu 2017, Shah 2021a, 
Wang 2020}. Two additional anti-CD19 CART cell therapies have also been approved-
tisagenlecleucel (KYMRIAH®) for DLBCL and ALL {Maude 2018, Schuster 2019, Schuster 
2021}, and lisocabtagene ciloleucel (BREY ANZI®) for DLBCL { Abramson 2020}. B-cell 
maturation antigen (BCMA) is a different antigen targeted by idecabtagene vicleucel 
(ABECMA ®) and has also been approved for the treatment of multiple myeloma {Munshi 
2021}. 
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KITE-222 is an autologous CAR T-cell therapy directed against CLL-1. Human CLL-1 is a 
275-amino acid, type II transmembrane glycoprotein expressed in hematopoietic lineage cells, 
particularly in myeloid cell {Bakker 2004, Jiang 2018}. CLL-1 inhibits granulocyte and 
monocyte activity during inflammation, and may play a role in regulating both innate and 
adaptive immunity {Chiffoleau 2018, Han 2004, Ma 2019, Marshall 2004, Redelinghuys 2011}. 
CLL-1 is a promising target antigen for CAR therapy in AML because CLL-1 expression is 
restricted to the surface of myeloid cells, limiting off tumor toxicities to the hematologic 
compartment {Bakker 2004, Bill 2018, Chen 2006, Jiang 2018, Marshall 2006, Morsink 2019, 
van Rhenen 2007a, van Rhenen 2007b, Wang 2018}. As an autologous anti-CLL-1 CAR T-cell 
product, KITE-222 offers a promising approach to expand the scope of effective eACT to 
patients with AML.
1.4.2.
Rationale for the Use of CLL-1 as a Target Antigen for AML
Human CLL-1 is a 275-amino acid, type II transmembrane glycoprotein expressed in 
hematopoietic lineage cells, particularly in myeloid cell {Bakker 2004, Jiang 2018}. CLL-1 
inhibits granulocyte and monocyte activity during inflammation, and it may play a role in 
regulating both innate and adaptive immunity {Chiffoleau 2018, Han 2004, Ma 2019, Marshall 
2004, Redelinghuys 2011}. CLL-1 is a promising target antigen for CAR therapy in AML, 
because CLL-1 expression is restricted to the surface of myeloid cells, limiting off-tumor 
toxicities to the hematologic compartment {Bakker 2004, Bill 2018, Chen 2006, Jiang 2018, 
Marshall 2006, Morsink 2019, van Rhenen 2007a, van Rhenen 2007b, Wang 2018}.
In previous studies, CLL-1 expression was found to be positive in 77% to 92% of patient 
samples by flow cytometry as defined by CLL-1 presence on > 20% of blasts; {Bakker 2004, 
Wang 2018}. Expression has been detected across AML French-American-British, 
morphological, and cytogenetic subtypes {Bakker 2004, Jiang 2018, Wang 2018, Zhao 2010}. 
Interestingly, CLL-1 is not only expressed in AML blasts, but also in hard-to-treat CD34+ 
leukemic stem cells from patients with AML {Jiang 2018, van Rhenen 2007b}. Of note, in vitro 
non-clinical studies of KITE-222 have demonstrated target-specific killing of AML tumor lines 
that have a significant proportion of blasts with undetectable CLL-1 by multiparametric flow 
cytometry (MFC), including KG-1; please refer to the current IB for additional information.
Importantly, surface CLL-1 may be a safer target than alternate surface antigens evaluated in 
AML. CLL-1 has minimal to no expression on CD34+ hematopoietic stem cells (HSCs); CD34+ 
hematopoietic progenitors, erythrocytes, megakaryocytes, platelets, NK cells, B cells, T cells, or 
dendritic cells. Furthermore, CLL-1 is not expressed by normal BM CD34+CD38- stem cells or 
by peripheral blood CD34+CD38- cells mobilized with growth factors {Bakker 2004, Bill 2018, 
Chen 2006, Jiang 2018, Marshall 2006, Morsink 2019, van Rhenen 2007a, van Rhenen 2007b, 
Wang 2018}. Additionally, CLL-1 expression is limited to the myeloid compartment, with no 
expression detected in other organ tissue. Taken together, CLL-1 directed CAR T cells have 
promise to eliminate leukemic blasts and stem cells, without harming important HSCs, 
lymphocytes, or other organ tissues.
There have been several clinical experiences of treating AML with experimental drugs targeting 
CLL-1, including antibody-drug conjugates, bispecific antibodies, and chimeric-antigenic-
receptors:


KITE-222
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
DCLL9718S was an antibody-drug conjugate developed by Roche that was discontinued 
{Daver 2021}. Eighteen safety evaluable patients were assigned to 5 escalating dose level 
cohorts. The most common Grade 3 or higher adverse events (AEs) were febrile neutropenia 
(33%) and pneumonia (28%). No dose-limiting toxicities (DLTs) were reported. Based on 
2 patients with Grade 3 hepatic events observed at the highest dose and lack of anti-leukemic 
activity, the dose escalation was stopped {Daver 2021}.

MCLA-117 was a bispecific antibody developed by Merus Pharmaceuticals. Fifty-eight 
patients were treated across 11 dose levels and received a median of 5 infusions in a Phase I 
trial. Grade 3 or 4 cytokine release syndrome (CRS) and febrile neutropenia were reported in 
8.6% and 5.2% of patients, respectively. No DLTs were observed. Further development was 
discontinued {Mascarenhas 2020}.

A few trials have explored different constructs of autologous anti-CLL-1 CAR T cells, 
mainly in pediatric AML patients, and in some cases with multiple targets (Table 2).
Table 2.
Clinical Trials Evaluating Anti-CLL-1 CAR T-cell Therapies in AML
Product / Sponsor / 
Trial
Construct
N / 
Median 
Age
Dose
Grade ≥ 3 AEs
Efficacy
Reference
4SCAR-CLL1 /
Guangzhou Women 
and Children’s 
Medical Center / 
NCT03222674
Different targets: 
CLL-1, Lewis-Y, 
CD33, CD38
CD28-CD27 
costimulatory 
domain
FKBP-caspase 9 
switch-off
4 
pediatric 
/ 8.4 
years
1-2 × 
106/kg
No Grade ≥ 3 
CRS or ICANS
Three patients 
had prolonged 
Grade 4 
neutropenia for 
4 to 6 weeks
3 out of 4 
patients 
achieved 
MRD 
negativity
{Zhang 2020, 
Zhang 
2021b}
ICG144 /
iCell Gene 
Therapeutics / 
NCT03795779
Biscistronic 
CLL1-CD28 and 
CD33-41BB
8 adults 
and 1 
pediatric 
/ 32 years
0.7-3.7 
× 
106/kg
CRS 2/9
ICANS 3/9
cytopenias 9/9
7 out of 9 
MRD 
negative 
at 4 
weeks
{Liu 2020}
BG1805 /
Guangzhou Biogene 
Therapeutics
ChiCTR1900027684 
Two CAR-Ts: 
CLL-1-4-1BB or 
CLL1-CD33-4-
1BB
11 
pediatric 
/ 12 years 
0.35-
1 × 
106/kg
No Grade ≥ 3 
CRS or ICANS
cytopenias 
11/11
6 out of 
11 MRD 
negative 
at 4 
weeks
{Zhang 
2021a, Zhang 
2022}
NCT04884984
PD-1 silenced 
CD28 OX40
2 adults / 
28 years
5-10 × 
106/kg 
with 
splitted 
dose
No Grade ≥ 3 
CRS or ICANS
Cytopenias 2/2
2 out 2 
CRi 
MRD 
negative 
at 4 
weeks
{Ma 2022}
ChiCTR2000041054
4-1BB 2nd 
generation
10 adults 
/ 42 years
1–2 × 
106 /kg
CRS 6/10
No ICANS 
observed
10/10 
Cytopenias
7 out of 
10 
achieved 
CR/CRi 
at 4 
weeks
{Jin 2022}


KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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Abbreviations: AML, acute myeloid leukemia; CAR, chimeric antigen receptor; CD, cluster of differentiation; CLL-1, C-type 
lectin-like molecule-1; CR, complete remission; CRi, complete remission with incomplete hematologic recovery; CRS, cytokine 
release syndrome; ICANS, immune-effector cell-associated neurotoxicity syndrome; MRD, minimal residual disease 
1.4.3.
Rationale for KITE-222 Starting Dose
Historically, there have only been few AML-directed cell therapies assessed in the clinical 
setting. In order to determine an initial starting dose and appropriate dose escalation for this 
study, it is important to evaluate both the AML-directed cell therapy landscape and experience 
from other CAR T-cell products.
Within AML-directed trials, no specific trial with published data represents an autologous 
approach similar to KITE-222; there is no US-based autologous anti-CLL-1 CAR T-cell trial to 
date {Budde 2017, Cellectis 2017}. However, initial data are available from a Phase I trial 
conducted in China evaluating safety of a dual-targeting CLL-1-CD33 CAR-T therapy {Liu 
2020}. Nine subjects received conditioning chemotherapy with 3-day administration of 
cyclophosphamide (300 mg/m2/day) and fludarabine (30 mg/m2/day) followed by escalating 
doses of the CLL-1-CD33 CAR-T (starting dose 1 × 106 cells/kg up to 3 × 106 cells/kg). CRS 
was observed in the majority of subjects, with 2 of 9 patients experiencing Grade 3 CRS. 
Four patients developed neurotoxicity (3 patients with Grade 3 neurotoxicity). All subjects 
experienced Grade 4 pancytopenia and 3 subjects developed sepsis, 2 subjects developed fungal 
infections, and 3 subjects developed pneumonia. Efficacy was encouraging, as 7 of 9 subjects 
experienced measurable residual disease (MRD) negativity. Six of 7 responders proceeded to 
allo-SCT; 1 subject died of sepsis on Day 6 after allo-SCT. Overall, the study provides 
preliminary evidence of anti-leukemia activity of a dual-targeting CAR-T with no unexpected 
safety findings suggestive of on-target, off-tumor toxicity. It is important to note that CD33 is 
expressed on HSCs and targeting this antigen is thus expected to induce deep and durable 
cytopenias with risk of infectious complications. In contrast, KITE-222 only targets CLL-1, 
which is not expressed in HSCs, and thus has the potential for a more favorable safety profile. 
Another CAR T-cell therapy for AML with available data is MB-102, an anti-CD123 CAR 
T-cell product developed initially at the City of Hope {Budde 2017, ClinicalTrials.gov 2019a}. 
The treatment regimen for MB-102 utilizes standard conditioning chemotherapy followed by 
administration of MB-102. Dose escalation started with a flat dose of 50 million anti-CD123 
CAR T cells that were well tolerated by 2 subjects; in the next dose level, subjects were treated 
with 200 million anti-CD123 CAR T cells. Subsequent studies with MB-102 have planned a flat 
dose of up to 600 million cells {ClinicalTrials.gov 2019c}. MB-102 has been manufactured in 
most published cases from donor-derived T cells in subjects who have already undergone 
allo-SCT from that donor {Budde 2017}.
UCART123 is another allogeneic product targeting CD123 that was initially studied at a dose of 
6.25 × 105 anti-CD123 CAR T cells/kg, comparable in most subjects to the 50 million cells used 
as a flat starting dose in the MB-102 clinical study {Cellectis 2017, ClinicalTrials.gov 2019b}. 
Compared with the MB-102 study, the UCART123 study includes a more aggressive 
conditioning chemotherapy regimen that involves more days of fludarabine and higher doses of 
cyclophosphamide, possibly designed to prevent rejection of the allogeneic product {Graham 
2018}. With the more intensive lymphodepleting chemotherapy administered in UCART123, 
Grade 5 CRS/capillary leak was observed at the starting dose of 6.25 × 105 CAR T cells/kg in a 


KITE-222
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Amendment 4.0
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subject with blastic plasmacytoid dendritic cell neoplasm and Grade 4 capillary leak was noted in 
the first subject treated with AML. The toxicities noted at the initial doses of UCART123 may 
have been exacerbated by on-target, off-tumor effects on endothelial cells, which express CD123 
{Sun 2019}. Of note, CLL-1 is not known to be expressed in endothelial cells and thus, similar 
on-target, off-tumor toxicity is not expected.
Outside of AML, recent trials of autologous anti-CD19 and anti-BCMA CAR therapies also 
informed the initial dose selection and dose-escalation cohorts for this study of KITE-222. While 
anti-CD19 CAR T-cell therapy has used weight-based dosing, doses in the range of 
60 to 100 million cells (approximately 1 × 106 anti-CD19 CAR T cells/kg) have been found to be 
safe in subjects across various B-cell malignancies including large BCL and acute lymphoblastic 
leukemia. CD19 is a particularly highly expressed target, and anti-CD19 CAR T cells have 
shown higher expansion and toxicity in the face of CD19-based activation {Neelapu 2017, 
Schuster 2019} than anti-BCMA CAR T-cell counterparts {Raje 2019}. Phase 1 experience with 
autologous anti-BCMA CAR T cells has demonstrated that flat dosing at 50 million cells or 
equivalent is a safe starting dose, and that DLTs may not be seen even at doses of up to 800 
million cells for antigens other than CD19 {Brudno 2018, Raje 2019}. Dose-escalation cohorts 
across CAR T-cell therapy studies have typically been on the order of a half-log or 3-fold 
increase in the dose for initial cohorts, but up to a 4-fold increase from the initial dose has been 
tolerated {Budde 2017, Raje 2019}.
In conclusion, the starting dose proposed for KITE-222 
 
 is below the starting dose used for other CAR-T therapies in AML (CLL-1 CD33 
CAR-T, MB-102, UCART123) as well as below starting doses applied for CD19- or 
BCMA-targeting CAR-T therapies. The
 dose-escalation steps are well aligned with the 
dose-escalation steps used in above Phase 1 CAR-T trials and aim at providing an optimal 
balance of benefit/risk.
1.4.4.
Rationale for Trial Design to Address KITE-222 Safety Risk
Targeting CLL-1 may exacerbate prolonged neutropenia that can be seen in the setting of 
successful B-cell and plasma cell targeting CAR T-cell therapies {Neelapu 2017, Raje 2019, 
Schuster 2019}. Most notably, the expression pattern of CLL-1 within the myeloid compartment 
may lead to agranulocytosis. Although CLL-1 expression is low on normal CD34+ common 
myeloid progenitor cells and megakaryocyte-erythroid progenitors, CLL-1 is expressed on the 
majority of granulocyte-macrophage progenitor cells, ranging from 62% to 81% CLL-1+ cells by 
flow cytometry {Bill 2018}. These granulocyte-macrophage progenitor cells give rise to mature 
myeloid cells, including monocytes and granulocytes which typically express CLL-1 (98.1% and 
99.6% of cells, respectively) {Bill 2018, Wang 2018}. The expression of CLL-1 across 
myeloid-lineage cells speaks to the risk of agranulocytosis, but this risk is felt to be manageable 
in the context of treating r/r AML subjects.
The risks of anti-CLL-1 CAR T-cell therapy with KITE-222 for agranulocytosis is felt to be 
mitigated by a few key features. First, as described in Section 1.4.2, CLL-1 is not present on 
HSCs. This is in contrast with other potential AML antigen targets for CAR T-cell therapy, such 
as CD33, CD123, and even fms-like tyrosine kinase (FLT)-3. Sparing HSC in the context of an 
CCI
CCI
-
-


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
anti-CLL-1 CAR T-cell therapy may allow for the re-establishment of nonnal hematopoiesis in 
the weeks to months after anti-CLL-1 CART-cell infusion. Second, KITE-222 has been 
specifically designed with a- co-stimulation domain. The KITE-222-
co-stimulation is likely to decrease the ersistence of anti-CLL-1 CART cells in KITE-222 
versus other co-stimulation domains, 
{van der Stegen 2015}. Finally, the 
intensive chemotherapy regimens use 
or r r AML salvage therapy frequently result in Grade 4 
neutropenia. These treatments are generally followed by allo-SCT to consolidate response in fit 
patients who had not previously undergone allo-SCT {Dohner 2017}. In this study, allo-SCT 
may be used to rescue persistent agranulocytosis and/or to consolidate response; therefore, 
subjects in this study will be required to have an identified stem-cell donor available before 
emollment for prolonged neutrophil recove1y. 
1.4.5. 
Rationale for Bridging Therapy 
Patients undergoing CART therapies often receive interim disease-directed therapy, refe1Ted to 
as bridging therapy, to maintain disease control and/or to prevent or treat progressive disease 
while awaiting CART cell manufacture and infusion {Amini 2022, Bhaskar 2022} . 
. Similar findings have been described in other 
CAR T therapies like brexucabtagene autoleucel or others in ALL { Cunan 2019, 
Shah 2021a} or chronic lymphocytic leukeinia {Brentjens 2011, Davids 2022}. Thus, debulking 
strategies in patients with high tumor bmden could improve the efficacy and safety of CAR T 
therapies. 
1.4.6. 
Rationale for Lymphodepleting Chemotherapy 
Before receiving KITE-222, subjects will receive a nonm-l
oablative lymphodepleting 
conditionin regimen consisting of cyclophosphamide 
and fludarabine 
to enhance anti-CLL-1 CART-cell function y creatmg an optimal environment 
fo • 
a sion of KITE-222 in vivo. Sub·ects will receive 1 m hode leting chemotherapy 
The use oflymphodepletion in this study is based on data from ZUMA-1, Kite's open-label, 
multicenter clinical study of the safety and efficacy of anti-CD19 CART cells in subjects with 
advanced fonns of non-Hodgkin lymphoma {Locke 2017, Neelapu 2017}, an NCI trial of anti-
CDl 9 CAR-T cells in subjects with advanced B-cell malignancies {Kochenderfer 2017}, earlier 
nonclinical publications that showed an association between adequate lymphodepletion and 
expansion, and function of adoptively transfe1Ted T cells in animal models {Dudley 2008, 
Gattinoni 2005}, and other repo1i ed experiences with autologous or allogenic anti-CD 19 CAR-T 
therapies. Lymphodepletion may function by eradicating cytokine sinks for the transfe1Ted cells, 
eliininating regulato1y T cells, or enhancing antigen-presenting cell activation {Amini 2022, 
Klebanoff 2005}. The proposed fludarabine dose is aligned with the approved use for 
axicabtagene ciloleucel and brexucabta ene ciloleucel in mantle cell l m homa. The dose of 
c clo hos hamide was initiall 
mTent 
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KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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protocol (through Amendment 3.0) to optimize expansion while minimizing the duration of 
hematopoietic recovery. After initial translational data suggested an inverse relation between 
tumor burden and expansion of cells in vivo, the dose of cyclophosphamide was increased to 
. Some trials in cell therapy have already administered higher doses of 
cyclophosphamide than in the ZUMA studies. Thus, Curran et al. found that high doses of 
cyclophosphamide (3 g/m2) achieved better in vivo expansion of CAR T cells than patients 
receiving 1.5 mg/m2 or lower in a trial with 
 CAR T cells in ALL without increasing 
CAR T cell toxicity {Curran 2019}. In addition, a dose of 750 mg/m2 of cyclophosphamide for 
3 days is being used in similar CAR-T trials in progress, like UCART123 in BPDCN 
(NCT03203369), CYAD-211 (NCT04613557) in multiple myeloma, and PBCAR0191 
(NCT03666000) in lymphoma {Shah 2021b}.
1.5.
Benefit/Risk Assessment for the Study
KITE-222 is an autologous T-cell product, and to date, there are no nonclinical models to obtain 
relevant safety information. However, KITE-222 has demonstrated anti-tumor efficacy in 
nonclinical mouse models. Given the lack of suitable murine models to formally assess the safety 
of KITE-222 in a nonclinical setting, this Phase 1 clinical study will employ a gradual 
dose-escalation strategy with close safety review team (SRT) oversight.
Although we do not have data to date for the risks associated with KITE-222 in the clinical 
setting, the risks of other CAR T-cell therapies with other tumor targets have been well 
described, most notably for anti-CD19 CAR T-cell therapies. The identified risks of anti-CD19 
CAR T-cell therapies include CRS and neurologic events of which severe and life-threatening 
events have occurred. Strategies have been developed for these AEs to monitor for early 
detection and management, and the rates of severe CRS and neurologic events have decreased as 
these therapeutic treatments have matured.
The advent of clinically efficacious immunotherapy for cancer over the last decade may 
represent a turning point in the care of subjects with advanced malignancies. Given the impact of 
myeloid cancers to the subject and the potential benefits considered in the context of potential 
risk, further development of KITE-222 in this study is justified.
Refer to the current IB for a summary of potential risks associated with KITE-222.
1.6.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory and local legal requirements.
CCI
CCI-


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
2_ 
OBJECTIVES 
2.1. 
Primary Objective 
The prima1y objective of this study is to evaluate the feasibility, safety, maximum tolerated dose 
(MID), and optimal dose of KITE-222 in the treatment of subjects with r/r AML. 
2.2. 
Secondary Objectives 
The secondaiy objectives of this study ai·e as follows: 
• 
To evaluate the efficacy of KITE-222 in ti·eating subjects with r/r AML 
• 
To evaluate the phannacokinetic and pha1macodynamic profiles ofKITE-222 in subjects 
withr/r AML 
I 
I 
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KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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17 January 2023
3.
STUDY DESIGN
3.1.
Endpoints
3.1.1.
Primary Endpoints
The primary endpoint of this study is to evaluate the incidence of DLTs in subjects treated with 
KITE-222.
3.1.2.
Secondary Endpoints
The secondary endpoints of this study are to evaluate:

Incidence of AEs

Clinically significant changes in laboratory parameters

Time to neutrophil recovery

Time to platelet recovery

Composite complete remission (CCR) rate, defined as the proportion of subjects who achieve 
a CR plus the proportion of subjects who achieve a CR without measurable residual disease 
(CRMRD−) plus the proportion of subjects who achieve a CR with incomplete hematologic 
recovery (CRi) per the ELN 2017 Classification {Dohner 2017}, as determined by the study 
investigators.

Overall remission (OR) rate (CR + CRMRD− + CRi + morphologic leukemia-free state 
[MLFS] + partial remission [PR]) per the ELN 2017 Classification {Dohner 2017}, as 
determined by the study investigators.

Relapse-free survival (RFS)

Allo-SCT rate

Event-free survival (EFS)

OS

30- and 60-day all-cause mortality

Pharmacokinetics: peak and area-under-the-curve (AUC) of KITE-222 CAR T cells in 
subjects with r/r AML treated with KITE-222

Pharmacodynamics: peak and AUC of selected biomarkers in subjects with r/r AML treated 
with KITE-222


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
• 
Analysis of antibodies against the KITE-222 CAR 
-
I 
I 
3.2. 
Study Design 
Study KT-US-486-0201 is a Phase 1, open-label, multicenter study evaluating the feasibility, 
safety, and tolerability of KITE-222 in subjects with r/r AML. The Phase 1 study will consist of 
dose-escalation coho1is and an expansion coho1i. In the dose-escalation part, 3 dose coho1is will 
be assessed to detennine the MID using a 3 + 3 study design. 
All subjects enrolled in the study will proceed through treatment as outlined in Figure 1 with the 
dose ofKITE-222 determined accordin to dose-escalation coho1i and b the MID in the 
. Subjects must be hospitalized from 
infusion (Day 0) until Day 14 at a minimum. From Day 14, subjects may be evaluated for 
discharge and considered for outpatient follow-up if toxicities have returned to Grade 1, have 
resolved, returned to baseline, or are deemed clinically insignificant by the investigator ( eg, renal 
insufficiency that is improving). Assessments detailed in the schedule of assessments (SOA) 
(Table 10, Table 11, and Table 12) can be obtained on an outpatient basis, including complete 
blood count (CBC), if KITE-222-related Grade 4 neutropenia persists. 
Subjects who enroll will have a pre-identified stem-cell donor source for potential allo-SCT, 
which can be initiated at the discretion of the investigating physician after completion of the 
Day 28 disease response assessment. 
In the dose-escalation coho1is, the 3 + 3 design will be used to establish the MTD. In the 3 + 3 
design, 3 subjects are initially treated in a given dose coho1i. If there is no DLT observed in any 
of these subjects, the study proceeds to enroll additional subjects into the next higher dose 
coho1i . If 1 subject develops a DLT at a specific dose, an additional 3 subjects are enrolled into 
that same dose coho1i, and dose escalation is only suggested if no additional DLTs are observed 
CONFIDENTIAL 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
in this dose cohort. Development of DLTs in more than 1 subject in a specific dose coho1i 
suggests the MTD has been exceeded, and fmiher dose escalation is not pursued. The MTD is 
established when 6 subjects are treated at the highest dose level with < 2 DLTs. 
An SRT, consisting ofrepresentatives of the study sponsor and at least 1 active study 
investigator, will review the safety data and make recommendations on study conduct during the 
dose-escalation paii (Section 8.9). The SRT will meet to make decisions on the dose escalation 
during the 3 + 3 period and is responsible for establishing the MTD; as such, in ce1iain 
circumstances, additional dose coho1is may be explored ifKITE-222 is found to be safe at the 
highest dose level by the SRT. 
The study staiis with 3 subjects per dose-escalation cohort. After the first subject is enrolled in 
each coho1i, the subsequent 2 subjects treated in that dose coho1i will be enrolled 1 by 1, and 
dosing of each subject will occur only after the previous subject is clinically stable and has been 
monitored for at least 28 days after the KITE-222 infusion. Dosing subjects in the next coho1i 
will require completion of the 28-day DLT window for the first 3 subjects treated and SRT 
confinnation of advancing the dose-escalation. Approximately 18 subjects will be enrolled for 
the dose-escalation paii of this study, up to 6 subjects evaluable for DLT in each coho1i. Once 
the evaluation of the dose-escalation coho1is is completed, the SRT will meet again to detennine 
the MTD by reviewing the safety profile and other clinical data for subjects at all tested dose 
levels. 
During the dose-escalation paii, the SRT may adjust dose-escalation coho1i dose levels to 
enhance safety before subject enrollment to said coho1i, and after review of the safety data .. 
Additional dose coho1is may be explored at the discretion of the SRT. Additional subjects treated 
at a new dose level suggested by the SRT may be added to the total subject number for the dose-
escalation paii. 
After the MID is established, the study will enter the expansion coho1i stage and enroll and treat 
approximately additional 22 subjects to that coho1i. A minimum of28 subjects across the 
MID-dose coho1i and the expansion coho1i will be treated for additional safety and prelimina1y 
efficacy assessments of the MTD detennined by the SRT. After approximately the first 
6 subjects ai·e treated and followed for 28 days in the expansion coho1i, the SRT will convene to 
assess the feasibility, safety, and preliminaiy efficacy of the MTD after the last treated subject 
completes the 28-day visit, including disease assessment. 
The anticipated enrollment in this study should allow for having 40 subjects treated: up to 
18 subjects for the 3 + 3 based dose-escalation pa1i and approximately 22 subjects for the 
expansion coho1i pait. 
3.3. 
3.3.1. 
Study Treatments 
Leukapheresis 
Subjects will undergo leuka 
manufacture ofKITE-222 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
from subjects at paiiicipating study sites will be packaged for expedited shipment to the cell 
processing facility (CPF) for the manufacture of KITE-222. Refer to Section 7.6.1 for more 
infonnation about the leukapheresis procedure. 
-
3.3.3. 
Lymphodepleting Chemotherapy 
Lymphodepleting chemotherapy will be administered on Day - 5 through Day - 3 before 
administration of KITE-222 in order to induce lymphocyte depletion and create an optimal 
environment for the expansion of KITE-222 CART cells in vivo. Refer to Section 1.4.5 for 
additional infonnation about the rationale for administration of lymphodepleting chemotherapy. 
Th 1 I • 
• 
I 
• 
I 
h d 1 f 
h 
th 
·11 
• t f 
lophosphamide 
and fludarabine 
Cyclophosphamide is a nitrogen mustai·d-derivative alkylating agent that also possesses potent 
immunosuppressive activity. Fludai·abine phosphate is a synthetic purine antagonist 
antimetabolite. 
Refer to Section 7.6.3 for details about the lymphodepleting chemotherapy procedures. 
3.3.4. 
KITE-222 Dose Cohorts 
KITE-222 will be administered as a single IV infusion at a tai·get dose ofKITE-222 CART cells 
per the assigned dose level coho1i. Dose coho1is and dose levels ai·e presented in Table 3. In the 
event that Dose-escalation Coho1i 1 is found to be unsafe, the study will pause and the SRT will 
make adjustments to the treatment regimen to enhance safety ( eg, a reduction in the intensity of 
the lymphodepleting chemotherapy and/or selection of the reduced dose for lower weight 
subjects for all coho1is). In order to enhance safety, the SRT may adjust dose-escalation coho1i 
dose level for higher dose-escalation coho1is prior to subject enrollment to said coho1i and after 
review of safety data from the study to date. 
CONFIDENTIAL 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
Table 3. 
Dose Cohorts 
Dose Cohort 
Dose-escalation Coho1t 1 
Dose-escalation Coho1t 2 
Dose-escalation Coho1t 3 
Expansion Coho1t 
a 
Number of KITE-222 CART Cells•,b 
The optimal dose for the expansion cohort will be dete1mined by the SRT 
after completion of dose-escalation part 
b 
su 1ect may receive t 1e 10 est ose manu acture 1 1t 1s ess than the targeted dose after discussion with the Kite 
medical monitor. Out-of-specification product may be administered in line with the local regulation both during dose 
escalation and expansion phase. 
The staiiing dose ofKITE-222 
has been selected based on previous CAR 
T-cell therapy experience described in Section 1.4. 3. It is anticipated that KITE-222 will have a 
safety profile compai·able to that of other clinically tested CAR therapies such as anti-CD19 
CART cells and anti-BCMA CART cells, except for an increased potential risk of prolonged 
neutrophil recove1y compai·ed with lymphodepleting chemotherapy or alternate CAR T-cell 
therapies. 
Dose-escalation steps ai·e no greater than half-log increases, based on the experience of other 
CART-cell product trials. A flat dose will be used for all subjects, as seen in anti-BCMA CAR 
T-cell trials and eai·ly anti-CD123 CAR trials· however sub'ects wei hin less than 50 k will 
have a dose reduction of 
to 
n01malize dosing in the event of high subject variability from the expected mean weight (80 to 
85 kg). 
Additional doses beyond the cmTent schema may be explored at the discretion of the SRT as 
described in Section 3 .2. 
For any emolled subject whose manufacturing cannot reach the target dose level, the subject may 
receive the highest manufactured dose after discussion with the Kite medical monitor. 
3.3.5. 
Conditioning Chemotherapy and Allo-SCT 
Subjects treated with KITE-222 may initiate conditioning chemotherapy for allo-SCT only after 
disease assessment at Day 28. The decision to proceed to allo-SCT rests with the investigator, 
except if the patient is leukeinia-free and has an ongoing KITE-222-related Grade 4 neutropenia 
by Day 28. The decision to staii the conditioning chemotherapy should be discussed with the 
Kite medical monitor. Allo-SCT may also be used to consolidate response in subjects treated 
with KITE-222. Allo-SCT should be perfonned according to the treating institutions standard for 
the donor somce, subject eligibility, conditioning chemotherapy regimen, cell dose, and 
management after allo-SCT. 
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3.4.
Duration of Treatment and Study
3.4.1.
Duration of Treatment
KITE-222 is a single dose treatment for subjects with r/r AML. After treatment, the subject will 
be monitored as an inpatient for a recommended 28 days (minimum of 14 days), unless discussed 
with the Kite medical monitor (additional information is in Section 3.2).
3.4.2.
Duration of Subject Participation
The study consists of the screening period, enrollment, lymphodepleting chemotherapy, 
KITE-222 infusion, post-treatment follow-up after the infusion, and a follow-up period prior to 
transition onto a separate Kite Long-term Follow-up (LTFU) study (discussed in Section 3.5). 
The duration of the study for individual subjects will vary depending on a subject’s response to 
treatment, survival, and timing of the transition onto the LTFU study.
For a subject who completes participation in this study and also completes the LTFU period in 
the separate LTFU study, the entire duration of a subject’s participation in both studies will be up 
to approximately 15 years from the time of the initial infusion of KITE-222. The need for 
prolonged follow-up is based
 
 the need to understand and mitigate the potential risks of delayed onset 
AEs that could be the potential consequence of this emerging technology.
For patients who are enrolled but not dosed, the end of the study will be 30 days after the last 
procedure has been completed.
3.4.3.
End of Study Definition
The end-of-study is defined as when the last remaining subject completes their last visit on this 
study and transitions to a separate LTFU study (Section 3.5), or when the last remaining subject, 
while still a participant in this study, is considered lost to follow-up, withdraws full consent, or 
dies.
3.5.
Long-term Follow-up Study
After completing at least 24 months of assessments in this study, all subjects who received an 
infusion of KITE-222 will be transitioned to a separate LTFU study after providing informed 
consent, where they will be monitored for occurrence of late-onset targeted AEs/serious AEs 
(SAEs) including secondary malignancies and the presence of 
 suspected to be related to 
KITE-222 through 15 years from the time of the initial KITE-222 infusion (refer also to 
Section 7.9). In the LTFU study, subjects will continue assessments at timepoints contiguous 
with their timepoints in this study.
3.6.
Study Discontinuation Criteria
The SRT can make a recommendation to the sponsor to discontinue the study early based on the 
guidelines in the SRT charter. Refer to Section 8.9 for more information.
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3.7.
Number of Participating Sites
Approximately 15 study sites located in the US and European Union (EU) will participate in this 
study. During the conduct of the study, additional regions, countries, or sites may be added as 
necessary.
3.8.
Source Data
The source data for this study will be obtained from original documents/records, central 
laboratory, local laboratory, specialty laboratory (for pharmacokinetics and/or 
pharmacodynamics data), and/or electronic data capture (EDC).


KITE-222
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Protocol KT-US-486-0201
Amendment 4.0
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
It is anticipated that approximately 40 subjects will be treated in this study as defined below:

Dose-escalation Cohort: approximately 18 subjects, with the intent of identifying the MTD

Expansion Cohort: approximately 22 subjects, with the intent to treat a minimum of 
28 subjects across Phase 1 at the MTD
4.2.
Eligibility Criteria
4.2.1.
Inclusion Criteria
To be enrolled in the study, subjects must meet all of the following criteria:
1) R/R de novo or secondary AML as defined by the ELN 2017 Classification {Dohner 2017}, 
excluding acute promyelocytic leukemia (see specific requirements for France in 
Section 12.4):
a) Refractory disease is defined as one of the following:
i)
Failed at least 2 cycles of a 7 + 3-based induction regimen, which may have been 
given in combination with a targeted agent, an antibody-based therapy, or a B-cell 
lymphoma (BCL)-2 inhibitor. For other agents added to the 7 + 3-based induction 
regimen, please discuss with the Kite medical monitor.
ii) Failed at least 1 cycle of a purine analogue-based induction therapy, such as 
fludarabine or cladribine paired with anthracyclines and cytarabine (eg, FLAG-Ida, 
cladribine, ara-C, granulocyte colony-stimulating factor, and mitoxantrone 
[CLAG-M])
iii) Failed any intensive re-induction regimen after at least 1 prior cycle of induction 
chemotherapy
iv) Persistent AML after 4 cycles of therapy with an HMA (eg, decitabine or azacitidine)
v) Persistent AML after 2 cycles of low-intensity venetoclax-based combinations such 
as venetoclax + HMA or venetoclax + LDAC
vi) Failed therapy after remission (eg, consolidation) during any number of cycles 
(maximum of 4) of high- or intermediate-dose cytarabine
b) Relapsed disease is defined as one of the following:
i)
First relapse, if RFS was less than 12 months following achievement of CR


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ii) Relapsed disease after 2 or more lines of systemic therapy
iii) r/r disease after allo-SCT provided subject is at least 100 days from SCT at the time 
of enrollment and withdrawn from immunosuppressive medications for at least 
4 weeks prior to enrollment
2) Aged 18 years or older
3) Morphological disease in the BM (≥ 5% blasts) and/or peripheral blood within 28 days 
before enrollment and no subsequent anti-AML therapy (except for hydroxyurea given for 
cytoreduction purposes). All subjects will require BM evaluation between screening and 
enrollment.
4) Prior exposure to the relevant agent class for subjects with AML characterized by a mutation 
targeted by an approved therapy (eg, FLT3- internal tandem duplication [ITD], isocitrate 
dehydrogenase [IDH]1, or IDH2).
5) Institutional criteria for allo-SCT fitness must be met: subjects must have an identified 
stem-cell donor readily available for potential allo-SCT after therapy with KITE-222. The 
donor may be matched or mismatched, cord, haplo-identical, or other and declared suitable 
according to the treating institution’s standard criteria.
6) Prior medications:
a) At the time the subject is planned for leukapheresis, at least 2 weeks or 5 half-lives, 
whichever is shorter, must have elapsed since any prior systemic or targeted agents 
(eg, chemotherapy, HMA, BCL-2 inhibitor, IDH inhibitors, FLT3-ITD inhibitors, 
antibody-drug conjugates, or monoclonal antibodies).
b) At the time the subject is planned for leukapheresis, at least 6 months must have elapsed 
since treatment with alemtuzumab and at least 3 months must have elapsed since 
treatment with clofarabine, fludarabine, or cladribine.
c) At the time the subject is planned for leukapheresis, at least 3 half-lives must have 
elapsed since any prior systemic inhibitory or stimulatory immune checkpoint molecule 
therapy (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 
4-1BB agonists, or T-cell engagers).
d) Corticosteroid therapy at a pharmacologic dose (≥ 5 mg/day of prednisone or equivalent 
doses of other corticosteroids; any physiologic steroid replacement is an exception) and 
other immunosuppressive drugs must be avoided for 7 days before enrollment
e) Toxicities due to prior therapy must be stable and have recovered to Grade 1 or lower 
(except for clinically nonsignificant toxicities such as alopecia)
7) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1


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8) Adequate hematologic status, defined as:
a) Absolute neutrophil count (ANC) ≥ 1000/µL unless, in the opinion of the investigator, 
cytopenia is due to underlying leukemia
b) Platelet count ≥ 50,000/µL unless, in the opinion of the investigator, thrombocytopenia is 
due to underlying leukemia
c) Absolute lymphocyte count (ALC) ≥ 100/µL
9) Adequate renal, hepatic, pulmonary and cardiac function defined as:
a) Creatinine clearance (as estimated by the Cockcroft-Gault formula) ≥ 60 mL/min
b) Serum alanine aminotransferase/aspartate aminotransferase ≤ 2.5 × upper limit of normal
c) Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert’s syndrome
d) Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion as 
determined by an echocardiogram (ECHO), and no clinically significant 
electrocardiogram (ECG) findings
e) Baseline oxygen saturation > 92% on room air and no clinically significant pleural 
effusion as determined by chest imaging.
10) Contraception: male and female subjects of childbearing potential must agree to use an 
effective method of contraception for a minimum of 12 months after the study treatment
11) Pregnancy testing: females of childbearing potential must have a negative serum or urine 
pregnancy test (females who have undergone surgical sterilization or who have been 
postmenopausal for at least 2 years before enrollment are not considered to be of 
childbearing potential).
4.2.2.
Exclusion Criteria
To be enrolled in the study, subjects must not meet any of the following criteria:
1) Diagnosis of acute promyelocytic leukemia
2) Auto-SCT within the 6 weeks before enrollment
3) DLI within 28 days prior to enrollment
4) Any drug used for graft-versus-host disease (GVHD) within 4 weeks prior to enrollment 
(eg, calcineurin inhibitors, methotrexate, mycophenolate, rapamycin, thalidomide, or JAK-2 
inhibitors) or immunosuppressive antibody used within 4 weeks prior to enrollment (eg, 
anti-CD20, anti-tumor necrosis factor (anti-TNF), anti-IL 6, anti-IL 6 receptor, or anti-IL-2)


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Protocol KT-US-486-0201
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5) Acute GVHD grade II-IV by Mount Sinai Acute GVHD International Consortium criteria 
{Harris 2016}; acute or chronic GVHD requiring systemic treatment within 4 weeks prior to 
enrollment
6) Active central nervous system (CNS) disease involvement. If the subject has had prior 
history of CNS AML, they must have a negative cerebrospinal fluid (CSF) cytospin and 
magnetic resonance imaging (MRI) or computed tomography (CT) (if MRI is not feasible) of 
the brain demonstrating no evidence of CNS disease.
7) Requirement for urgent therapy due to ongoing or impending oncologic emergency 
(eg, leukostasis or tumor lysis syndrome [TLS]) or the possible requirement for urgent 
therapy due to ongoing or impending oncologic emergency (eg, spinal cord compression, 
bowel obstruction, leukostasis, or TLS) at the time of enrollment or KITE-222 infusion
8) History of CLL-1-directed therapy or genetically modified T-cell therapy
9) History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, 
bladder, or breast) unless disease free for at least 3 years after the last definitive therapy
10) History of severe hypersensitivity reaction to aminoglycosides or any of the agents (including 
fludarabine and cyclophosphamide) used in this study
11) History of concomitant genetic syndrome associated with BM failure such as Fanconi 
anemia, Kostmann syndrome, or Shwachman-Diamond syndrome
12) Subjects with a genetic syndrome that increases the risk of allo-SCT, including Down 
syndrome (trisomy 21)
13) History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York 
Heart Association Class II or greater congestive heart failure, atrial fibrillation, or other 
clinically significant cardiac disease within 12 months before enrollment
14) Subjects with cardiac atrial or ventricular leukemia involvement
15) History of symptomatic deep vein thrombosis (DVT) or a pulmonary embolism within 
6 months of enrollment. History of upper extremity line related DVT within the 3 months of 
conditioning chemotherapy.
16) Primary immunodeficiency disorders
17) History of a human immunodeficiency virus (HIV) infection or acute or chronic active 
hepatitis B or C infection. Subjects with history of hepatitis infection must have cleared their 
infection as determined by standard serological and genetic testing per the current Infectious 
Diseases Society of America or applicable country guidelines


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18) History of an autoimmune disease (eg, Crohns disease, rheumatoid arthritis, or systemic 
lupus) resulting in end-organ injury or requiring systemic immunosuppression or systemic 
disease modifying agents within the last 2 years. Subjects with a history of autoimmune-
related thyroiditis on a stable dose of thyroid replacement hormone and subjects with 
controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study.
19) History or presence of cerebrovascular ischemia, dementia, cerebellar disease, cerebral 
edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS 
involvement. History of seizures is acceptable if there are no episodes in the last 5 years. 
History of bleeding in the CNS is acceptable if related to thrombocytopenia of the AML, 
more than 12 months have elapsed, and there is complete resolution of symptoms and 
cerebral imaging.
20) Presence or suspicion of a fungal, bacterial, viral, or other infection that is uncontrolled or 
requiring antimicrobials for management. Prophylactic antimicrobial therapy is acceptable. 
Simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if they 
are responding to active treatment and after consultation with the Kite medical monitor.
21) Live vaccine received within the ≤ 4 weeks before enrollment, or anticipation of the need for 
a live vaccination during the course of the study
22) Inability to tolerate prophylactic antifungal and antibacterial therapy.
23) Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling 
Foley catheter, or biliary drain, or pleural, peritoneal, or pericardial catheter). Ommaya 
reservoirs and dedicated central venous access catheters such as a Port-a-Cath or Hickman 
catheter are permitted.
24) Ongoing Grade 2 or higher toxicities from previous therapies, excluding hematologic 
toxicities. Subjects with peripheral neuropathy of any grade or clinically nonsignificant 
toxicities (eg, alopecia) of any grade may be eligible.
25) Females of childbearing potential who are pregnant or breastfeeding (the required preparative 
chemotherapy may have dangerous effects on the fetus or infant). Females who have 
undergone surgical sterilization or who have been postmenopausal for at least 2 years are not 
considered to be of childbearing potential.
26) Any medical or psychiatric condition likely to interfere with the assessment of safety or 
efficacy of the study treatment
27) In the investigator’s judgment, the subject is unlikely to complete all protocol-required study 
visits or procedures, including the follow-up visits, or is unlikely to comply with the study 
requirements for participation.


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Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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4.3.
Subject Withdrawal
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the physician or at the institution.
Subjects can decline to continue to receive the study-required treatment and/or other 
protocol-required procedures at any time during the study but continue to participate in the study. 
This is referred to as partial withdrawal of consent. The investigator is to discuss with the subject 
about the appropriate procedures for withdrawal from the study (refer to Section 7.13).
Withdrawal of full consent from a study means that the subject does not wish to receive further 
protocol-required therapy or undergo procedures and the subject does not wish to continue 
further study follow-up. The investigator is to discuss with the subject about the appropriate 
procedures for withdrawal from the study (refer to Section 7.13).
The investigator and/or sponsor can also decide to withdraw a subject from the investigational 
product (IP) and/or other protocol-required therapies, protocol procedures, or the study as a 
whole or at any time prior to the study completion.
4.3.1.
Reasons for Removal From Treatment
Reasons for removal of a subject from protocol-required Ips or procedures include any of the 
following:

AE

Withdrawal by the subject

Product not available

Subject is lost to follow-up

Subjects dies

Termination of the study by the sponsor

Other (eg, investigator decision or noncompliance)
4.3.2.
Reasons for Removal From Study
Reasons for removal of a subject from the study are as follows:

Withdrawal by the subject

Subject is lost to follow-up

Subject dies

Termination of the study by the sponsor

Other (eg, investigator decision or noncompliance)


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4.4.
Replacement of Subjects
Subjects will continue to be enrolled until the specified number of subjects are attained in the 
DLT-evaluable and modified intent-to-treat (mITT) analysis sets. Subjects who discontinue the 
study before the end of the study will not be replaced. Refer to Section 9.7.1 for the definition of 
the DLT-evaluable and mITT analysis sets.
4.5.
Pregnancy and Lactation
There is no relevant clinical experience with KITE-222 in pregnant or lactating women, and 
animal reproductive studies have not been performed. This experimental therapy should not be 
administered to pregnant females or females who are breastfeeding. Females of childbearing 
potential must have a negative pregnancy test before enrollment because of the potentially 
dangerous effects of the preparative chemotherapy on the fetus. Females of childbearing 
potential should be monitored according to the local and country-specific regulations. Refer to 
Section 12.3 for the definition of childbearing potential.
Female subjects and female partners of male subjects are recommended to use a highly effective 
contraception (the method must achieve an annual failure rate of < 1%) through at least 
12 months after the lymphodepleting chemotherapy dosing or the administration of KITE-222, 
whichever is longer. Male subjects are recommended to not father a child for at least 12 months 
after completing the lymphodepleting chemotherapy dosing or administration of KITE-222, 
whichever is longer. Refer to Section 12.3 for a complete list of highly effective contraception 
methods.
Refer to Section 8.8.2.1 for reporting instructions for any pregnancy or lactation cases.
Refer to Table 10 footnote Q for recommended pregnancy testing during the trial.


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
5_ 
INVESTIGATIONAL PRODUCT 
5.1. 
Randomization, Blinding, and Treatment Codes 
Not applicable. 
5.2. 
Description of Investigational Product 
KITE-222 is an autologous CART-cell therapy that is manufactured from a subject's own 
T cells. The subject's T cells are collected by leukapheresis and genetically engineered ex vivo to 
express a CAR specific for the CLL-1 target antigen. 
Each sub·ect's leuka heresed cells are shi 
ed to the CPF, where they are processedl 
. Selected cells are then activated and trnnsduced 
wit a 
vector to mtro uce t e anti-CLL-1 CAR gene. The engineered T cells are then 
fmther expanded and c1yopreserved to generate the IP (KITE-222) per CPF standard operating 
procedures. 
After manufacture and passing the release criteria, KITE-222 will be delivered to the clinical site 
frozen in c1yostorage bags in a liquid nitrogen diy shipper, as described in the Investigational 
Product Manual (IPM). The bags must be stored in vapor phase of liquid nib'ogen and the 
product must remain frozen until the subject is ready for the treatment. Upon receipt of 
KITE-222 at the treatment facility, verification that the product and subject-specific labels match 
the subject's infonnation (subject identification [ID] number) is essential. 
Refer to the IPM for details about shipping of the leukapheresis material to the CPF, manufacture 
of KITE-222, and delive1y of the product to the clinical site. 
In exceptional cases, a KITE-222 product lot that does not meet ce1iain release specification 
criteria may be adininistered to a subject, when necessa1y to avoid an immediate significant 
hazard to the subject and having considered alternative options including the product lot 
remanufacture. Relevant counby regulations will be followed and notifications to concerned 
regulato1y agencies and Institutional Review Boards (IRBs )/Independent Ethics Committees 
(IECs) will be perfo1med as necessaiy per local requirements, in case such out-of-specification 
product lot is supplied and adininistered to a subject. 
5.3. 
Packaging, Labeling, Storage, and Handling of Investigational Product 
Refer to the IPM for details about the KITE-222 fo1mulation, packaging and labeling, 
instru ctions for storage and handling, and ordering of clinical supplies. 
5.4. 
Dosage and Administration 
Refer to Section 3.3.4 for KITE-222 planned dose levels. Refer to Section 7.7.3 for list of the 
assessments and procedures to be perfo1med on the day of KITE-222 adininisb'ation. Refer to the 
IPM for details and instru ction on adininistl'ation of KITE-222. 
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Administration or dosing errors (eg, whether the complete volume in the bag was administered to 
the subject) should be documented in the subject’s source documentation and respective 
electronic case report form (eCRF).
5.5.
Prior and Concomitant Medications
During the course of the study, investigators may prescribe any concomitant medications or 
treatment deemed necessary to provide adequate supportive care to the subject except those 
medications listed in Section 5.6. Prior medications contained in the excluded medications list 
should be discussed with the Kite medical monitor. Refer to current IB for more information 
about supportive therapy, and to Section 6.3.12 for information about recording prior and 
concomitant medications.
5.6.
Excluded Medications
Corticosteroid therapy at a pharmacologic dose (≥ 5 mg/day of prednisone or equivalent doses of 
other corticosteroids; any physiologic steroid replacement is an exception) and other 
immunosuppressive drugs must be avoided for the 7 days before leukapheresis and 5 days before 
KITE-222 administration but may be continued if required as a replacement therapy.
Systemic corticosteroids must also be avoided as a premedication in subjects for whom CT scans 
with contrast are contraindicated (ie, subjects with contrast allergy or impaired renal clearance) if 
the administration is within the 7 days before leukapheresis or 5 days before KITE-222 
administration. Such subjects should instead undergo MRI scans with contrast or CT scans 
without contrast during the washout period specified above. In such cases, alternative or 
alternative dyes such as gadolinium may be considered at the investigator’s discretion.
Corticosteroids and other immunosuppressive drugs (with the exception of physiologic steroid 
replacement) should also be avoided for 3 months after KITE-222 administration, unless they are 
used to manage KITE-222-related toxicities, are used as conditioning for allo-SCT, or their use is 
discussed with the Kite medical monitor. Other medications that might interfere with the 
evaluation of KITE-222, such as nonsteroidal anti-inflammatory agents, should also be avoided 
for the same period unless medically necessary.
Therapeutic doses of systemic anticoagulants, such as unfractionated heparin and low-molecular 
weight heparin, should be avoided whenever possible for subjects who are at risk of bleeding due 
to thrombocytopenia. If a subject requires initiation of the therapeutic anticoagulant doses before 
initiation of the lymphodepleting chemotherapy or before KITE-222 infusion, the 
lymphodepleting chemotherapy or KITE-222 infusion must be held and the case discussed with 
the Kite medical monitor.
Treatment for a subject’s leukemia, such as chemotherapy, immunotherapy, targeted agents, 
radiation, high-dose corticosteroids (other than those defined or allowed in this protocol or as 
part of the conditioning chemotherapy before the allo-SCT), and other investigational agents are 
prohibited, except as needed for the treatment of disease progression or relapse after KITE-222 
infusion.


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
Medications with sedative prope1iies should be avoided if possible in the setting of neurologic 
events (refer to cunent IB). If pennissibility of a specific medication or treatment is in question, 
please contact the Kite medical monitor. 
5.7. 
Accountability and Return of Investigational Product 
Refer to the KITE-222 IPM for details about accountability ofKITE-222. 
The study monitor will review study drng records at periodic intervals. 
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6.
STUDY ASSESSMENTS
Study assessments described in this section are to be performed according to the schedule 
presented in the SOA (Table 10, Table 11 [follow-up without allo-SCT], and Table 12 
[follow-up after allo-SCT]) in Section 12.2.
6.1.
Demographic Data
Demographic data will be collected at screening for each subject as per country and local 
regulations and guidelines. Where applicable, demographic data will include sex, year of birth, 
race, ethnicity, and country of enrollment with the intent to assess the possible association of 
demographics with subject safety and treatment effectiveness.
6.2.
Medical and Treatment History
Relevant medical history before the start of AE reporting (ie, from before enrollment 
[leukapheresis]) will be collected. Relevant medical history is defined as data about the subject’s 
concurrent medical condition that would be typically shared in a referral letter. All findings will 
be recorded in the eCRFs.
In addition to the medical history, all history related to the subject’s disease, treatment and 
response to treatment will be collected and must date back to the original diagnosis. Copies from 
the subjects’ chart should be obtained for subjects who are being referred from another clinic or 
institution to the participating study sites.
6.3.
Safety Assessments
Safety assessments will include collection of AEs, clinical laboratory tests, physical examination, 
weight, vital signs, neurologic examinations, ECOG performance status, cardiac function, brain 
MRI or CT (if MRI is not feasible), lumbar puncture, collection of concomitant medications, and 
assessment of the presence of anti-KITE-222 antibodies 
, as described in the following 
sections.
Safety assessments will be conducted according to the schedule presented in the SOA (Table 10, 
Table 11, and Table 12).
6.3.1.
AEs
All AEs, SAEs, and DLTs will be collected at each study visit as indicated in the SOA (Table 10, 
Table 11, and Table 12). Subjects will be asked about any AEs that might have occurred since 
the last study visit.
6.3.2.
Clinical Laboratory Tests
Blood, serum, or urine samples will be collected for clinical laboratory tests at the time points 
indicated in the SOA (Table 10, Table 11, and Table 12). Additional samples may be collected as 
CCI-


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
needed for further safety testing if clinically indicated. Except for assays for anti-KITE-222 CAR 
antibodies-
(perfo1med at the central laborato1y), all clinical laborato1y test assessments 
listed in Table 4 will be perfo1med at the local laborato1y. 
Table 4. 
Clinical Laboratory Tests for Safety Assessments 
Sernm Chemishies (Serum) 
Album.in 
ALT 
ALP 
AST 
Bicarbonate (CO:!) total (as 
clinically indicated) 
Bilimbin total and dit·ect 
BUN or urea• 
Calcium total 
Chloride 
Creatinine 
Creatinine clearance (as 
estimated by Cockcroft-Gault 
formula) (screening and prior to 
lymphodepleting chemotherapy 
only) 
Glucose 
Inorganic phosphorus 
Lactic acid ( as clinically 
indicated) 
LDH 
Magnesium total 
Potassium 
Sodium 
Uric acid 
Hematology (Blood) 
CBC with differentialb 
Absolute lymphocyte count 
PBMCs: 
Other (Sernm) 
Pregnancy test" 
CR.¥ 
Ferritinf 
Serologic testingf 
Anti-KITE-222 CAR 
antibodies ( central 
laboratory) 
Other (Plasma) 
Coagulationg 
Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea 
nitrogen; CAR, chinteric antigen receptor; CBC, complete blood count; CRP, C-reactive protein; EU, Euro~, 
human immunodeficiency vit·us; LDH, lactate dehydrogenase; PBMC, peripheral blood mononuclear cell;----
~
sts listed above are pe1fo1med at the local laborato1y, except for anti-KITE-222 CAR antibodies,.
and 
unless otherwise indicated. 
a. 
IfBUN test cannot be analyzed by the local laboratory, urea should be analyzed. 
b. 
Per institutional guidelines, but must include white blood cell count, neutrophils or absolute neutrophil count, lymphocytes 
or absolute lymphocyte count, hemogl.
bin latelets, and quantification of the percentage of blasts. 
c. 
Refer to Section 6.7 for info1mation o 
testing. 
d. 
A urine or semm sample will be collecte and assessed locally for females of childbearing potential. If the screening 
pregnancy test (beta-human chorionic gonadotropin [~-hCG]) is positive, the subject should not be enrolled. If a standard-of-
care pregnancy test is collected during the course of the study, and the result is positive, the investigator should report the 
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Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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pregnancy to Kite per instructions specified in Section 8.8.2.1. If a female partner of a male subject becomes pregnant 
during the conduct of the study, the pregnancy must be reported to Kite per instructions specified in Section 8.8.2.1.
e.
CRP and ferritin will also be tested at the central laboratory as part of the pharmacodynamics evaluation (ie, key analytes 
including cytokines; refer to Section 6.6) at the time points listed in the schedule of assessments (Table 10, Table 11, and 
Table 12).
f.
At EU sites, serologic tests (ie, HIV, hepatitis B virus, hepatitis C virus, and syphilis) will be carried out per institutional 
guidelines and EU regulations. This may be done within 30 days before leukapheresis and/or on the day of leukapheresis.
g.
Coagulation must include prothrombin time, activated partial thromboplastin time, D-dimer, and fibrinogen at the time 
points listed in the schedule of assessments (Table 10).
6.3.3.
Physical Examination
Physical examinations will be performed during screening and at times noted in the SOA 
(Table 10, Table 11, and Table 12). At subsequent examinations, clinically significant adverse 
changes (as determined by the investigator) when compared with the baseline exam will be 
reported as AEs.
6.3.4.
Weight
Weight (and height) will be collected during screening and at times noted in the SOA (Table 10), 
and as per local standard of care.
6.3.5.
Vital Signs
Vital signs include blood pressure, heart rate, respiration rate, oxygen saturation, and 
temperature. Vital signs will be monitored as indicated in the SOA (Table 10, Table 11, and 
Table 12).
During KITE-222 administration, vital signs will be monitored before and after the KITE-222 
infusion and then routinely per institutional guidelines. Vital signs may be monitored more 
frequently as clinically indicated.
6.3.6.
Cardiac Function
Each subject’s cardiac function, as measured by ECHO, will be assessed during the screening 
period to confirm study eligibility. No evidence of clinically significant pericardial effusion, as 
required by eligibility criteria, will also be confirmed by ECHO.
If the last chemotherapy regimen the subject received is not considered cardiotoxic, then an 
ECHO performed within the 28 days before signing the informed consent may be used for 
eligibility. If the last chemotherapy regimen the subject received is considered cardiotoxic, then 
an ECHO performed at least 14 days after the subject received their last chemotherapy treatment 
and within the 28 days before signing the consent may be used for confirmation of eligibility.
To establish a baseline, an ECG will be performed during the screening period. ECG assessments 
will include PR interval, QRS interval, QT interval with corrected QT (QTc), and RR interval. 
QTc interval will be calculated using Fridericia’s formula (QTcF) {Fridericia 2003}.


KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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6.3.7.
Chest Imaging
As indicated in the SOA (Table 10), each subject must have screening chest imaging performed 
within 7 days before enrollment to confirm eligibility. Either a chest x-ray or CT or MRI scan of 
the chest with or without contrast can be used to demonstrate no significant pulmonary 
pathology. Refer to Section 12.4 for country-specific requirements.
6.3.8.
Neurologic Examinations and Assessments
The subject’s neurological status will be evaluated at screening to establish a baseline. After 
enrollment/leukapheresis, subjects will be evaluated for any neurological symptoms at each of 
the time points specified in the SOA (Table 10). During the hospitalization period for subjects 
treated with KITE-222, evaluations of neurological status may need to be increased. Changes in 
neurological status should be reported as an AE if considered clinically significant at the 
discretion of the investigator.
Neurological assessments will be standardized by using the immune-effector cell-associated 
encephalopathy (ICE) score (Section 12.6) {Lee 2019}. The ICE is a 10-point, 5-question 
evaluation that covers orientation, naming, following commands, writing, and attention.
In subjects who developed Grade 2 or higher immune-effector cell-associated neurotoxicity 
syndrome (ICANS), ICE score should be determined daily until resolution of ICANS and return 
to baseline neurological status.
6.3.9.
ECOG
Subject’s performance status as measured by the ECOG scale will be performed at time points 
specified in the SOA (Table 10) to quantify the subject’s general well-being and ability to 
perform activities of daily life.
6.3.10.
Brain Magnetic Resonance Imaging
Subjects with a prior history of CNS involvement by AML or clinical symptoms suggestive of 
neurological involvement will undergo a brain MRI or CT (if MRI is not feasible) during the 
screening period to rule out CNS disease and to establish a baseline. The MRI scan will be 
performed with contrast wherever possible or without contrast in case of contraindication. 
An MRI performed after the subject’s last chemotherapy treatment and ≤ 28 days before signing 
the informed consent may be used for confirmation of eligibility.
Refer to the current IB for radiological examination to be performed as part of the evaluation of 
any new onset of neurologic toxicities of severity Grade 2 or higher.
6.3.11.
Lumbar Puncture
Lumbar puncture will be performed at the time points specified in the SOA (Table 10). Opening 
pressures should be measured with each lumbar puncture when possible and recorded in the 
subject’s site chart.


KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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
Screening: Subjects with a history of CNS malignancy, leptomeningeal carcinomatosis, 
symptoms of CNS malignancy, such as new onset severe headaches, neck stiffness, or any 
focal neurologic findings on physical examination, will undergo lumbar puncture at the 
screening visit for examination of CSF to determine the presence of CNS malignancy.

After infusion: A lumbar puncture is recommended for subjects with new onset of clinically 
significant neurologic toxicities of severity Grade 2 or higher after KITE-222 infusion unless 
contraindicated. CSF samples obtained after the infusion will be submitted to the central 
laboratory and analyzed for levels of key analytes (including cytokines) and the presence of 
CAR T cells.
6.3.12.
Concomitant Medications
Information about concomitant medications will be collected at time points specified in the SOA 
(Table 10, Table 11, and Table 12). Reporting requirements for concomitant medications are 
provided in Table 5. Specific concomitant medication collection requirements and instructions 
are included in the eCRF completion guidelines. Refer to Sections 5.5 and 5.6 for information 
about allowed/excluded medications.
Table 5.
Reporting Requirements for Concomitant Medications
Not Enrolled (ie, Screen Fails, or 
Not Leukapheresed)
Enrolled (Leukapheresed),
But Do Not Receive KITE-222
Enrolled (Leukapheresed),
And Receive KITE-222
Concomitant therapies related to 
SAEs will be recorded from the 
date of the screening informed 
consent through 30 days after the 
last study-specific screening 
procedure.
Concomitant therapies will be recorded 
from the date of the informed consent 
until 30 days after the last study-specific 
procedure has occurred 
(eg, leukapheresis, lymphodepleting 
chemotherapy) or until the initiation of a 
new anticancer therapy, whichever 
occurs first.
Concomitant therapiesa including 
medications, oxygen, and blood 
products will be recorded from the date 
of the informed consent until 3 months 
after completing treatment with 
KITE-222.
After the 3-month follow-up period or 
after the start of the conditioning 
regimen for allo-SCT, whichever occurs 
first, only targeted concomitant 
therapies will be recorded until either 
24 months after KITE-222 infusion or 
until disease progression or relapse, 
whichever occurs first. If a targeted 
AE/SAE occurs after the concomitant 
medication follow-up period, all 
relevant concomitant medications 
administered for the treatment of the 
targeted AE/SAE shall also be recorded.
Targeted concomitant therapies 
include immunosuppressive drugs, 
anti-infective drugs, marrow growth 
factors, tyrosine kinase inhibitors, 
and vaccinations.
Abbreviations: AE, adverse event; allo-SCT, allogeneic hematopoietic stem-cell transplantation; SAE, serious adverse event.
Concomitant procedures of intubation and dialysis will follow the same reporting requirements as for concomitant therapies.


KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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17 January 2023
6.3.13.
Other Safety Assessments
6.3.13.1.
Anti-KITE-222 Antibodies
The presence of anti-KITE-222 antibodies in the subject’s serum will be monitored at time points 
identified in the SOA (Table 10, Table 11, and Table 12).
6.3.13.2.
As KITE-222 comprises 
 vector-transduced T cells, the presence of
 in the blood of 
treated subjects will be monitored. PBMCs for 
 testing will be obtained at baseline (before 
leukapheresis), and at Month 3, Month 6, and Month 12. Samples will be held for up to 15 years. 
Only if a subject’s PBMC sample tests positive for 
 at any time point within the first year, 
samples will continue to be collected and tested annually for up to 15 years or as clinically 
indicated (ie, if any clinical reason to suspect 
).
6.3.13.3.
Assessments in the Event of a Secondary Malignancy
Secondary malignancies are defined as the development of any new malignancies, with the 
exception of a relapse of the primary malignancy, occurring after the administration of 
KITE-222.
In the case of a secondary malignancy, every effort will be made to obtain a blood sample 
(PBMC) and a biopsy sample of the neoplastic tissue or the pertinent autopsy tissue to start a 
testing workflow, including tests such as transgene elements, 
 presence of common cancer-
drivers/mutations and insertional mutagenesis. Please refer to Section 12.4 for additional 
country-specific requirements.
6.4.
Disease Assessments
Disease assessments will be performed according to the schedule presented in the SOA 
(Table 10, Table 11, and Table 12). Subjects with symptoms suggestive of disease progression or 
relapse should be evaluated for progression at the time symptoms occur even if this requires an 
unscheduled visit.
Subjects will be evaluated for disease assessment by the site investigator at times indicated in the 
SOA. Whether or not subjects are in morphologic remission (BM blasts are < 5%), samples 
should be sent to the central laboratory for potential evaluation of MRD (eg, MFC for MRD and 
quantitative polymerase chain reaction [qPCR] for nucleophosmin [NPM]1 mutations in 
applicable subjects). The percentage of locally evaluated BM blasts should be entered in the 
eCRF. In addition, local CBC with differential, including the percentage of blasts, should be 
assessed within 3 days of any marrow sampling, although the date of marrow sampling is 
assigned as the date of disease assessment.
In subjects with prior extramedullary disease, disease assessment requires imaging evaluation of 
extra medullary disease to confirm remission and should be entered into the eCRF.
After Day 28, no subsequent disease assessments are needed if progression or relapse has already 
been shown in the previous assessment.
CCI
CCI
CCI
CCI
CCI
CCI
CCI
- -
-
-
--
-


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
6.4.1. 
Bone Marrow Evaluation and Disease Assessment 
BM aspirates and biopsies will be collected throughout the study per the SOA (Table 10, 
Table 11, and Table 12) and/or standard of care. BM aspirate and biopsy samples will be 
processed and submitted to the centrnl laborato1y as outlined in the central laborato1y manual. 
Refer to the laborato1y manual for collection, processing, and shipment requirements; note that 
some samples ( eg, BM sample for MRD and CLL-1 expression) must be shipped on the same 
day of collection. An overview of the sample types that will be required is provided below. 
To confnm a CR, CRMRD-, Cri, or MLFS, the BM must show no evidence of disease by 
morphology. Disease assessments will be evaluated per the ELN 2017 Classification {Dohner 
2017} (Section 12.5). 
Screening BM evaluations will include the following: 
• 
Archival fo1malin-fixed paraffin-embedded (FFPE) BM block and/or unstained slides used 
for the original diagnosis of AML (if available), to be submitted to the central laborato1y 
along with the pathology report. 
• 
BM aspirate and biopsy samples, to be collected after the last dose of systemic chemotherapy 
and within approximately 14 days before emollment. 
-
If a fresh BM aspirate and biopsy was recently perfonned and collected samples were 
properly stored before consent was given, the Kite medical monitor should be consulted 
to confnm the sample is acceptable for screening and central laborato1y purposes. 
• 
In subjects who receive bridging therapy, an additional BM sample must be acquired to 
ensure m01phologic disease, regardless of whether there is evidence of disease by circulating 
peripheral blasts. This assessment should occur between the end of bridging therapy and 
Day-5. 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
On-study BM evaluations will include the following: 
• 
BM aspirates and biopsy samples for subjects who do not proceed to allo-SCT, as per the 
SOA (Table 10 and Table 11) and in those who do proceed to allo-SCT, as per the SOA 
(Table 10 and Table 12). 
-
No more than 1 BM evaluation would be required per week in the event of an 
unscheduled BM evaluation or planned initiation of allo-SCT conditioning 
chemotherapy. 
-
If a subject has a BM evaluation earlier than the indicated per-protocol time point, then 
the BM samples should be processed and submitted to the central laboratory per the 
centrnl laborato1y manual. 
-
For subjects who undergo an allo-SCT, BM evaluations for response assessment are 
required 30 days after allo-SCT. 
• 
BM biopsies will be perfo1med as per the SOA (Table 10, Table 11, and Table 12) and at any 
time when the BM aspirate is either a diy tap or hemodiluted, the BM biopsy will be used to 
dete1mine disease burden by immunohistochemistiy analyses. Refer to Section 12.4 for 
countiy-specific requirements. 
• 
Fresh BM aspirates are submitted to the centi·al laborato1y as outlined in the centi·al 
laborato1y manual. 
• 
BM biopsies are submitted to the centi·al laborato1y as outlined in the cenu-al laborato1y 
manual. 
The conesponding pathology report should be submitted to the cenu-al laborato1y along with the 
archival and on-study BM samples. 
BM aspirate/biopsy should also be considered to evaluate hemophagocytic lymphohistiocytosis 
(HLH) as indicated in the IB. A po1iion of the BM sample collected to evaluate HLH or other 
toxicities should be submitted to the cenu-al laborato1y as outlined in the centi·al laborato1y 
manual. 
6.4.2. 
Measurable Residual Disease 
Whether or not subjects are in m01phologic remission (BM blasts are < 5%) additional studies 
will be perfo1med via cenu-al laborato1y for potential evaluation of MRD. 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
Monitoring of MRD 
• 
In addition, in subjects with a known NPMl mutation, detection of mutated NPMl in peripheral 
blood is a well-validated method to detect MRD {Ivey 2016}. Disease assessments for both 
subjects who do and do not undergo allo-SCT will include peripheral blood NPMl analysis if 
applicable based on disease histo1y . Samples should be submitted to the central laborato1y at 
disease assessment time points as noted in the SOA (Table 10, Table 11, and Table 12) as paii of 
the blood draws for CLL-1 expression. 
-
6.4.4. 
Imaging Requirements (for Subjects with Known Non-CNS Extramedullary 
Disease at Baseline) 
Extramedulla1y disease will be assessed at screening with an imaging modality appropriate for 
the anatomical site and clinical scenai·io. For all subjects with known non-CNS extramedullaiy 
disease, images must be taken within 28 days before emollment and after the last anticancer 
therapy. In addition, for subjects receiving bridging therapy, images must be repeated after 
bridging therapy has completed. 
After KITE-222 infusion, repeat imaging with disease assessments is required from Week 4 
through Month 24 or relapse (Table 10, Table 11, and Table 12), whichever occurs first. In 
subjects who achieve CR, CRMRD-, or CRi, imaging may be stopped until evidence of disease 
relapse. 
All on-study assessments of extramedullaiy disease detected through imaging should be made 
with the same imaging modality and of the same anatomical locations as imaged at baseline. 
For all subjects, extramedullaiy disease imaging assessments should be perfo1med per standard 
of cai·e anytime the subject presents with symptoms suggestive of disease progression or relapse, 
as per the SOA (Table 10, Table 11, and Table 12). 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
6.5. 
Pharmacokinetic Assessments 
PBMC samples for phannacokinetic assessments will be drawn according to the schedule 
presented in the SOA (Table 10, Table 11, and Table 12). 
Phaim acokinetic assessments include monitoring of the presence, expansion, persistence, and 
immunophenotype of transduced anti-CLL-1 CAR T cells in the blood over time, primai·ily by 
polymerase chain reaction (PCR) analysis and complemented by flow cytometiy. Expansion and 
persistence in peripheral blood is monitored by a CLL-1 CAR-specific ddPCR assay. 
6.6. 
Pharmacodynamic Assessments 
Sernm samples for phaim acodynamic assessments will be drawn according to the schedule 
presented in the SOA (Table 10, Table 11, and Table 12). 
Phaim acodynamic assessments of KITE-222 will include monitorin 
the sennn over time. 
I 
I 
I 
I 
I 
Biomai·ker analysis will be perfo1med on blood and tumor samples to evaluate predictive and 
phaim acodynamic markers for KITE-222. Prognostic markers specific for AML and related to 
the tumor immune environment may also be evaluated in archived and fresh ext:I'ainedulla1y 
tumor biopsies. 
CSF, as well as additional sainples, may be haivested from subjects who develop !CANS or 
CRS to enable the evaluation of inflainmato1y cytokines and chemokine levels. As applicable, 
lymphocyte or myeloid populations residing in the CSF, or other subject samples, may also be 
monitored for the pmpose of understanding the safety profile of KITE-222. 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
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KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
CONFIDENTIAL
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7.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are described below 
and will be performed at the time points presented in the SOA (Table 10, Table 11, and 
Table 12) in Section 12.2.
The investigator must document any deviation from the protocol procedures and notify Kite or 
contract research organization (CRO).
7.1.
Subject Informed Consent
Before a prospective subject can participate in the clinical study, the investigator must obtain 
written informed consent from the subject after adequate explanation of the study design, the 
anticipated benefits, and the potential risks. Subjects should sign the most current 
IRB/IEC-approved ICF before any study-specific activity or procedure is performed. Refer to 
Section 10.1.3 for more information about the informed consent process.
All subjects who are enrolled into the study should be reconsented with any updated version of 
the IRB/IEC-approved ICF if relevant to their participation in the study.
7.2.
Subject ID Assignment
Each subject who enters the screening period will receive a unique subject ID number before any 
study-specific procedure or activity is initiated. This number will be used to identify the subject 
throughout the study and must be used on all study documentation related to the subject. 
Furthermore, the subject ID number must remain constant throughout the entire clinical study 
and must not be changed after enrollment or if the subject is rescreened or enrolled in a LTFU 
study.
7.3.
Screening Period
The 14-day screening period begins on the date the subject signs the IRB/IEC-approved ICF and 
continues through the confirmation of enrollment (ie, commencement of leukapheresis 
[Section 7.6.1]) or until the subject withdraws consent before enrollment or it is determined that 
the subject is a screen failure (ie, does not meet the eligibility criteria per Section 4.2). 
Investigative sites will maintain a log of all screened subjects who were reviewed and evaluated 
for study participation. Information collected on the screening log should include limited 
information such as the date of screening, the date the subject was enrolled, or the reason for 
why the subject failed the screening. These data will be entered in the eCRF.
Informed consent must be obtained before completion of any nonstandard of care study-specific 
procedures. Procedures that are part of the standard of care are not considered study-specific 
procedures and may be performed before obtaining consent and used to confirm study eligibility. 
Confirmation of this data must occur within the time allowance as outlined below and in the 
SOA (Table 10).


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Protocol KT-US-486-0201
Amendment 4.0
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After written informed consent has been obtained, the subject will be screened to confirm study 
eligibility and participation. Only subjects who meet the eligibility criteria listed in Section 4.2 
and who commence leukapheresis will be enrolled in the study. If at any time before enrollment 
the subject fails to meet the eligibility criteria, the subject should be designated as a screen 
failure on the subject screening log and the reasons for failing screening should be documented.
The following assessments/procedures are to be completed during the screening period at the 
time points indicated in the SOA (Table 10):

Demographic data

Medical history and disease assessments

Identification of donor source and assessment of fitness for allo-SCT per institutional 
standard

Previous cancer treatment history

Physical examination including height and weight

Vital signs

ECOG performance status

Neurologic examination and assessment

ECHO for left ventricular ejection fraction and pericardial effusion assessment

ECG

Brain MRI or CT (if MRI is not feasible) if there is a prior history of CNS involvement by 
AML or if clinical symptoms are suggestive of neurological involvement

Chest imaging: x-ray or CT or MRI scan. Refer to Section 12.4 for country-specific 
requirements.

Lumbar puncture for collection of CSF for determination of the presence of CNS 
malignancy, as indicated by a history of CNS malignancy, history of leptomeningeal 
carcinomatosis, or presence of clinical signs and symptoms of CNS malignancy

Local laboratory assessments
Chemistry panel (including creatinine clearance, as estimated by the Cockcroft-Gault 
formula) (serum)
Coagulation (plasma)


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Protocol KT-US-486-0201
Amendment 4.0
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CBC with differential and percentage of blasts (blood)
Beta-human chorionic gonadotropin (β-hCG) pregnancy test (serum or urine) on all 
females of childbearing potential
For EU sites, serologic tests (ie, HIV, hepatitis B virus, hepatitis C virus, and syphilis) 
will be carried out per institutional guidelines and EU regulations. This may be done 
within 30 days before leukapheresis and/or on the day of leukapheresis. Refer to 
Section 12.4 for additional country-specific requirements.

Screening BM evaluation
If there is > 4 week delay between screening BM sample collection and the planned 
administration of KITE-222, the Kite medical monitor should be consulted for guidance 
on whether the BM evaluation needs to be repeated prior to lymphodepleting 
chemotherapy.
If a fresh BM aspirate and biopsy was recently performed and collected samples were 
properly stored before consent was given, the Kite medical monitor should be consulted 
to confirm the sample is acceptable for screening and central laboratory purposes.
If available, an archival FFPE BM block and/or slides used for the original diagnosis of 
AML will be submitted to the central laboratory.

Imaging studies as required for extramedullary disease (refer to Section 6.4.3)

SAE reporting (refer to Section 8.5 for safety reporting guidelines)

Concomitant medications documentation
7.3.1.
Antiproliferative Treatment Administered During the Screening Period
 can be administered if a patient requires antiproliferative treatment during the 
screening period, provided the corresponding washing-out period before the planned apheresis is 
met (described in inclusion criterion 6). If it has been administered after the marrow assessment 
has been performed, a repeat assessment will be needed before the lymphodepleting regimen 
starts (see Section 7.6.2).
7.4.
Rescreening
Subjects who are unable to complete or meet the eligibility criteria during the 14-day screening 
period will be permitted to rescreen once for an additional second 14-day screening period. 
Subjects will retain the same subject ID number assigned at the original screening. If rescreening 
occurs within 14 days after signing of the original informed consent, the assessment or procedure 
that initially resulted in the subject failing screening will be performed, including any other 
procedures that fell outside of the designated screening window (eg, laboratory assessments and 
BM aspirate and biopsy); all other initial screening procedures/assessments do not need to be 
CCI


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
repeated. If rescreening occurs, or leukapheresis is delayed for more than 28 days after the 
signing of the original infonned consent, the subject must be reconsented and all screening 
procedures/assessments must be repeated. 
7.5. 
Enrollment 
A subject is considered to be enrolled in the study at the commencement of leukapheresis. Before 
commencement of leukapheresis, subjects must have undergone screening procedures and their 
results must have been confmned to meet the study eligibility criteria (Section 4.2). If there is a 
need for a subject to have the leukapheresis repeated, then they must continue to meet the study 
eligibility criteria before the repeat leukapheresis procedure is perfo1med. 
7.6. 
7.6.1. 
Pretreatment Period 
Leukapheresis/Enrollment 
Leukapheresis/enrollment is to be perfonned approximately 7 days after eligibility confomation. 
Refer to Section 3.3.1 for a description and definition of leukapheresis. Before leukapheresis 
commences, the following criteria must be met: 
• 
In general, all eligibility criteria that were confomed during screening must not be known to 
be violated before leukapheresis. Additionally, the investigator must review and confom that 
the last CBC with differential and percentage of blasts and chemistiy panel drawn before the 
staii of leukapheresis must meet the eligibility criteria detailed in inclusion criteria 8) and 9) 
(Section 4.2.1). If any screening assessments or procedures are repeated between the 
confmnation of eligibility and the staii of leukapheresis and results ai·e outside of the 
eligibility criteria listed in Section 4.2.2, the subject should not be leukapheresed and the Kite 
medical monitor must be consulted. 
• 
Subjects must have no evidence of a clinically significant infection before leukapheresis. 
Should a subject have a clinically significant infection immediately before leukapheresis, cell 
collection must be delayed until the event resolves. 
• 
If leukapheresis is delayed for more than 7 days after eligibility confmnation, a CBC with 
differential and percentage of blasts and chemistiy panel must be repeated. 
• 
If the WBC count from a sample collected at the time of leukapheresis is 
the Kite medical monitor must be consulted before proceeding with leukapheresis. 
irmnunosuppressive diugs must be avoided for 7 days before leukapheresis (see Section 5.6). 
In case of a manufacturing or leukapheresis failure, leukapheresis may be repeated. 
See Section 5.6 for medications that are not allowed before leukapheresis occurs. 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
The following assessments/procedmes are to be completed on the leukapheresis collection day 
(emollment) and as outlined in the SOA (Table 10): 
• 
Vital signs 
• 
Weight 
• 
Local laborato1y assessments: Blood or sernm samples for the following laborato1y 
assessments must be drawn before leukapheresis either on the day of or the day before 
leukapheresis, unless othe1wise noted: 
-
Chemistry panel (sernm) 
-
Coagulation (plasma), includes prothrombin time, activated pa1tial thromboplastin time, 
D-dimer, and fibrinogen 
-
CBC with differential and percentage of blasts (blood) 
-
CRP, fen itin, and lactate dehydrogenase (LDH) (senun) (within 7 days before 
leukapheresis); if CRP is > 100 mg/L, the Kite medical monitor must be consulted before 
proceeding with the leukapheresis 
-
Assay for donor chimerism (when available) for subjects with prior allo-SCT 
• 
Centi-al laborato1y assessments; samples for the following to be collected within 7 days after 
eligibility confinnation and before leukapheresis: 
-
Anti-KITE-222 CAR antibodies (senun) 
-
Levels of key analytes including cytokines (sernm) 
-
KITE-222 CART cells for hannacokinetic baseline, 
-
CBC with differential (blood) 
• 
Leukapheresis; refer to the IPM for details about the leukapheresis procedme, packaging, and 
shipment of apheresis product to the manufacturing facility. 
• 
AE/SAE repo1ting; refer to Section 8.5 for safety repo1ting guidelines (may be perfo1m ed the 
day before leukapheresis, unless othe1wise specified). 
• 
Concomitant medications documentation; refer to Section 6.3.12 (may be perfo1med the day 
before leukapheresis, unless othe1wise specified). 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
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KITE-222 
Protocol KT-US-486-0201 
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7.6.3. 
Lymphodepleting Chemotherapy 
Kite Pha1ma, Inc. 
Amendment 4.0 
before administrntion of KITE-222, subjects will receive a 
nonmyeloablative lymphodepleting chemotherapy regimen consisting of cyclophosphamide and 
fludarabine to induce lymphocyte depletion and create an optimal environment for the expansion 
ofKITE-222 CART cells in vivo. 
Subjects will receive the following 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
I 
Any consideration for changes in the conditioning chemotherapy must be discussed with the Kite 
medical monitor. 
Lymphodepleting chemotherapy will be supplied by the investigative site unless othe1wise noted. 
Refer to the cunent product label for guidance on the packaging, storage, preparation, 
administration, and toxicity management associated with the administration of chemotherapy 
agents. 
7.6.3.1. 
Requirements for Initiating Lymphodepleting Chemotherapy 
Administration of KITE-222 cells to subjects with ongoing infection or inflammation, even if 
subjects are asymptomatic, may increase the risk of high-grade and fatal toxicity. All efforts 
should be made to mle out such conditions before administration of both lymphodepleting 
chemotherapy and KITE-222 infusion. If any of the following criteria are met before the 
initiation of lymphodepleting chemotherapy, the medical monitor must be consulted and the 
workup listed in Section 7.7.5 must be perfo1med to dete1mine the potential cause if there is no 
identified source of infection. 
• 
Temperature > 38°C within the 72 hours before the lymphodepleting chemotherapy 
• 
Both CRP > 100 mg/L and an increase of 10% from the screening value at any time between 
emollment through the staii of lymphodepleting chemotherapy 
Additionally: 
• 
All eligibility criteria of the protocol must be met except: the requirement for cytopenia 
thresholds ( described in inclusion criterion 8) and the requirement for a morphological 
disease in the post-bridging assessment (described in inclusion criterion 3). If any other 
screening assessments or procedures ai·e repeated between confnmation of study eligibility 
and the staii of lymphodepleting chemotherapy and the results ai·e outside of the eligibility 
criteria listed in Section 4.2 (and exceeding 5% of the laborato1y test value cutoffs noted in 
the inclusion criteria), then the condition must resolve before proceeding with 
lymphodepleting chemotherapy. 
• 
In subjects who receive bridging therapy, an additional BM sample must have been collected 
between the end of bridging therapy and initiation of lymphodepleting chemotherapy to 
ensure m01phologic disease, regai·dless of whether there is evidence of disease by circulating 
peripheral blasts. 
• 
A complete histo1y and physical exainination including the head, eyes, ears, nose, and throat 
(HEENT), cai·diac, vasculai·, respirato1y, gastrointestinal, integumentaiy, and neurological 
systems must not reveal evidence of infection/inflammation. 
CONFIDENTIAL 
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KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
CONFIDENTIAL
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17 January 2023

The subject must not have received systemic antimicrobials for the treatment of a known or 
suspected infection within the 48 hours before lymphodepleting chemotherapy (prophylactic 
use of antimicrobials is allowed).

A treatment course of any antimicrobials given for a known or suspected antecedent infection 
should be complete as per infectious disease consult recommendation (if applicable) before 
stopping or switching to prophylactic antimicrobials.

If a subject is confirmed to have an infectious process for which antimicrobials are not 
available (eg, viral pneumonia), the infection must be clinically resolved as determined by 
the investigator in consultation with infectious disease service (if applicable).

The most recently collected blood, urine, or other body fluid cultures must show no growth 
for at least 48 hours, and any other infectious workup performed (eg, bacterial, viral 
serologies, PCR, stool studies, or imaging studies) must be negative. If there is clinical 
suspicion of an infection for which cultures are unlikely to be positive within 48 hours 
(eg, fungal infection), adequate time must be allowed for the cultures to become positive.
Once the above criteria are met, then the subject can proceed with lymphodepleting 
chemotherapy.
7.6.3.2.
Administration of Lymphodepleting Chemotherapy
The following assessments/procedures will be completed
 at the 
time points outlined in the SOA (Table 10):

Physical examination

Vital signs

ECOG performance status (to be assessed before initiation of chemotherapy)

Local laboratory assessments (samples to be drawn before the initiation of the 
lymphodepleting chemotherapy)
Chemistry panel (serum)
Coagulation (plasma)
CBC with differential and percentage of blasts (blood)
CRP, ferritin, and LDH (serum)
EU sites (within 7 days before lymphodepleting chemotherapy): β-hCG pregnancy test 
(serum or urine) on all females of childbearing potential
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KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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
Central laboratory assessments (to be collected before the initiation of lymphodepleting 
chemotherapy):
Levels of key analytes including cytokines (serum)
CLL-1 expression (blood)
CBC with differential (blood)

Lymphodepleting chemotherapy administration

AE/SAE reporting (refer to Section 8.5 for safety reporting guidelines)

Concomitant medications documentation (refer to Section 6.3.12)
Subjects should be instructed to drink plenty of liquids during and for 24 hours following the 
chemotherapy. In general, subjects should be kept well hydrated but closely monitored to prevent 
fluid overload.
7.7.
Treatment Period
The assessments and procedures to be performed during the treatment period will be according to 
the schedule presented in the SOA (Table 10).
All subjects will be hospitalized during the treatment period, from before KITE-222 infusion 
(Day 0) for a recommended 28 days (minimum of 14 days) after treatment (Day 14) to monitor 
for signs and symptoms of infectious complications related to agranulocytosis, CRS, and 
neurologic toxicities. Subjects should be instructed to remain within proximity of the clinical 
study site until complete count recovery or transition to allo-SCT conditioning, at which time 
subjects should follow the institutional guidelines regarding proximity to the treating facility.
Subjects must be hospitalized from infusion (Day 0) until Day 14 at a minimum. From Day 14, 
subjects may be evaluated for discharge and considered for outpatient follow-up if toxicities 
have returned to Grade 1, have resolved, returned to baseline, or are deemed clinically 
insignificant by the investigator (eg, renal insufficiency that is improving). Assessments detailed 
in the SOA (Table 10) can be obtained on an outpatient basis, including CBC, if 
KITE-222-related Grade 4 neutropenia persists.
Subjects should remain hospitalized for ongoing KITE-222-related fever, hypotension, hypoxia, 
or ongoing neurologic toxicities with a severity of greater than Grade 1, or if deemed necessary 
by the investigator.
Central venous access, such as a port or a peripherally inserted central catheter, is required for 
the administration of KITE-222. Catheter care, per institutional guidelines, should be followed.
KITE-222 is a subject-specific product and the product must not be infused if the information on 
the subject-specific label does not match the intended subject’s information (eg, the initials and 
subject ID number). The volume of KITE-222 infused, the thaw start/stop time, and KITE-222 


KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
CONFIDENTIAL
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17 January 2023
administration start and stop time must all be noted in the subject’s medical record. The product 
must not be thawed until the subject is ready for the infusion.
The materials and instructions for the thawing, timing, and administering of KITE-222 are 
outlined in the IPM. The IPM must be reviewed before administration of KITE-222. Research 
sites should follow institutional guidelines for the infusion of cell products.
7.7.1.
Requirements for KITE-222 Infusion
If any of the following criteria are met before initiation of KITE-222 infusion, the medical 
monitor must be consulted and the workup listed in Section 7.7.5 must be performed to 
determine the potential cause if there is no identified source of infection.

Temperature > 38°C within the 72 hours before KITE-222 infusion

Both CRP > 100 mg/L and an increase of 10% from the screening value at any time between 
enrollment to the start of KITE-222 infusion
Additionally:

All eligibility criteria of the protocol must be met except: the requirement for cytopenia 
thresholds (described in inclusion criterion 8) and the requirement for a morphological 
disease in the post-bridging assessment (described in inclusion criterion 3). Laboratory test 
values can also be within 5% of the cutoffs noted in the inclusion criteria. If any other 
screening assessments or procedures are repeated between confirmation of study eligibility 
and the start of KITE-222 infusion and results are outside of the eligibility criteria listed in 
Section 4.2 (and exceeding 5% of the laboratory test value cutoffs noted in the inclusion 
criteria), then the condition must resolve before proceeding with KITE-222 infusion (except 
for peripheral blood cell counts that have been impacted by lymphodepleting chemotherapy).

A complete history and physical examination, including HEENT and cardiac, vascular, 
respiratory, gastrointestinal, integumentary, and neurological systems, must not reveal 
evidence of infection/inflammation.

The subject must not have received systemic antimicrobials for the treatment of a known or 
suspected infection within the 48 hours before the infusion of KITE-222 (prophylactic use of 
antimicrobials is allowed).

A treatment course of any antimicrobials given for known or suspected antecedent infection 
should be complete as per infectious disease consult recommendation (if applicable) before 
stopping or switching to prophylactic antimicrobials.

If a subject is confirmed to have an infectious process for which antimicrobials are not 
available (eg, viral pneumonia), the infection must be clinically resolved as determined by 
the investigator in consultation with an infectious disease service (if applicable).


KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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
The most recently collected blood, urine, or other body fluid cultures must show no growth 
for at least 48 hours, and any other infectious workup performed (eg, bacterial, viral 
serologies, PCR, stool studies, or imaging studies) must be negative. If there is clinical 
suspicion of an infection for which cultures are unlikely to be positive within 48 hours 
(eg, fungal infection), adequate time must be allowed for cultures to become positive.
Once the above criteria are met, the subject can then proceed with the administration of 
KITE-222, following procedures described in Section 7.7.2 and Section 7.7.3.
If the KITE-222 infusion is delayed > 2 weeks, the protocol guidelines should be followed 
regarding the need for repeat lymphodepleting chemotherapy (refer to Section 7.6.3).
7.7.2.
KITE-222 Premedications (Day 0)
The following premedications should be administered 
before KITE-222 
infusion. Alternatives to the recommendations below should be discussed with the Kite medical 
monitor:
7.7.3.
KITE-222 Infusion (Day 0) and After (Days 1 to 13, Day 14 [Week 2], 
Days 15 to 27, and Day 28 [Week 4])
The following assessments and procedures are to be completed on the day of KITE-222 
administration, and on additional days during the treatment period as outlined in the SOA 
(Table 10):

Physical examination

Vital signs during and after study treatment and then routinely during hospitalization per 
institutional guidelines

ECOG performance status

Neurologic assessment (refer to the SOA [Table 10] for frequency)

Samples for the following local laboratory assessments should be drawn before the 
KITE-222 infusion on Day 0 (refer to the SOA [Table 10, Table 11, and Table 12] for 
frequency during the treatment period)
Chemistry panel (serum)
Coagulation (plasma)
CBC with differential, including percentage of blasts (blood)
CCI
CCI
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Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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Monitoring of CRP, ferritin, and LDH (only if LDH is elevated at baseline) levels may 
assist with the diagnosis and define the clinical course regarding CRS/neurologic events. 
It is therefore recommended that CRP, ferritin, and LDH (if elevated at baseline) be 
monitored daily starting at Day 0 and continuing through Day 7. In addition, LDH should 
be monitored as clinically indicated.

Central laboratory assessments (refer to the SOA [Table 10, Table 11, and Table 12] for 
frequency during the treatment period):
Anti-KITE-222 CAR antibodies (serum)
Key analytes including cytokines (serum):
■
As applicable, an additional serum sample for assessment of levels of key analytes, 
including cytokines, should be drawn at the first onset and first re-occurrence of any 
Grade 2 or higher CRS (refer to Section 8.3.1.1 for information on CRS grading) if 
not already collected on that day.
CBC with differential (blood)
CLL-1 expression (blood)

Lumbar puncture:
Lumbar puncture is recommended for subjects with a new onset of clinically significant 
neurologic toxicities of severity Grade 2 or higher after KITE 222 infusion, unless 
contraindicated (refer to Section 6.3.11).

Disease Assessments (see Section 6.4) including BM evaluation (see Section 6.4.1) and 
extramedullary disease assessment (only for subjects with non-CNS extramedullary disease)

KITE-222 premedications on Day 0 (refer to Section 7.7.2)

Infusion of KITE-222

AE/SAE reporting (refer to Section 8.5 for safety reporting guidelines)

Concomitant medications documentation (refer to Section 6.3.12)
7.7.4.
Monitoring After KITE-222 Infusion
Subjects must be hospitalized from infusion (Day 0) until Day 14 at a minimum. From Day 14, 
subjects may be evaluated for discharge and considered for outpatient follow-up if toxicities 
have returned to Grade 1, have resolved, returned to baseline, or are deemed clinically 
insignificant by the investigator (eg, a renal insufficiency that is improving). Assessments 
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KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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detailed in the SOA (Table 10) can be obtained on an outpatient basis, including CBC, if 
KITE-222-related Grade 4 neutropenia persists. Subjects should remain hospitalized for ongoing 
KITE-222-related fever, hypotension, hypoxia, or ongoing neurologic toxicities with a severity 
of greater than Grade 1, or if deemed necessary by the treating investigator.
Subjects should be instructed to remain within proximity of the clinical study site until allo-SCT, 
at which time the subject should follow institutional standards regarding proximity to the clinical 
site. Subjects and their family members/caregivers should be educated on potential CRS and 
neurologic symptoms, such as fever, dyspnea, confusion, aphasia, dysphagia, somnolence, 
encephalopathy, ataxia, or tremor. Subjects or their family members/caregivers should be 
instructed to immediately contact the treating investigator or seek immediate medical attention if 
any of these symptoms develop.
Refer to Sections 5.5 and 5.6 for descriptions of medications that should not be taken before and 
after KITE-222 infusion.
7.7.5.
Requirements for Workup for Potential Infectious and/or Inflammatory 
States
In the absence of an identified source of infection (eg, line infection, pneumonia on chest x-ray), 
the minimum workup to be performed before administration of lymphodepleting chemotherapy 
and/or KITE-222 consists of the following:

Consult the Kite medical monitor

Infectious disease service consult (if available)

Perform CT imaging of the chest with IV contrast. CT imaging of the abdomen and pelvis 
with IV contrast should also be considered as clinically indicated. If there is a medical 
contraindication to contrast, then non-contrast CT is allowed. Refer to Secction 12.4 for 
country-specific requirements.

The following must be performed (before initiation of antimicrobials if clinically feasible):
Blood cultures (aerobic and anaerobic × 2 bottles each), urinalysis, and urine culture. 
Deep/induced sputum culture if clinically indicated.
All indwelling lines, such as central venous catheters, should be examined for any signs 
of infection and additional cultures should be drawn from the line
Nasopharyngeal-throat swab or equivalent assay for viral infection such as influenza A/B 
(including H1N1), parainfluenza 1/2/3, adenovirus, respiratory syncytial virus, 
coronavirus, and metapneumovirus
Collection of fungal cultures and markers as appropriate (eg, galactomannan, Fungitell®)
Collection of appropriate serum viral studies (eg, cytomegalovirus [CMV])


KITE-222
Kite Pharma, Inc.
Protocol KT-US-486-0201
Amendment 4.0
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
If a CNS process is suspected, then appropriate brain imaging and subsequent lumbar 
puncture with cytology, culture, Gram stain, and viral PCR should be performed.

Any additional sign or symptom-directed investigation should be performed as clinically 
indicated.
Before proceeding with lymphodepleting chemotherapy and/or KITE-222 infusion, the above 
workup must not suggest the presence of an active infection and all requirements for 
lymphodepleting chemotherapy and/or KITE-222 infusion must be satisfied. If the KITE-222 
infusion is delayed for more than 2 weeks following lymphodepleting chemotherapy, protocol 
guidelines should be followed regarding the need for repeat lymphodepleting chemotherapy 
(refer to Section 7.6.3).
If the above workup was triggered due to both CRP > 100 mg/L and an increase of 10% from the 
screening value, CRP testing should be repeated. If CRP continues to increase significantly, an 
evaluation should be performed for any other potential infectious or inflammatory condition that 
was not previously evaluated.
7.8.
Post-treatment Follow-up Period
7.8.1.
Post-treatment Follow-up Assessment Visits
Assessments and procedures to be performed during the post-treatment assessment period will be 
according to the schedule presented in the SOA (Table 10).
After completing KITE-222 infusion and after being discharged from the hospital, all subjects 
will be followed during the post-treatment assessment period. Counting from Day 0 (day of 
KITE-222 infusion), subjects will return to the clinic for an evaluation at the following time 
points:

Week 5, Day 35 (± 3 days; for subjects who have not initiated conditioning chemotherapy for 
allo-SCT)

Week 6, Day 42 (± 3 days; for subjects who have not initiated conditioning chemotherapy for 
allo-SCT)

Week 7, Day 49 (± 3 days; for subjects who have not initiated conditioning chemotherapy for 
allo-SCT)

Month 2 (± 1 week; for subjects who have not initiated conditioning chemotherapy for 
allo-SCT)

Month 3 (± 1 week; for subjects who have not initiated conditioning chemotherapy for 
allo-SCT)

Within one week before the conditioning chemotherapy for allo-SCT is initiated 
(if applicable)


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
• 
One day before the allo-SCT is administered (if applicable) 
Subjects will allow key sponsor contacts to continue to access their medical records so that 
infonnation related to subjects' health condition and initial treatment response may be obtained. 
The following procedures are to be completed for subjects as outlined in the SOA (Table 10): 
• 
Physical examination 
• 
Vital signs 
• 
Neurologic assessment (refer to Section 6.3.8) 
• 
Local laborato1y assessments for the following: 
-
Chemistry panel (sernm) 
-
Coagulation (plasma) 
-
CBC with differential, including percentage of blasts (blood) 
-
~-hCG pregnancy test (sernm or urine) on all females of childbearing potential 
• 
Central laborato1y assessments for the following: 
-
Anti-KITE-222 CAR antibodies (sennn) 
-
Key analytes including cytokines (sennn) 
-
CBC with differential (blood) 
-
CLL-1 expression (Blood) 
-
As applicable, an additional sample for assessment oflevels of key analytes including 
cytokines (sernm) and KITE-222 T cells (PBMCs) should be drawn at the first onset and 
first re-occmTence of any Grade 2 or higher KITE-222-related toxicity, such as Grade 2 
CRS or neurologic event, and upon resolution of the event, if not ah-eady collected on 
that day. 
• 
Disease assessment (refer to SOA [Table 10]), including BM evaluation (see Section 6.4.1) 
and exti·amedullaiy disease assessment ( only for subjects with non-CNS extramedulla1y 
disease) 
• 
AE/SAE repo1ting (refer to Section 8.5 for safety repo1ting guidelines) 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
• 
Concomitant medications documentation (refer to Section 6.3.12) 
If a subject is readmitted to the hospital with any KITE-222-related AE after the initial 
hospitalization for the KITE-222 infusion, the following samples will be collected on the day of 
admission, then weekly, and on the day of discharge; samples will be sent to the centrnl 
laborato1y: 
• 
Key analytes (including cytokines) (sennn) 
• 
KITE-222 CART cells (PBMCs) 
7.8.2. 
Evaluation Visit at the Time of Disease Progression or Relapse 
If a subject's disease progresses or the subject experiences a relapse before completion of 
allo-SCT, the procedures listed below will be completed. If disease progression is identified at 
a scheduled visit, the assessments scheduled for that visit will be perfonned in addition to any 
additional disease assessment or other procedures listed below; if necessaiy, some of these 
procedures can be perfo1m ed at an additional unscheduled visit. If disease progression or relapse 
is identified between the scheduled visits, the subject will be asked to attend an unscheduled visit 
for disease assessment and procedures listed below. 
The following assessments/procedures are to be completed at the time of disease progression or 
relapse (also identified in Table 11 and Table 12): 
• 
• 
Physical examination 
• 
Vital signs 
• 
Local laborato1y assessments (if not ah-eady collected at visit in which progressive 
disease/relapse was confomed) for the following: 
-
CBC with differential, including percentage of blasts (blood) 
• 
Central laborato1y assessments for the following: 
-
Key analytes, including cytokines (sennn) to be collected at the time point that disease 
progression was identified and before the subject initiates subsequent anticancer therapy 
-
CLL-1 expression (blood) 
-
Anti-KITE-222 CAR antibodies (sennn) 
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Protocol KT-US-486-0201
Amendment 4.0
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CBC with differential (blood)

AE/SAE reporting (refer to Section 8.5 for safety reporting guidelines)

Concomitant medications documentation (refer to Section 6.3.12)
Refer to Section 7.9.2 for information on follow-up for subjects whose disease progresses or 
relapses after receiving KITE-222.
7.9.
Follow-up Period (After Month 3 Post-treatment Until Transition to LTFU 
Study)
Assessments and procedures to be performed during the follow-up period will be according to 
the schedule presented in the SOA (Table 11 and Table 12).
As described in Section 3.4 and Section 3.5, after completing at least 24 months of assessments 
in this study, all subjects who received an infusion of KITE-222 will be transitioned to a separate 
LTFU study, after providing informed consent. Until this timepoint, subjects will complete the 
post-treatment follow-up visits within this protocol per the SOA Table 11 and Table 12 and the 
descriptions below. Subjects will begin the follow-up period after they have completed the 
Month 3 visit of the post-treatment follow-up period (whether they have responded to treatment 
or went straight to follow-up due to disease progression). The follow-up period will include the 
following visits for subjects who do not proceed to allo-SCT:

Month 6 through Month 18 after the infusion of KITE-222, every 3 months (± 2 weeks)

Month 18 through Month 24 after the infusion of KITE-222, every 6 months (± 1 month)

Month 24 until up to Month 60 after the infusion of KITE 222, every 12 months (± 1 months)

Month 60 until up to 15 years after the infusion of KITE-222, every 12 months (± 3 months)
The follow-up period will include the following visits for subjects who proceed to allo-SCT 
(calculated from the day of allo-SCT unless otherwise specified):

Month 1 (± 3 days)

Month 3 through Month 18, every 3 months (± 2 weeks) 

Month 24 to 15 years after the infusion of KITE-222, every 12 months (± 3 months)

At relapse post allo-SCT disease assessment
Should the subject fail to return to the clinic for a scheduled protocol-specific visit, sites will 
need to make 2 attempts by a combination of telephone and mail to contact the subject. Sites 
must document both attempts to contact the subject. If a subject does not respond within 1 month 
after the second contact the subject will be considered lost to follow-up and no additional contact 
will be required.


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Protocol KT-US-486-0201
Amendment 4.0
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Subjects who are unable or unwilling to return to the study site may have post-treatment follow-
up data for this period obtained from clinical, laboratory, and/or diagnostic assessments 
conducted by the referring HCP and/or GP. In addition, other health status information may be 
obtained from the subject and/or the subject’s referring HCP and/or GP via telephone or email 
communication. This information will be used to detect late-onset targeted AEs and SAEs that 
may be related to KITE-222.
Subjects and/or the subject’s referring HCP and/or GP may be contacted directly by telephone or 
email to confirm survival status and obtain information about targeted concomitant medication 
use, subsequent anticancer therapy, and late-onset targeted AEs/SAEs (if the SAE does not 
require a test to be performed in the clinic).
7.9.1.
Follow-up Assessments and Procedures for Enrolled Subjects Who Received 
KITE-222
The following assessments/procedures are to be completed at the time points indicated in the 
SOA (Table 11 and Table 12) for enrolled subjects who received KITE-222, regardless of 
whether they did or did not undergo an allo-SCT:

Physical examination

Disease assessment (refer to Section 6.4 and the SOA [Table 11 and Table 12]).
Disease assessment will be performed per the SOA through Month 24 or until disease 
progression or relapse, whichever occurs first.
If the subject’s disease has not progressed by Month 24, disease assessments will be 
performed per standard of care after Month 24.

Local laboratory assessments of CBC with differential (blood) is not required after disease 
progression.

Central laboratory assessments for the following:
CBC with differential and inflammatory markers (blood)
Anti-KITE-222 CAR antibodies (serum)
KITE-222 CAR T cells, 
 
CLL-1 expression (blood)

Targeted AE reporting (refer to Section 8.5.1.1; not required after disease progression)

Targeted SAE reporting (refer to Section 8.5.1.2 for safety reporting guidelines)
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
• 
Repo1iing of all KITE-222-related SAEs and any deaths, regardless of causality 
• 
Targeted concomitant medication documentation (refer to Section 6.3.12) 
• 
Subsequent anticancer therapy for the treatment of AML (refer to Section 7.12) 
• 
Survival status: Subjects may be contacted by telephone to confmn their smvival status 
7.9.2. 
Follow-up Procedures for Enrolled Subjects Whose Disease Progressed After 
KITE-222 Treatment 
The following procedmes/assessments are to be completed at the time points outlined in the SOA 
(Table 10, Table 11, and Table 12) for emolled subjects whose disease progressed after 
KITE-222 treatment: 
• 
Local laborato1y assessments of the DLT window period up to Week 4 as per Table 10, if 
possible 
• 
Disease assessment per standard of care 
• 
Smvival status: Subjects may be contacted by telephone to confmn their smvival status 
• 
Subsequent anticancer therapy for the treatment of AML (refer to Section 7.12) 
• 
AE/SAE repo1iing until 30 days after last procedme ( eg, leukapheresis, lymphodepleting 
chemotherapy) (refer to Section 8.5 for safety repo1iing guidelines) 
• 
Concomitant medication documentation until 30 days after the last study-specific procedme 
has occuned (eg, leukapheresis, lymphodepleting chemotherapy) or until the initiation of 
new anticancer therapy, whichever occms first (refer to Section 6.3.12) 
• 
Targeted SAE repo1iing for secondaiy malignancies (refer to Section 8.5.1.2) 
• 
• 
7.9.3. 
Procedures for Enrolled Subjects Who Were Not Treated With KITE-222 
The following procedmes/assessments are to be completed for emolled subjects who were not 
treated with KITE-222: 
• 
AE/SAE repo1iing until 30 days after last procedme ( eg, leukapheresis, lymphodepleting 
chemotherapy) (refer to Section 8.5 for safety repo1iing guidelines) 
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
Concomitant medication documentation until 30 days after the last study-specific procedure 
has occurred (eg, leukapheresis, lymphodepleting chemotherapy) or until the initiation of 
new anticancer therapy, whichever occurs first (refer to Section 6.3.12)
For subjects who are enrolled but not dosed, the end of the study will be 30 days after the last 
procedure has been completed.
7.10.
Retreatment
Retreatment with KITE-222 is not allowed.
7.11.
Poststudy Care
Kite will not provide additional care for study subjects after their participation in the study has 
ended.
7.12.
Subsequent Anticancer Therapy
Subsequent anticancer therapy (apart from allo-SCT) should not be administered except where 
disease progression has been documented and confirmed. Subsequent anticancer therapy refers to 
treatment administered after KITE-222 infusion that is necessary to treat a subject’s disease, such 
as non-study-specified chemotherapy, immunotherapy, targeted agents, radiation therapy, and 
other investigational agents.
Subsequent anticancer therapy administered after KITE-222 infusion for a subject’s disease will 
be recorded in eCRFs for all enrolled subjects until one of the following occurs: subject completes 
the long-term follow-up period, is considered lost to follow-up, withdraws consent, or dies.
For subjects who are enrolled, but do not receive KITE-222 infusion, information about any 
additional anticancer therapy will also be collected until the subject completes the long-term 
follow-up period, is considered lost to follow-up, withdraws consent, or dies.
7.13.
Instructions for Follow-up and Data to Be Collected for Subjects Withdrawn 
From Study
If partial withdrawal of consent occurs (defined in Section 4.3), the investigator must discuss 
with the subject the appropriate process for continued participation, completion of procedures, 
and the associated data collection as outlined in the SOA (Table 10, Table 11, and Table 12).
The level of follow-up and method of communication should also be discussed between the 
research staff and the subject and documented in the source documents.
If withdrawal of full consent occurs (defined in Section 4.3), the investigator must discuss with 
the subject appropriate procedures for withdrawal from the study. Subject data collected up to 
full withdrawal of consent will be retained and included in the analysis of the study, and where 
permitted by local regulations, publicly available data (eg, death records) can be included after 
withdrawal of consent.


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Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
As pa1t of the study, sites may be asked to conduct searches of public records such as those 
establishing the survival status of a subject, if available, to obtain survival data for any subject 
for whom the smvival sta.tus is not known. Sites may be also asked to retrieve autopsy repoits to 
confinn status of disease at the time of death, if possible, per the local laws. 
7.14. 
Sample Storage 
. Each subject will 
have the right to have their sample material destrnyed at any time by conta.cting the investigator 
who in tum can contact the sponsor. The investigator should provide the sponsor with the study 
and subject ID number so that the sample can be located and destroyed. For subjects who 
withdraw consent, any samples that were not requested to be returned or destroyed will remain 
with the sponsor and any data that may be generated will be entered in the study database. 
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8.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
8.1.
Definitions of AEs and SAEs
8.1.1.
AEs
An AE is defined as any untoward medical occurrence in a clinical trial subject. The event does 
not necessarily have a relationship with the study treatment. The investigator is responsible for 
ensuring that any AEs observed by the investigator or reported by the subject are recorded in the 
subject’s medical record.
The definition of an AE includes a worsening of a pre-existing medical condition. Worsening 
indicates that the pre-existing medical condition has increased in severity, frequency, and/or 
duration or has an association with a worse outcome. When recording such events, descriptions 
that the pre-existing condition has changed (eg, more frequent headaches for a subject with 
pre-existing headaches or blood pressure is now more increased in a subject with pre-existing 
hypertension) must be provided.
An AE does not include the following:

A pre-existing condition that has not worsened during the study or involves an intervention 
such as elective cosmetic surgery or a medical procedure while on study is not considered an 
AE. Interventions for pretreatment conditions (such as elective cosmetic surgery) or medical 
procedures that were planned before study participation are not considered AEs.

Hospitalization for study treatment infusions or study-mandated procedures, or 
hospitalization as a precautionary measures per institutional policy are not considered AEs 
(refer also to Section 8.4).

The term “disease progression” as assessed by measurement of malignant lesions on 
radiographs or other methods is not considered to be an AE. Worsening of signs and 
symptoms of the malignancy under study are considered to be AEs.
Refer to Section 8.5.1 for information and instructions for recording and reporting AEs. Refer to 
Section 8.5.3 for information and instructions for recording and reporting AEs due to disease 
progression.
8.1.2.
DLTs
DLTs are defined as the following KITE-222-related events with an onset within the first 
28 days after the KITE-222 infusion unless otherwise specified:

Grade 5 event

Grade 4 CRS of any duration or Grade 3 CRS not improving to Grade 2 or less within 
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Grade 3 or higher cardiac and/or pulmonary events are DLTs unless the events:
Are related to CRS and improve to Grade 2 or less within 72 hours
Can be managed with appropriate noninvasive supportive care (eg, cough, atelectasis, 
dyspnea) that resolves to baseline by Day 28

Grade 4 ICANS or other Grade 4 AEs associated with neurologic events

Grade 3 ICANS
Exception: Grade 3 ICANS with grading based only on ICE score and/or depressed level 
of consciousness that improves to Grade 2 or less within 72 hours

Grade 3 or higher infusion or immediate hypersensitivity reaction

Ongoing Grade 4 neutropenia or thrombocytopenia that is not due to leukemia persistence by 
Day 42 for subjects who have not started the conditioning regimen for an allo-SCT

All other KITE-222 related Grade 3 non-hematologic AEs lasting more than 7 days, and all 
KITE-222-related Grade 4 non-hematologic AEs. The following exceptions are not 
considered DLTs:
Grade 3 or 4 fever
Grade 3 febrile neutropenia returning to baseline within 2 weeks or Grade 3 infection that 
resolves to Grade 2 or less within 2 weeks
Renal toxicity, including the need for dialysis, improving to Grade 2 or lower in ≤ 7 days
TLS including associated manifestations attributable to TLS (eg, electrolyte 
abnormalities, renal function, or hyperuricemia)
Grade 4 AST, ALT, alkaline phosphatase, bilirubin, or other liver function test elevation, 
provided there is resolution to severity of Grade 2 or lower within 7 days
Grade 3 nausea and/or anorexia
As noted in Section 8.7, CRS and ICANS will be graded according to a revised grading system 
{Lee 2019}. AEs attributed to CRS will be mapped to the overall CRS grading assessment for 
the determination of DLT. AEs attributed to ICANS will be mapped to the overall ICANS 
grading assessment for the determination of a DLT. The severity of individual signs/symptoms 
of CRS and ICANS will be graded according to the NCI Common Terminology Criteria for 
Adverse Events (CTCAE) v5.0 for those signs/symptoms that are not part of the grading scale.


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8.1.3.
SAEs
An SAE is defined as an AE that meets at least one of the following serious criteria:

Fatal

Life threatening (ie, an event that places the subject at an immediate risk of death; it does not 
refer to an event that hypothetically might have caused death if it were more severe)

Requires inpatient hospitalization or prolongation of existing hospitalization (refer to 
Section 8.4 for the definition of prolongation of planned hospitalization for this study)
An AE would meet the criterion of “requires hospitalization” if the event necessitated an 
admission to a healthcare facility and occurs outside of the recommended 28-day 
hospitalization.
Events that require an escalation of care when the subject is already hospitalized should 
be recorded as an SAE. Examples of such events include movement from routine care in 
the hospital to the intensive care unit or if that event resulted in a prolongation of the 
existing planned hospitalization.
Refer to Section 8.4 for hospitalizations that are not considered as SAEs.

Results in persistent or significant disability/incapacity

Congenital anomaly/birth defect

Other medically important serious event. If an investigator considers an event to be clinically 
important, but it does not meet any of the serious criteria, the event could be classified as an 
SAE with the criterion of “other medically important serious event.”
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an AE 
according to the NCI CTCAE; the event itself may be of relatively minor medical significance 
and, therefore, may not meet the seriousness criteria. Severity and seriousness need to be 
independently assessed for each AE recorded on the eCRF.
Progression of the malignancy during the study is not considered to be an SAE; signs and 
symptoms of disease progression can be considered to be SAEs (and documented as being due to 
disease progression).
Refer to Section 8.5 for information and instructions on the recording and reporting SAEs. Refer 
to Section 8.5.3 for information and instructions on the recording and reporting SAEs due to 
disease progression.


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8.1.4.
Targeted AEs and SAEs
For subjects who do not receive a subsequent allo-SCT, targeted AEs and SAEs are to include 
neurologic, hematologic, infection, new occurrence, or aggravation of GVHD, and secondary 
malignancy events.
For subjects who receive a subsequent allo-SCT, targeted AEs and SAEs are to include 
neurologic, primary graft failure, infection, new occurrence, or aggravation of GVHD, and 
secondary malignancy events.
Although only secondary malignancies are considered to be targeted AEs/SAEs, all new 
malignancies will be reported. New malignancies are defined as the development of any new 
malignancies occurring after the KITE-222 infusion. A secondary malignancy is defined as a 
new malignancy suspected to be possibly related to KITE-222 (ie, temporally associated with 
KITE-222 and without compelling alternate etiologies).
Refer to Section 8.5.1.1 and 8.5.1.2 for information and instructions for recording and reporting 
targeted AEs and targeted SAEs, respectively.
8.2.
Clinical Laboratory and Vital Sign Abnormalities
8.2.1.
Abnormal Clinical Laboratory Findings
The investigator is responsible for reviewing laboratory test results and determining whether an 
abnormal value in an individual study subject represents a clinically significant change from the 
subject’s baseline values. In general, abnormal laboratory findings without clinical significance 
(based on the investigator’s judgment) are not to be recorded as AEs. However, abnormal 
laboratory findings that result in new or worsening clinical sequelae or that require therapy or an 
adjustment in current therapy, are considered AEs. Where applicable, clinical sequelae (not the 
laboratory abnormality) are to be recorded as an AE.
An abnormal laboratory test result must be reported as an AE if it is a change from baseline and 
meets any of the following criteria:

Is associated with clinical symptoms

Results in a medical intervention (eg, potassium supplementation for hypokalemia or iron 
replacement therapy for anemia) or a change in concomitant therapy

Is clinically significant in the investigator’s judgment
8.2.2.
Abnormal Vital Sign Values
Not all vital sign abnormalities qualify as an AE. A vital sign result must be reported as an AE if 
it is a change from baseline and meets any of the following criteria:

Is accompanied by clinical symptoms


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
Results in a medical intervention or a change in concomitant therapy

Is clinically significant in the investigator’s judgment
It is the investigator’s responsibility to review all vital sign findings. Medical and scientific 
judgment should be exercised in deciding if an isolated vital sign abnormality should be 
classified as an AE. However, if a clinically significant vital sign abnormality is a sign of a 
disease or syndrome (eg, high blood pressure), only the diagnosis (ie, hypertension) should be 
recorded on the eCRF.
8.3.
Assessments of AE and SAE Severity and Causality
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of the accuracy of the event 
information and assessments.
8.3.1.
Assessment of AE/SAE Severity
The severity of AEs will be graded according to the NCI CTCAE version 5. A copy of the 
grading scale can be downloaded from the Cancer Therapy Evaluation Program home page 
(http://ctep.cancer.gov).
8.3.1.1.
Grading of CRS and Neurologic Events
The severity of CRS and ICANS events will be graded according to the American Society for 
Transplantation and Cellular Therapy (ASTCT) consensus grading {Lee 2019}. Copies of the 
ASTCT CRS and ICANS grading scales can be downloaded from (http://tgapp.asbmt.org). The 
severity of individual signs/symptoms of CRS and neurologic events will be graded according to 
the NCI CTCAE version 5.0 for those signs/symptoms that are not part of the grading scale. 
Refer to the current IB for details on toxicity management and CRS grading.
8.3.2.
Assessment of AE/SAE Relationship to IP and Study Procedures
When reviewing AEs, investigators must assess whether the AE is possibly related to 1) the IP 
(KITE-222), 2) leukapheresis, 3) bridging therapy, 4) lymphodepleting chemotherapy, or 5) any 
protocol-required study procedure. The relationship is indicated by a “related” or “not related” 
response and entered in the eCRF. When assessing causality, the investigator or qualified 
subinvestigator will use clinical judgment and the following considerations:

Not Related: There is evidence that the AE has an etiology other than the IP or study 
procedure. For SAEs, an alternative causality must be provided (eg, disease progression, 
concurrent disease[s], concomitant medications, or other).

Related: There is a reasonable possibility that the event may have been caused by the IP or as 
a result of a study procedure.


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8.4.
Hospitalization and Prolonged Hospitalization
Any AE that results in hospitalization or prolonged hospitalization should be documented and 
reported as an SAE as described in Section 8.5.1.2. Hospitalization is considered prolonged 
when a subject is hospitalized for > 28 days after the infusion of KITE-222 with the exception of 
extended hospitalization for a planned allo-SCT.
The following hospitalization scenarios are not considered to be SAEs:

Hospitalization for palliative care or hospice care

Planned hospitalization required by the protocol (eg, for monitoring of the subject or to 
perform an efficacy measurement for the study)

Planned hospitalization for a pre-existing condition

Hospitalization for Grade 4 or lower hematologic toxicity < 42 days after the KITE-222 
infusion

Hospitalization for an allo-SCT

Hospitalization due to the progression of the underlying cancer (refer to Section 8.5.3 for 
instructions on reporting of the signs/symptoms of the underlying malignancy or disease 
progression as AEs or SAEs.)
8.5.
Investigator Requirements and Instructions for Reporting AEs, SAEs, and 
Deaths to the Sponsor
8.5.1.
Reporting AEs and SAEs
The investigator or qualified subinvestigator must address the below for AEs/SAEs:

AE diagnosis or syndrome (or, if not known, signs or symptoms)

Dates of the onset and resolution

Severity (Section 8.3.1)

Assessment of relatedness to KITE-222, lymphodepleting chemotherapy, or study procedures 
(Section 8.3.2)

Action taken
Additional relevant data with respect to describing the AE/SAE will be collected in the eCRFs. 
For AEs/SAEs, a diagnosis (if known) rather than the individual signs and symptoms should be 
recorded on the eCRF AE form. The exception is for CRS where both the diagnosis and 
significant signs and symptoms will be captured on the eCRF AE form.


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The investigator is expected to follow the reported AEs/SAEs until stabilization or resolution. If 
a subject begins a new anticancer therapy, the AE reporting period for non-SAEs ends at the time 
the new treatment is started.
Refer to Section 8.5.3 for instructions on reporting AEs/SAEs associated with disease 
progression.
The investigator’s clinical judgment will be used to determine whether a subject is to be removed 
from the study treatment due to an AE/SAE. In the event a subject requests to withdraw from 
protocol-required therapies or the study due to an AE/SAE, the subject should undergo the 
procedures outlined in the Month 3 visit of the SOA (Table 10).
Refer to Section 8.5.1.1 and Section 8.5.1.2 for additional information on reporting AEs and 
SAEs, respectively.
8.5.1.1.
Reporting AEs
The investigator is responsible for reporting all AEs observed by the investigator or reported by 
the subject during the AE-reporting period, as described in Table 7. Refer to Section 8.5.3 for 
instructions on reporting AEs associated with disease progression.
Table 7.
Reporting Requirements for AEs
Subjects Who Are 
Enrolled, but Do 
Not Receive 
KITE-222 Infusion
Subjects Who Are Enrolled and Receive KITE-222 Infusion
AEs that occur from enrollment (ie, commencement of leukapheresis) through 3 months 
after KITE-222 infusion or until initiation of another anticancer therapy, whichever 
occurs first, are to be monitored and reported.
In subjects who do not receive a subsequent allo-SCT, after 3 months, only targeted AEs 
will be reported through 24 months after KITE-222 infusion or until disease progression 
or relapse, whichever occurs first, and will be recorded in the eCRF.
Targeted AEs include neurological events, hematological events, infections, new 
occurrence or aggravation of GVHD, and secondary malignanciesa.

Notea: all new malignancies are to be reported; however, only secondary 
malignancies are considered to be targeted AEs.
All AEs deemed related to KITE-222 infusion should be recorded in the eCRF and 
reported regardless of study period.
AEs that occur from 
enrollment 
(ie, commencement 
of leukapheresis) 
through 30 days after 
the last study-specific 
procedure 
(eg, leukapheresis, 
bridging therapy, 
lymphodepleting 
chemotherapy) or 
until initiation of a 
new anticancer 
therapy, whichever 
occurs first, will be 
reported.
In subjects who receive a subsequent allo-SCT, only targeted AEs will be reported after 
the start of the conditioning regimen for the allo-SCT, through 24 months or until disease 
progression or relapse, whichever occurs first, and will be recorded in the eCRF.
Targeted AEs include neurological events, primary graft failureb events, infections, 
new occurrence or aggravation of GVHD, and secondary malignanciesa.

Notea: all new malignancies are to be reported; however, only secondary 
malignancies are considered to be targeted AEs.
All AEs deemed related to KITE-222 infusion should be recorded in the eCRF and 
reported regardless of study period.


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Abbreviations: AE, adverse event; allo-SCT, allogeneic stem-cell transplantation; eCRF, electronic case report form; GVHD, 
graft-versus-host disease.
a.
New malignancies are defined as the development of any new malignancies occurring after the KITE-222 infusion. 
Secondary malignancies are defined as the development of any new malignancies, with the exception of a relapse of the 
primary malignancy, occurring after the administration of KITE-222. Secondary malignancies will continue to be reported 
through 15 years after KITE-222 infusion.
b.
Primary graft failure is defined as no evidence of engraftment or hematological recovery of donor cells, within the first 
month after transplant, without evidence of disease relapse. Engraftment is defined as the first of 3 consecutive days with an 
absolute neutrophil count higher than 0.5 × 109/L (sustained >20 × 109/L platelets and hemoglobin >80 g/L, free of 
transfusion requirements).
8.5.1.2.
Reporting SAEs
The investigator is responsible for reporting all SAEs observed by the investigator or reported by 
the subject during the SAE-reporting periods described in Table 8. Refer to Section 8.5.3 for 
instructions on reporting SAEs associated with disease progression.
Table 8.
Reporting Requirements for SAEs
Subjects Who Are:

Screen Failures

Enrolled But Do Not Receive 
KITE-222 Infusion

Enrolled and Received KITE-222 Infusion
All SAEs that occur from signing of the screening ICF through 3 months 
after the KITE-222 infusion or until initiation of another anticancer 
therapy, whichever occurs first, will be recorded in the eCRF and 
reported. 
In subjects who do not receive a subsequent allo-SCT, after 3 months, 
only targeted SAEs will be reported through 24 months after KITE-222 
infusion or until disease progression or relapse, whichever occurs first, 
and will be recorded in the eCRF. 

Targeted SAEs include neurological events, hematological events, 
infections, new occurrence or aggravation of GVHD, and secondary 
malignanciesa. 

Notea: all new malignancies are to be reported; however, only 
secondary malignancies are considered to be targeted AEs.
In subjects who receive a subsequent allo-SCT, only targeted SAEs will 
be reported after the start of the conditioning regimen for the allo-SCT, 
through 24 months or until disease progression or relapse, whichever 
occurs first, and will be recorded in the eCRF. 

Targeted SAEs include neurological events, primary graft failure 
eventb, infections, new occurrence or aggravation of GVHD, and 
secondary malignanciesa. 

Notea: all new malignancies are to be reported; however, only 
secondary malignancies are considered to be targeted AEs. 
After 24 months, targeted SAEs of secondary malignanciesa will continue 
to be reported through 15 years after KITE-222 infusion and will be 
recorded in the eCRF. 
All SAEs deemed related to KITE-222 infusion should be recorded in the 
eCRF and reported regardless of study period. 
All SAEs that occur from signing of 
screening ICF through 30 days after 
the last study-specific procedure (eg 
screening procedure, leukapheresis, 
bridging therapy, or lymphodepleting 
chemotherapy) or until the initiation 
of a new anticancer therapy, 
whichever occurs first, will be 
recorded in the eCRF and reported.
All deaths that occur from signing of the screening ICF. Refer to 
Sections 8.5.2 and 8.5.3 for instructions on reporting deaths. 


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Abbreviations: AE, adverse event; allo-SCT allogeneic stem-cell transplantation; eCRF, electronic case report form; GVHD, 
graft-versus-host disease; ICF, informed consent form; SAE, serious adverse event. 
a.
New malignancies are defined as the development of any new malignancies occurring after the KITE-222 infusion. Targeted 
SAEs of secondary malignancies will be reported during the entire reporting period (ie, through 15 years after KITE-222 
infusion) for all subjects, including those whose disease progresses. Secondary malignancies are defined as the development 
of any new malignancies, with the exception of a relapse of the primary malignancy, occurring after the administration of 
KITE-222. 
b.
Primary graft failure is defined as no evidence of engraftment or hematological recovery of donor cells, within the first 
month after transplant, without evidence of disease relapse. Engraftment is defined as the first of 3 consecutive days with an 
absolute neutrophil count higher than 0.5 × 109/L (sustained >20 × 109/L platelets and hemoglobin >80 g/L, free of 
transfusion requirements). 
Unless otherwise indicated in Table 8:

The following must be submitted to Kite via the electronic SAE (eSAE) system within 
24 hours after the investigator’s knowledge of the event:
All SAEs

The following events must be submitted as SAEs via the eSAE system within the 24 hours 
after the investigator’s knowledge of the event:
CRS events Grade 3 or higher
ICANS events Grade 3 or higher
All events of cerebral edema
All events of HLH/macrophage activation syndrome
If the eSAE system is unavailable (eg, system outage), then the SAE must be submitted using the 
paper SAE Report Form and sent via email to the SAE Reporting mailbox at 
Safety_FC@gilead.com. Subsequently, SAEs will be entered into the eSAE system once it 
becomes available. All SAEs will be reported to the health authorities per local reporting 
guidelines.
8.5.2.
Reporting Deaths
Death must be reported if it occurs during the SAE-reporting period, irrespective of any 
intervening treatment. Refer to Section 8.5.3 for instructions on reporting deaths associated with 
the underlying malignancy/disease progression.
Any death occurring after signing of the ICF and within 3 months after the KITE-222 infusion or 
until the conditioning chemotherapy for allo-SCT (whichever is shorter), regardless of attribution 
to treatment, requires expedited reporting within 24 hours of the event. Any death occurring after 
the 3-month SAE-reporting period requires expedited reporting within 24 hours only if it is 
considered related to treatment, KITE-222 infusion, and/or study-required treatments (eg, 
lymphodepleting chemotherapy).


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Death is an outcome and not a distinct event. The event or condition that caused or contributed to 
the fatal outcome should be recorded on the eCRF AE form with entries including the start date 
of the event and the death date as the stop date of the event. Every effort should be made to 
capture the established cause of death, which may become available later on (eg, after an 
autopsy).
8.5.3.
Reporting AEs, SAEs, and Deaths Associated With Disease Progression or 
Relapse
Progression or relapse of AML (“disease progression”) as assessed by measurement of marrow, 
peripheral blood or extramedullary malignant lesions, should not be reported as an AE or SAE.
For situations when an AE or SAE is due to the malignancy under investigation, the sign(s) and 
symptom(s), including worsening of sign(s) and symptom(s), of the malignancy under study 
should be reported as an AE/SAE in the appropriate section of the eCRF and the investigator 
should check the appropriate data field to indicate that these signs and symptoms are due to the 
underlying disease/disease progression.
If the malignancy has a fatal outcome within 3 months after the KITE-222 infusion, and is 
deemed by the investigator as the event leading to death, it must be recorded as an SAE with a 
CTCAE v5.0 severity of Grade 5 and outcome of “fatal”. Within this 3-month period, the death 
that is due to the underlying disease/disease progression must be reported immediately to the 
sponsor as an SAE, as follows:

If there are no signs and symptoms of alternate underlying disease associated with the death 
(although the death has been determined to be due to disease progression), the death should 
be reported immediately to the sponsor as an SAE with the primary tumor type (eg, “acute 
myeloid leukemia”) as the event term.

If the death is due to a sign or symptom of the underlying disease/disease progression and the 
sign or symptom is a targeted SAE, then the SAE will be reported as the event term. The 
investigator should check the appropriate eCRF data field to indicate that these signs and 
symptoms are due to the underlying disease/disease progression.
8.6.
Sponsor Reporting Requirements (Includes Reporting of SAEs and Deaths) 
Depending on the relevant local legislation or regulations, including the applicable US FDA 
Code of Federal Regulations (CFR), the EU Clinical Trials Directive (2001/20/EC) and relevant 
updates, and other country-specific legislation or regulations, Kite may be required to expedite to 
worldwide regulatory agencies reports of serious adverse drug reactions or suspected unexpected 
serious adverse reactions (SUSARs). In accordance with the EU Clinical Trials Directive 
(2001/20/EC), Kite or a specified designee will notify worldwide regulatory agencies and the 
relevant IEC in concerned Member States of applicable SUSARs as outlined in current 
regulations.
The assessment of expectedness for SAEs will be determined by Kite using reference safety 
information specified in the current IB or relevant local label as applicable.


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All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study drug. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy.
8.7.
Toxicity Management
To date, the following important identified risks have been associated with CAR therapy and are 
considered important potential risks for KITE-222: CRS, neurologic events, infections, 
cytopenias, and hypogammaglobulinemia. Refer to the current IB, Guidelines for Management 
of Important Risks, for details regarding these events and management guidance.
As the safety experience with KITE-222 increases, the management guidance may be updated. 
Therefore, it is important to always refer to the most recent version of the IB for guidance 
regarding the management of KITE-222 related toxicities.
Additional information and management recommendations can also be found in the IB regarding 
important potential risks associated with KITE-222, as well as possible complications associated 
with malignancy and cancer treatment.
8.8.
Special Situations Reports
8.8.1.
Definitions of Special Situations
Special situation reports include all reports of medication error – actual or potential, abuse, 
misuse, overdose, occupational exposure, drug interactions, exposure via breastfeeding, 
unexpected benefit, transmission of infectious agents via the product, counterfeit or falsified 
medicine, and pregnancy reports (Maternal Pregnancy and Partner Pregnancy) regardless of an 
associated AE.
A medication error (actual or potential) is any unintentional error in the prescribing, dispensing, 
preparation for administration or administration of an IP while the medication is in the control of 
a health care professional, patient, or consumer. Medication errors may be classified as a 
medication error without an AE, which includes situations of missed dose; medication error with 
an AE; intercepted medication error; or potential medication error.
Abuse is defined as persistent or sporadic intentional excessive use of an IP by a clinical study 
subject.
Misuse is defined as any intentional and inappropriate use of an IP that is not in accordance with 
the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of an IP (eg, 
lymphodepleting chemotherapy or other study-specified IP) given per administration or 
cumulatively which is above the maximum recommended dose as per protocol or in the product 
labeling (as it applies to the daily dose of the subject in question). In cases of a discrepancy in 
drug accountability, an overdose will be established only when it is clear that the subject has 


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taken the excess dose(s). An overdose cannot be established when the subject cannot account for 
the discrepancy except in cases in which the investigator has reason to suspect that the subject 
has taken the additional dose(s).
An occupational exposure is defined as exposure to an IP as a result of one’s professional or non-
professional occupation.
A drug interaction is defined as any drug/drug, drug/food, or drug/device interaction.
An unexpected benefit is defined as an unintended therapeutic effect where the results are judged 
to be desirable and beneficial.
Transmission of infectious agents is defined as any suspected transmission of an infected agent 
through a Kite IP.
Counterfeit or falsified medicine is defined as any IP with a false representation of: a) its 
identity, b) its source, or c) its history.
8.8.2.
Instructions for Reporting Special Situations
8.8.2.1.
Instructions for Reporting Pregnancies
Any pregnancy in a female subject enrolled into the study must be reported, regardless of the 
time after KITE-222 infusion. If the pregnancy occurs in a female partner of a male subject 
within 12 months after completing lymphodepleting chemotherapy or the administration of 
KITE-222, whichever is longer, the pregnancy must be reported. All such pregnancies must be 
reported to Kite Patient Safety and Pharmacovigilance using the Pregnancy Report Form within 
24 hours after becoming aware of the pregnancy. Information regarding the pregnancy and/or the 
outcome will be requested by the sponsor. Pregnancy Report Forms should be reported to Kite 
Patient Safety and Pharmacovigilance at Safety_FC@gilead.com or fax: +1 (650) 522-5477.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons. Any premature termination of pregnancy (eg, a spontaneous 
abortion, an induced therapeutic abortion due to complications or other medical reasons) must be 
reported within 24 hours as an SAE. The underlying medical reason for this procedure should be 
recorded as the AE term. Any SAE occurring as an adverse pregnancy outcome after the study 
has been completed must be reported to Kite Patient Safety and Pharmacovigilance.
The pregnant subject or subject partner should receive appropriate monitoring and care until the 
conclusion of the pregnancy. The outcome should be reported to Kite Patient Safety and 
Pharmacovigilance using the Pregnancy Outcome Report Form. If the end of the pregnancy 
occurs after the study has been completed, the outcome should be reported directly to Kite 
Patient Safety and Pharmacovigilance.
Pregnancies of female partners of male study subjects exposed to KITE-222 or other study drugs 
must also be reported, and relevant information should be submitted to Kite Patient Safety and 
Pharmacovigilance using the pregnancy and pregnancy outcome forms within 24 hours after 


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becoming aware of the pregnancy. If the end of the pregnancy occurs after the study has been 
completed, the outcome should be reported directly to Kite Patient Safety and 
Pharmacovigilance.
If a lactation case occurs in a female subject in the study, the lactation case must be reported to 
Kite Patient Safety and Pharmacovigilance within 24 hours after the investigator’s awareness of 
the event using the Special Situations Reporting Form. In addition to reporting a lactation case 
during the study, investigators should monitor for pregnancy and lactation cases throughout the 
follow-up and LTFU period. Investigators should report the lactation case and forward the 
Special Situations Reporting Forms to Kite Patient Safety and Pharmacovigilance at 
Safety_FC@gilead.com or fax: +1 (650) 522-5477.
8.8.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the Special Situations Reporting Form and 
forwarded to Kite Patient Safety and Pharmacovigilance within 24 hours after the investigator 
becomes aware of the situation. These reports must consist of situations that involve study drug 
and/or Kite concomitant medications, but do not apply to non-Kite concomitant medications.
Special situations involving non-Kite concomitant medications do not need to be reported on the 
special situations report form; however, special situations that result in AEs due to a non-Kite 
concomitant medication, must be reported as an AE.
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome of the AEs or SAEs will be reported, when available. 
Refer to Section 8.8.2.1 and the eCRF completion guidelines for instructions on special situation 
reporting.
8.9.
Safety Review Team
The SRT is comprised of the Kite medical monitor, drug safety physician, study statistician, and 
at least 1 active study investigator. The SRT will be specifically chartered to review the safety 
data during this Phase 1 study. The SRT will assess DLTs in the dose-escalation part and AEs 
throughout the study. Additional SRT oversight includes ensuring the correct interpretation of 
the 3 + 3 design on dose escalation or de-escalation decisions, assessing criteria to pause 
enrollment for safety issues, confirming the optimal dose of KITE-222 for use with the 
expansion cohort and adding or adjusting the dose cohorts in the dose-escalation part. 
Furthermore, the SRT will meet after the sixth subject in the expansion cohort has been dosed 
and followed for 28 days to continue in-depth monitoring of AEs and SAEs. The SRT will meet 
at least once for each dose-escalation cohort and Ad Hoc throughout the course of the study to 
address emerging safety or study conduct concerns.
The SRT recommendations will be formally communicated to the participating sites.


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8.10.
Criteria to Pause or Stop Enrollment
As part of its oversight of the study, the SRT will assess the criteria to pause or stop enrollment.
Enrollment will be paused or stopped if the following KITE-222-related AEs are observed:

After approximately 14 subjects have been treated with KITE-222 and have had the 
opportunity to be followed for 21 days, the incidence of Grade 4 CRS is greater than 25%

Any new malignancy (ie, a malignancy that is not recurrence/progression of the previously 
treated malignancy) that is possibly related to KITE-222

Any life-threatening (Grade 4) toxicity attributable to KITE-222 that is unmanageable and 
not described as a potential risk in the IB or seen in the underlying disease

Any Grade 4 or higher infections related to KITE-222 or lymphodepleting chemotherapy

Any Grade 4 infusion reaction/hypersensitivity

Any Grade 4 cardiac event

Any Grade 4 neurologic toxicity

Any Grade 5 SAE after KITE-222 infusion at least possibly related to KITE-222
The appropriate regulatory authorities will be notified within the applicable safety reporting 
timelines if any of these stopping or pausing rules occur. Accrual will be resumed upon the 
recommendation of the SRT.


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9.
STATISTICAL CONSIDERATIONS
9.1.
Statistical Analysis Plan
An overview of the statistical analysis plan (SAP) is provided below. Details will be provided in 
the SAP.
9.2.
Hypothesis
No formal hypothesis will be tested in this Phase 1 study.
9.3.
Determination of Sample Size
The anticipated enrollment in this study should allow for having 40 subjects treated; up to 
18 subjects will be enrolled in the dose-escalation part and 22 subjects will be the target number 
for enrollment in the expansion cohort. Refer to Section 3.2 for more details on the study design.
With a total sample size of 28 subjects at the selected dose level, an observed CCR rate of 50% 
(14 of 28 subjects) will yield an exact 95% confidence intervals (CIs) of 31% and 69%. 
Additional assumptions and corresponding 2-sided 95% exact CIs are provided in Table 9.
Table 9.
Exact 95% Confidence Intervals Corresponding to Composite 
Complete Remission Rate
Subjects with CCR
Observed CCR Rate*
95% Confidence Interval
10
36%
[19%, 56%]
12
43%
[24%, 63%]
14
50%
[31%, 69%]
16
57%
[37%, 76%]
18
64%
[44%, 81%]
Abbreviations: CCR, composite complete remission
* Total of 28 treated subjects at the selected dose level
9.4.
Access to Individual Subject Treatment Assignments and Minimization of 
Bias
This is a single-arm, open-label study, and subjects and investigators will be aware of treatment 
received. Data handling procedures for the study will be devised to reduce potential sources of 
bias and maintain the validity and credibility of the study. These procedures will be outlined in 
the study SAP and SRT charter.
9.5.
Planned Analysis
9.5.1.
Interim Analysis and Early Stopping Guidelines
Formal interim analyses of efficacy are not planned for the early trial stopping purpose.


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An SRT will be chartered to review safety during the Phase 1 dose-escalation part of the study 
and to make recommendations on further study conduct in the Phase 1 dose-escalation cohorts.
Before the final analysis, interim analyses may be conducted and submitted to regulatory 
agencies to seek guidance for the overall clinical development program.
9.6.
Primary Analysis
The primary analysis of the primary endpoint will be conducted when the last treated subject in 
the dose expansion cohort has had the opportunity to be evaluated for response 3 months after 
KITE-222 infusion or 1 month after allo-SCT, whichever occurs first. Additional analyses may 
occur after the primary analysis has been completed; these additional analyses will be 
descriptive.
9.6.1.
Final Analysis
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.
9.6.2.
Long-term Data Analysis 
All subjects will be followed for survival for up to approximately 15 years after the last subject 
receives KITE-222; LTFU will be performed on subjects after the transition to the LTFU study 
(refer to Section 3.4 and Section 3.5).
No formal hypothesis testing will be performed on the data obtained after the data cutoff date for 
the primary analysis. Descriptive estimates of key efficacy and safety analyses may be updated 
to assess the overall treatment profile.
9.7.
Analysis Conventions
9.7.1.
Analysis Sets
The following analysis sets will be used to analyze study data:

Full analysis set (FAS): consists of all enrolled subjects. The FAS will be used for summaries 
of subject disposition.

mITT set: consists of all subjects enrolled and treated with at least 50% of the optimal dose 
of KITE-222 including all subjects treated in both the dose-escalation cohort and the 
expansion cohort. The mITT analysis set will be used for all efficacy analyses unless 
otherwise specified.

DLT-evaluable set: defined for each dosing cohort in the dose-escalation part of the study, 
consists of subjects treated in each dose-escalation cohort who:


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Received the target dose and were followed for at least 28 days after infusion of 
KITE-222; or
Received a dose of KITE-222 that was lower than the target for that cohort and 
experienced a DLT during the 28-day post infusion period

Safety analysis set: consists of all subjects treated with any dose of KITE-222
9.8.
Demographic Data and Baseline Characteristics
Demographic and baseline measurements will include sex, race/ethnicity, age, disease 
characteristics, and will be summarized using standard descriptive methods.
9.9.
Efficacy Analysis
9.9.1.
Composite Complete Remission Rate
The incidence of CCR (CR + CRMRD− + CRi as defined by the ELN 2017 Classification and 
described in Section 12.5) and exact 2-sided 95% CIs will be generated. All subjects who do not 
meet the criteria for CR, CRMRD−, or CRi by the analysis data cutoff date will be considered 
nonresponders for the overall CR rate evaluation.
9.9.2.
Overall Remission Rate
The incidence of the OR rate (CR + CRMRD− + CRi + MLFS + PR as defined by the ELN 2017 
Classification and described in Section 12.5) and exact 2-sided 95% CIs will be generated. All 
subjects who do not meet the criteria for CR, CRMRD−, CRi, MLFS, or PR by the analysis data 
cutoff date will be considered nonresponders for the OR rate evaluation.
9.9.3.
Relapse-free Survival
For subjects who experience CR, CRMRD−, or CRi, RFS is defined as the time between their 
first CR/ CRMRD−/CRi to relapse or death due to any cause. Subjects not meeting the criteria for 
relapse or death by the analysis data cutoff date will be censored at their last evaluable disease 
assessment date and their response will be noted as ongoing. The RFS for subjects that undergo 
new anticancer therapies (except for allo-SCT) in the absence of a documented relapse will be 
censored at the last evaluable disease assessment before initiation of any new anticancer 
therapies. Subjects who received subsequent allo-SCT will not be censored at the last disease 
assessment before the allo-SCT; instead, the response after allo-SCT will contribute to the 
derivation of RFS.
Both hematological and molecular RFS (as defined in Section 12.5) Kaplan-Meier estimates and 
2-sided 95% CIs will be generated for RFS. Estimates of the proportion of subjects in remission 
at 3-month intervals from the first response will be provided.


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9.9.4.
Allo-SCT Rate
The incidence of on study allo-SCT will be summarized by overall, subjects achieving 
CRMRD−, and subjects achieving CR + CRi. Corresponding 2-sided 95% CIs will be generated.
9.9.5.
Event-free Survival
EFS is defined as the time from the KITE-222 infusion date to the earliest date of disease 
relapse, progressive disease, refractory disease, or death due to any cause. Refractory disease is 
defined as the subject not experiencing CR, CRMRD−, or CRi by the Week 6 disease assessment 
as defined in Section 12.5.
The following criteria will be used to further define events and event times:

Subjects with an established CR, CRMRD−, or CRi who subsequently commence new 
anticancer therapy (except for allo-SCT) in the absence of documented relapse will have their 
EFS time defined as the time from the KITE-222 infusion date to the last evaluable disease 
assessment prior to the new anticancer therapy.

Subjects with best response of MLFS, PR or stable disease (SD) and who subsequently 
commence new anticancer therapy (including allo-SCT) in the absence of documented 
disease progression before the Week 6 assessment, will have their EFS time defined as the 
time from the KITE-222 infusion date to the disease assessment prior to the new anticancer 
therapy.
The following criteria will be used to further define censoring times:

Subjects alive, in response (CR, CRMRD−, or CRi), and with no new anticancer therapy 
(except for allo-SCT) will be censored at the last evaluable disease assessment

Subjects with no evaluable disease assessment at the data cutoff date, who are yet to reach 
the Week 6 disease assessment, will be censored at the KITE-222 infusion date.
KM estimates and 2-sided 95% CIs will be generated for EFS. Estimates of the proportion of 
subjects with EFS at 3-month intervals will be provided.
9.9.6.
Overall Survival
OS is defined as the time from KITE-222 infusion to the date of death from any cause. Subjects 
who have not died by the analysis data cutoff date will be censored at their last contact date.
Kaplan-Meier (KM) estimates and 2-sided 95% CIs will be generated for OS. Estimates of the 
proportion of subjects alive at 3-month intervals will be provided.


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9.9.7.
30- and 60-day All-cause Mortality
The mortality rate is calculated by number of deaths, regardless of cause, within 30 or 60 days 
from the KITE-222 infusion date divided by the total number of subjects included in the safety 
analysis set. The incidence of 30- and 60-day mortality and exact 2-sided 95% CIs will be 
generated.
9.9.8.
MRD− Response Rate
The incidence of MRD− response per the ELN 2017 Classification (as defined in Section 12.5) 
will be summarized. Corresponding exact 2-sided 95% CIs will be generated.
For subjects achieving CR who have not undergone allo-SCT, MRD− at 6 months, 12 months 
and 24 months will also be summarized.
9.10.
Safety Analysis
Subject incidence of treatment-emergent adverse events (TEAEs), defined as any AEs with onset 
on or after the date of KITE-222 infusion, will be summarized. TEAEs, including all, serious, 
fatal, CTCAE version 5.0 Grade 3 or higher, and treatment-related AEs will be tabulated by 
preferred term (PT) and/or system organ class (SOC). CTCAE grade changes in safety laboratory 
values will be summarized with descriptive statistics. The incidence of concomitant medications 
will be summarized. Clinical and laboratory AEs will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA).
Time to neutrophil recovery and time to platelet recovery after KITE-222 infusion and before the 
start of the conditioning therapy for allo-SCT will be summarized with descriptive statistics as 
follows:

Time to neutrophil recovery will be calculated as the time from the date of KITE-222 
infusion to the first day when neutrophils are 0.5 × 109/L, and as the time from the date of 
KITE-222 infusion to the first day when neutrophils are 1.0 × 109/L.

Time to platelet recovery will be calculated as the time from the date of KITE-222 infusion 
to the first day when platelets are 50 × 109/L, and the time from the date of KITE-222 
infusion to the first day platelets are 100 × 109/L.
The percentage of primary graft failure after allo-SCT with the 95% CIs will be summarized.
The incidence of anti-KITE-222 CAR antibodies will be summarized. Tables and/or narratives of 
deaths through the long-term follow-up period and treatment-related SAEs will be provided.
9.11.
Pharmacokinetics Analysis
For each pharmacokinetic time point, the peak, AUC, and time to peak will be tabulated for 
KITE-222 CAR T cells.


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Additional pharmacokinetic analyses may also be performed and details of these analyses will be 
included in the supplementary SAP.
9.12.
Pharmacodynamics Analysis
For each pharmacodynamics time point, the peak, AUC, and time to peak will be tabulated for 
key analytes (pro-inflammatory and immune-modulating cytokines, chemokines, and effector 
molecules) in serum over time.
Additional pharmacodynamic analyses may also be performed, and details of these analyses will 
be included in the supplementary SAP.


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


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
10.1.4. 
Confidentiality 
The investigator must assure that subjects' anonymity will be strictly maintained and that their 
identities are protected from unauthorized pa1iies. Only an ID code and any other unique 
identifier(s) as allowed by local law (such as subject's year of bi1ih) will be recorded on any 
fo1m or biological sample submitted to Kite or the laborato1y . Laborato1y specimens must be 
labeled in such a way as to protect subject identity while allowing the results to be recorded to 
the proper subject (refer to specific laborato1y instructions for finiher info1mation). Subject data 
will be processed in accordance with all applicable regulations. 
The investigator agrees that all info1mation received from Kite, including but not limited to the 
IB, this protocol, eCRFs, the study drng, and any other study info1mation, remain the sole and 
exclusive prope1iy of Kite during the conduct of the study and thereafter. This infonnation is not 
to be disclosed to any third paiiy ( except employees or agents directly involved in the conduct of 
the study or as required by law) without prior written consent from Kite. The investigator finiher 
agrees to take all reasonable precautions to prevent the disclosure by any employee or agent of 
the study site to any third paiiy or othe1wise into the public domain. 
Per the Federal regulations and International Council for Haimonisation of Technical 
Requirements for Phannaceuticals for Human Use (ICH)/GCP guidelines, investigators and 
institutions are required to pennit authorization to the sponsor, CRO, IRB/IEC and regulato1y 
agencies to subject's original source documents for the verification of study data. The 
investigator is responsible for infonning potential subjects that such individuals will have access 
to their medical records, which include personal infonnation. 
Subject confidentiality must be maintained on all material submitted to the key sponsor contact. 
The following rnles ai·e to be applied: 
• 
Subjects will be identified by a unique ID number 
• 
Subject's year ofbiii h/age at the time of emollment will be repo1i ed according to local laws 
and regulations 
For repo1iing of SAEs, subjects will be identified by theii· respective subject ID number and yeai· 
of bi1i h (as per theii· local reporting requii·ements). 
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10.1.5.
Study Files and Retention of Records
The investigator will maintain a list of qualified staff to whom study responsibilities have been 
delegated. These individuals authorized to fulfil these responsibilities should be outlined and 
included in the Delegation of Authority Form.
Source documents are original documents, data, and records for which the study data are 
collected and verified. Example of such source documents may include, but are not limited to, 
hospital records and patient charts, laboratory, pharmacy, radiology and records, subject diaries, 
microfiches, correspondence and death registries.
The investigator and study staff are responsible for maintaining a comprehensive filing system of 
all subject records that are readily retrieved to be monitored and or audited at any time by the key 
sponsor contact, regulatory authorities and IRB/IECs. The filing system will include, at a 
minimum, the following:

Subject content including the ICFs and subject ID lists

Essential documents for the conduct of this clinical study

Proof of receipt, experimental treatment flow records, and experimental product-related 
correspondence
Original source documents supporting entries into eCRFs must be maintained at the site and 
readily available upon request. No study documents should be discarded without prior written 
agreement between Kite and the investigator. Should storage no longer be available to archive 
source documents or if they must be moved to an alternative location, the study staff should 
notify the key sponsor contact before shipping the documents.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject ID

Documentation that the subject meets the eligibility criteria (ie, medical history, physical 
examination, and confirmation of diagnosis [to support eligibility criteria])

Documentation of the reason(s) a consented subject is not enrolled

Participation in the study (including study number/name)

Study discussed and the date of informed consent

Dates of all visits

Documentation that protocol-specific procedures were performed


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
Results of efficacy parameters, as required by the protocol

Start and end date (including the dose regimen) of IP, including start and stop times of 
KITE-222 administration

Record of all AEs and other safety parameters (the start and end date, and including causality 
and severity), and documentation that adequate medical care has been provided for any AE

Concomitant medication (including the start and end date, dose if relevant; dose changes)

Date of study completion and reason for early discontinuation, if it occurs
Traceability records for the product, from procurement through manufacture to the 
administration of the product, should be kept by each relevant party (eg, the sponsor and the 
investigator/institution) for a minimum of 30 years after the expiry date of the product, or longer 
if required by the terms of the clinical trial authorization or by agreement with the sponsor. 
Before, during, and after completion or termination of the trial, each party should hold the 
necessary information available at all times to ensure bidirectional traceability, linking the 
subject information at the procurement site to the product and the subject information at the 
clinical trial site to the product, while ensuring the data protection legally required for the 
subject.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Kite to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
If a subject transfers to another study site, the investigator must notify Kite in advance before 
assigning the subject’s study records to another party or moving them to another location.
10.1.6.
Electronic Case Report Forms
All data will be collected in an eCRF system. All entries must be completed in English and 
concomitant medications should be identified by tradenames. For further details surrounding the 
completion of the eCRFs, refer to the eCRF completion guidelines.
For each subject consented, an eCRF casebook will be completed by an authorized study staff 
member whose training for this function is completed in the EDC system. The eCRF casebook 
will only capture the data required per the protocol SOA. The eligibility criteria and enrollment 
eCRFs should be completed only after all the data related to the study eligibility have been 
received. Data entry should be performed in accordance with the eCRF completion guidelines 
provided by the sponsor.
Subsequent to the data entry, a study monitor will perform source data verification within the 
EDC system. System-generated or manual queries will be issued in the EDC system as data 
discrepancies are identified by the monitor or Kite staff, who routinely review the data for 


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completeness, correctness, and consistency. The site investigator or site coordinator or other 
designee is responsible for responding to the queries in a timely manner, within the system, 
either by confirming the data as correct or updating the original entry, and providing the reason 
for the update (eg, data entry error). The original entries as well as any changes to data fields will 
be stored in the audit trail of the system. At a minimum, before any interim time points or 
database lock (as instructed by Kite), the investigator will use his/her log in credentials to 
confirm that the forms have been reviewed, and that the entries accurately reflect the information 
in the source documents.
At the conclusion of the study, Kite will provide the site investigator with a read-only archive 
copy of the data entered by that site. This archive must be stored in accordance with the records 
retention requirements outlined in Section 10.1.5.
10.1.7.
Access to Study Information
The investigator will make available all source documents and other records for this study to 
Kite’s appointed study monitors, to IRBs/IECs, or to regulatory authority or health authority 
inspectors. By signing the investigator statement, the investigator agrees to cooperate with the 
monitor to address and resolve issues identified during monitoring visits, audits, and regulatory 
authority inspections.
10.1.8.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations as described in this protocol.
10.2.
Sponsor Responsibilities
10.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce an immediate risk to study subjects, may 
be made only by Kite. The investigator must submit all protocol modifications to the IRB/IEC in 
accordance with local requirements and receive documented approval from the IRB/IEC before 
modifications can be implemented. Documentation acknowledging the agreement with the 
protocol amendment from the investigator and approval from the IRB/IEC are to be submitted to 
the key sponsor contact.
10.2.2.
Study Report and Publications
A clinical study report will be prepared and provided to the regulatory agency. Kite will ensure 
that the report meets the standards set out in the ICH Guideline for Structure and Content of 
Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in certain 
cases.
Investigators in this study may not communicate study results via oral presentation, scientific 
publication, or other scholarly media until the following conditions have been met:


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
The results of the study in their entirety have been publicly disclosed by or with the consent 
of Kite in an abstract, manuscript, or presentation form or the study has been completed at all 
study sites for at least 2 years.

The investigator will submit to Kite any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before the submission of 
the publication or presentation.

No such communication, presentation, or publication will include Kite’s confidential 
information (see Section 10.1.4).
The investigator will comply with Kite’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
10.2.3.
Financing and Insurance
Kite will provide compensation for study-related illness or injury pursuant to the information 
outlined in the injury section of the ICF.
Investigators and their study staff may be asked to provide services performed under this 
protocol (eg, attendance at investigator meetings). If required under the applicable statutory and 
regulatory requirements, Kite will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical study payments, meal, 
travel expenses or reimbursements, consulting fees, and any other transfer of value.
10.3.
Joint Investigator/Sponsor Responsibilities
10.3.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the ICH E6 (R2) 
addendum to its guideline for GCP and applicable laws and regulations.
10.3.2.
Ethics
Study KT-US-486-0201 will be conducted under a US investigational new drug (IND) 
application or equivalent and in accordance with recognized international scientific and ethical 
standards, including but not limited to the ICH guideline for GCP, and the original principles 
embodied in the Declaration of Helsinki. These standards are consistent with the requirements of 
the US CFR Title 21, Part 312 [(21CFR312)], and the European Community Directive 
2001/20/EC, as well as other local legislation.


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10.3.3.
Quality Control and Quality Assurance
The key sponsor contact, monitors, auditors or regulatory inspectors are responsible for 
contacting and visiting the investigator for the purpose of inspecting the facilities and verifying 
source documents and records assuring that subject confidentially is respected.
The monitor is responsible for source document verification of eCRF data at regular intervals 
during the study. Protocol adherence, accuracy and consistency of study conduct and data 
collection with respect to local regulations will be confirmed.
In accordance with ICH GCP and the audit plan, a site may be chosen for a Kite Quality 
Assurance site audit. A Kite Quality Assurance site audit would include, but is not limited to, an 
inspection of the facility(ies), review of subject and study-related records, and compliance with 
protocol requirements as well as ICH GCP and applicable regulatory policies. Investigators will 
provide the Kite Quality Assurance auditors access to subject records.
Representatives of regulatory authorities may conduct inspections of the clinical study. If the 
investigator is notified of an inspection by a regulatory authority, the investigator agrees to notify 
the Kite medical monitor immediately. The investigator agrees to provide to representatives of a 
regulatory agency access to records, facilities, and personnel for the effective conduct of any 
inspection or audit.
10.3.4.
Study Discontinuation
Both Kite and the investigator reserve the right to terminate the investigator’s participation in the 
study as per the terms of the agreement in the study contract. The investigator is to provide 
written communication to the IRB/IEC of the trial completion or early termination.


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11.
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Induction Therapy [Author Manuscript]. Biol Blood Marrow Transplant 2015;21 
(3):559-64.
Passweg JR, Baldomero H, Chabannon C, Basak GW, Corbacioglu S, Duarte R, et al. The 
EBMT activity survey on hematopoietic-cell transplantation and cellular therapy 
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Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, et al. Gilteritinib or 
Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med 
2019;381 (18):1728-40.
Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, et al. Anti-BCMA CAR T-Cell 
Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. N Engl J Med 
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Redelinghuys P, Brown GD. Inhibitory C-type lectin receptors in myeloid cells. Immunol Lett 
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Roboz GJ, Rosenblat T, Arellano M, Gobbi M, Altman JK, Montesinos P, et al. International 
Randomized Phase III Study of Elacytarabine Versus Investigator Choice in 
Patients With Relapsed/Refractory Acute Myeloid Leukemia. J Clin Oncol 
2014;32 (18):1919-26.
Sant M, Minicozzi P, Mounier M, Anderson LA, Brenner H, Holleczek B, et al. Survival for 
haematological malignancies in Europe between 1997 and 2008 by region and 
age: results of EUROCARE-5, a population-based study. Lancet Oncol 2014;15 
(9):931-42.
Sarkozy C, Gardin C, Gachard N, Merabet F, Turlure P, Malfuson JV, et al. Outcome of Older 
Patients with Acute Myeloid Leukemia in First Relapse. Am J Hematol 
2013;88:758-64.
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. 
Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell 
Lymphoma. N Engl J Med 2019;380 (1):45-56.
Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, et al. Long-term clinical 
outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-
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Lancet Oncol 2021;22 (10):1403-15.
Shah BD, Ghobadi A, Oluwole OO, Logan AC, Boissel N, Cassaday RD, et al. KTE-X19 for 
relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results 
of the single-arm, open-label, multicentre ZUMA-3 study. Lancet 2021a;398 
(10299):491-502.
Shah BD, Jacobson CA, Solomon S, Jain N, Vainorius M, Johnson MC, et al. Preliminary Safety 
and Efficacy of PBCAR0191, an Allogeneic, Off-the-shelf CD19-targeting CAR-
T Product, in Relapsed/Refractory (r/r) CD19+ NHL [Poster]. American Society 
of Clinical Oncology (ASCO); 2021b 4-8 June; Virtual. 
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Stahl M, DeVeaux M, Montesinos P, Itzykson R, Ritchie EK, Sekeres MA, et al. 
Hypomethylating Agents in Relapsed and Refractory AML: Outcomes and Their 
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Stein EM, DiNardo CD, Fathi AT, Pollyea DA, Stone RM, Altman JK, et al. Molecular 
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leukemia treated with enasidenib. Blood 2019;133 (7):676-87.
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mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 2017;130 
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Sun Y, Wang S, Zhao L, Zhang B, Chen H. IFN-gamma and TNF-alpha Aggravate Endothelial 
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safety profile of fractionated doses of Mylotarg as induction therapy in patients 
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Leukemia 2007;21 (1):66-71.
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De Novo Acute Myeloid Leukemia [Author Manuscript]. N Engl J Med 2013;368 
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12.
APPENDICES
Section 12.1
Sponsor and Investigator Signature Page
Section 12.2
Schedule of Assessments
Section 12.3
Childbearing Potential and Birth Control
Section 12.4
Country-specific Requirements
Section 12.5
Response Criteria in AML (Based on European Leukemia Net 2017 Classification)
Section 12.6
Immune Effector Cell-associated Encephalopathy Score
Section 12.7
Pandemic Risk Assessment and Mitigation Plan


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12.1.
Sponsor and Investigator Signature Page
KITE PHARMA, INC.
2400 BROADWAY
SANTA MONICA, CA 90404
STUDY ACKNOWLEDGMENT
A Phase 1 Open-label, Multicenter Study Evaluating the Safety of KITE-222,
an Autologous Anti-CLL-1 CAR T-cell Therapy in Subjects with 
Relapsed/Refractory Acute Myeloid Leukemia
Version: Amendment 4.0, 17 January 2023
This protocol has been approved by Kite Pharma, Inc. The following signature documents this 
approval.
Name (Printed)
Kite Medical Monitor
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 the 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
Site Number
DocuSign Envelope ID: 7560AD13-A6A7-4023-A45F-B65A08F7BDA7
18-Jan-2023
PPD
PPD


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12.2.
Schedule of Assessments
The SOA and procedures to be performed during the treatment and post-treatment follow-up 
periods are presented in Table 10. The SOAs and procedures to be performed during the 
follow-up period are presented in Table 11 and Table 12.


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
Table 10. 
Schedule of Assessments -Treatment Period and Post-treatment Follow-up Period 
Timeframe: 
Procedures 
Demographic data 
Medical history1' 
Previous cancer treatment history 
Physical examinationE.F 
Vital signsF,G 
ECOG performance status 
Weight (plus height at screening) 
Neurologic examination and 
assessment (ICE score)H 
ECG 
ECHCY 
Brain MRI or CT (if MRI is not 
feasible)2 
Chest imaging (x-ray or CT or MRI 
scan) 
Lumbar puncture (for CSF)E.1 
CONFIDENTIAL 
Screening 
(Days 
Before 
Enroll-
ment) 
:S14d 7d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
xi 
Pretreatment Period 
Enrollment/ 
Leuka-
pheresis 
Within 
approx. 7 days 
afte1· eligibility 
confirmationA 
X 
X 
Lympho-
depleting 
Chemo-
therapy 
Inpatient Hospitalization 
Period 
Infusion of KITE-222 (DO) and 
Monito1ing 
Post-tr eatment Follow-up 
Without Allo-SCT 
( calculated from DO) 
With Allo-SCT 
Allo-SCT: 
within 
D-1 of 
IP D1 to W2 
15 to w4c WS 
wc;<: W7 M2c 
M3c 
1 week 
Allo-
DO D13 (±2d) D27 (±3d) (±3d) (±3d) (±3d) (±1 w) (±1 w) before CC SCT 
X 
X 
X 
X 
X 
X 
X 
X 
QOD 
X 
QOD 
X 
X 
X 
X 
X 
X 
X 
QOD 
X 
X 
X 
X 
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17 Janua1y 2023 


KITE-222 
Protocol KT-US-486-0201 
Timeframe: 
Procedures 
Disease assessments 
BM aspirateK and MRD 
BM biopsy!( 
Extramedulla1y disease 
assessment (only subjects with 
non-CNS extramedullaiy 
disease)L 
Local laboratory assessments 
Chemistiy p311el (includes CrCl 
at screening and before 
lymphodepleting chemotherapy) 
(semm)f 
Coagulation (plasma)N 
CBC with differential (blood)0 
CRP, fen-i.tin, LDHP (serum) 
Pregnancy test ( semm or m-i.ne )Q 
Donor chimerismR 
Serology (EU sites)S 
CONFIDENTIAL 
Pretreatment Period 
Screening1-----~ 
(Days 
Before 
Enroll-
ment) 
~14d 
X 
X 
X 
X 
X 
X 
X 
XQ 
x s 
Enrollment/ 
Leuka-
pheresis 
Within 
X 
X 
X 
X 
Lympho-
depleting 
Chemo-
therapy 
Inpatient Hospitalization 
Period 
Infusion of KITE-222 (DO) and 
Monito1ing 
Kite Pha1m a, Inc. 
Amendment 4.0 
Post-treatment Follow-up 
Without Allo-SCT 
( calculated from DO) 
With Allo-SCT 
Allo-SCT: 
within 
D-1 of 
D1 to W2 
15 to W4c WS W6c W7 
M2c 
M3c 
1 week 
Allo-
D13 (±2d) D27 (±3d) (±3d) (±3d) (±3d) (±1 w) (±1 w) before CC SCT 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
D21 
X 
X 
X 
X 
X 
±2d 
X 
X 
X 
D21 
X 
X 
X 
X 
X 
±2d 
X 
X 
X 
QOD 
X 
X 
X 
X 
X 
X 
X 
X 
XP Dl-7P 
XP 
XQ 
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17 Janua1y 2023 


KITE-222 
Protocol KT-US-486-0201 
Timeframe: 
Procedures 
Central laboratory assessments 
Anti-KITE-222 CAR antibodies 
(senun)f,T 
CLL-1 expression (blood) 
KITE-222 IV infusion 
Subsequent therapy for AMLX 
Concomitant medicationsF,Y 
Pretreatment Period 
Screeningi-------
(Days 
Before 
Enroll-
ment) 
~14d 
X 
Enrollment/ 
Leuka-
pheresis 
Within 
Lympho-
depleting 
Chemo-
therapy 
Inpatient Hospitalization 
Period 
Infusion of KITE-222 (DO) and 
Monito1ing 
Kite Pha1m a, Inc. 
Amendment 4.0 
Post-treatment Follow-up 
Without Allo-SCT 
( calculated from DO) 
With Allo-SCT 
Allo-SCT: 
within 
D-1 of 
D1 to W2 
15 to W4c WS 
W6c W7 
M2c 
M3c 
1 week 
Allo-
D13 (±2d) D27 (±3d) (±3d) (±3d) (±3d) (±1 w) (±1 w) before CC SCT 
X 
QOD 
X 
X 
X 
X 
X 
X 
D21 
±2d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AE, adverse event; allo-SCT, allogenic stem-cell transplant; AML, acute myeloid leukemia; approx., approximately; BM, bone ma11'0w; CAR, chimeric antigen 
receptor; CBC, complete blood count; CLL-1, C-type lectin-Iike molecule-I; CC, conditioning chemotherapy; CNS, central nervous system; CrCI, creat.in.ine clearance; CRP, 
C-reactive protein; CRS, cytokine release syndrome; CSF, cerebral spinal fluid; CT, computed tomography; D, Day of study; d, day; ECG, electrocardiogram; ECHO, 
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echocardiogram; ECOG, Eastern Cooperative Oncology Group; EU, European Union; HIV, human immunodeficiency virus; ICE, immune-effector cell-associated 
encephalopathy; ICF, informed consent form; IP, investigational product; IV, intravenous(ly); LDH, lactate dehydrogenase; M, month; MRD, measurable residual disease; MRI, 
magnetic resonance imaging; PBMC, peripheral blood mononuclear cell; QOD, every other day;
; SAE, serious adverse event; SOA, 
schedule of assessments; W, Week of study; w, week. 
A. Assessments must be done before the start of leukapheresis. 
B. Assessments must be done before the start of the dosing of the lymphodepleting chemotherapy. 
C. Week (W) or Month (M) X refers to the end of X weeks or months, respectively, after infusion of KITE-222 (eg, Month 6 = 6 months after infusion). 
D. Medical history: Medical history will include description of the features of the AML at time of diagnosis (including cytogenetics and molecular classification, prior therapies, 
and responses). It will also include identification of the donor source for a potential allo-SCT. 
E. Physical examination: Subjects with new-onset symptoms related to CRS should undergo physical examination at least daily until symptoms resolve to baseline. Subjects with 
symptoms of CNS malignancy, such as new onset severe headaches, neck stiffness, seizures, encephalopathy, cranial nerve deficits, or any focal neurologic findings from the 
physical examination, will have a brain MRI or CT (if MRI is not feasible) and lumbar puncture for examination of CSF. 
F. Assessments to be performed at disease progression: If a subject’s disease progresses, the following procedures will be completed (refer to Section 7.8.2): Disease 
assessment (including a BM aspirate and
); 
 
s); key analytes (including cytokines) (serum), CLL-1 expression (blood), anti-KITE-222 CAR antibodies (serum), AE/SAE reporting; 
and documentation of concomitant medications.
G. Vital signs: Includes blood pressure, heart rate, respiration rate, oxygen saturation, and temperature. In addition to the time points outlined in the SOA, 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. 
H. Neurologic examination and assessment: A neurologic examination including an ICE cognition assessment, should be done during the screening period and before the 
KITE-222 infusion on Day 0, then every other day until W2 and again on W4, M3 and within 1 week before the conditioning chemotherapy for allo-SCT. If subject has a 
change in the baseline neurologic examination and assessment, an evaluation should be performed daily until the symptoms return to baseline status. For new onset of 
neurologic symptoms, a neurologic examination should be performed at least daily until symptoms resolve to baseline (refer to Section 6.3.8).
I.
ECHO: An ECHO performed after the subject’s last chemotherapy treatment and within the 28 days before signing the ICF may be used to confirm eligibility (if the last 
chemotherapy regimen is not considered cardiotoxic).
J.
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, leptomeningeal carcinomatosis, or symptoms of CNS malignancy (such as new onset severe headaches, neck 
stiffness, or any focal neurological findings) will undergo a lumbar puncture at the screening visit for examination of CSF to determine the presence of a CNS 
malignancy.

After infusion: During D1 to W4, a lumbar puncture is recommended for subjects with new onset of clinically significant neurologic toxicities of severity Grade 2 or 
higher after KITE-222 infusion unless contraindicated. CSF samples obtained after KITE-222 infusion will be submitted to the central laboratory and analyzed for levels 
of key analytes (including cytokines) and presence of CAR T cells.
K. BM aspirate/biopsy and MRD: 

All BM samples are to be submitted to the central laboratory. Biopsy must also be obtained if the corresponding aspiration results in a dry tap. For each BM aspirate 
collected, a portion of the aspirate will be submitted to the central laboratory on the day of collection and analyzed for MRD; refer to the central laboratory manual for 
details. 

Screening/pretreatment period: Both a BM aspirate and biopsy will be required during the screening period and must be obtained after the most recent anti-cancer 
therapy. An archived sample from the original diagnosis should be submitted to the central laboratory if possible. This is in addition to the fresh BM sample (aspirate and 
biopsy) obtained at screening disease assessment. The archived sample may be either a formalin-fixed paraffin-embedded BM biopsy or approximately 20 unstained 
slides. The archived samples will be submitted to the central laboratory once the study eligibility has been confirmed. 

Bridging therapy: BM aspirate and biopsy sample must be repeated in subjects receiving bridging therapy. This assessment should occur 1 to 2 days before the initiation 
of lymphodepleting chemotherapy or as close to the planned date of lymphodepleting chemotherapy as feasible to ensure the subject still meets eligibility criteria for the 
study based on morphologic disease. 
CCI
CCI
CCI
CCI


KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
• 
Inpatient hospitalization period and post-treatment follow-up: BM aspirate and biopsy will be requit·ed at Week 2. Please refer to Section 12.4 for additional 
country-specific requirements. Additionally, BM aspit·ates are required at Week 4, Week 6, and Month 3; if the BM aspit·ate is either a diy tap or is hemodiluted, a biopsy 
must be obtained. 
• 
Allo-SCT: BM aspit·ate and biopsy (only if diy tap aspirate) must be pe1fo1med within 1 week before the sta,t of the conditioning chemotherapy for allo-SCT. 
L. Extramedullary Disease Assessment: Extramedullaiy disease assessment must be repeated for subjects who received bridging therapy. This assessment should occur 1 to 
M . 
2 days before the initiation of lymphodepleting chemotherapy or as close to the planned date of lymphodepleting chemotherapy as feasible to ensure the subject still meets 
eligibility criteria for the study based on morphologic disease. Subjects should undergo extramedullaiy disease assessment within 1 week before the start of conditioning 
chemothera 
for allo-SCT, unless obtained within 4 weeks before the start of conditionino chemothera . 
N. 
oagt ation 
oo : cu es pro 
0 . CBC with differential (blood): 
• 
Local laboratory assessments: Blood should be collected at the tinie points specified or until disease progression or relapse, whichever occurs first, and sent to the local 
laborato1y for clinical/safety evaluation. CBC with differential including percentage blasts should continue to be sent to the local laboratory daily until the subject's 
absolute neutrophil count is> 1.0 x 109/L and platelets are > 100 x 109/L while the subject is hospitalized or until they start a conditioning regitnen for allo-SCT. After 
allo-SCT, institutional !luidelines will be followed. In addition, a CBC with differential, including blast uantification, is needed within 3 da s of an BM sam !in . 
• 
Central laboratory assessments: With each PBMC submission to the central laborato,y, a blood sample for assessment of CBC with differential should be submitted to 
the central laborato,y to allow for more rapid analysis of KITE-222 CART-cell levels in the blood. These samples are in addition to samples collected at specified titue 
points and that are sent to the local laborato1y for assessment of CBC with differential for clinical/safety evaluation. 
P. LDH (semm): Monitoring ofLDH after KITE-222 infusion is recommended only ifLDH is elevated at baseline. In addition, LDH should be monitored as clinically indicated. 
Q. Pregnancy test (semm or mine): After transplantation, routine surveillance testing according to institutional guidelines should be followed. For EU sites, the test is to be 
completed within the 7 days before leukapheresis, lymphodepleting chemotherapy, and conditioning chemotherapy in case of allo-SCT for females of childbea,ing potential. 
Check country-specific requirements in Section 12.4. 
R. Donor chimerism: For subjects with a prior history of allo-SCT, donor chitnerism should be assessed within approxiniately 7 days after eligibility confumation (when 
available per the local laborato,y). 
S. Serology (semm): For EU sites, vit·al serologic tests (eg, HIV, hepatitis B, hepatitis C, and syphilis) will be carried out per institutional guidelines and EU regulations. Testing 
may be pe1fo1med within 30 days before leukapheresis/enrollment and/or on the day of leukapheresis/enrollment. 
T. Anti-KITE-222 CAR antibodies (senuu): Baseline antibody samples are to be collected before the start ofleukapheresis. 
U. Key analytes (including cytokines) (senllll) and KITE-222 CART cells (PBMCs): 
V 
• 
If a subject is readmitted to the hospital with any KITE-222-related AE after the initial hospitalization for KITE-222 infusion, a senllll sample for the assessment of the 
levels of key analytes (including cytokines) and KITE-222 CART cells will be collected on the day of hospital readmission and then weekly through, and including, the 
day of discharge. 
• 
If the subject experiences a Grade 2 or higher KITE-222-related toxicity, such as Grade 2 CRS or nem·ologic event, 1 additional blood di·aw for key analytes (including 
cytokines) and KITE-222 CART cells will be taken at the tinie of the Grade 2 or higher KITE222 related toxicity and upon resolution of the event. 
• 
Senllll for assessment of key analytes (including cytokines) and PBMCs for KITE-222 CART cells will also be collected at the tinie of disease progression before starting 
an subse uent anticancer thera 
W. 
PBMCs will be collected for-
testing at baseline (before leukapheresis) and at Month 3, Month 6, and Month 12. Thereafter, samples will be held for up to 
years. n y ,fa subject's PBMC sample tests positive for-
~ 
tinie point within the first year, samples will continue to be collected and tested annually for up 15 
years or as clinically indicated (ie, if there is any reason to suspect-
). If a seconda,y malignancy is suspected dming the study or follow-up, eve,y effo,t will be made to 
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obtain a blood sample (PBMC) and a biopsy sample of the neoplastic tissue or the pertinent autopsy tissue to start a testing workflow, including tests such as transgene 
elements, 
 presence of common cancer-drivers/mutations and insertional mutagenesis. Please refer to Section 12.4 for additional country-specific requirements. 
X. Subsequent anticancer therapy for AML: In the case of disease progression, subsequent anticancer therapy administered after KITE-222 infusion for a subject’s disease will be 
recorded in the electronic case report forms for all enrolled subjects until one of the following occurs: subject completes the long-term follow-up period, is considered lost to 
follow-up, withdraws consent, or dies.
Y. AEs, SAEs, and concomitant medications: Collection of AEs starts from the commencement of the leukapheresis procedure. Collection of SAEs starts from signing of the 
screening ICF. AEs/SAEs/concomitant medications should be collected through 3 months after KITE-222 infusion. After the 3-month follow-up period or start of the 
conditioning regimen for allo-SCT, whichever occurs first, only targeted concomitant therapies, targeted AEs and targeted SAEs will be recorded. This will continue for 
24 months after KITE-222 infusion, or until disease progression or relapse, whichever occurs first. Secondary malignancies will be reported through 15 years after the 
KITE-222 infusion. All AEs and SAEs deemed related to KITE-222 infusion should be recorded and reported regardless of study period (Table 11 and Table 12). In the case of 
a secondary malignancy, every effort will be made to obtain a blood sample (PBMC) and biopsy sample or the pertinent autopsy of the neoplastic tissue. This will be 
investigated with a workflow including tests such as transgene elements, 
 presence of common cancer-drivers/mutations, and insertional mutagenesis. Please refer to 
Section 12.4 for additional EU country-specific guidance.
Z. Brain MRI scan: In the case of a prior history of CNS involvement by AML or clinical symptoms suggesting neurological involvement. A CT scan may be performed if the 
MRI is not feasible.
CCI
CCI
-
-


KITE-222 
Protocol KT-US-486-0201 
Table 11. 
Schedule of Assessments - Follow-up Period Without Allo-SCTA 
Procedure (see Notes) 
Physical examination 
Disease assessments 
Extramedulla1y disease assessmentB 
Bone marrow aspirateC 
Bone marrow biopsyC 
Overall disease assessment 
Local laboratory tests 
CBC with differential (blood)D 
Central laboratory tests 
CBC with differential (blood)D 
Anti-KITE-222 CAR antibodies (semm) 
CLL-1 expression (blood) 
Key analytes, including cytokines (semm) 
Targeted AE/SAEsG 
Targeted concomitant medications8 
All KITE-222-related SAEs and any deaths regardless 
of causality 
Subsequent therapy for AMU 
Stuvival statusK 
Month6 
± 2w 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Month 9 Month 12 Month 15 Month 18 
± 2 w 
± 2 w 
± 2w 
± 2 w 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Kite Pha1ma, Inc. 
Amendment 4.0 
Month 72 
Month24 
± 3 m; 
At Disease 
(see 
Annually Progression 
Notes) Month 36 Month48 Month 60 Through 
or 
±lm 
±lm 
± lm 
± lm 
Year 15 
Relapse 
X 
X 
X 
X 
X 
X 
Standard of care 
X 
X 
Standard of care 
X 
I 
I 
I 
x c 
X 
Standard of care 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Notes: After completing at least 24 months of assessments in this study, all subjects who received an infusion ofKITE-222 will be transitioned to a separate LTFU study, after 
providing informed consent, to complete the remainder of the 15-year follow-up period. See abbreviations and footnotes below Table 12. 
CONFIDENTIAL 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
Table 12. 
Schedule of Assessments - Follow-up Period After Allo-SCTA 
Month 72 
Timeframe After Allo-SCT: 
± 3m; 
Month 24 
Annually 
Month 1 Month 3 Month 6 Month9 Month 12 Month 15 Month 18 (see Notes) Month 36 Month 48 Month60 Through 
At 
Procedure (see Notes) 
±3d 
±l w 
±2w 
± 2w 
±2w 
± 2 w 
±2w 
± lm 
± lm 
± lm 
±lm 
Year 15 Relapse 
Physical examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Disease assessments 
Extramedulla1y disease 
assessment8 
X 
X 
X 
X 
X 
X 
Standard of care 
X 
Bone marrow aspiratec 
X 
X 
X 
X 
X 
X 
Standard of care 
X 
Bone marrow biopsy 
I 
I 
I 
X 
Overall disease assessment 
X 
X 
X 
X 
X 
X 
Standard of care 
X 
Local laboratory assessments 
CBC with differential (blood)° 
X 
X 
X 
X 
X 
X 
X 
X 
Central laboratory assessments 
CBC with differential (blood)° 
X 
X 
X 
X 
X 
X 
Anti-KITE-222 CAR antibodies 
X 
X 
X 
X 
X 
(serum) 
----------------------------------------------
CLL-1 expression (blood) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Key analytes, including cytokines 
X 
(serum) 
Targeted AE/SAEsG 
x o 
X 
Targeted concomitant medications8 
XH 
X 
X 
X 
X 
X 
X 
X 
X 
Engraftment assessment1 
X 
All KITE-222-related SAEs and any 
X 
deaths regardless of causality 
Subsequent therapy for AMU 
X 
Stuvival statusK 
X 
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KITE-222 
Kite Pha1ma, Inc. 
Protocol KT-US-486-0201 
Amendment 4.0 
Abbreviations: AE, adverse event; allo-SCT, allogenic stem-cell transplant; AML, acute myeloid leukemia; BM, bone ma1l'Ow; CAR, chimeric antigen receptor; CBC, complete 
blood count; CLL-1, C-type lectin-like molecule-1; CR, complete remission; CR.i, complete remission with incomplete hematolooic recover ; d, da ; eCRF, electronic case repo1t 
fo1m; GVHD, graft-versus-host disease; LTFU, long-term follow-up; m, month; PBMC, peripheral blood mononuclear cell; 
; SAE, serious 
adverse event; w, we.ek. 
Notes: After completing at least 24 months of assessments in this study, all subjects who received an infusion ofKITE-222 will be transitioned to a separate LTFU study, after 
providing informed consent, to complete the remainder of the 15-year follow-up period. 
A. Table 11: Month X refers to the end ofX months after infusion ofKITE-222 (eg, Month 6 = 6 months after infusion). 
Table 12: Month X refers to the end ofX months after allo-SCT (eg, Month 6 = 6 months after allo-SCT). 
B. Extramedullary disease imaging: Extramedullary disease imaging can be stopped after subject is in CR or CR.i if they do not proceed to allo-SCT, until relapse. 
C. All BM sam !es are to be submitted to the central laborato1 . Bio s must also be obtained if the corres ondino as iration results in a di ta or is hemodiluted. 
D. 
E. 
F. 
• 
• 
00 
: 
Local laboratory assessments: Blood, including quantification of the percentage of blasts, should be collected at the time points specified through Month 24 or until 
disease progression or relapse, whichever occtu·s first, and sent to the local laborato1y for clinical/safety evaluation. 
Central laboratory assessments: With each PBMC submission to the central laborato1y, a blood sample for assessment of CBC with differential should be submitted to 
the central laborato1y to allow for more rapid analysis of KITE-222 CART-cell levels in the blood. These samples are in addition to samples collected at specified time 
oints and that are sent to the local laborato1 for assessment of CBC with differential for clinical/safe 
evaluation. 
: 
e o ow-up peno , samp es s 1ou 
e co e.cte. at 
ont 1s , , an 
. 
y I a su ~ect tests positive or 
at any trme pornt wit 1rn e 
-st year, 
samp es w1 continue to be tested yearly for up 15 years or as clinically indicated, ie, if any clinical reason to suspect •
. If a seconda1y malignancy is suspected during the 
study or follow-up, eve1y effort will be made to obtain a blood sample (PBMC) and a biopsy sample of the neoplastic tissue or the pertinent autopsy tissue to start a testing 
workflow, including tests such as ti·ansgene elements,.
, presence of common cancer-drive1-s/mutations and insertional mutagenesis. Please refer to Section 12.4 for 
additional com1try-specific requirements. 
G. Targeted AEs and SAEs: Targeted AEs/SAEs include neurologic, hematologic (only for subjects who do not tmdergo allo-SCT), primary graft failure (only for subjects who 
tmdergo allo-SCT), infections, new occtm·ence, or aggravation of GVHD, and seconda1y malignancy events. 
• 
Subjects who do not tmdergo allo-SCT (Table 11): Targeted AEs/SAEs should be collected for 24 months after KITE222 infusion or until disease progression or relapse, 
whichever occurs first. Only reports of secondary malignancies ( defrned as the development of any new malignancies, except for a relapse of the prima1y malignancy, 
occtming after the KITE-222 ti·eatinent) will be collected for up to 15 yea1-s. 
• 
• 
• 
Subjects who tmdergo allo-SCT (Table 12): Targeted AEs/SAEs should be collected after the start of the conditioning regimen for allo-SCT, through 24 months after 
KITE-222 infusion or tmtil disease progression or relapse, whichever occtu·s first. Only repo1ts of seconda1y malignancies ( defrned as the development of any new 
malignancies, except for a relapse of the p11llla1y malignancy, occtll11llg after the KITE-222 treatinent) will be collected for up to 15 years. 
All AEs and SAEs deemed related to KITE-222 infusion should be recorded and reported regardless of study period . 
In the case of a secondary malignancy, eve1y effort. will be made to obtain a blood s~BMC) and biopsy sample or the pertinent autopsy of the neoplastic tissue . 
This will be investigated with a workflow including tests such as transgene elements,_ 
presence of common cancer-drivers/mutations and insertional mutagenesis. 
H. Targeted concomitant medications: 
• 
Subjects who do not tmdergo allo-SCT (Table 11): Concomitant medications should be collected through 3 months after KITE-222 infusion. From Month 3 onwards 
targeted concomitant medications should be collected for 24 months or tmtil disease progression or relapse, whichever occurs fu-st. Targeted concomitant medications are 
inimtmosuppressive di·ugs, anti-infective drugs, maffow growth factors, tyrosine kinase inl1ibitors, and vaccinations. 
• 
Subjects who tmdergo allo-SCT (Table 12): Concomitant medications should be collected after KITE-222 infusion through 3 months or until the sta1t of the conditioning 
regimen for allo-SCT, whichever occurs first. Thereafter, targeted concomitant medications should be collected through 24 months after KITE-222 infusion or tmtil 
CONFIDENTIAL 
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disease progression or relapse, whichever occurs first. Targeted concomitant medications are immunosuppressive drugs, anti-infective drugs, marrow growth factors, 
tyrosine kinase inhibitors, and vaccinations.
I.
Engraftment: date of engraftment of neutrophils and platelets will be captured in the eCRF
J.
Subsequent anticancer therapy for AML: Subsequent anticancer therapy administered after KITE-222 infusion for a subject’s disease will be recorded in the eCRFs for all 
enrolled subjects until one of the following occurs: subject completes the long-term follow-up period, is considered lost to follow-up, withdraws consent, or dies. Subjects may 
be contacted by telephone to collect information about subsequent therapy for AML. 
K. Survival status: Subjects may be contacted by telephone to assess their survival status. 


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12.3.
Childbearing Potential and Birth Control
This study will follow the recommendations from the Clinical Trial Facilitation Group (CTFG) 
{Clinical Trials Facilitation Group (CTFG) 2014}, as described below.
12.3.1.
Definition of Childbearing Potential
A woman is considered of childbearing potential (ie, fertile) following menarche and until 
becoming postmenopausal unless permanently sterile. Permanent sterilization methods include 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
A postmenopausal state is defined as having no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in females not using hormonal contraception or 
hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single 
FSH measurement is insufficient.
For the purpose of this study, a man is considered fertile after puberty unless permanently sterile 
by bilateral orchidectomy.
12.3.2.
Birth Control Methods That May Be Considered as Highly Effective
Methods that can achieve a failure rate of less than 1% per year when used consistently and 
correctly are considered as highly effective birth control methods. Such methods include:

Combined (estrogen- and progesterone-containing) hormonal contraception associated with 
inhibition of ovulation1:
Oral
Intravaginal
Transdermal

Progestogen-only hormonal contraception associated with inhibition of ovulation1:
Oral
Injectable
Implantable2

Intrauterine device (IUD)2
1 Hormonal contraception may be susceptible to interaction with the investigational product, which may reduce the 
efficacy of the contraception method.
2 Contraception methods that in the context of this guidance are considered to have low user dependency.


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
Intrauterine hormone-releasing system (IUS)2

Bilateral tubal occlusion2

Vasectomized partner2,3 

Sexual abstinence4
12.3.3.
Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (calendar, 
symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhoea method (LAM). A female condom and a male condom should not be 
used together.
3 Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of 
the woman of childbearing potential trial participant and that the vasectomized partner has received medical 
assessment of the surgical success.
4 In the context of this guidance sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the subject.


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12.4.
Country-specific Requirements
France
Inclusion and Exclusion Criteria
The inclusion criterion 1) for France must be considered as follows: “For France, r/r de novo or 
secondary AML as defined by the ELN 2017 Classification {Dohner 2017} excluding acute 
promyelocytic leukemia and low-risk ELN patients treated with less than 2 lines of therapy (in 
the dose-escalation part)"
At the discretion of the investigator and in line with exclusion criterion 26): “Any medical or 
psychiatric condition likely to interfere with assessment of safety or efficacy of study treatment”, 
the following should be considered:

Subjects should not have undergone cerebral radiotherapy within 8 weeks prior to KITE-222 
administration.

Subject inclusion in the clinical trial requires validation through a multidisciplinary collective 
review.
In addition, it is recommended that subjects should undergo a neurological examination by a 
neurologist prior to inclusion into the trial, in order to better exclude any neurologic involvement 
and to facilitate subsequent management in the event of an adverse neurologic event.
Bone Marrow Evaluation and Disease Assessment
Conditioning Chemotherapy
Investigators should be aware of AEs potentially caused by the lymphodepleting agents.
Risk – Cytokine Release Syndrome
Hemophagocytic lymphohistiocytosis (HLH) has similar clinical presentation to that of CRS 
with similar initial therapeutic management. Investigators should be particularly alert to the need 
to quickly adjust the management of the event in cases of non-response to CRS treatment.
Table 10. Schedule of Assessments
B-hCG pregnancy test (serum or urine) on all females of childbearing potential within 7 days 
before the initiation of leukapheresis, at Day 0 (end of exposition to fludarabine and 
cyclophosphamide), Week 4 and Month 2 and within 1 week before the start of the conditioning 
chemotherapy before allo-SCT serology (HIV, hepatitis B, hepatitis C, and syphilis) (within 
30 days before leukapheresis and/or on the day of leukapheresis).
CCI


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Germany
An MRI scan will be preferred for the imaging requirements in protocol Section 6.3.7, 
Section 7.3 and Section 7.7.5.
Table 10. Schedule of Assessments
B-hCG pregnancy test (serum or urine) on all females of childbearing potential within 7 days 
before the initiation of leukapheresis, at Day 0 (end of exposition to fludarabine and 
cyclophosphamide), Week 4 and Month 2 and within 1 week before the start of the conditioning 
chemotherapy before allo-SCT serology (HIV, hepatitis B, hepatitis C, and syphilis) (within 30 
days before leukapheresis and/or on the day of leukapheresis).
Criteria to Stop or Pause Enrollment
The appropriate regulatory authorities will be notified within the applicable safety reporting 
timelines if any of these stopping or pausing rules occur. Accrual will be resumed upon the 
recommendation of the SRT that may also decide the complete discontinuation of enrollment 
based on review of all relevant data available.
After enrollment and leukapheresis, a subject must not proceed to the lymphodepleting 
chemotherapy if criteria described in Section 7.6.3.1 are not satisfied. If it is deemed a subject 
cannot continue to lymphodepleting chemotherapy, reporting of concomitant medications, AEs 
and SAEs will follow Table 5, Table 7, and Table 8, respectively.
After the lymphodepleting chemotherapy, a subject must not proceed to the infusion of 
KITE-222 if criteria described in Section 7.7.1 are not satisfied. If it is deemed a subject cannot 
continue to KITE-222 infusion, reporting of concomitant medications, AEs and SAEs will follow 
Table 5, Table 7, and Table 8, respectively.


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12.5.
Response Criteria in AML (Based on European Leukemia Net 2017 
Classification)
Disease assessments at the time points specified in Table 10, Table 11, and Table 12 will be 
performed by the investigator using the local laboratory (peripheral blood, marrow, and if 
available, measurable residual disease), physical examination, and extramedullary imaging 
determinations. Assessments will be captured in the eCRF as described in Section 6.4.
The response criteria for r/r AML are based on the ELN 2017 Classification {Dohner 2017} and 
are presented in Table 13.
If a hematological or molecular relapse is documented, the date of relapse will be captured in the 
eCRF.
Extramedullary disease assessment is needed if a baseline extramedullary disease exists or if new 
symptoms are suggestive of relapse as per Section 6.4.4.
Table 13.
Response Criteria in AML (Based on ELN 2017 Classification)
Category
Definition
Comment
Response
CR without measurable 
(formerly called 
minimal) residual 
disease 
If studied pretreatment, CR with 
negativity for a genetic marker by 
RT-qPCR, or CR with negativity by 
MFC
Sensitivities vary by marker tested, and by 
method used; therefore, test used, and 
sensitivity of the assay should be reported
CR 
BM blasts <5%; absence of circulating 
blasts and blasts with Auer rods; absence 
of extramedullary disease; ANC ≥1.0  
109/L (1000/µL); platelet count ≥100  
109/L (100000/µL)
MRD+ or unknown
CR with incomplete 
hematologic recovery 
All CR criteria except for residual 
neutropenia (<1.0  109/L [1000/µL]) or 
thrombocytopenia (<100  109/L 
[100000/µL])
−
Morphologic 
leukemia-free state 
BM blasts <5%; absence of blasts with 
Auer rods; absence of extramedullary 
disease; no hematologic recovery 
required
The marrow should not merely be “aplastic”; 
at least 200 cells should be enumerated, or 
cellularity should be at least 10%
PR 
All hematologic criteria of CR; decrease 
of BM blast percentage to 5% to 25%; 
and decrease of pretreatment BM blast 
percentage by at least 50%
−
Stable disease
Absence of CRMRD−, CR, CRi, PR, and 
MLFS and criteria for PD not met
−
PD
Evidence for an increase in BM blast 
percentage and/or increase of absolute 
blast counts in the blood:
−


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Category
Definition
Comment
> 50% increase in marrow blasts over 
baseline (a minimum 15% point 
increase is required in cases with 
< 30% blasts at baseline or persistent 
marrow blast percentage of > 70% 
over at least 3 months without ≥ 100% 
improvement in ANC to an absolute 
level (> 0.5 × 109/L [500/µL], and/or 
platelet count to > 50 × 109/L 
[50,000/µL] nontransfused)
> 50% increase in peripheral blasts 
(WBC x % blasts) to > 25 × 109/L 
(>25,000/μL) (in the absence of 
differentiation syndrome)
New extramedullary disease
Relapse
Hematologic relapse 
(after a prior 
assessment with 
CRMRD−, CR, or CRi)
BM blasts ≥ 5%, reappearance of blasts 
in the blood, or development of 
extramedullary disease
−
Molecular relapse (after 
a prior assessment 
CRMRD−)
If studied before treatment, re-occurrence 
of MRD as assessed by RT-qPCR or by 
MFC
Test applied, sensitivity of the assay, and 
cutoff values used must be reported 
Abbreviations: AML, acute myeloid leukemia; ANC, absolutely neutrophil count; BM, bone marrow; CR, complete remission; 
CRi, complete remission with incomplete hematologic recovery; CRMRD−, complete remission without measurable residual 
disease; MFC, multiparameter flow cytometry; MLFS, morphologic leukemia-free state; MRD, measurable residual disease; PD, 
progressive disease; PR, partial remission; RT-PCR, real-time polymerase chain reaction, WBC, white blood cell. 
Source: {Dohner 2017} 


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12.6.
Immune Effector Cell-associated Encephalopathy Score
A guide to the immune effector cell-associated encephalopathy score is presented in Table 14.
Table 14.
Immune-effector Cell-associated Encephalopathy Score
Task
Score
Orientation:
Orientation to year, month, city, hospital 
4 points
Naming:
Ability to name 3 objects 
(eg, point to clock, pen, button) 
3 points
Following commands:
Ability to follow simple commands
(eg, “Show me 2 fingers” or “Close your eyes and stick out your tongue”) 
1 point
Writing:
Ability to write a standard sentence 
(eg, “Our national bird is the bald eagle”) 
1 point
Attention:
Ability to count backwards from 100 by 10 
1 point
Note: Immune-effector cell-associated encephalopathy score as developed by the American Society for Transplantation and 
Cellular Therapy consensus grading for cytokine release syndrome and neurologic toxicity associated with immune-effector cells 
{Lee 2019}. 


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12.7.
Pandemic Risk Assessment and Mitigation Plan
During an ongoing pandemic, potential risks associated with subjects being unable to attend 
study visits have been identified for this study.
These risks can be summarized as follows:
1) Subject safety monitoring and follow-up:
a) Subjects may be unable or unwilling to come to the investigational site for their 
scheduled study visits as required per protocol.
Mitigation plan: For subjects who may be unable or unwilling to visit the investigational 
site for their scheduled study visits as required per protocol, the principal investigator or 
qualified delegate will conduct a remote study visit, via phone or video conferencing, to 
assess the subjects within the target visit window date whenever possible. During the 
remote study visit, the following information at minimum will be reviewed:
i)
Confirm if subject has experienced any adverse events (AEs)/serious adverse events 
(SAEs)/special situations (including pregnancy) and follow-up on any unresolved 
AEs/SAEs.
ii) Review the current list of concomitant medications and document any new 
concomitant medications.
iii) If applicable, confirm electronic/paper diary questionnaires and patient reported 
outcomes have been completed and transmitted.
b) Subjects may be unable or unwilling to travel to the site for planned assessments 
(eg, blood draws, imaging, physical exams).
Mitigation plan: Local laboratories or other vendors may be utilized as appropriate to 
monitor subject safety until the subject can return to the site for their regular follow-up 
per protocol. Any changes in the party conducting laboratory assessments for the study 
because of the pandemic will be documented accordingly. Pregnancy testing may be 
performed using a home urine pregnancy test if local laboratory pregnancy testing is not 
feasible. Central lab kits may be sent to subject’s local hospital lab for sample collection. 
Relevant imaging (eg, PET-CT, CT) can be done at the subject’s local hospital and 
images transferred or sent to the investigative site. Physical exams can be completed by 
a local physician with results sent to investigative site.
c) Subjects may be unable or unwilling to attend the study visit to sign an updated informed 
consent form version.
Mitigation plan: The site staff will follow their approved informed consent process and 
remain in compliance with the local ethics committee/institutional review board and 
national laws and regulations. Remote consent will be allowed if has been approved by 
the local ethics committee/institutional review board. The consent process will be 
documented and confirmed by normal consent procedure at the investigative site at the 
earliest opportunity.


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2) Protocol and monitoring compliance:
a) Protocol deviations may occur in situations where scheduled visits or procedures cannot 
be conducted as planned per protocol.
Mitigation plan: If it is not possible to complete a required procedure at a protocol-
specified time point, an unscheduled visit should be conducted as soon as possible when 
conditions allow so that the required procedure can be performed. The situation should be 
recorded and explained as a protocol deviation. Any missed subject visits must be 
reported in the eCRF, if possible, and recorded as deviations to the protocol because of 
the pandemic, so that they can be appropriately documented and described in the clinical 
study report. Any remote study visits that are conducted in lieu of clinic visits because of 
the pandemic will be documented as protocol deviations related to the pandemic.
b) Study monitors may be unable to carry out source data review or source data verification, 
or study drug accountability, or assess protocol and Good Clinical Practice compliance. 
This may lead to delays in source data verification, an increase in protocol deviations, or 
underreporting of AEs.
Mitigation plan: The study monitor is to remain in close communication with the site to 
ensure ongoing data entry and query resolution. Remote source data verification may be 
arranged if allowed by local regulation and the Study Monitoring Plan. The study monitor 
is to reference the Study Monitoring Plan for guidance on how to conduct an off-site 
monitoring visit. The study staff is to save and document all relevant communication in 
the study files. The status of sites that cannot accept monitoring visits and/or subjects 
on-site must be tracked centrally and updated on a regular basis.
3) Missing data and data integrity:
There may be an increased amount of missing data because of subject’s missing 
visits/assessments. This could have an impact on the analysis and the interpretation of 
clinical study data.
Mitigation plan: Implications of a pandemic on methodological aspects for the study will be 
thoroughly assessed and documented, and relevant actions will be taken as appropriate (eg, 
modification of the statistical analysis plan) and in compliance with regulatory authorities’ 
guidance. Overall, the clinical study report will describe the impact of the pandemic on the 
interpretability of study data.
Risks will be assessed continuously, and temporary measures will be implemented to 
mitigate these risks as part of a mitigation plan, as described above. These measures will be 
communicated to the relevant stakeholders as appropriate and are intended to provide 
alternative methods that will ensure the evaluation and assessment of the safety of subjects 
who are enrolled in this study.
Since these potential risks are considered mitigated with the implementation of these 
measures, the expected benefit-risk assessment of KITE-222 in study subjects remains 
unchanged.

SAP_001.pdf: 
  
STATISTICAL ANALYSIS PLAN
Sponsor:
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
United States of America
Product Name:
KITE-222
Protocol:
A Phase 1 Open-label, Multicenter Study Evaluating the Safety of 
KITE-222, an Autologous Anti-CLL-1 CAR T-cell Therapy, in 
Subjects with Relapsed/Refractory Acute Myeloid Leukemia
Version Number
V1.0
Release Date:
28 June 2022
Replaces Previous 
Version(s):
N/A
CONFIDENTIALITY NOTICE
This document contains confidential information of Kite Pharma Inc. (hereafter referred to as 
Kite), a wholly owned subsidiary of Gilead Sciences Inc. This document must not be disclosed to 
anyone other than the site research staffs, 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. Questions regarding 
how this document should be used or the conduct of the clinical trial should be directed to the 
key sponsor contacts.
Kite 
A GILEAu Company 


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Statistical Analysis Plan
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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................2
LIST OF TABLES..........................................................................................................................................................3
LIST OF FIGURES ........................................................................................................................................................4
LIST OF ABBREVIATIONS.........................................................................................................................................5
1.
INTRODUCTION..................................................................................................................................................7
2.
OBJECTIVES AND ENDPOINTS........................................................................................................................8
2.1.
Objectives..................................................................................................................................................8
2.1.1.
Primary Objective....................................................................................................................8
2.1.2.
Secondary Objectives ..............................................................................................................8
2.2.
Endpoints...................................................................................................................................................8
2.2.1.
Primary Endpoints...................................................................................................................8
2.2.2.
Secondary Endpoints...............................................................................................................8
3.
STUDY DESIGN.................................................................................................................................................10
3.1.
Overview .................................................................................................................................................10
3.2.
Hypothesis ...............................................................................................................................................11
3.3.
Sample Size Consideration......................................................................................................................12
4.
COVARIATES.....................................................................................................................................................13
4.1.
Baseline Covariates .................................................................................................................................13
5.
DEFINITIONS .....................................................................................................................................................14
5.1.
General ....................................................................................................................................................14
5.2.
Safety.......................................................................................................................................................15
5.2.1.
Treatment-emergent Adverse Event (TEAE)........................................................................15
5.2.2.
Time to Onset of a TEAE of Interest.....................................................................................15
5.2.3.
Resolution of a TEAE of Interest ..........................................................................................15
5.2.4.
Duration of a TEAE of Interest .............................................................................................15
5.2.5.
TEAEs of Interest..................................................................................................................15
5.2.6.
Concomitant Medications of Interest ....................................................................................19
5.2.7.
Concomitant Procedure .........................................................................................................19
5.3.
Efficacy....................................................................................................................................................20
5.3.1.
Composite Complete Remission Rate...................................................................................20
5.3.2.
Overall remission (OR) rate ..................................................................................................20
5.3.3.
Relapse-free survival (RFS) ..................................................................................................20
5.3.4.
Allo-SCT Rate.......................................................................................................................20
5.3.5.
Event-free Survival................................................................................................................20
5.3.6.
Overall Survival.....................................................................................................................21
5.3.7.
30- and 60-day All-cause Mortality ......................................................................................21
6.
ANALYSIS SETS................................................................................................................................................22
6.1.
DLT-evaluable Set...................................................................................................................................22
6.2.
Full Analysis Set......................................................................................................................................22
6.3.
Safety Analysis Set..................................................................................................................................22
6.4.
Modified Intention to Treat Analysis Set ................................................................................................22
7.
SAFETY REVIEW AND EARLY STOPPING GUIDELINES..........................................................................23
CCI
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7.1.
Safety Interim Analysis ...........................................................................................................................23
8.
DATA SCREENING AND ACCEPTANCE.......................................................................................................24
8.1.
General Principles ...................................................................................................................................24
8.2.
Electronic Transfer and Archiving of Data .............................................................................................24
8.3.
Handling of Missing and Incomplete Data..............................................................................................24
8.3.1.
Efficacy Data.........................................................................................................................24
8.3.2.
Safety Data ............................................................................................................................25
8.4.
Detection of Bias .....................................................................................................................................25
8.5.
Outliers ....................................................................................................................................................25
8.6.
Distributional Characteristics ..................................................................................................................25
8.7.
Validation and Configuration Management ............................................................................................25
9.
STATISTICAL METHODS OF ANALYSIS......................................................................................................26
9.1.
General Principles ...................................................................................................................................26
9.2.
Subject Accountability ............................................................................................................................26
9.3.
Important Protocol Deviations ................................................................................................................26
9.4.
Demographic and Baseline Characteristics.............................................................................................26
9.5.
Safety Analyses .......................................................................................................................................28
9.5.1.
Exposure to Study Treatment ................................................................................................28
9.5.2.
AEs ........................................................................................................................................28
9.5.3.
Concomitant Medications and Procedures ............................................................................30
9.5.4.
Laboratory Test Results.........................................................................................................30
9.5.5.
Vital Signs and Physical Examinations.................................................................................30
9.6.
Efficacy Analyses....................................................................................................................................30
9.6.1.
Composite Complete Remission Rate...................................................................................31
9.6.2.
Overall Remission Rate.........................................................................................................31
9.6.3.
RFS........................................................................................................................................31
9.6.4.
Allo-SCT Rate.......................................................................................................................31
9.6.5.
EFS ........................................................................................................................................31
9.6.6.
OS..........................................................................................................................................32
9.6.7.
30- and 60-day All-cause Mortality ......................................................................................32
9.7.
Pharmacokinetics and Pharmacodynamics..............................................................................................32
9.8.
Study Key Metrics...................................................................................................................................32
10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES..............................................................................33
11.
REFERENCES.....................................................................................................................................................34
12.
APPENDICES......................................................................................................................................................35
Appendix 1.
Conventions for Clinical Data That Require Imputation for Partial or Missing Dates ...........36
Appendix 2.
Derivation of Time to Event Endpoints...................................................................................38
Appendix 3.
Censoring Criterion for OS and Derivation of Last Date Known to Be Alive........................39
LIST OF TABLES
Table 1.
Dose Cohorts ...........................................................................................................................11
Table 2.
Exact 95% Confidence Intervals Corresponding to Composite Complete Remission 
Rate..........................................................................................................................................12
Table 3.
ASTCT CRS Consensus Grading............................................................................................16


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Table 4.
ASTCT ICANS Consensus Grading for Adults......................................................................16
Table 5.
Immune Effector Cell-associated Encephalopathy Score........................................................17
Table 6.
Imputation Rules for Partial or Missing Start Dates................................................................36
Table 7.
RFS Analysis ...........................................................................................................................38
Table 8.
EFS Analysis ...........................................................................................................................38
Table 9.
OS Analysis .............................................................................................................................39
LIST OF FIGURES
Figure 1.
Study Schema ..........................................................................................................................11


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LIST OF ABBREVIATIONS
Abbreviation
Definition
ADaM
analysis data model
AE
adverse event
Allo-SCT
allogeneic stem cell transplantation
AML
acute myeloid leukemia
ASTCT
American Society for Transplantation and Cellular Therapy
BM
bone marrow
CAR
chimeric antigen receptor
CCR
composite complete remission
CLL-1
C-type lectin-like molecule-1
CNS
central nervous system
CR
complete remission
CRF
case report form
CRi
complete remission with incomplete hematologic recovery
CRMRD−
complete remission without measurable residual disease
CRS
cytokine release syndrome
CI
confidence interval
CTCAE
common terminology criteria for adverse event
DLI
Donor lymphocyte infusions
DLT
dose limiting toxicity
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EDC
electronic data capture
FAS
full analysis set
EFS
event-free survival
ELN
European Leukemia Net
GVHD
graft-versus-host-disease
HMA
hypomethylating agent
ICANS
immune-effector cell-associated neurotoxicity syndrome
ICE
immune-effector cell-associated encephalopathy
KM
Kaplan-Meier
MedDRA
medical dictionary for regulatory activities
mITT
modified intent-to-treat
MLFS
morphologic leukemia-free state 
MRD
measurable or minimal residual disease
MRI
magnetic resonance imaging
MST
MedDRA search term
MTD
maximum tolerated dose
OR
overall remission


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OS
overall survival
PBMC
peripheral blood mononuclear cell
PR
partial remission
RCL
replication-competent lentivirus
RP2D
recommended phase 2 dose
R/R
relapsed/refractory 
SAE
serious adverse event
SAP
statistical analysis plan
SD
stable disease
SDTM
study data tabulation model 
SMQ
standardized MedDRA query 
SOC
system organ class
SRT
safety review team
TEAE
treatment-emergent adverse event
TLS
tumor lysis syndrome
WHO
world health organization


KITE-222 
Kite Pha1ma, Inc. 
Statistical Analysis Plan 
L 
INTRODUCTION 
This statistical analysis plan (SAP) sets fo1th prospectively the details of statistical analyses that 
are outlined in protocol KT-US-486-0201 entitled "A Phase 1 Open-label, Multicenter Study 
Evaluating the Safety of KITE-222, an Autologous Anti-CLL-1 CAR T-cell Therapy, in Subjects 
With Relapsed/Refracto1y Acute Myeloid Leukemia". 
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KITE-222 
Kite Pha1ma, Inc. 
Statistical Analysis Plan 
2-
OBJECTIVES AND ENDPOINTS 
2.1. 
Objectives 
2.1.1. 
Primary Objective 
The prima1y objective of this study is to evaluate the feasibility, safety, maximum tolerated dose 
(MID), and optimal dose of KITE-222 in the treatment of subjects with relapsed or refracto1y 
(r/r) acute myeloid leukemia (AML). 
2.1.2. 
Secondary Objectives 
The secondaiy objectives of this study are as follows: 
• 
To evaluate the efficacy of KITE-222 in treating subjects with r/r AML 
• 
To evaluate the phaimacokinetic and pha1macodynamic profiles of KITE-222 in subjects 
withr/r AML 
-
I 
I 
2.2. 
Endpoints 
2.2.1. 
Primary Endpoints 
The primaiy endpoint of this study is to evaluate the incidence of dose limiting toxicity (DLT) in 
subjects treated with KITE-222. 
2.2.2. 
Secondary Endpoints 
The secondaiy endpoints of this study ai·e to evaluate: 
• 
Incidence of adverse event (AE) 
• 
Clinically significant changes in laborato1y parameters 
• 
Time to neutrophil recove1y 
• 
Time to platelet recove1y 
CONFIDENTIAL 
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KITE-222 
Kite Pha1ma, Inc. 
Statistical Analysis Plan 
• 
Composite complete remission (CCR) rate 
• 
Overall remission (OR) rate 
• 
Relapse-free smvival (RFS) 
• 
Allogeneic stem cell trnnsplant (allo-SCT) rate 
• 
Event-free smvival (EFS) 
• 
Overall survival (OS) 
• 
30- and 60-day all-cause m01tality 
• 
Phaim acokinetics: peak and ai·ea-under-the-cmve (AUC) of KITE-222 CAR T cells in 
subjects with r/r AML treated with KITE-222 
• 
Phaim acodynamics: peak and AUC of selected biomai·kers in subjects with r/r AML treated 
with KITE-222 
• 
Analysis of antibodies against the KITE-222 CAR 
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KITE-222 
Kite Pha1ma, Inc. 
Statistical Analysis Plan 
3_ 
STUDY DESIGN 
3.1. 
Overview 
Study KT-US-486-0201 is a Phase 1, open-label, multicenter study evaluating the feasibility, 
safety, and tolerability of KITE-222 in subjects with r/r AML. The study consists of dose 
escalation coho1is and an expansion coho1i. 
In the dose-escalation paii, 3 dose cohorts 
will be assessed to detennine the 
MID using a 3 + 3 study design. In the 3 + 3 design, 3 subjects ai·e initially treated in a given 
dose coho1i . If there is no DLT observed in any of these subjects, the study proceeds to enroll 
additional subjects into the next higher dose coho1i. If 1 subject develops a DL T at a specific 
dose, an additional 3 subjects ai·e enrolled into that same dose coho1i, and dose escalation is only 
suggested if no additional DLTs ai·e observed in this dose cohort. Development ofDLTs in more 
than 1 subject in a specific dose coho1i suggests the MTD has been exceeded, and fmiher dose 
escalation is not pursued. The MID is established when 6 subjects ai·e treated at the highest dose 
level with < 2 DLTs. 
After the MID is established, the study will enter the expansion coho1i stage and enroll and treat 
approximately additional 22 subjects to that cohort. A minimum of28 subjects across the 
MID-dose coho1i and the expansion coho1i will be treated for additional safety and prelimina1y 
efficacy assessments. 
All subjects enrolled in the study will proceed through treatment as outlined in Figure 1 with the 
dose ofKITE-222 detennined accordin to dose-escalation cohort and b the MID in the 
. Subjects must be hospitalized from 
infusion (Day 0) until Day 14 at a minimum. From Day 14, the subject may be evaluated for 
discharge and considered for outpatient follow-up if toxicities have returned to Grade 1, have 
resolved, returned to baseline, or are deemed clinically insignificant by the investigator. 
Subjects who enroll will have a pre identified stem-cell donor source for potential allo-SCT, 
which can be initiated at the discretion of the investigating physician after completion of the 
Day 28 disease response assessment. 
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Figure 1.
Study Schema
3.2.
Hypothesis
There is no formal hypothesis testing in this study. All endpoints will be analyzed by descriptive 
statistics.
CCI
Enrollment 
/Leu kap heresi s 
Lymphodepleting 
Chemotherapy 
Day-5 
DayO 
Manufacturing 
Day 7 
Safety monitoring, 
correlatives and tumor 
assessments 
Day14 
Inpatient Hospitalization Period 
Conditioning 
and Allogeneic 
SCT 
Days28-42 
> 


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3.3.
Sample Size Consideration
The anticipated enrollment in this study should allow for having 40 subjects treated; up to 
18 subjects will be enrolled in the dose-escalation part and 22 subjects will be the target number 
for enrollment in the expansion cohort. Refer to Section 3.1 for more details on the study design.
With a total sample size of 28 subjects at the selected dose level, an observed CCR rate of 50% 
(14 of 28 subjects) will yield an exact 95% confidence interval (CIs) of 31% and 69%. 
Additional assumptions and corresponding 2-sided 95% exact CIs are provided in Table 2.
Table 2.
Exact 95% Confidence Intervals Corresponding to Composite 
Complete Remission Rate
Subjects with CCR
Observed CCR Rate*
95% Confidence Interval
10
36%
[19%, 56%]
12
43%
[24%, 63%]
14
50%
[31%, 69%]
16
57%
[37%, 76%]
18
64%
[44%, 81%]
Abbreviations: CCR, composite complete remission 
* Total of 28 treated subjects at the selected dose level 


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4.
COVARIATES
4.1.
Baseline Covariates
The following baseline covariates may be used to examine efficacy and/or safety in subgroups or 
covariate analyses:

Age (in years) at baseline: < 65, ≥ 65

Sex 

Race

ECOG PS

AML type

Extramedullary disease assessment

Risk category per ELN 2017 criteria

CNS infiltration at diagnosis

Disseminated intravascular coagulation at diagnosis

Number of prior chemotherapy lines of therapy

Prior transplant (yes/no)

Bridging therapy after leukapheresis and before administration of lymphodepleting 
chemotherapy (yes/no) and types of bridging

% of CLL-1+ Blasts in Bone Marrow and peripheral blood
Covariate levels that are sparse may be collapsed for purposes of subgroup analyses. Additional 
covariates not specified above may be examined for exploration purpose. 


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5.
DEFINITIONS
5.1.
General
Study enrollment: Study enrollment occurs when a subject is confirmed to be eligible for the 
study and commences leukapheresis.
Day 0: Day 0 is defined as the day the subject received the KITE-222 infusion. The day before 
Day 0 will be Day −1. Any days after enrollment and before Day −1 will be sequential and 
negative integer-valued relative to Day 0. Any days after Day 0 will be sequential and positive 
integer-valued relative to Day 0. 
Baseline: The baseline value is defined as the last non-missing value measured prior to the date 
of lymphodepleting chemotherapy.
Actual follow-up time: Actual follow-up time among all subjects treated with KITE-222 is 
calculated as the time from the KITE-222 infusion to the date of death or last date known alive, 
whichever is later.
Potential follow-up time: Potential follow-up time is defined as the time from the KITE-222 
infusion to the data cutoff date for the analysis.
Relapsed/refractory subgroup: Relapsed/refractory subgroups are defined as below for AML 
and collected in the eligibility page from the eCRF:
a) Refractory disease is defined as one of the following:
i)
Failed at least 2 cycles of a 7 + 3-based induction regimen, which may have been 
given in combination with a targeted agent, an antibody-based therapy, or a B-cell 
lymphoma (BCL)-2 inhibitor. For other agents added to the 7 + 3-based induction 
regimen, please discuss with the Kite medical monitor.
ii) Failed at least 1 cycle of a purine analogue-based induction therapy, such as 
fludarabine or cladribine paired with anthracyclines and cytarabine (eg, FLAG-Ida, 
cladribine, ara-C, granulocyte colony-stimulating factor, and mitoxantrone [CLAG-
M])
iii) Failed any intensive re-induction regimen after at least 1 prior cycle of induction 
chemotherapy
iv) Persistent AML after 4 cycles of therapy with an hypomethylating agent (HMA) (eg, 
decitabine or azacitidine)
v) Persistent AML after 2 cycles of low-intensity venetoclax-based combinations such 
as venetoclax + HMA or venetoclax + LDAC


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vi) Failed therapy after remission (eg, consolidation) during any number of cycles 
(maximum of 4) of high- or intermediate-dose cytarabine
b) Relapsed disease is defined as one of the following:
i)
First relapse, if RFS was less than 12 months following achievement of CR
ii) Relapsed disease after 2 or more lines of systemic therapy
iii) r/r disease after allo-SCT provided subject is at least 100 days from SCT at the time 
of enrollment and withdrawn from immunosuppressive medications for at least 
4 weeks prior to enrollment
5.2.
Safety
5.2.1.
Treatment-emergent Adverse Event (TEAE)
TEAE is defined as any AE with onset on or after the infusion of KITE-222.
5.2.2.
Time to Onset of a TEAE of Interest
Time to onset of a TEAE of interest is defined as the time from the date of the infusion of 
KITE-222 until the earliest date of onset of the TEAE in the event class of interest, using the 
following equation: the start date of the first TEAE in the event class – the date of the infusion of 
KITE-222 + 1.
5.2.3.
Resolution of a TEAE of Interest
A TEAE of interest is considered to be resolved if all TEAEs in the event class of interest are 
resolved at the time of the analysis data cutoff date. Any TEAE with an end date that is the same 
as the death date is not considered to be resolved.
5.2.4.
Duration of a TEAE of Interest
Duration of a TEAE of interest is defined as the time from the earliest onset date of the TEAE in 
the event class of interest until the resolution date of the last TEAE in the event class, regardless 
of any gaps occurring between events (i.e., the resolution date of the last TEAE in the event class 
– the start date of the first TEAE in the event class + 1). The duration of an AE of interest may 
be derived only among subjects for whom all events of the class have resolved by the analysis 
data cutoff date.
5.2.5.
TEAEs of Interest
5.2.5.1.
Cytokine Release Syndrome 
Cytokine release syndrome (CRS) is identified via collection of the syndrome on a CRF 
specifically designed to collect CRS.  Specific symptoms of the CRS are collected on the AE log 
form and are linked to the CRS syndrome.  CRS syndrome severity is graded according to 


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American Society for Transplantation and Cellular Therapy (ASTCT) grading {Lee 2019}, as 
shown in Table 3.
Table 3.
ASTCT CRS Consensus Grading
CRS 
Parameter
Grade 1
Grade 2
Grade 3
Grade 4
Fevera
Temperature ≥ 38°C
Temperature ≥ 38°C
Temperature ≥ 38°C
Temperature ≥ 38°C
With
Hypotension
None
Not requiring 
vasopressors
Requiring a 
vasopressor with or 
without vasopressin
Requiring multiple 
vasopressors 
(excluding 
vasopressin)
And/orb
Hypoxia
None
Requiring low flow 
nasal cannula c or 
blow-by 
Requiring high flow 
nasal cannula c, face 
mask, non-rebreather 
mask, or Venturi 
mask
Requiring positive 
pressure (CPAP, 
BiPAP, intubation 
and mechanical 
ventilation)
Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; BiPAP, bilevel positive airway pressure; 
CPAP, continuous positive airway pressure; CRS, cytokine release syndrome.
Notes: Organ toxicities associated with CRS may be graded according to the Common Terminology Criteria for Adverse Events 
version 5.0 but they do not influence CRS grading.
a
Fever is defined as temperature ≥ 38°C not attributable to any other cause. In patients who have CRS then receive 
antipyretic or anticytokine therapy such as tocilizumab or corticosteroids, fever is no longer required to grade subsequent 
CRS severity. In this case, CRS grading is driven by hypotension and/or hypoxia.
b
The CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. For 
example, a patient with temperature of 39.5° C, hypotension requiring 1 vasopressor, and hypoxia requiring low-flow nasal 
cannula is classified as Grade 3 CRS.
c
Low-flow nasal cannula is defined as oxygen delivered at ≤ 6 L/minute. Low flow also includes blow-by oxygen delivery, 
sometimes used in pediatrics. High-flow nasal cannula is defined as oxygen delivered at > 6 L/minute.
5.2.5.2.
Immune effector cell-associated neurotoxicity syndrome 
Immune effector cell-associated neurotoxicity syndrome (ICANS) will be assessed by the 
ASTCT grading {Lee 2019}, as shown in Table 4. (Using immune-effector cell-associated 
encephalopathy [ICE] scores as determined by Table 5)
Table 4.
ASTCT ICANS Consensus Grading for Adults
Neurotoxicity 
Domain
Grade 1
Grade 2
Grade 3
Grade 4
ICE score a
7 to 9
3 to 6
0 to 2
0 (patient is unarousable and 
unable to perform ICE)
Depressed level of 
consciousnessb
Awakens 
spontaneously
Awakens to 
voice
Awakens only to tactile 
stimulus
Patient is unarousable or 
requires vigorous or 
repetitive tactile stimuli to 
arouse. 
Stupor or coma


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Neurotoxicity 
Domain
Grade 1
Grade 2
Grade 3
Grade 4
Seizure
N/A
N/A
Any clinical seizure 
focal or generalized that 
resolved rapidly or 
nonconvulsive seizures 
on EEG that resolve 
with intervention
Life-threatening prolonged 
seizure (> 5 min); or 
Repetitive clinical or 
electrical seizures without 
return to baseline in between
Motor findingsc
N/A
N/A
N/A
Deep focal motor weakness 
such as hemiparesis or 
paraparesis
Elevated ICP/ 
cerebral edema
N/A
N/A
Focal/local edema on 
neuroimagingd
Diffuse cerebral edema on 
neuroimaging; decerebrate or 
decorticate posturing; or 
cranial nerve VI palsy; or 
papilledema; or Cushing's 
triad
Abbreviation: ASTCT, American Society for Transplantation and Cellular Therapy; CTCAE, Common Terminology Criteria for 
Adverse Events; EEG, electroencephalogram; ICANS, immune effector cell-associated neurotoxicity syndrome; ICE, immune- 
effector cell-associated encephalopathy; ICP, Intracranial Pressure; N/A, not applicable; v, version
Notes: ICANS grade is determined by the most severe event (ICE score, level of consciousness, seizure, motor findings, and 
raised ICP/cerebral edema) not attributable to any other cause; for example, a patient with an ICE score of 3 who has a 
generalized seizure is classified as Grade 3 ICANS.
a
A patient with an ICE score of 0 may be classified as Grade 3 ICANS if awake with global aphasia, but a patient with an 
ICE score of 0 may be classified as Grade 4 ICANS if unarousable.
b
Depressed level of consciousness should be attributable to no other cause (eg, no sedating medication).
c
Tremors and myoclonus associated with immune effector cell therapies may be graded according to CTCAE version 5.0, but 
they do not influence ICANS grading.
d
Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is excluded from 
ICANS grading. It may be graded according to CTCAE version 5.0.
Table 5.
Immune Effector Cell-associated Encephalopathy Score
Task
Direction
Score
Orientation
State: year, month, city, hospital 
4
Naming
Name: 3 objects
3
Following simple command 
Follow: simple command 
1
Writing
Ability to write a simple sentence 
1
Attention
Count: backwards from 100 by 10’s 
1
Abbreviation: ICANS, immune effector cell-associated neurotoxicity syndrome; ICE, immune effector cell-associated 
encephalopathy.
Notes: Scoring: 10, no impairment; 7-9, Grade 1 ICANS; 3-6, Grade 2 ICANS; 0-2, Grade 3 ICANS; 0 due to patient 
unarousable and unable to perform ICE assessment, Grade 4 ICANS.


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5.2.5.3.
Infections
Infections will be identified as AEs within the system organ class (SOC) of infections and 
infestations that occur on or after treatment with KITE-222, in standardized medical dictionary 
for regulatory activities (MedDRA) query (SMQ) of opportunistic infections (narrow search), 
and in MedDRA high level group terms (HLGT) that capture events of:
Bacterial infection, encompassing preferred terms within the MedDRA HLGT of

bacterial infectious disorders

chlamydial infectious disorders
Viral infection, encompassing preferred terms within the MedDRA HLGT of viral infectious 
disorders.
Unspecified pathogen infections, encompassing preferred terms within the MedDRA HLGT of 
infections – pathogen unspecified.
In addition, fungal infections will be identified using HLGT of fungal infectious disorders, and 
summarized in separate category.
5.2.5.4.
Cytopenias (Thrombocytopenia, Neutropenia, or Anemia, Including Aplastic 
Anemia)
Cytopenias (Neutropenia or Thrombocytopenia or Anemia) will be identified as follows:

Thrombocytopenia will be identified using the SMQ for haematopoietic thrombocytopenia 
(narrow search).

Neutropenia will be identified using the following MedDRA preferred terms: febrile 
neutropenia, neutropenia, neutrophil count decreased

Anemia will be identified using the SMQ haematopoietic erythropenia (broad search).
Prolonged cytopenias will be defined by any cytopenia present on or after Day 30 post KITE-222 
infusion.
5.2.5.5.
Hypogammaglobulinemia
Hypogammaglobulinemia will be identified using an MedDRA search term (MST) search 
strategy defined by Kite.
5.2.5.6.
Secondary Malignancies
AEs coded within the SOC of neoplasms benign, malignant, and unspecified (including cysts and 
polyps) and deaths due to any reason will be reviewed by the Kite Safety and Pharmacovigilance 
Team for potential secondary malignancies. 


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5.2.5.7.
Tumor Lysis Syndrome 
Tumor lysis syndrome (TLS) will be identified as events with MedDRA preferred terms in the 
SMQ of tumor lysis syndrome. The narrow version of this SMQ will be used.
5.2.5.8.
Graft-Versus-Host Disease 
New occurrence, or aggravation of graft-versus-host disease (GVHD) will be collected through 
eCRF.  The severity of acute GVHD will be graded per Mount Sinai Acute GVHD International 
Consortium (MAGIC) criteria {Harris 2016}, and the severity of chronic GVHD will be graded 
per National Cancer Institute (NIH) score {Jagasia 2015}.
5.2.5.9.
Immunogenicity
Immunogenicity will be defined as the development of treatment-emergent anti-KITE-222 
antibodies specific to the CAR. The incidence of immunogenicity will be identified for subjects 
who have developed treatment-emergent anti-KITE-222 CAR antibodies.
5.2.5.10.
Replication-competent Lentivirus 
Pathogenicity of replication-competent lentivirus (RCL) is a potential risk in human gene therapy 
products and requires longitudinal testing, before and after infusion of KITE-222. A positive 
RCL test result is defined by detection of RCL in a blood test.
5.2.5.11.
Autoimmune Disorders
Autoimmune disorders will be identified using the SMQ of immune-mediated/autoimmune 
disorders. The narrow version of this SMQ will be used.
5.2.6.
Concomitant Medications of Interest
Concomitant medications are defined as the medications administered to subjects on or after the 
infusion of KITE-222.
Concomitant medication drug baskets of interest for systemic steroids, vasopressors, nonsteroidal 
immunosuppressants other than tocilizumab, and intravenous (IV) immunoglobulins are defined 
by Kite and are documented separately.
5.2.7.
Concomitant Procedure
Concomitant procedures are defined as the procedures administered on or after the infusion of 
KITE-222.


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5.3.
Efficacy
5.3.1.
Composite Complete Remission Rate 
Composite complete remission (CCR) rate, defined as the proportion of subjects who achieve a 
CR plus the proportion of subjects who achieve a CR without measurable residual disease 
(CRMRD−) plus the proportion of subjects who achieve a CR with incomplete hematologic 
recovery (CRi) per the ELN 2017 Classification {Dohner 2017}, as determined by the study 
investigators.
MRD− response rate is defined as the proportion of subjects who achieve CRMRD− per the ELN 
2017 Classification, as determined by the study investigators.
5.3.2.
Overall remission (OR) rate
Overall remission (OR) rate (CR + CRMRD− + CRi + morphologic leukemia-free state [MLFS] 
+ partial remission [PR]) per the ELN 2017 Classification, as determined by the study 
investigators.
5.3.3.
Relapse-free survival (RFS)
For subjects who experience CR, CRMRD−, or CRi, RFS is defined as the time between their 
first CR/CRMRD−/CRi to relapse or death due to any cause. Subjects not meeting the criteria for 
relapse or death by the analysis data cutoff date will be censored at their last evaluable disease 
assessment date and their response will be noted as ongoing. The RFS for subjects that undergo 
new anticancer therapies (except for allo-SCT) in the absence of a documented relapse will be 
censored at the last evaluable disease assessment before initiation of any new anticancer 
therapies. Subjects who received subsequent allo-SCT will not be censored at the last disease 
assessment before the allo-SCT; instead, the response after allo-SCT will contribute to the 
derivation of RFS.
5.3.4.
Allo-SCT Rate
The allo-SCT rate is defined as the number of subjects who receive allo-SCT after being treated 
with KITE-222 divided by the total number of subjects included in the safety analysis set. 
5.3.5.
Event-free Survival
EFS is defined as the time from the KITE-222 infusion date to the earliest date of disease 
relapse, progressive disease, refractory disease, or death due to any cause. Refractory disease is 
defined as the subject not experiencing CR, CRMRD−, or CRi by the Week 6 disease assessment 
as defined in Appendix 5 from the study protocol.
The following criteria will be used to further define events and event times:

Subjects with an established CR, CRMRD−, or CRi who subsequently commence new 
anticancer therapy (except for allo-SCT) in the absence of documented relapse will have their 
EFS time defined as the time from the KITE-222 infusion date to the last evaluable disease 
assessment prior to the new anticancer therapy.


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
Subjects with best response of MLFS, PR or stable disease (SD) and who subsequently 
commence new anticancer therapy (including allo-SCT) in the absence of documented 
disease progression before the Week 6 assessment, will have their EFS time defined as the 
time from the KITE 222 infusion date to the disease assessment prior to the new anticancer 
therapy.
The following criteria will be used to further define censoring times:

Subjects alive, in response (CR, CRMRD−, or CRi), and with no new anticancer therapy 
(except for allo SCT) will be censored at the last evaluable disease assessment

Subjects with no evaluable disease assessment at the data cutoff date, who are yet to reach 
the Week 6 disease assessment, will be censored at the KITE-222 infusion date
5.3.6.
Overall Survival
Overall survival (OS) is defined as the time from KITE-222 infusion to the date of death from 
any cause. Subjects who have not died by the analysis data cutoff date will be censored at their 
last contact date.
Additional details on the derivation of OS and the specific data modules that will be used to 
derive the last date known to be alive are provided in Appendix 3.
5.3.7.
30- and 60-day All-cause Mortality
The mortality rate is calculated by number of deaths, regardless of cause, within 30 and within 
60 days from the KITE-222 infusion date divided by the total number of subjects included in the 
safety analysis set.


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6.
ANALYSIS SETS
6.1.
DLT-evaluable Set
The DLT-evaluable set, defined for each dosing cohort in the dose-escalation part of the study, 
consists of subjects treated in each dose-escalation cohort who:

Receive the target dose level for that cohort and are followed for at least 28 days after the 
infusion of KITE-222; or

Receive a dose of KITE-222 lower than the target level for that cohort and experience a DLT 
during the 28-day period after the KITE-222 infusion.
6.2.
Full Analysis Set
The full analysis set (FAS) consists of all enrolled subjects. The full analysis set will be used for 
the summary of subject disposition and the listing of deaths.
6.3.
Safety Analysis Set
The safety analysis set is defined as all subjects treated with any dose of KITE-222. This is the 
primary analysis set for safety analyses.
6.4.
Modified Intention to Treat Analysis Set
Modified intention to treat (mITT) analysis set consists of all subjects enrolled and treated with 
at least 50% of the optimal dose of KITE-222 including all subjects treated in both the dose-
escalation cohort and the expansion cohort. The mITT analysis set will be used for all efficacy 
analyses unless otherwise specified.


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7.
SAFETY REVIEW AND EARLY STOPPING GUIDELINES
Formal interim analysis of efficacy is not planned for the early trial stopping purpose.
7.1.
Safety Interim Analysis
A Safety Review Team (SRT), consisting of study sponsor representatives and including at least 
one active study investigator, will be chartered to review safety data and make recommendations 
on further study conduct during the study.
The SRT will convene with a pause in treatment to confirm each dose escalation or de-escalation 
according to the 3 + 3 study design. The SRT will review safety data once the last treated subject 
of the 3 subject group has had the opportunity to be followed for 28 days and evaluated for the 
incidence of DLTs.
During the expansion cohort, the SRT will convene to review AEs and serious AEs after 
approximately the first 6 subjects have had the opportunity to be followed for 28 days after 
administration of the optimal dose of KITE-222. Additional SRT meetings will occur as 
necessary through the course of the study to address safety concerns or other matters affecting 
study conduct.


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8.
DATA SCREENING AND ACCEPTANCE
8.1.
General Principles
The data collection, management, and processing will follow good clinical practice. The 
database will be subject to the edit checks outlined in the Data Management Plan and additional 
manual data reviews defined by the study team. Data inconsistencies will be reviewed and 
resolved before the database snapshot for the primary analysis and the final database lock. For 
the safety interim analyses, snapshots may include data that have not passed all data cleaning 
procedures at the time the data are extracted for snapshot.
8.2.
Electronic Transfer and Archiving of Data
The Medidata Rave system will be used to collect the data in this study. Raw data extracted from 
Medidata Rave will be archived prior to any further processing. Datasets including raw data, 
study data tabulation model (SDTM) data, and analysis data model (ADaM) data for planned 
analyses will be archived. Any additional unplanned analyses that occur after the primary 
analysis and prior to the final analysis will also be archived. Key data external to the clinical 
study database (see below) will be included in the relevant SDTM and ADaM modules when the 
external data are available.
Data from the central laboratories (including % of blasts, target (CLL-1) expression in the tumor 
and Measurable Residual Disease (MRD)), the product manufacture (e.g. total T cells infused, 
CAR T cell transduction rate, duration of manufacturing time, vector copy number per 
transduced cells, T cell phenotype), central laboratory assessment of subject blood samples 
(including CAR T cell levels in the peripheral blood, antibody/immunogenicity assays, serum 
inflammatory markers, RCL testing) will be generated from contract laboratories and Kite. These 
data will be transferred to Kite data management and held in a peripheral directory and not built 
into the clinical trial database. Before any analysis, these external data will be merged with the 
SDTM and ADaM datasets.
8.3.
Handling of Missing and Incomplete Data
8.3.1.
Efficacy Data
The method for handling missing efficacy data is described in the definition for each efficacy 
endpoint. Every effort will be made to obtain complete data for all important data points.
If certain data points are missing after all efforts are taken, the missing data may be imputed. In 
the event of a partial or missing death date, the algorithm in Appendix 1 will be used. 
Completely missing death dates or partial missing death dates with only the year reported will 
not be imputed.


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8.3.2.
Safety Data
Partial AE start dates will be imputed. If AE start dates are missing or incomplete, the algorithm 
defined in Appendix 1 will be used.
8.4.
Detection of Bias
A listing of subjects with important protocol deviations (IPDs) will be generated. The deviations 
included in this list will include, but are not limited to, violations of eligibility criteria and use of 
exclusionary medication during the study. Lack of protocol compliance will be evaluated by 
summarizing the subject incidence of IPDs. High rates of IPDs may indicate bias.
8.5.
Outliers
Descriptive statistics may be used to identify potential outliers in any key variables analyzed. 
Suspected outliers will be included in all analyses unless there is sufficient scientific justification 
to exclude them.
8.6.
Distributional Characteristics
The Clopper-Pearson (an exact interval) method is used to generate 95% CI for the disease 
response rate. This method assumes that individual subject responses are independent with 
binomial distribution. While the Clopper-Pearson interval provides adequate coverage 
probability, it is commonly wider than necessary {Brown 2002}, leading to overly conservative 
estimates of the lower bound of response rate.
8.7.
Validation and Configuration Management
All programs to create the SDTM and ADaM datasets, and tables, listings and figures (TLFs) of 
analyses and summaries will be validated and maintained according to Standard Operating 
Procedures to Cell Therapy Studies. The software and version used to generate analyses will be 
indicated in the archived documentation.


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9.
STATISTICAL METHODS OF ANALYSIS
9.1.
General Principles
The primary analysis of the primary endpoint will be conducted when the last treated subject in 
the dose expansion cohort has had the opportunity to be evaluated for response 3 months after 
KITE-222 infusion or 1 month after allo-SCT, whichever occurs first. Additional analyses may 
occur after the primary analysis has been completed; these additional analyses will be 
descriptive.
9.2.
Subject Accountability
Summary statistics will be provided for the following:

The number of subjects in each analysis set

The number of subjects screened

The number of subjects enrolled/leukapheresed

The number of subjects treated with bridging therapy

The number of subjects treated with lymphodepleting chemotherapy

The number of subjects treated with KITE-222

The number of subjects received subsequent allo-SCT

Summaries of actual and potential follow-up time

The number of subjects enrolled and treated by site
The reasons for discontinuing treatment and discontinuing study will be summarized.
9.3.
Important Protocol Deviations
The clinical study team will define IPD categories and review all potential IPDs. The list of 
subjects with important protocol deviations will be identified and documented before the 
database snapshot for the primary efficacy analysis is performed. IPDs will be categorized by 
deviation type (e.g., study eligibility and use of excluded medication). The subject incidence of 
IPDs will be summarized overall and by deviation category.
9.4.
Demographic and Baseline Characteristics
Summary statistics and frequencies for the demographic and baseline characteristics will be 
tabulated:


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
Age (in years) at baseline and by category (< 65, ≥ 65) 

Sex 

Ethnicity and race 

Weight at leukapheresis

ECOG performance status at baseline

Immune Effector Cell-Associated (ICE) score at baseline

Number of prior chemotherapy lines of treatment and best overall response to the first and to 
the last prior regimen

AML type and specification of secondary AML type

Duration of diagnosis 

Risk category per ELN 2017 criteria

Genetic abnormality

WHO classification of AML {Heuser 2020}

CNS infiltration at diagnosis

Disseminated intravascular coagulation at diagnosis

Prior allo-SCT and best overall response corresponding to the allo-SCT. 

The percentage of donor chimerism and DLI treatment (Yes/No) for subjects who have 
received a prior allo-SCT 

Prior radiotherapy and body site

Relapsed/refractory subgroup

Baseline hematological status: absolute white blood cells count, absolute neutrophil count, 
absolute lymphocyte count, percentage of myeloblasts in peripheral blood, percentage of 
myeloblasts in marrow.

% of CLL-1+ Blasts in Bone Marrow and peripheral blood at baseline


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9.5.
Safety Analyses
Safety analyses will be conducted using the safety analysis set. The primary analysis of safety 
data will summarize TEAEs, death, and laboratory test results with onset on or after the KITE-
222 infusion date and before allo-SCT (if applicable).
AEs will be coded according to the latest version of MedDRA at the time of each analysis. The 
version of MedDRA may vary over time as the current version in use is updated. The severity of 
AEs will be graded using the NCI CTCAE version 5.0. The severity of CRS and ICANS events 
will be graded according to the ASTCT consensus grading {Lee 2019}, and individual 
symptoms associated with CRS and ICANS will be graded per the NCI CTCAE version 5.0. The 
severity of acute GVHD will be graded by the MAGIC criteria {Harris 2016} and the severity of 
chronic GVHD will be graded by the NIH 2014 criteria {Jagasia 2015}.
Fatal AEs that are attributed to deaths associated with disease progression or relapse may be 
included in the death summary with a primary death reason of “Progressive Disease” regardless 
of the coded preferred term.
Subjects enrolled, but not dosed with KITE-222, will be followed for AEs for 30 days after the 
last study-specific procedure, or until initiation of a new anticancer therapy, whichever occurs 
first. AEs reported for these subjects will be archived in the study database and available in 
SDTM and ADaM datasets, but will not be tabulated in AE summaries.
Safety summaries will be presented by dose-level cohorts.
9.5.1.
Exposure to Study Treatment
Summary statistics and subject listings will be provided for the following:

Total body surface area-adjusted dose of cyclophosphamide and fludarabine administered as 
lymphodepleting chemotherapy

Total CAR T cells in the KITE-222 infusion

Total T cells in the KITE-222 infusion

Transduction rate (%)

Percentages of CD4 and CD8 T cells

Percentages of T-cell phenotypes

Interferon-gamma (IFN-γ) by Co-culture
9.5.2.
AEs
The subject incidence of the following TEAEs will be tabulated:


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
Summary of AEs (including categories such as any, serious, worst severity, AE of interest, 
treatment-related AE)

All AEs (by SOC and preferred term)

All SAEs (by SOC and preferred term)

All KITE-222-related AEs (by SOC and preferred term)

All KITE-222-related SAEs (by SOC and preferred term)

All Grade 3 or higher AEs (by SOC and preferred term)

All Grade 3 or higher KITE-222-related AEs (by SOC and preferred term)

Fatal AEs

AEs of interest 
The incidence of neutropenia overlapping with fever will be summarized, and fever group term 
includes MedDRA preferred terms of pyrexia and hyperthermia.
Summary statistics for the study day of onset, the study day of resolution, and the duration of 
AEs of interest will be provided. The subject incidence summary of deaths by time periods and a 
subject listing of deaths will be provided. The primary reasons for death will also be 
summarized.
Time to neutrophil recovery and time to platelet recovery after KITE-222 infusion and before the 
start of the conditioning therapy for subsequent allo-SCT will be summarized with descriptive 
statistics as follows:

Time to neutrophil recovery will be calculated as the time from the date of KITE-222 
infusion to the first day when neutrophils are 0.5 109/L, and as the time from the date of 
KITE-222 infusion to the first day when neutrophils are 1.0  109/L. A graph plot will be 
provided, with the horizontal axis representing the follow-up time from the time of baseline 
and on the vertical axis the absolute neutrophil count. The time of the subsequent allo-SCT 
will be marked with a vertical line.

Time to platelet recovery will be calculated as the time from the date of KITE-222 infusion 
to the first day when platelets are 50  109/L, and the time from the date of KITE-222 
infusion to the first day platelets are 100  109/L. A graph plot will be provided, with the 
horizontal axis representing the follow-up time from the time of baseline and on the vertical 
axis the absolute platelet count. The time of the subsequent allo-SCT will be marked with a 
vertical line.
For patients who receive a subsequent allo-SCT after KITE-222, the following descriptive 
statistics will be presented:


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
The percentage of primary graft failure after allo-SCT with the 95% CIs will be summarized. 
Primary graft failure is collected from eCRF and defined as no evidence of engraftment or 
hematological recovery of donor cells within the first month after transplant, without 
evidence of disease relapse. 

The time to engraftment of neutrophils and platelets will be calculated from the date of the 
subsequent allo-SCT to the first day of engraftment of neutrophils and platelets. Engraftment 
is defined as the first of 3 consecutive days with an absolute neutrophil count higher than 
0.5 × 109/L, and sustained >20 × 109/L platelets, free of transfusion requirements.
The incidence of anti-KITE-222 CAR antibodies will be summarized.
Subgroup analyses of AEs may be generated for selected covariates from the list presented in 
Section 4.1.
9.5.3.
Concomitant Medications and Procedures
The incidences of concomitant medications and procedures used to manage AEs will be 
tabulated. The subject incidence of concomitant medications will be summarized by medication 
category and World Health Organization (WHO) Drug coded term. The duration and indication 
of concomitant medications of interest (eg, systemic steroids, tocilizumab, vasopressors, 
nonsteroidal immunosuppressants other than tocilizumab, and IV immunoglobulins) may be 
summarized.
9.5.4.
Laboratory Test Results
Laboratory test results will be graded according to the NCI CTCAE version 5.0. The incidence 
of worst grade laboratory abnormalities post-baseline by grade for all analytes will be 
summarized. Additional summaries for the shift from baseline to the worst laboratory 
abnormality grade on or after the KITE-222 infusion may also be generated.
9.5.5.
Vital Signs and Physical Examinations
Vital sign and physical examination data will be summarized at selected time points by 
descriptive statistics. Subject listings may also be provided.
9.6.
Efficacy Analyses
Efficacy analyses will be conducted on the mITT analysis set, and the investigator assessment of 
disease status per the ELN 2017 Classification (Appendix 5 in the study protocol) will be used 
for disease response related analyses. Sensitivity analysis using FAS may also be provided for 
key efficacy analyses.  
A waterfall plot will be provided representing the percentage change in marrow myeloblasts 
from baseline to the assessment on Week 4 in the mITT set. 


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Three separate line plots with median, lower quartile (Q1) and upper quartile (Q3) will be 
provided for the percentage of myeloblasts in the marrow, the percentage of myelocytes in the 
marrow, and the percentage of metamyelocytes in the marrow using the mITT analysis set, with 
the x-axis representing the follow-up time from the baseline. For the subjects received post allo-
SCT, the follow-up time will be up to the conditioning chemo for the allo-SCT.
A listing of the extramedullary disease assessment evaluation with be provided sorted by Dose 
Level, patient identification and time.
A listing of the text reports of the marrow disease assessments will be provided sorted by Dose 
Level, patient identification and time.
9.6.1.
Composite Complete Remission Rate
The incidence of CCR and exact 2-sided 95% CIs will be generated. All subjects who do not 
meet the criteria for CR, CRMRD−, or CRi by the analysis data cutoff date will be considered 
non-responders for the CCR rate evaluation.
Additional analysis of CCR using the FAS and by dose level cohorts will be provided.
. 
9.6.2.
Overall Remission Rate 
The incidence of the OR rate and exact 2 sided 95% CIs will be generated. All subjects who do 
not meet the criteria for CR, CRMRD−, CRi, MLFS, or PR by the analysis data cutoff date will 
be considered non-responders for the OR rate evaluation.
9.6.3.
RFS 
Kaplan-Meier (KM) estimates and 2-sided 95% CIs will be generated for RFS. Estimates of the 
proportion of subjects in remission at 3-month intervals from the first response will be provided.
The number of subjects censored and the reasons for censoring will be summarized.
9.6.4.
Allo-SCT Rate
The incidence of on study allo-SCT will be summarized by overall, subjects achieving 
CRMRD−, and subjects achieving CR + CRi. Corresponding 2-sided 95% CIs will be generated.
9.6.5.
EFS
KM estimates and 2-sided 95% CIs will be generated for EFS. Estimates of the proportion of 
subjects with EFS at 3-month intervals from KITE222 infusion will be provided.
The number of subjects censored and the reasons for censoring will be summarized.
CCI


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9.6.6.
OS
KM estimates and 2-sided 95% CIs will be generated for OS. Estimates of the proportion of 
subjects alive at 3-month intervals from KITE222 infusion will be provided.
A swim lane plot will be provided, with the horizontal axis representing the follow-up time from 
the time of the KITE-222 infusion and each lane representing a subject. On each lane, endpoints 
of interests such as disease responses, subsequent allo-SCT, first subsequent AML therapy (apart 
from allo-SCT), and death will be marked at the time when they occur. The swim lane will be 
sorted by dose level and longest survival time within each level. 
9.6.7.
30- and 60-day All-cause Mortality
The incidence of 30- and 60-day mortality and exact 2-sided 95% CIs will be generated.
9.7.
Pharmacokinetics and Pharmacodynamics
Details of pharmacokinetic (PK) and pharmacodynamic (PD) analyses will be described in a 
separate Translational SAP.
9.8.
Study Key Metrics 
Summary statistics will be provided for the following durations:

Days from leukapheresis to commencement of lymphodepleting chemotherapy

Days from leukapheresis to the KITE-222 product release

Days from leukapheresis to delivery of KITE-222 at the study site

Days from leukapheresis to administration of KITE-222

Days from lymphodepleting chemotherapy to administration of KITE-222

Days from the administration of KITE-222 to the day of receiving subsequent allo-SCT

Duration of hospitalization for the KITE-222 infusion

Number and duration of ICU hospitalizations in the first month from KITE-222 infusion
Successful manufacturing rate of KITE-222 will be calculated as number of KITE-222 product 
release divided by the total number of subjects included in the FAS at each dose level.


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10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES
None.


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11.
REFERENCES
Brown LD, Cai TT, DasGupta A. Confidence Intervals for a Binomial Proportion and 
Asymptotic Expansions. The Annals of Statistics 2002;30 (1):160-201.
Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, et al. Diagnosis and 
Management of AML in Adults: 2017 ELN Recommendations from an 
International Expert Panel. Blood 2017;129 (4):424-47.
Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, Bunworasate U, et al. International, 
Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data 
Collection: A Report from the Mount Sinai Acute GVHD International 
Consortium. Biol Blood Marrow Transplant 2016;22:4-10.
Heuser M, Ofran Y, Boissel N, Brunet Mauri S, Craddock C, Janssen J, et al. Acute myeloid 
leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, 
treatment and follow-up. Annals of Oncology 2020;31 (6):697-712.
Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes 
of Health Consensus Development Project on Criteria for Clinical Trials in 
Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working 
Group Report. Biol Blood Marrow Transplant 2015;21:389-401 e1.
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT 
Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity 
Associated with Immune Effector Cells. Biol Blood Marrow Transplant 
2019;25:625-38.


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12.
APPENDICES
Appendix 1.
Conventions for Clinical Data That Require Imputation for Partial or Missing Dates
Appendix 2.
Derivation of Time to Event Endpoints
Appendix 3.
Censoring Criterion for OS and Derivation of Last Date Known to Be Alive


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Appendix 1.
Conventions for Clinical Data That Require Imputation for Partial or 
Missing Dates
The following dates will be imputed using the algorithm in Table 1:

Adverse event (AE) start dates

Concomitant medication start dates
Table 6.
Imputation Rules for Partial or Missing Start Dates
Start Date
Stop Date
Complete:  yyyymmdd
Partial:  yyyymm
Partial:  yyyy
< Day 0
≥ Day 0
< Day 0 
yyyymm
≥ Day 0
yyyymm
< Day 0 
yyyy
≥ Day 0
yyyy
Missing
= Day 0
yyyymm
1
1
n/a
1
1
Partial
yyyymm
≠ day 0
yyyymm
2
2
2
2
2
2
2
= Day 0
yyyy
1
1
n/a
1
1
Partial
yyyy
≠ Day 0
yyyy
3
3
3
3
3
3
3
Missing
4
1
4
1
4
1
1
Abbreviation:  n/a, not applicable.
Notes: If the start date imputation leads to a start date that is after the stop date, then do not impute the start date.
1 = impute the date of Day 0.
2 = impute the first of the month.
3 = impute January 1 of the year.
4 = impute January 1 of the stop year.
Imputation rules for partial or missing death dates:

If death year and month are available, but day is missing:
If mmyyyy for the last date known to be alive = mmyyyy for death date, set death date to 
the day after the last date known to be alive.
If mmyyyy for the last date known to be alive < mmyyyy for death date, set death date to 
the first day of the death month.
If mmyyyy for last date known to be alive > mmyyyy for death date, data error and do not 
impute.

If both month and day are missing for death date or a death date is completely missing, do 
not impute, and censor the subject survival time per rules in Appendix 3.


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Kite Pharma, Inc.
Statistical Analysis Plan
CONFIDENTIAL
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28 June 2022
Imputation rules for original date of diagnosis:
1) 1. If year and month are available but day is missing, then impute the first day of the month.
2) 2. If year is available but month and day are missing, then impute January 1 of the year.


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Kite Pharma, Inc.
Statistical Analysis Plan
CONFIDENTIAL
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28 June 2022
Appendix 2.
Derivation of Time to Event Endpoints 
The derivations of RFS, EFS, and OS are provided below.
RFS
Table 7.
RFS Analysis
Circumstance by Data Cutoff for Analysis 
Event/Censored
Date of Event / Censoring
Relapse 
Event
First relapse date 
Death due to any reason
Event
Death date 
Receive SCT before relapse
Censored
Last evaluable disease assessment 
date prior to data cutoff
New anti-cancer therapy (excluding SCT) 
started before relapse
Censored
Last evaluable disease assessment 
date prior to the first new therapy 
(excluding SCT)
Withdrawal of consent or lost to follow-up 
without relapse
Censored
Last evaluable disease assessment 
date prior to data cutoff date
Remain in response without new anti-cancer 
therapy (including SCT) by data cutoff
Censored
Last evaluable disease assessment 
date prior to data cutoff date
Abbreviations:  SCT, stem cell transplant.
Note: Time to event = Event / Censoring date - First response date + 1.
EFS
Table 8.
EFS Analysis
Circumstance by Data Cutoff for Analysis
Event/Censored
Date of Event/Censoring
Disease progression 
Event
First progression date 
Death due to any reason
Event
Death date
Relapse
Event 
First relapse date
refractory disease*
Event
Disease assessment date at Week6 
New anti-cancer therapy (excluding SCT) 
started before PD, relapse or refractory disease
Censored
Last evaluable disease assessment date 
prior to the first new therapy (excluding 
SCT)
Withdrawal of consent or lost to follow-up 
before PD, relapse or refractory disease
Censored
Last evaluable disease assessment date 
prior to data cutoff date
Remain in response** without new anti-cancer 
therapy (including SCT) by data cutoff
Censored
Last evaluable disease assessment date 
prior to data cutoff date
Disease response yet to be assessed and not 
reach to Week 6 disease assessment
Censored
KITE-222 infusion date
Abbreviations:  PFS, progression-free survival; SCT, stem cell transplant. PD, progressive disease.
* defined as the subject not experiencing CR, CRMRD−, or CRi by the Week 6 disease assessment.
**defined as alive, in response (CR, CRMRD−, or CRi)
Note: Time to event = Event / Censoring date - First infusion date + 1


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Kite Pharma, Inc.
Statistical Analysis Plan
CONFIDENTIAL
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28 June 2022
Appendix 3.
Censoring Criterion for OS and Derivation of Last Date Known to Be 
Alive
The scenarios describing when the event occurs or the subject is censored for the analysis of OS 
are presented in Table 9.
Table 9.
OS Analysis
Circumstance 
Event/Censored
Date of Event/Censoring
Death before data cutoff date for analysis
Event
Death date
Death after data cutoff date for analysis
Censored
Data cutoff date
Known to be alive after data cutoff date for 
analysis
Censored
Data cutoff date
Alive up through the discontinuation of study, or 
data cutoff date and no further information 
available afterwards
Censored
Last date known to be alive date up 
through the date of discontinuation of 
study, or data cutoff date, whichever is 
earlier
Note: Time to event = Event / Censoring date - First infusion date + 1
Last Date Known to be Alive
The last date known to be alive with be derived by obtaining the maximum complete date among 
the following data modules:

Leukapheresis dates

Bridging therapy administration dates

Lymphodepleting chemo administration dates

KITE-222 infusion dates

Start date of AE and end date of AE if the date is available 

Disease response assessment date

The last date the lab data or vital sign measured

The last date the concomitant medication received

The last date of subsequent therapy for AML

Long-term follow-up subject status date where status = alive

End of treatment disposition where status is not equal to death, lost to follow-up

End of study date where end of study reason is not equal to death, lost to follow-up


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Statistical Analysis Plan
CONFIDENTIAL
Page 40
28 June 2022

Date of subsequent allo-SCT

Date of engraftment after allo-SCT


Statistical Analysis Plan -KT-US-486-0201
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
14-Jul-2022
13:40:25
Global Patient
Safety eSigned
14-Jul-2022
17:49:21
Clinical Research eSigned
14-Jul-2022
18:12:01
Clinical Pharmacology
eSigned
15-Jul-2022
11:54:17
PPD
PPD
PPD
PPD-