A Phase 1 Study Evaluating the Safety and Efficacy of HPV16 E7 T Cell Receptor Engineered T Cells (KITE-439) in HLA-A*02:01+ Subjects With Relapsed/Refractory HPV16+ Cancers
Phase: PHASE1
Conditions: Human Papillomavirus (HPV) 16+ Relapsed/Refractory Cancer
Sponsor: Gilead Sciences



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PROTOCOL SYNOPSIS
Title:
A Phase 1 Study Evaluating the Safety and Efficacy of HPV16 E7 
T Cell Receptor Engineered T Cells (KITE-439) in HLA-A*02:01+ 
Subjects with Relapsed/Refractory HPV16+ Cancers
Indication:
Treatment of human leukocyte antigen (HLA)-A*02:01+ adult 
subjects with human papillomavirus (HPV)16+ relapsed/refractory 
cancer.
Study Design:
This is a Phase 1 open-label, multicenter study evaluating the safety 
and efficacy of KITE-439 in subjects who are HLA-A*02:01+ and 
have HPV16+ relapsed/refractory cancers.  The trial is separated into 
2 phases:  Phase 1A and Phase 1B.
PHASE 1A
Phase 1A is the single-subject, dose-escalation portion of the study.  
Phase 1A will enroll a minimum of 2 subjects and up to a maximum 
of approximately 36 subjects.
DOSE ESCALATION PERIOD
During Phase 1A, the study will employ a single-subject dose 
escalation scheme until Cohort 5 and 6 at which time a 3+3 design is 
implemented (see Section 9.7.2.1).  Subjects will be monitored for 
the occurrence of -dose-limiting toxicities (DLTs) within the first 
21 days after receiving the KITE-439 infusion (see Section 9.7.1 for 
DLT criteria).  In Cohorts 1 through 4, if the subject does not 
experience a DLT during the DLT window, then the next subject will 
be dosed at the next higher dose cohort.  If the subject does 
experience a DLT, then the rules as outlined in Section 9.7.2.1 will 
apply.
SAFETY REVIEW PERIOD
A safety review team (SRT) will make recommendations on the 
conduct of the study.  The SRT membership includes the study 
sponsor and at least one Phase 1 investigator with an enrolled and 
dosed subject in the study.  The SRT will assess overall safety and 
DLTs in Phase 1A as well as pausing criteria in Phase 1A and 
Phase 1B.  See Section 9.7.2 for additional details.

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PHASE 1B
After a dose has been selected based on Phase 1A, enrollment will 
commence in Phase 1B.  At Kite’s discretion, up to approximately 
35 subjects will be enrolled into the following 2 cohorts.

HPV16+ squamous cell carcinoma of the head and neck (n = 15)

Other HPV16+ tumors (Includes all HPV16+ tumors other than 
squamous cell carcinoma of the head and neck) (n = 20)
Note:  The subjects enrolled and treated in Phase 1A at the selected 
Phase 1B dose will contribute to the sample size for Phase 1B based 
on their relevant tumor type.
Independent of the phase of the study (Phase 1A or Phase 1B), each 
subject will follow the same study treatment schedule and procedural 
requirements.  Each subject will proceed through the following study 
periods:

Pre-screening

Screening (main study)

Enrollment/leukapheresis


Conditioning chemotherapy 

Investigational product (IP) treatment 

Posttreatment assessment 

Longterm follow-up (LTFU)
For study requirements assigned to each study period, refer to the 
schedule of assessments (SOA) and Section 7.11 for details.
A study schema is provided in Figure 1.
Study Objectives:
The primary objectives of Phase 1A are to evaluate the safety of 
KITE-439 and to determine a recommended Phase 1B dose.
The primary objective of Phase 1B is to estimate the efficacy of 
KITE-439, as measured by objective response rate (ORR).  
Secondary objectives include assessing the safety of KITE-439 and 
additional efficacy endpoints.
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Statistical 
Considerations:
The primary endpoint for the Phase 1A portion of the study is 
incidence of AEs defined as DLTs.
The primary endpoint for the Phase 1B portion of the study (subjects 
enrolled at the Phase 1B dose in the Phase 1A portion will be 
included) is ORR per the modified RECIST v1.1 (Appendix 1).  This 
endpoint will be based on a modified intent to treat (mITT) 
population consisting of all subjects who receive Phase 1B target 
dose of KITE-439 and with measurable disease 
 
 and prior to administration of 
conditioning chemotherapy.
The Phase 1B uses a single-arm design to estimate response rate in 
each of the 2 cohorts (n = 15 in the HPV16+ squamous cell cancer of 
the head and neck cohort and n = 20 in the other HPV16+ tumors 
cohort that includes all HPV16+ tumors other than squamous cell 
carcinoma of the head and neck) and in all Phase 1B cohorts 
combined (n = 35).  With the planned sample size in the two cohorts, 
the ORR can be estimated with a standard error not greater than 
13% and 11%, respectively.  Assuming an observed ORR of 40%, 
the lower bound of the 95% CI for the estimated ORR will exclude 
values less than 16% and 19%, respectively.  With a planned total 
sample size of 35 for all Phase 1B cohorts combined, the ORR can be 
estimated with a standard error no greater than 8%.  Assuming an 
observed ORR of 40%, the lower bound of the 95% CI for the 
estimated ORR will exclude values less than 24%.
No formal interim analysis is planned for the Phase 1B part of the 
study.  However, the SRT will review subject-level safety and 
efficacy data on an ongoing basis to monitor subject safety and 
ensure data quality.  Informal safety and efficacy analyses may be 
done with accumulating data when such a need arises during the 
study.  Within the Phase 1B HPV16+ squamous cell cancer of the 
head and neck cohort, if no response is observed in the first 
7 subjects treated with the target dose after a minimum of 1 month of 
follow-up, the sponsor may consider stopping enrollment for this 
cohort. Within the other Phase 1B HPV16+ tumors cohort, if no 
response is observed in the first 10 subjects treated with the target 
dose after a minimum of 1 month of follow-up, the sponsor may 
consider stopping enrollment for this cohort.
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One primary analysis is planned for each of the cohorts in Phase 1B 
and will be performed after all subjects accrued for a specific cohort 
to the study have had the opportunity to be assessed for response 
3 months after the KITE-439 infusion.  If an individual cohort takes 
> 24 months to accrue from the initiation of Phase 1B, the primary 
analysis can occur with < 15 subjects accrued for the HPV16+ 
squamous cell cancer of the head and neck cohort and < 20 subjects 
for the other HPV16+ tumors cohort excluding squamous cell 
carcinoma of the head and neck.  If the primary analysis for 2 cohorts 
is projected to occur within 3 months of each other, the cohorts may 
be combined and carried out at the same time.

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10.2.2.
Secondary ..............................................................................................................................78
10.3.
Sample Size Considerations ....................................................................................................................79
10.4.
Analysis Subsets......................................................................................................................................80
10.5.
Access to Individual Subject Treatment Assignments ............................................................................80
10.6.
Safety Review and Interim Analysis .......................................................................................................80
10.6.1.
Phase 1A Safety Review .......................................................................................................80
10.6.2.
Efficacy Interim Analysis......................................................................................................81
10.7.
Planned Method of Analysis ...................................................................................................................81
10.7.1.
Objective Response Rate.......................................................................................................81
10.7.2.
Duration of Response ............................................................................................................81
10.7.3.
Progression-free Survival ......................................................................................................81
10.7.4.
Overall Survival.....................................................................................................................81
10.7.5.
Safety.....................................................................................................................................81
10.7.6.
Long-term Data Analysis ......................................................................................................82
11.
REGULATORY OBLIGATIONS.......................................................................................................................83
11.1.
Independent Review Board/Independent Ethics Committee...................................................................83
11.2.
Subject Confidentiality............................................................................................................................83
11.2.1.
Investigator Signatory Obligations........................................................................................83
12.
PROTOCOL AMENDMENTS AND TERMINATION .....................................................................................84
13.
STUDY DOCUMENTATION AND ARCHIVE ................................................................................................85
14.
STUDY MONITORING AND DATA COLLECTION......................................................................................87
15.
PUBLICATION ...................................................................................................................................................88
16.
COMPENSATION...............................................................................................................................................89
17.
REFERENCES.....................................................................................................................................................90
18.
APPENDICES......................................................................................................................................................96
Appendix 1.
Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines Version 1.1 
with Modifications...................................................................................................................97
Appendix 2.
Practical Body Weight Calculation for Subjects Whose BMI is > 35...................................104
Appendix 3.
Childbearing Potential and Birth Control..............................................................................105
Appendix 4.
Country-specific Regulatory Agency Requirements.............................................................107
LIST OF IN-TEXT TABLES
Table 1.
Survival Rates for Patients Diagnosed with HPV-associated Cancers in the US:  
2001-2011a...............................................................................................................................21
Table 2.
Phase 1A Dose Cohorts ...........................................................................................................26
Table 3.
Reporting Requirements for Concomitant Medications..........................................................39
Table 4.
Clinical Laboratory Parameters...............................................................................................41
Table 5.
Schedule of Assessments (Pre-screening through Post-treatment follow-up).........................58
Table 6
Schedule of Assessments (LTFU) ...........................................................................................60
Table 7.
Reporting Requirements for Adverse Events ..........................................................................68
Table 8.
Reporting Requirements for Serious Adverse Events .............................................................71
Table 9.
Dose-limiting Toxicity (DLT).................................................................................................73
Table 10.
Evaluation of Target Lesions at Each Assessment Point.......................................................100
Table 11.
Evaluation of Non-target Lesions at Each Assessment Point................................................101
Table 12.
Time Point Response in Subjects with Target (± non-target) Disease..................................102
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Table 13.
Modifications from RECIST 1.1 ...........................................................................................103
LIST OF IN-TEXT FIGURES
Figure 1.
STUDY SCHEMA (PHASE 1A AND PHASE 1B)...............................................................11

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LIST OF ABBREVIATIONS
AE
Adverse event
ALT
Alanine transaminase
ANC
Absolute neutrophil count
AST
Aspartate aminotransferase
BLAST
Basic Local Alignment Search Tool 
BMI
Body mass index
CAR
Chimeric antigen receptor
CBC
Complete blood count
CDC
Centers for Disease Control and Prevention
CI
Confidence interval
CNS
Central nervous system
CPF
Cell processing facility
CR
Complete response
CRF
Case report form
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
DLT
Dose-limiting toxicity
DOR
Duration of response
DVT
Deep vein thrombosis
ECHO
Echocardiogram
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
EU
European Union
FAS
Full analysis set
FDA
Food and Drug Administration
FDG-PET
F-flurodeoxyglucose positron emission tomography
FFPE
Formalin-fixed paraffin embedded 
GCP
Good Clinical Practice
GPT
Glutamic-pyruvic transaminase
GVHD
Graft-versus-host-disease
HABA
Human anti-bovine antibodies
HEENT
Head, eyes, ears, nose, and throat
HLA
Human leukocyte antigen
HNSCC
Head and neck squamous cell carcinoma

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HIV
Human immunodeficiency virus
HLA
Human leukocyte antigen
HPV
Human papillomavirus
HSV
Herpes simplex virus
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Council for Harmonisation for Pharmaceuticals for Human Use
ICU
Intensive care unit
ID
Identification
IFN
Interferon
IHC
Immunohistochemistry
IL
Interleukin
IND
Investigational New Drug
IP
Investigational product
IPM
Investigational Product Manual
IRB
IEC
Institutional Review Board
Independent Ethics Committee
IV
Intravenous
IVPB
Intravenous piggyback
LDH
Lactate dehydrogenase
LMWH
Low molecular weight heparin
LTFU
Long-term follow-up
LVEF
Left ventricle ejection fraction
mITT
Modified intend to treat
MMSE
Mini-Mental Status Exam
MRI
Magnetic resonance imaging
MTD
Maximum tolerated dose
NCI
National Cancer Institute
NCCN
National Comprehensive Cancer Network
NE
Inevaluable
ORR
Objective response rate
OS
Overall survival
PBMC
Peripheral blood mononuclear cells
PCR
Polymerase chain reaction
PD
Progressive disease
PET-CT
Positron emission tomography-computed tomography
PFS
Progression-free survival
PK
Pharmacokinetic 
PO
Orally
PR
Partial response

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qPCR
Quantitative polymerase chain reaction
RCR 
Replication-competent retrovirus
RECIST
Response Evaluation Criteria in Solid Tumors 
SAE
Serious adverse event
SCC
Squamous cell carcinoma
SD
Stable disease
SOA
Schedule of assessment
SRT
Safety review team
SUSAR
Suspected unexpected serious adverse reactions
TCR
T-cell receptor
TIA
Transient ischemic attack
ULN
Upper limit normal
UTI
Urinary tract infection
WBC
White blood cell

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1.
OBJECTIVES
The primary objectives of Phase 1A are to evaluate the safety of KITE-439 and to determine a 
recommended Phase 1B dose.
The primary objective of Phase 1B is to estimate the efficacy of KITE-439, as measured by 
objective response rate (ORR).  Secondary objectives include assessing the safety of KITE-439 
and additional efficacy endpoints.

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2.
BACKGROUND AND RATIONALE
2.1.
HPV-associated Cancers
Human papilloma virus (HPV) infection is considered one of the predominant causes of 
infection-related cancers in both men and women globally {Serrano 2018}.  Over 120 HPV 
subtypes have been characterized, but a subset of 15 high-risk HPV subtypes are responsible for 
causing large proportions of cervical, head and neck, and anogenital (i.e., vulvar, vaginal, penile, 
anal) cancers {Arbyn 2012, Bansal 2016, Berman 2017}.  The HPV16 and HPV18 subtypes 
have the greatest oncogenic potential and cause approximately 70% of all cervical cancers 
worldwide {de Sanjose 2007}.  US Centers for Disease Control and Prevention (CDC) data from 
1993 to 2005 show that HPV16 or HPV18 was detected in the majority of anal (79%), cervical 
(66%), oropharyngeal (60%), and vaginal (55%) cancers, and in nearly half of all vulvar (49%) 
and penile (48%) cancers {Saraiya 2015}.  The analysis also showed that in the US, HPV16 was 
by far the most common subtype across invasive anogenital cancer, as well as head and neck 
cancers.
An estimated 20,000 to 30,000 HPV-associated cancers are diagnosed annually in the US 
{Razzaghi 2018, Viens 2016}. The American Cancer Society estimated in 2017 that over 
12,000 deaths occurred due to cancers located at anatomic sites with a high frequency of 
HPV-associated cancers (i.e., includes oral cavity/pharynx [not tongue/mouth]; cervix; vulva; 
vaginal/other genital, female; penis/other genital, male; and anus, anal canal, and anorectum) 
{ACS 2017}.  Razzaghi and colleagues recently analyzed survival of patients with 
HPV-associated cancers using data from 27 CDC cancer registries covering approximately 
59% of the US population {Razzaghi 2018}.  For this study, HPV-associated cancer were 
defined as invasive cancers occurring at anatomic sites where HPV DNA is frequently identified: 
all cervical cancers (squamous cell carcinomas [SCC] and adenocarcinomas) and SCC of the 
cervix, vulva, vagina, penis, oropharynx, anus, and rectum.  The study showed that over 
200,000 HPV-associated cancers were diagnosed from 2001 to 2011, and the 5-year, 
age-standardized relative survival rate was highest for cervical carcinomas, vulvar, and anal 
SCCs, and lowest for penile and oropharyngeal SCCs (Table 1).

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Table 1.
Survival Rates for Patients Diagnosed with HPV-associated Cancers 
in the US:  2001-2011a
HPV-associated 
Cancersb
Number of Patients 
Diagnosed
Percentage of 
Total
5-year Relative Survival Rate
Cervical carcinoma
79,425
36.1
64.2%
Vaginal SCC
4,871
2.2
52.8%
Vulvar SCC
19,345
8.8
66%
Penile SCC
6,248
2.8
47.4%
Anal SCC
26,026
11.8
65.9%
Rectal SCC
4,145
1.9
56.2%
Oropharyngeal SCC
80,151
36.4
51.2%
Total
220,211
100.0
-
Abbreviations:  HPV, human papillomavirus; SCC, squamous cell carcinoma
Adapted from: {Razzaghi 2018}
a.
Data were compiled from 27 population-based cancer registries that participate in the National Program of Cancer 
Registries, meet the data-quality standards for inclusion in US Cancer Statistics, and meet the criteria for inclusion in the 
survival data set, which covers approximately 59% of the US population.  Analyses were limited to invasive cancers 
diagnosed 2001 through 2011 and were followed through 2011, and met specified histologic criteria for HPV-associated 
cancers. 5-year survival rate was calculated from diagnosis until death.
b.
HPV-associated cancers were defined by Razzaghi and coauthors as invasive cancers at anatomic sites with cell types in 
which HPV DNA is frequently identified, which included all carcinomas of the cervix (including adenocarcinomas and 
SCCs), and SCCs only for the other anatomic sites.  To estimate the number of cancers attributed to HPV, the number of 
HPV-associated cancers was multiplied by the percentage of each cancer type attributable to HPV based on the genotyping 
study of Saraiya and coauthors {Saraiya 2015}.
2.2.
Available Therapy and Unmet Need
Depending upon the cancer type, patients with localized, early stage HPV-associated cancers 
may be successfully treated with surgery, radiation therapy, chemoradiotherapy, chemotherapy, 
or biologic therapy, but patients who relapse or are refractory to such therapies and patients with 
metastatic disease generally have poor prognoses {Stern 2012}.  Available therapies and 
reported outcomes according to anatomic site of disease are summarized below.  The collective 
data demonstrate the magnitude of this critical unmet medical need.
Head and Neck
The recurrence rate is approximately 10% to 20% in early-stage head and neck SCC (HNSCC) 
and 50% in locally advanced HNSCC, and patients with recurrent or metastatic HNSCC have a 
median overall survival (OS) less than 1 year with standard therapies {Argiris 2017, Price 2012}.  
Treatment for recurrent and/or metastatic HNSCC often consists of cetuximab, an anti-epidermal 
growth factor receptor (EGFR) monoclonal antibody, plus combination chemotherapy with 
cisplatin or carboplatin and 5-flourouracil (5-FU), followed by maintenance with cetuximab 
alone. Cetuximab has been approved for HNSCC treatment using this regimen {ERBITUX 
2012}.  In a Phase 3 study of patients with recurrent or metastatic oropharyngeal tumors, this 
treatment, known as the EXTREME regimen, was compared to chemotherapy-alone; results 

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combination chemotherapy (cisplatin/paclitaxel or topotecan-paclitaxel) in patients with 
recurrent, persistent or metastatic cervical cancer improved median OS to 17 months versus 
13.3 months with chemotherapy alone, but the majority of patients died within 2 years {Tewari 
2014}.  In June 2018, pembrolizumab was approved in the US for the treatment of patients with 
recurrent or metastatic cervical cancer whose tumors express PD-L1 
(https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm610572.htm). The approval 
was based on results from the treatment of 98 patients with relapsed/refractory or advanced 
PD-L1+ and PD-L1- cervical cancers in the KEYNOTE 158 open-label Phase 2 study {Chung 
2018}. ORR for patients in KEYNOTE 158 was 16% in the 81 patients with PD-L1+ tumors 
(13.3% in the overall cohort of 98 patients). Median OS was 9.4 months (range: 7.9 to 13.4 
months). Given the low survival rates and overall survival, even with this new therapy, patients 
with recurrent, persistent, or metastatic cervical cancer represent a critical unmet need.
Although anal cancer is a rare disease and accounts for less than 1% of all new cancer diagnoses, 
its incidence in the US has more than doubled from 1975 to 2015.  The prognosis of patients 
with inoperable progressive/recurrent or metastatic anal cancer is poor regardless of HPV status, 
with a 5-year relative survival rate of 30%.  Although recommendations for therapy are debated 
due to a lack of evidence from large prospective studies, treatment of metastatic anal cancers or 
locally advanced unresectable anal cancers generally consists of a combination regimen with a 
platinum agent and fluoropyrimidine.  Results from several retrospective studies showed ORRs 
ranging from 30% to 57%, with median progression-free survival (PFS) of 6 to 8 months in 
patients treated with a platinum agent and fluoropyrimidine {Sclafani 2018}.  Next-line 
treatment for advanced anal cancers refractory to platinum and fluoropyrimidine has included a 
variety of chemotherapy agents either as monotherapy or in combinations of 2 to 4 agents, 
although these results were from small retrospective studies with high variability in response 
rates {Sclafani 2018}.  Recently, the immune checkpoint inhibitors pembrolizumab and 
nivolumab were investigated as therapies for advanced anal cancer in 2 separate prospective 
studies.  In a small Phase 1b single-arm study, pembrolizumab treatment of patients with 
PD-L1+ recurrent/refractory anal cancer resulted in an ORR of 17% and median OS of 
9.3 months {Ott 2017}.  Similarly, in a small Phase 2 study of patients with previously treated 
unresectable metastatic anal cancer, treatment with nivolumab resulted in an ORR of 24% and 
median OS of 11.5 months {Morris 2017}.  Thus, outcomes for patients with recurrent, 
refractory, or metastatic anal cancers remain poor even with newer agent therapies.
In conclusion, the overall poor response and survival results from these studies of available 
treatment options indicate that novel therapies are needed for patients with recurrent/refractory 
HPV-associated tumors.

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2.3.
Engineered T-cell Therapy
T cells play a central role in the immune system by destroying diseased cells, including tumor 
cells, throughout the body.  Studies with tumor vaccines {Kantoff 2010}, immune checkpoint 
inhibitors {Hamid 2013}, and tumor infiltrating lymphocytes {Rosenberg 2011} have 
demonstrated the potential of T cells to treat cancer.  To be effective in combating cancer, T cells 
must possess the appropriate specificity for a tumor, be present in sufficient numbers, and be 
able to overcome any local immunosuppressive factors {Kershaw 2013}.
Engineered autologous cell therapy is a process by which a subject’s own T cells are collected 
and subsequently genetically engineered with a T-cell receptor (TCR) or a chimeric antigen 
receptor (CAR) specific for a target antigen expressed on the cell surface of specific 
malignancies {Johnson 2006, Kochenderfer 2013, Robbins 2015}.  Engagement of the TCR or 
CAR with its target antigen induces T-cell activation, resulting in the killing of the target cancer 
cell, production of therapeutic cytokines, and T-cell expansion.  The ability to genetically 
engineer human T cells and use them to mediate cancer regression in subjects has been 
demonstrated in a number of studies for a variety of cancers {Kochenderfer 2014, Lee 2015, 
Robbins 2015}.
Kite Pharma, Inc. (hereafter referred to as Kite) is developing T-cell products consisting of 
T cells that express a CAR or T cells that express an engineered TCR.  In contrast to 
antibody-based targeted therapies, such as CAR T cells or monoclonal antibodies, both of which 
generally recognize epitopes on intact proteins, TCRs recognize short peptide fragments (8 to 
18 amino acids) that are presented by class I or class II HLA molecules on the surface of tumor 
cells or other antigen-presenting cells.  CD8+ T cells require presentation of cognate peptide by a 
class I HLA molecule, and CD4+ T cells generally recognize peptides presented in context of 
HLA class II molecules.  Because TCRs recognize their cognate peptide only in the context of a 
specific HLA type, T-cell products that express engineered TCRs are of potential benefit only to 
patients with the corresponding HLA type.  Another advantage is the ability of TCRs to 
recognize HLA-presented peptides derived from transmembrane or intracellular proteins, thereby 
providing more potential targets than CARs.
To date, available cell products engineered with TCR genes have contained both CD4+ and 
CD8+ cells {Johnson 2009, Kageyama 2015, Morgan 2006, Robbins 2015, Tawara 2017} or only 
CD4+ cells.  With both categories of product, safety profiles have been acceptable when the TCR 
was not affinity enhanced (i.e., genetically engineered to have higher binding affinity for 
HLA-peptide complexes compared with native TCRs) and when the TCR did not exhibit 
nonspecific binding {Linette 2013, Robbins 2015}.

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2.3.1.
Description of the T-cell Therapy Product: KITE-439
Kite is developing an autologous T-cell product that targets HPV16-expressing 
relapsed/refractory solid tumors.  The HPV epitope targeted by the engineered TCR is a peptide 
consisting of amino acids 11 to 19 of the HPV16 E7 protein, hereafter referred to as HPV E7 
peptides 11-19.  HPV16 E7 is a viral protein that is constitutively expressed in, and important for 
the survival of, HPV-driven cancers {Honegger 2013, Longworth 2004, Sima 2008}.  The E7 
protein is not expressed by human tissue, making it an attractive target for anti-cancer therapy 
{Hinrichs 2013}.
The engineered TCR recognizes the HPV E7 peptides 11-19peptide presented by HLA-A*02:01, 
which is the most common class I HLA-A2 allele in humans, detected in approximately 20% to 
95% of individuals across many ethnic populations {Browning 1996, Ellis 2000}.  The HPV E7 
peptides 11-19 9-mer peptide is a naturally processed epitope that is conserved among HPV16 
strains.  When presented by HLA-A*02:01 on the surface of HPV16+ tumor cells, the peptide 
can be targeted by cytotoxic T cells, resulting in target cell killing in an in vitro assay {Riemer 
2010}.
Additional details, including a risk/benefit assessment of KITE-439, are provided in the 
Investigator’s Brochure (IB).
2.4.
Nonclinical Studies
Nonclinical studies were conducted by the National Cancer Institute (NCI) to assess the binding 
specificity, HLA restriction, potential for cross-reactivity, cytotoxicity, effector cytokine 
production (IFN-), and in vivo efficacy of E7 TCR T cells {Jin 2018}.  Details of these analyses 
are described in the IB.
2.5.
Previous Human Experience
NCI Protocol 16-C-0154 (Investigational New Drug [IND] 16959; NCT 02858310) entitled, “A 
Phase I Trial of T Cell Receptor Gene Therapy Targeting HPV-16 E7 with or without PD-1 
Blockade for HPV-Associated Cancers,” is a first-in-human, ongoing Phase 1 study of 
autologous E7 TCR T cells in HLA-A*02:01+ subjects who have metastatic or relapsed or 
refractory HPV16+ cancers.  This study uses T cells expressing the same genetically modified 
TCR construct and the same retroviral vector as those used in the production of KITE-439; 
however, the NCI manufacturing process differs from that of KITE-439.  Despite these 
manufacturing differences, KITE-439 is anticipated to retain activity of the E7 TCR T cells and 
preserve the low risk of cross-reactivity observed to date in the NCI trial.  Data from NCI 16-C-
0154 are therefore considered to provide initial evidence of the expected efficacy and safety of 
KITE-439.  Briefly, no off-target T-cell toxicity, cytokine release syndrome (CRS), or Grade 5 
adverse events (AEs) occurred in the NCI 16-C-0154 clinical study as of the 04 May 2018 data 
cut-off date. One dose-limiting toxicity (DLT) occurred at dose level 3 (1 x 1011 total E7 TCR T 
cells).  The most frequent Grade 3 or higher AEs were cytopenias.  Five of nine evaluable 
subjects had partial responses (PRs); 2 of these PR were unconfirmed.  Details are provided in 
the IB.

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For subjects weighing greater than 100 kg, each dose of E7 TCR T cells will be calculated based 
on a maximum weight of 100 kg. For Cohort 5, the maximum allowable dose to be administered 
is 5 x 109 E7 TCR T cells (± 20%). For Cohort 6, the target dose is 1 x 108 E7 TCR T cells/kg 
and the total number of cells will be calculated based on weight. The minimally acceptable dose 
for patients above 60 kg will be 6 x 109 E7 TCR T cells. The maximum total number of cells in 
this cohort will be 1 x 1010 E7 TCR T cells.
A safety review team (SRT) will make recommendations on the conduct of the study.  The SRT 
membership includes the study sponsor and at least one Phase 1 investigator with an enrolled and 
dosed subject in the study.  The SRT will assess overall safety and DLTs in Phase 1A as well as 
pausing criteria in Phase 1A and Phase 1B.  The dose selected for Phase 1B will be formally 
communicated to participating sites in a separate communication.  See Section 9.7.2 for 
additional details.
3.1.2.
Phase 1B
After a dose has been selected based on Phase 1A, enrollment will commence in Phase 1B.  At 
Kite’s discretion, up to approximately 35 subjects will be enrolled into the following 2 cohorts.

HPV16+ squamous cell cancer of the head and neck (n = 15)

Other HPV16+ tumors (Includes all HPV16+ tumors other than squamous cell carcinoma of 
the head and neck) (n = 20)
Note:  The subjects enrolled and treated in Phase 1A at the selected Phase 1B dose will 
contribute to the sample size for Phase 1B based on their relevant tumor type.
Conditioning chemotherapy may be given in an out-patient setting.  However, all subjects will be 
hospitalized for the KITE-439 infusion and remain hospitalized for at least 7 days after the 
KITE-439 infusion to monitor for toxicities.
Refer to the Investigational Product Manual (IPM) for details and instruction on storage, 
preparation, and administration of KITE-439.
Independent of the phase of the study (Phase 1A or Phase 1B), each subject will follow the same 
study treatment schedule and procedural requirements.  Each subject will proceed through the 
following study periods:

Pre-screening

Screening (main study)

Enrollment/leukapheresis
CCI

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
Conditioning chemotherapy

Investigational Product (IP) treatment

Post -treatment assessment

Long-term follow-up (LTFU); after the end or termination of KITE-478-0401, subjects who 
received an infusion of KITE-439 will complete the remainder of the 15-year follow-up 
assessments in a separate LTFU study, KT-US-982-5968.
For study requirements assigned to each study period, refer to the schedule of assessments 
(SOAs) Section 7.11 for details.
3.2.
Participating Sites
Approximately 32 centers located in North America and Europe will participate in this study.  
Additional regions, countries, or sites may be added as necessary.
3.3.
Number of Subjects
Participants in this trial will be referred to as “subjects.”
Phase 1A:  A minimum of 2 subjects and up to a maximum of approximately 36 subjects will 
participate in this study.  The number of subjects enrolled into Phase 1A is dependent upon the 
number of DLTs observed in each dose cohort (see Section 3.1.1 for the list of dose cohorts and 
Section 9.7 for details regarding DLTs and dose escalation rules).
Phase 1B:  After a dose has been selected based on Phase 1A, enrollment will commence in 
Phase 1B.  At Kite’s discretion, up to approximately 35 subjects will be enrolled into the 
following 2 cohorts.

HPV16+ squamous cell cancer of the head and neck (n = 15)

Other HPV16+ tumors (Includes all HPV16+ tumors other than squamous cell carcinoma of 
the head and neck) (n = 20)
Note:  The subjects enrolled and treated in Phase 1A at the selected Phase 1B dose will 
contribute to the sample size for Phase 1B based on their relevant tumor type.
It should be noted that Kite may choose to close enrollment at any time.  Refer to the statistical 
considerations in section 10.3 for sample size estimations.
3.4.
Replacement of Subjects
Subjects will continue to be enrolled in Phase 1A and Phase 1B until the specified number of 
subjects are attained in the DLT evaluable (Phase 1A) and modified intent-to-treat (mITT) sets 
(Phase 1B).  See Section 10.4 for details.

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If a subject is lost to follow-up or withdraws from the study prior to the 3-month assessment, the 
subject may be replaced.
3.5.
Study Duration
The study includes a 28-day screening period, a 5-day conditioning chemotherapy treatment 
period, KITE-439 treatment, post-treatment assessment period (Day 1 to Month 3), and a LTFU 
period (> Month 3 through 15 years after the KITE-439 infusion for safety and survival 
surveillance).
The duration of the study for individual subjects will vary depending on their screening 
requirements, response to treatment, survival, and if applicable, timing of transition to the 
separate LTFU study, KT-US-982-5968 (discussed in Section 3.5.1). 
3.5.1.
End of Study
Completion of the study is defined as the time at which the last subject completes at least 3 months of 
assessments (the post-treatment follow-up period), or the last subject is transitioned to the LTFU study. 
The end-of-study for each subject is defined as the last visit on this study, or when a subject is considered 
lost to follow-up, withdraws consent, or dies (whichever occurs first). 
3.5.2. Long-term Follow-up
If the study is terminated prior to completion of 15 years of follow-up for all subjects, those who received 
an infusion of KITE-439 will be transitioned to a separate LTFU study, KT-US-982-5968, where they 
will be monitored for occurrence of late-onset targeted AEs/serious AEs (SAEs) suspected to be possibly 
related to KITE-439 as defined in KT-US-982-5968, presence of replication-competent retrovirus and/or 
insertional mutagenesis for up to 15 years from the time of KITE-439 infusion (also refer to Section 
7.1.2.5).
For each subject, the final visit on this study may be combined with the subject’s first visit on the LTFU 
study. The timing of the subject’s final visit on KITE-439 protocol/first LTFU study visit will depend 
upon the timing of the collection of all the subject’s data that are required for the planned analysis for this 
study. In KT-US-982-5968, subjects will continue assessments at timepoints contiguous with the LTFU 
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4.
SUBJECT IDENTIFICATION
Screening to determine eligibility for enrollment is a 2-step process.  There is a pre-screening 
portion and screening portion.  These are further explained in Section 7.2.1 and Section 7.2.2.  
Both pre-screening and screening require a separate consent. Each subject who enters the 
pre-screening period will receive a unique subject identification (ID) number.
Eligibility criteria for the main study is in Section 5.

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5.
SUBJECT ELIGIBILITY (MAIN STUDY)
5.1.
Inclusion Criteria
101)
Age ≥ 18 years
102)
Advanced cancer defined as relapsed or refractory disease after at least 1 line of therapy 
that included systemic chemotherapy and that is not amenable to definitive locoregional 
therapy
103)
HPV16+ tumor as confirmed by the central laboratory
104)
HLA type is HLA-A*02:01+ per local assessment
105)
At least 1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors 
(RECIST) v1.1 (Appendix 1) per computed tomography (CT) or magnetic resonance 
imaging (MRI) performed after the last line of anti-cancer therapy and within 28 days 
before enrollment
106)
No evidence of central nervous system (CNS) disease by MRI or CT (if MRI is not 
feasible) of the brain performed within 28 days before enrollment 
Note:  Subjects with prior brain metastasis, which has been treated with definitive therapy 
(surgical resection or radiation therapy), are eligible provided that the definitive therapy 
was completed more than six months prior to screening
107)
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
108)
At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior 
systemic therapy at the time of enrollment (i.e., leukapheresis)
109)
Toxicities due to prior therapy must be recovered to baseline or ≤ Grade 1, except for 
clinically non-significant toxicities, such as alopecia
110)
Adequate bone marrow function (in absence of transfusion or growth factor support) as 
evidenced by:
a) Absolute neutrophil count (ANC) ≥ 1000/mm3
b) Platelet ≥ 100/mm3
c) Hemoglobin > 8 g/dL
111)
Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:
a) Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min (24-hour urine 
creatinine clearance is also acceptable)

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b) Alanine transaminase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 x upper limit 
normal (ULN) or ≤ 5 x ULN if documented liver metastases
c) Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert’s Syndrome in whom 
total bilirubin must be ≤ 3.0 mg/dL
d) Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion, as determined 
by an echocardiogram (ECHO), and no clinically significant electrocardiogram 
(ECG) findings (For ejection fraction only, MUGA scan is also acceptable)
e) No clinically significant pleural effusion
f)
Baseline oxygen saturation > 92% on room air
5.2.
Exclusion Criteria
201)
History of malignancy other than non-melanoma skin cancer, carcinoma in situ 
(e.g., cervix, bladder, breast), or low-grade prostate cancer for which watch-and-wait 
approach is standard of care, unless disease-free for at least 3 years prior to enrollment
202)
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, cardiac 
arrhythmia requiring antiarrhythmic or procedure, or other clinically significant cardiac 
disease within 12 months before enrollment
203)
History of stroke or transient ischemic attack (TIA) within 12 months before enrollment
204)
History of symptomatic deep vein thrombosis (DVT) or pulmonary embolism within 
6 months before enrollment, catheter associated thrombosis is not included as an 
exclusion criterion
205)
Prior T-cell therapy, including those that target HPV; vaccines are not included as an 
exclusion criterion
206)
Live vaccine ≤ 4 weeks prior to enrollment
207)
Systemic corticosteroid therapy within 7 days before enrollment 
Note:  Topical and inhaled corticosteroids in standard doses and physiologic replacement 
for subjects with adrenal insufficiency are allowed. Any new doses ≥ 5 mg/day of 
prednisone or equivalent doses of other corticosteroids are not allowed
208)
History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine  
209)
History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
210)
Presence of fungal, bacterial, viral, or other infection requiring anti-microbials for 
management
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6.8.
Concomitant Therapy
Concomitant therapy refers to treatment that subjects receive during the conduct of the study.
Investigators may prescribe any concomitant therapies deemed necessary to provide adequate 
supportive care except those medications listed in Section 6.9.
The investigator is responsible for reporting all concomitant medications as follows in Table 3:
Table 3.
Reporting Requirements for Concomitant Medications
Subjects who are pre-
screen or screen-fails
Subjects who are enrolled, but do 
not receive KITE-439 infusion
Subjects who are enrolled and receive 
KITE-439 infusion
Concomitant therapies 
related to serious adverse 
event(s) will be recorded 
from the date of the pre-
screening informed 
consent or screening 
informed consent through 
30 days after the last 
study-specific pre-
screening or screening 
procedure, respectively.
Concomitant therapies will be 
recorded from the date of the 
informed consent until 30 days after 
the last study-specific procedure has 
occurred (e.g., leukapheresis, 
conditioning chemotherapy) or until 
the initiation of new anti-cancer 
therapy, whichever occurs first.

Concomitant therapies including 
medications, intubation, dialysis, 
oxygen, and blood products will be 
recorded from the date of the informed 
consent until 3 months after 
completing treatment with KITE-439.

After this 3-month follow-up period, 
targeted concomitant therapies will be 
recorded for either 24 months after 
KITE-439 infusion or until disease 
progression, whichever occurs first.

Targeted concomitant therapies 
include gammaglobulin, 
immunosuppressive drugs, 
anti-infective drugs, and 
vaccinations.
Specific concomitant therapy collection requirements and instructions are included in the case 
report form (CRF) completion guidelines.
See Section 9.2 and Section 9.4 for targeted AE and targeted SAE reporting requirements.
6.9.
Excluded Medications
Corticosteroid therapy at a pharmacologic dose (≥ 5 mg/day of prednisone or equivalent doses of 
other corticosteroids) and other immunosuppressive drugs (with the exception of physiologic 
steroid replacement) must be avoided for at least 7 days before leukapheresis and at least 7 days 
before KITE-439 administration.
Corticosteroids and other immunosuppressive drugs (with the exception of physiologic steroid 
replacement) should also be avoided for at least 3 months after KITE-439 administration, unless 
used to manage KITE-439-related toxicities or discussed with the Kite medical monitor 
(see Section 7.8).
Treatment doses of anticoagulants (for example, low molecular weight heparin [LMWH] or 
coumadin for DVT) are not permitted until after platelet count has normalized after conditioning 

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chemotherapy and KITE-439 infusion, unless to treat an acute event that occurs any time after 
the subject has already initiated conditioning chemotherapy.
Treatment for the subject’s cancer, such as chemotherapy, immunotherapy, targeted agents, 
radiation, and high-dose corticosteroid, other than defined/allowed in this protocol, and other 
investigational agents are prohibited except as needed for treatment of disease progression after 
KITE-439 infusion.  If permissibility of a specific medication/treatment is in question, contact 
the Kite medical monitor.
6.10.
Subsequent Anti-cancer Therapy
Subsequent therapy refers to treatment administered after KITE-439 that is necessary to treat a 
subject’s disease.
Subsequent therapy administered after KITE-439 that is necessary to treat a subject’s disease, 
such as non-study specified chemotherapy, immunotherapy, targeted agents, stem cell transplant, 
or radiation therapy, will be recorded for all subjects until one of the following happens: the 
subject transitions to the KT-US-982-5968 LTFU study, is considered lost to follow-up, 
withdraws consent, or dies.
For subjects who are enrolled, but do not receive KITE-439 infusion, any additional anti-cancer 
therapy will also be collected until the subject completes their participation in the current study, 
is considered lost to follow up, withdraws consent, or dies.
6.11.
Neurological Assessments
A neurological consultation will be performed on the first day of conditioning chemotherapy or 
within 3 days prior to conditioning chemotherapy (Days –10, –9, –8, or –7). This consultation 
will be performed by a trained and licensed neurologist and will serve as a baseline for 
subsequent evaluation should the subject require additional neurological consultation due to 
adverse event(s).
In addition, the subject will complete a standardized assessment called the Mini-Mental Status 
Exam (MMSE) standard version 2.0 blue form.  The (MMSE) will be completed at baseline 
(Day –7) during the baseline neurological consultation and then once daily from Day 0 through 
Day 7 and on Day 14.
For new onset of neurologic symptoms suspected to be related to KITE-439, refer to Section 7.8.

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7.
STUDY PROCEDURES
Research staff should refer to the SOA in Section 7.11 for an outline of the procedures required.  
Additional information related to a few study assessments/procedures is described below.
The visit schedule is calculated from KITE-439 infusion on Day 0.
Refer to the CRF completion guidelines for data collection requirements and best practices for 
documentation of study procedures.
7.1.
Laboratory Assessments
7.1.1.
Local and Central Lab Analysis
Assessments listed in Table 4 will be performed at the local or central laboratory at the time 
points indicated in the SOA.
Table 4.
Clinical Laboratory Parameters
Local Lab
Central Labf
Serum Chemistries
Hematology
Other
Albumin
ALT/GPT
ALP
AST/GOP
Bicarbonate total
Bilirubin totala
BUN or ureaa 
Calcium total
Chloride
Creatinine
Glucose
LDH
Magnesium total
Phosphorus 
Potassium
Sodium
Uric acid 
CBC with differentialb 
Urine toxicology panelc
Viral testingd
HLA-A*02:01 typing
CRP
Pregnancy test (urine or 
serum)e
Recommended:

Ferritin

Lactate
HPV16 genotyping
Anti-KITE-439 antibodies 
Cytokines
PBMCs
Archival and fresh tumor 
tissue 
Abbreviations:  ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea 
nitrogen; CBC, complete blood count; CRP, C-reactive protein; GOP, serum glutamic-oxaloacetic transaminase; GPT, serum 
glutamic-pyruvic transaminase; LDH, lactate dehydrogenase; PBMC, peripheral blood mononuclear cell; HLA, human leukocyte 
antigen.
a.
If BUN test cannot be analyzed by the local lab, urea should be analyzed. If total bilirubin is elevated, then direct bilirubin 
should be obtained.
b.
Must include white blood cell (WBC), neutrophils or ANC, lymphocytes or ALC, hemoglobin, platelets, except in 
circumstances where institutional guideline permits for differential to not routinely be performed when ordered (e.g., WBC 
count is too low)
c.
Standard urine toxicology panel as per institutional guidelines
d.
Serology tests for European sites (serum): Serology tests (i.e., human immunodeficiency virus, hepatitis B virus, hepatitis C 
virus, and syphilis) will be done per institutional guidelines and regional regulations. Testing may be done within the 
30 days before leukapheresis/enrollment and/or on the day of leukapheresis/enrollment. 
e.
Pregnancy test (serum or urine): For European sites, the test will be completed within 7 days before both leukapheresis and 
lymphodepleting chemotherapy for women of childbearing potential.
f.
Refer to the central laboratory manual (provided separately) for details on collection, processing, and shipment of the central 
laboratory samples.

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timing of blood draws for determination of the presence of RCR is specified in the SOA or may 
be done as clinically indicated.
RCR testing will occur at baseline, Month 3 of the main study, Month 6, and Month 12 of the 
LTFU study.  Thereafter, samples will be collected yearly and held for up to 15 years.  If a 
subject tests positive for RCR at any time point within the first year, samples will continue to be 
collected and tested yearly for up to 15 years or as clinically indicated.
If a subject dies or develops a secondary malignancy during the study or follow-up and RCR is 
suspected, every effort should be made to obtain a blood sample to assay for RCR and vector 
elements. In the case of a solid tumor new/secondary malignancy, every effort will be made to 
obtain a biopsy sample of the neoplastic tissue or the pertinent autopsy tissue to assay for 
presence of vector elements.
Samples for RCR testing are collected as part of the blood draw for PBMCs as noted in the SOA 
(Section 7.11).
7.2.
Informed Consent
Screening to determine eligibility for enrollment is a 2-step process.  There is a pre-screening 
portion and a screening portion.  These are further explained in Section 7.2.1 and Section 7.2.2.  
Both pre-screening and screening require a separate consent.
The consent process and the subject’s agreement or refusal to participate are to be documented in 
the subject’s medical records.  If the subject agrees to participate, the most recent (IRB/IEC) 
approved informed consent form(s) (ICF) is to be signed and personally dated by the subject and 
by the person who conducted the informed consent discussion.
The ICF should be signed prior to any study-specific activity or procedure being performed.  The 
original signed ICF(s) will be retained in accordance with institution policy and IRB/IEC 
requirements with a copy of the ICF(s) provided to the subject.
Investigative sites will maintain a log of all pre-screened and screened subjects who were 
reviewed and evaluated for participation in the respective portions of the study.  Information 
collected on the pre-screening and screening log should include limited information, such as the 
date of pre-screening, date the subject was enrolled, or the reason for why the subject failed 
pre-screening.  These data will be entered into the CRF.
7.2.1.
Informed Consent to Prescreen
Per the eligibility criteria, subjects are required to be HLA-A*02:01+ and have HPV16+ tumors.  
Because only a portion of cancer patients will meet these criteria, subjects will be pre-screened 
for HLA-A*02:01+ and HPV16 virus type.  This approach to pre-screening will ensure that 
subjects who do not qualify based on HLA type and/or HPV virus type are not subjected to other 
screening procedures unnecessarily.

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Signs, symptoms or abnormal laboratory results attributed to the malignancy (e.g. “tumor fever,” 
elevated C-reactive protein [CRP]) are diagnoses of exclusion that require a documented workup 
to establish.
Conditioning chemotherapy and KITE-439 infusion should be initiated only once it is reasonably 
assured that cell infusion can safely proceed. Any consideration for changes in the dose for the 
conditioning chemotherapy should be discussed with the Kite medical monitor.
Refer to Section 7.5.5 for Requirements to Work-up Potential Infectious and/or Inflammatory 
States.
7.5.3.1.
Conditioning Chemotherapy Period
7.5.3.1.1.
Requirements for Initiating Conditioning Chemotherapy
If any of the following criteria are met prior to the initiation of conditioning chemotherapy, then 
the work-up listed in Section 7.5.5 must be performed to determine the potential cause if there is 
no identified source of infection.

Temperature > 38°C within 72 hours before conditioning chemotherapy

CRP > 100 mg/L any time between enrollment to start of conditioning chemotherapy

WBC count or WBC differential concerning for infectious process between enrollment to 
start of conditioning chemotherapy (e.g., WBC > 20,000, rapidly increasing WBC, or 
differential with high percentage of segments/bands)
Additionally:

All eligibility criteria of the protocol must be met.  If any screening assessments or 
procedures are repeated between confirmation of eligibility and the start of conditioning 
chemotherapy and results are outside the eligibility criteria listed in Section 5, then the 
condition must resolve prior to proceeding with conditioning chemotherapy.  Expected 
normal variation is allowed for laboratory values noted in the eligibility criteria (±5%)

Complete history and physical exam including head, eye, ear, nose, and throat (HEENT), and 
cardiac, vascular, respiratory, gastrointestinal, integumentary, and neurological systems must 
not reveal evidence of infection/inflammation

The subject must not have received systemic anti-microbials for the treatment of a known or 
suspected infection within 48 hours before conditioning chemotherapy (prophylactic use of 
anti-microbials is allowed)

Treatment course of any anti-microbials given for known or suspected antecedent infection 
should be complete as per infectious disease consult (if applicable) recommendation before 
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
If a subject is confirmed to have an infectious process for which anti-microbials are not 
available (e.g., viral pneumonia), the infection must be clinically resolved as determined by 
the investigator in consultation with infectious disease service (if applicable)

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 (e.g., bacterial, viral serologies, 
polymerase chain reaction [PCR], stool studies, imaging studies) must be negative.  If 
clinical suspicion is for an infection for which cultures are unlikely to be positive within 
48 hours (e.g., fungal infection), adequate time must be allowed for cultures to become 
positive
Once the above criteria are met, then the subject can proceed with conditioning chemotherapy.
7.5.3.1.2.
Conditioning Chemotherapy Administration (Day –7 through Day –3 prior to 
KITE-439 infusion)
The 5-day conditioning chemotherapy regimen containing cyclophosphamide and fludarabine 
may be administered in an out-patient setting.  Following the 5-day conditioning chemotherapy 
regimen, subjects will have a two-day rest period prior to KITE-439 infusion. Conditioning 
chemotherapy can be administered as inpatient per investigator’s discretion.
Before conditioning chemotherapy commences, the criteria outlined in Section 7.5.3.1.1 must be 
met.
Provided the criteria for conditioning chemotherapy are met, the conditioning chemotherapy 
regimen will be administered in accordance with the following daily dosing instructions.
Cyclophosphamide 
Cyclophosphamide:  
 IV administered on 
 infused over 60 minutes. 
See Section 7.5 for practical versus actual body weight-based dose calculation.
IV hydration recommendations:

0.9% NaCl with 10 mEq/L of KCl recommended at 150 ml/hour to start 2 hours prior to each 
cyclophosphamide dose and continue for 6 hours after the completion of each dose.  The 
fluid may continue during the cyclophosphamide infusion.

It is recommended that urinary output and body weight be monitored starting the first hour 
after cyclophosphamide infusion and for at least 6 hours after cyclophosphamide.  If urine 
output is less than 200 ml total during the first 2 hourly voids or body weight is > 2 kg over 
pre-cyclophosphamide value, consider furosemide 
 IV as a one-time dose (or 
equivalent diuretic).  If any subsequent 2 hourly voids are also less than 200 ml, consider 
additional diuretic administration.

Serum potassium should be monitored and treated as indicated following administration of 
diuretic.  Infusions may be slowed as medically indicated.
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
The subject must not have received systemic anti-microbials for the treatment of a known or 
suspected infection within 48 hours before KITE-439 (prophylactic use of anti-microbials is 
allowed).

Treatment course of any antimicrobials given for known or suspected antecedent infection 
should be complete as per infectious disease consult (if applicable) recommendation before 
stopping or switching to prophylactic antimicrobials.

If a subject is confirmed to have an infectious process for which antimicrobials are not 
available (e.g., viral pneumonia), the infection must be clinically resolved as determined by 
the investigator in consultation with infectious disease service (if applicable).

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 (e.g., bacterial, viral serologies, 
PCR, stool studies, imaging studies) must be negative.  If clinical suspicion is for an infection 
for which cultures are unlikely to be positive within 48 hours (e.g., fungal infection), 
adequate time must be allowed for cultures to become positive.
Once the above criteria are met, then the subject can proceed with administration of KITE-439.
If the KITE-439 infusion is delayed > 2 weeks, consideration for repeat conditioning 
chemotherapy must be made in consultation with a Kite medical monitor.
7.5.4.1.2.
Hospitalization for KITE-439 Infusion
Subjects will remain hospitalized for at least 7 days after the KITE-439 infusion, unless 
otherwise required by country regulatory agencies (refer to Appendix 4), for daily monitoring of 
signs and symptoms of CRS and neurologic events. In addition, the assessments described in 
Section 7.11 and the SOA (Table 5) will be performed during this period.
Subjects should not be discharged from the hospital until all KITE-439-related nonhematological 
toxicities resolve to ≤ Grade 1 or return to baseline.  Subjects may be discharged with non-
critical and clinically stable or improving toxicities (e.g., renal insufficiency) even if > Grade 1, 
if deemed appropriate by the investigator.  Subjects should remain in a hospital for ongoing 
KITE-439-related fever, hypotension, hypoxia, or ongoing neurologic events > Grade 1, or if 
deemed necessary by the investigator.
Subjects should be instructed to remain within proximity of the clinical study site for at least 
4 weeks following KITE-439 infusion.  Subjects and their family members/caregivers should be 
educated on potential CRS and neurologic symptoms, such as fever, dyspnea, confusion, aphasia, 
dysphasia, 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.

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7.5.4.1.3.
KITE-439 Premedication Dosing
The following pre KITE-439 infusion medications should be administered approximately 1 hour 
prior to infusion.  Alternatives to the recommendations below should be discussed with the Kite 
medical monitor.

Acetaminophen 650 mg PO or equivalent

Diphenhydramine 12.5 mg administered either PO or via IV or equivalent
7.5.4.1.4.
KITE-439 Administration Day 0
KITE-439 will be administered at one of the dose levels as outlined in Section 3.1.1, Table 2.
Refer to the SOA (Section 7.11) for a listing of study procedures to be completed during the 
KITE-439 treatment period.
Central venous access, such as a port or a peripherally inserted central catheter, is required for 
the administration of KITE-439.  Catheter care, per institutional guidelines, should be followed.  
Materials and instructions for the thawing, timing, and administering of KITE-439 are outlined 
in the IPM.  It is recommended that vital signs are recorded before KITE-439 infusion and then 
routinely as clinically indicated (e.g., fever ≥ 38.3°C).
The IPM must be reviewed prior to administration of KITE-439.
Research sites should follow institutional guidelines for the infusion of cell products.
7.5.5.
Requirements to Work-Up Potential Infectious and/or Inflammatory States 
Prior to KITE-439 Infusion
In the absence of an identified source of infection (e.g., line infection, pneumonia on chest x-ray 
), the minimum workup to be performed prior to administration of conditioning chemotherapy 
and/or KITE-439 consists of:

Call Kite medical monitor

Infectious disease service consultation (if applicable)

CT imaging of the chest, abdomen, and pelvis with IV contrast.  If there is a medical 
contraindication to contrast, then non-contrast CT is allowed

The following must be performed (prior to the initiation of anti-microbials if clinically 
feasible):
Blood cultures (aerobic and anaerobic x2 bottles each) and urinalysis and urine culture.  
Deep/induced sputum culture if clinically indicated

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The following procedures/assessments will be completed for subjects who are enrolled, but do 
not receive KITE-439, at the time points outlined in the SOA, unless otherwise noted:

Disease assessment per standard of care

Survival status – subjects may be contacted by telephone to confirm survival status

AE/SAE reporting (see Section 9.2 and Section 9.5)

Concomitant medications documentation (see Section 6.8)

Subsequent therapy for disease (see Section 6.10)
Subjects may also be contacted by telephone to confirm survival status and subsequent 
anti-cancer therapy use.  If the subject fails to return to the clinic for a scheduled 
protocol-specific visit, sites will need to make 2 attempts, using both the telephone and either 
mail or e-mail to contact the subject.  Sites must document both attempts to contact the subject.  
If a subject does not respond within 1 month after the second contact, then the subject will be 
considered lost to follow-up, and no additional contact will be required.  However, sites will be 
required to continue to provide survival status as permitted by local regulations.

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7.11.
Schedule of Assessments
Table 5.
Schedule of Assessments (Pre-screening through Post-treatment follow-up)
Procedures
Pre-
screeninga
Screeningc
Leukapheresis
/Enrollment
Conditioning 
Chemotherapyi
IPj, v
Post-treatment Follow-up
(each visit calculated from Day 0)
≤ 28 days 
before 
enrollment
Day
Week
(± 3 d)
Month
(± 1 w)
D-7
D-6
D-5 to D-3 D0 D1 D2 D3 D4 D5 D6 D7 W2 W4
M2
M3y
Consent (pre-screen and 
screen)
x
x
Medical historyb
x
x
Physical exam; height 
and ECOG (scr only)d
x
x
x
x
x
x
x
Vital signs including 
BP, HR, O2, temp
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Weight
x
x
x
Neurology consultationu
x
MMSEu
x
x
x
x
x
x
x
x
x
x
ECG
x
LVEF and PE 
assessment by ECHOf
x
Imaging
Brain MRI or CT (if 
MRI is not feasible)
x
CT or MRI neck 
(if appl), chest, 
abdomen, pelvis and 
Disease assessment 
per RECISTe
x
x 
x
Local laboratory 
samples 
HLA-A*02:01 typing
x
Chemistry panel
x
x
x
x
x
x
x
x
x
x
x
x
x
x
CBC w/differentialm
x
x
x
x
x
x
x
x
x
x
x
x
x
x
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Table 6
Schedule of Assessments (LTFU)
Long-term Follow-up Periodzz
(Each visit calculated from Day 0)
Month
6
9
12
15
18
24
30
36
42
48
54
60
Month 72, then 
annually through 
Year 15
Procedure
(± 2 weeks)
(± 1 month)
Physical exam
x
x
x
x
x
x
Vitals including BP, HR, O2, temp
x
x
x
x
x
x
CT or MRI neck (if appl), chest, 
abdomen, pelvis and Disease 
assessment per RECISTe
x
x
x
x
x
x
x – per SOC
Local laboratory samples
Chemistry
x
x
x
x
x
x
CBC w/differentialm
x
x
x
x 
x 
x 
Central laboratory samples
Antibodym, z
x 
PBMCs, z
x
x
x
x
x
x
x
Targeted AE/SAE reportingn 
x
x
x
x
x
x
x
x
x
x
x
x
x
Targeted concomitant medicationo
x
x
x
x
x
x
KITE-439-related SAEs and deathsn
x
Subsequent therapy reportingp, z
x
x
x
x
x
x
x
x
x
x
x
x
x
Survival status telephone callsq, z
x
x
x
x
x
x
x
x
x
x
x
x
x
Abbreviations:  IP, investigational product, KITE-439; 
; ECOG, Eastern Cooperative Oncology Group; scr, screen; BP, blood pressure; HR, heart rate; ECG, electrocardiogram; 
LVEF, left ventricular ejection fraction; PE, pulmonary embolism; ECHO, echocardiogram; CT, computed tomography; MRI, magnetic resonance imaging; RECIST, Response Evaluation 
Criteria in Solid Tumors; 
 CRP, C-reactive protein; PBMC, peripheral blood mononuclear cell; SAE, serious adverse event; AE, adverse event; Con, concomitant; 
CBC, complete blood count; temp, temperature; HLA, human leukocyte antigen; 
; CSF, cerebrospinal fluid; SOC, standard of care; M, month; D, day; MMSE, Mini-mental 
status exam; LTFU, Long-Term-follow-up; SAE, Significant Adverse Event
Schedule of Assessment Footnotes
a
Pre-screening for HLA typing and HPV genotyping (Section 7.2.1):  Before subjects consent to pre-screening, the investigators should perform a preliminary review of the 
subjects’ medical history to ensure they meet the known eligibility criteria.
b
Medical history: Demographic information (e.g., sex, year of birth, race, ethnicity, country of enrollment) about the subject will be collected as allowed per country, local 
regulations, and guidelines as applicable; these data will be entered into the CRF. For patients transitioning to LTFU study (KT-US-982-5968), medical history also includes 
AEs/SAEs that are ongoing at the time of completion of KT-US-478-0401.
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additional serum samples approximately every 3 months until the antibody levels return to baseline, become negative, or up to 1 year after the KITE-439 treatment, whichever 
occurs first.  Site will be notified if the Month 3 antibody sample tests positive.
n
AE/SAE reporting (Section 9.2 and Section 9.5):  Procedure related SAE reporting for pre-screened subjects will begin at the time the pre-screening consent form is signed 
and will continue until 30 days after the last pre-screening procedure is completed.  If the subject is screened for the main study within 30 days after signing the pre-screening 
consent, then SAE reporting will continue (Section 9.4).For enrolled subjects, after 3 months, only serious targeted adverse events observed by the investigator or reported by 
the subject will be reported for 15 years after KITE-439 infusion or until enrollment into the LTFU study.  SAEs are reported within 24 hours using the SAE Report Form and 
in the CRF.  Targeted adverse events include serious neurological, serious hematological, serious Kite product-related infections, GVHD, serious autoimmune disorders, and 
new/secondary malignancies.  In addition to the above SAE reporting requirements, anytime a KITE-439 related SAE occurs it will be reported within 24 hours using the SAE 
report form and in the CRF.  All deaths that occur from ICF through end of study will be reported in the CRF. 
o
Concomitant medications reporting (Section 6.8):  After 3 months of follow-up, only targeted concomitant medications will be collected for 24 months after KITE-439 
infusion or disease progression, whichever occurs first.  Targeted concomitant medications include gammaglobulin, immunosuppressive drugs, anti-infective drugs, and 
vaccinations.
p
Subsequent therapy for disease (Section 6.10):  Documentation of subsequent therapy for the subject’s disease will continue to be documented while the subject remains on 
study.  Subjects may be contacted by telephone.
q
Survival Status (Section 7.10):  Subjects may be contacted by telephone to confirm survival status.  Publicly available data (death records) can be included after withdrawal 
of consent or if lost to follow-up if local regulations permit.  
r
Recommended labs related to CRS:  

Monitoring of CRP, ferritin, and LDH (only if LDH is elevated at baseline) levels may assist with the diagnosis and define the clinical course in regards to CRS.  It is, 
therefore, recommended that CRP, ferritin, and LDH (if LDH is elevated at baseline) be monitored daily starting at Day 0.  Daily CRP should be monitored for at least 
7 days after KITE-439 infusion or until resolution of any CRS, whichever is later. In addition, lactate should be monitored as clinically indicated. Reference Table 4 for 
required local lab assessments. 

CSF central lab draws and additional subject samples (e.g., pleural fluid) may be obtained from subjects who develop Grade ≥ 2 neurologic events 
s
Additional AE related blood draws for PBMCs and cytokines:

Following the initial hospitalization for the KITE-439 infusion, if the subject is hospitalized with any KITE-439 related adverse events, blood samples for PBMCs and 
cytokines will be collected on day of admission, then weekly, and on day of discharge.  

If the subject experiences a Grade ≥ 3 KITE-439-related toxicity, such as Grade 3 CRS or neurologic event, one additional blood draw for cytokines will be taken at the 
time of the Grade ≥ 3 KITE-439-related toxicity and upon resolution of the event.  
t
If the subject experiences a Grade ≥ 2 CRS (per Lee 2014 criteria), an additional cytokine sample should be drawn at the first onset and first reoccurrence of any 
≥ Grade 2 CRS if not already collected on that day.
u
See neurological assessments section 6.11. Note: baseline neurological consultation will include baseline MMSE. Baseline neurological consultation and MMSE may occur 
on Days -10, -9, -8, or -7. In the event of a ≥ Grade 1 neurological toxicity please refer to IB Section 6.5.2 for management guidelines.
v
Subjects will be hospitalized to receive KITE-439 infusion and will remain in the hospital for at least 7 days to monitor for signs and symptoms of CRS and neurologic 
events, unless otherwise required by country regulatory agencies (refer to Appendix 4). See Section 7.5.4.1.2. Hospitalization for KITE-439 infusion.
w
Serology tests for European sites (serum): Serology tests (i.e., human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and syphilis) will be done per 
institutional guidelines and regional regulations. Testing may be done within the 30 days before leukapheresis/enrollment and/or on the day of leukapheresis/enrollment.
x
Pregnancy test (serum or urine): For European sites, the test will be completed within 7 days before both leukapheresis and lymphodepleting chemotherapy for women of 
childbearing potential.
y
If the subject progresses before Month 3: The subject will proceed directly to the Month 3 visit, complete the Month 3 visit, and then be followed in the long-term follow-
up (LTFU) period of the study.
z
If the subject progresses in the LTFU phase: The subject will be followed in the LTFU phase for survival status and subsequent therapy for his or her cancer, and then have 
blood drawn for PBMCs and, if applicable, anti-KITE-439 antibodies.

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zz If this study is terminated prior to the completion of the 15-year follow-up, all subjects who received an infusion of KITE-439 will be provided the opportunity to transition 
to a LTFU study (KT-US-982-5968) after providing signed informed consent. For each subject, the final on-study visit may be combined with the subject’s first visit on the LTFU 
study. The timing of the final on-study visit/first LTFU study visit will depend on the timing of the collection of all the subject’s data that are required for the planned analysis for 
this study.

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8.
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 study-required treatment and/or other protocol-
required procedures at any time during the study while continuing to participate in the study.  
This is referred to as partial withdrawal of consent.
If partial withdrawal of consent occurs, the investigator must discuss with the subject the 
appropriate process for discontinuation from the investigational product, study treatment, or 
other protocol-required therapies and must also discuss options for continued participation, 
completion of procedures, and the associated data collection as outlined in the SOA.  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.
Withdrawal of full consent from a study means that the subject does not wish to receive further 
protocol-required therapy, undergo procedures, and continue participating in study follow-up.  
Subject data collected up until withdrawal of consent will be retained and included in the 
analysis of the study.  Publicly available data (death records) can be included after withdrawal of 
consent if local regulations permit.  The investigator is to discuss with the subject appropriate 
procedures for withdrawal from the study. 
As part of the study, sites may be asked to conduct searches of public records, such as those 
establishing survival status, if available, to obtain survival data for any subject for whom the 
survival status is not known.  Sites may also be asked to also retrieve autopsy reports to confirm 
status of disease at the time of death.
The investigator and/or sponsor can also decide to withdraw a subject from the investigational 
product and/or other protocol-required therapies, protocol procedures, or the study as a whole at 
any time prior to study completion.
8.1.
Reasons for Removal from Treatment
Reasons for removal from protocol-required IPs or procedures include any of the following:

AE

Subject request

Product not available

Lost to follow-up

Death

Decision by sponsor

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8.2.
Reasons for Removal from Study
Reasons for removal of a subject from the study are as follows:

Subject withdrawal of consent from additional follow-up

Investigator decision

Lost to follow-up

Death

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9.
SAFETY REPORTING
9.1.
Definition of Adverse Events
An AE is defined as any untoward medical occurrence in a clinical trial subject.  The event does 
not necessarily have a relationship with study treatment.  The investigator is responsible for 
ensuring that any adverse events observed by the investigator or reported by the subject are 
recorded in the subject’s medical record.  The definition of AEs includes worsening of a 
pre-existing medical condition.  Worsening indicates that the pre-existing medical condition has 
increased in severity, frequency, and/or duration or has an association with a worse outcome.  
When recording such events, provide descriptions that the pre-existing condition has changed 
(e.g., more frequent headaches for a subject with pre-existing headaches or blood pressure is now 
more increased in a subject with pre-existing hypertension).
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 precautionary measures per institutional policy are not 
considered AEs.
The term “disease progression,” as assessed by measurement of malignant lesions on radiographs 
or other methods, should not be reported as AEs.  Death due to disease progression in the 
absence of signs and symptoms should be reported as the primary tumor type (e.g., B-cell 
lymphoma).
When an AE or SAE is due to the disease under investigation, it is necessary to report the signs 
and symptoms.  Worsening of signs and symptoms of the malignancy under study should also be 
reported as AEs in the appropriate section of the CRF.
The investigator’s clinical judgment is used to determine whether a subject is to be removed 
from treatment due to an AE.  If a subject requests to withdraw from protocol-required therapies 
or the study because of an AE, then the subject should undergo the procedures outlined in the 
Month 3 visit of the SOA.
9.1.1.
Diagnosis Versus Signs and Symptoms
For AEs, a diagnosis (if known) rather than individual signs and symptoms should be recorded 
on the AE form.  The exception is for CRS where both the diagnosis and signs and symptoms 
will be captured on the CRF AE form.  For signs and symptoms of the underlying cancer, the 
signs and symptoms should be captured.  However, on the AE form, the investigator should state 
that these signs and symptoms are due to the underlying disease.

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9.1.2.
Abnormal Vital Sign Values
Not all vital sign abnormalities qualify as an adverse event.  A vital sign result must be reported 
as an adverse event if it is a change from baseline and meets any of the following criteria:

Accompanied by clinical symptoms

Results in a medical intervention or a change in concomitant therapy

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 adverse event.  However, if a clinically significant vital sign abnormality is a sign 
of a disease or syndrome (e.g., high blood pressure), only the diagnosis (i.e., hypertension) 
should be recorded on the CRF.
9.1.3.
Reporting Abnormal 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 
adjustment in current therapy, are considered AEs.  Where applicable, clinical sequelae (not the 
laboratory abnormality) are to be recorded as the AE.
An abnormal laboratory test result must be reported as an adverse event if it is a change from 
baseline and meets any of the following criteria:

Associated with clinical symptoms

Results in a medical intervention (e.g., potassium supplementation for hypokalemia or iron 
replacement therapy for anemia) or a change in concomitant therapy

Clinically significant in the investigator’s judgment
9.2.
Reporting of Adverse Events
The investigator is responsible for reporting all AEs observed by the investigator or reported by 
the subject as follows in Table 7:

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Table 7.
Reporting Requirements for Adverse Events
Subjects who are enrolled, but do not receive KITE-
439 infusion
Subjects who are enrolled and receive KITE-439 
infusion
Adverse events that occur from enrollment (i.e., 
commencement of leukapheresis) through 30 days after 
the last study specific procedure (e.g., leukapheresis, 
bridging chemotherapy, conditioning chemotherapy) or 
until initiation of a new anti-cancer therapy, whichever 
occurs first, will be reported

AEs that occur from enrollment (i.e., 
commencement of leukapheresis through 3 months 
after treatment with KITE-439 infusion will be 
reported

After 3 months, only serious targeted AEs will be 
reported for 15 years after KITE-439 infusion or 
until enrollment into the LTFU study
Targeted adverse events include serious 
neurological events, serious hematological 
events, serious Kite product-related infections, 
GVHD, serious autoimmune disorders, and 
new/secondary malignancies.
Abbreviations:  GVHD, graft-versus-host-disease.
See Section 6.8 for concomitant medication and Section 9.5 for SAE reporting requirements.
The investigator must provide the information listed below regarding the AEs being reported:

AE diagnosis or syndrome (if not known, signs or symptoms)

Dates of onset and resolution

Severity

Assessment of relatedness to investigational product, conditioning chemotherapy, or study 
procedures

Action taken
The AE grading scale used will be the NCI CTCAE version 5.0.  A copy of the grading scale can 
be downloaded from the Cancer Therapy Evaluation Program (CTEP) home page 
(http://ctep.cancer.gov).
Individual CRS symptoms will be graded according to NCI CTCAE v5.0.  CRS syndrome will 
be reported using the modified grading scale by Lee and colleagues {Lee 2014} outlined in the 
KITE-439 IB.  AEs attributed to CRS will be mapped to the overall CRS grading assessment for 
the determination of DLT.
In reviewing AEs, investigators must assess whether the AE is possibly related to 1) KITE-439, 
, 3) conditioning chemotherapy, 4) any protocol-required study procedure 
(including leukapheresis) or treatment, 5) disease progression, 6) concurrent disease, 7) 
concomitant medication, or 8) other.  The relationship is indicated by a yes or no response and 
entered into the CRF.  A yes response should indicate that there is evidence to suggest a causal 
relationship between the study treatment or procedure and the AE.  Additional relevant data with 
respect to describing the AE will be collected in the CRFs.
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The investigator is expected to follow reported AEs until stabilization or resolution.  If a subject 
begins a new anti-cancer therapy, the AE reporting period for non-SAEs ends at the time the new 
treatment is started.
9.3.
Definition of Serious Adverse Events
An SAE is defined as an AE (as defined in Section 9.2) that meets at least 1 of the following 
serious criteria:

Fatal

Life-threatening (places the subject at immediate risk of death)

Requires in-patient hospitalization or prolongation of existing hospitalization
An AE would meet the criterion of “requires hospitalization” if the event necessitated an 
admission to a healthcare facility (e.g., overnight stay).
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 (ICU) or if that event resulted in a prolongation of 
the existing planned hospitalization

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 
adverse event according to NCI CTCAE criteria; 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 adverse event recorded on the CRF.
Disease progression of the malignancy is not considered an AE.  However, signs and symptoms 
of disease progression may be recorded as AEs or SAEs and indicated as being due to disease 
progression with the CRF.  If the malignancy has a fatal outcome before the end of the SAE 
reporting period, then the event leading to the death must be recorded as a SAE with the outcome 
being fatal.

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9.3.1.
Hospitalization and Prolonged Hospitalization
Any AE that results in hospitalization or prolonged hospitalization should be documented and 
reported as a SAE as described in Section 9.5.
The following hospitalization scenarios are not considered to be SAEs:

Hospitalization for palliative care or hospice care

Planned hospitalization required by the protocol (e.g., for monitoring of the subject or to 
perform an efficacy measurement for the study)

Planned hospitalization for a pre-existing condition

Hospitalization due to progression of the underlying cancer
9.4.
Reporting Deaths
Death must be reported if it occurs during the SAE reporting period, irrespective of any 
intervening treatment.
Any death occurring after signing of the main study informed consent and within 3 months of 
KITE-439 infusion, regardless of attribution to treatment, requires expedited reporting within 
24 hours.  Any death occurring after the 3-month SAE reporting period requires expedited 
reporting within 24 hours only if it is considered related to treatment.
Deaths that occur during the protocol-specified AE reporting period that are attributed by the 
investigator solely to progression of underlying malignancy should be recorded as SAEs with the 
preferred term being the subject’s underlying cancer and must be reported immediately to the 
sponsor.
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 AE form.  Every effort should be made to capture 
the established cause of death, which may become available later on (e.g., after autopsy).
9.5.
Reporting of Serious Adverse Events
The investigator is responsible for reporting all SAEs observed by the investigator or reported by 
the subject.  Unless otherwise indicated in Table 8 below, all SAEs will be reported within 
24 hours and recorded in the CRF.

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Table 8.
Reporting Requirements for Serious Adverse Events
Subjects who are pre-screen fails, 
screen-fails or who are enrolled, but 
do not receive KITE-439 infusion
Subjects who are enrolled and receive KITE-439 infusion
For subjects who are pre-screen 
failures, only SAEs related to a pre-
screening procedure that occurs from 
signing of the pre-screening informed 
consent form through 30 days after the 
last study-specific pre-screening 
procedure will be recorded in the CRF 
and reported.
For subjects who are screen failures or 
are enrolled but do not receive KITE-
439 infusion, all SAEs that occur from 
signing of the screening informed 
consent form through 30 days after the 
last study specific procedure (e.g., 
screening procedure, leukapheresis, 
 conditioning 
chemotherapy) or until initiation of a 
new anti-cancer therapy, whichever 
occurs first, will be recorded in the 
CRF and reported.

All SAEs that occur from signing of the screening informed 
consent form through 3 months after the KITE-439 infusion or 
until initiation of another anti-cancer therapy, whichever occurs 
first, will be recorded in the CRF and reported

After 3 months, only targeted SAEs will be reported for 15 years 
after KITE-439 infusion until enrollment into the LTFU study

Targeted SAEs include serious neurological events, serious 
hematological events, serious Kite product-related infections, 
GVHD, serious autoimmune disorders, and new/secondary 
malignancies.  

All SAEs deemed related to KITE-439 infusion regardless of time 
period

All deaths that occur from signing of the ICF through the end of 
study will be recorded in the CRF
Abbreviations:  SAE, serious adverse event; GVHD, graft-versus-host-disease; CRF, case report form; ICF, informed consent form.
See Section 6.8 for concomitant medication and Section 9.5 for targeted AE reporting requirements.
The following must be submitted to Kite via the eSAE system within 24 hours following the 
Investigators’ knowledge of the event:

All serious adverse events 

CRS (cytokine release syndrome) events grade ≥ 3 per {Lee 2014}

Neurologic events grade ≥ 3

All events of cerebral edema

Pregnancy or lactation exposure
If the eSAE system is unavailable (e.g., system outage), then the SAE must be submitted using 
the SAE Report Form and sent via email to the SAE Reporting mailbox:  
Following completion of KT-US-478-0401, any relevant information on ongoing SAEs must be 
submitted to the Kite Pharma within 24 hours of the investigator’s knowledge of the event using 
the paper SAE Report Form and sent via e-mail to the SAE Reporting mailbox: 
  
PPD
PPD
CCI

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Subsequently, all SAEs will be reported to the health authorities per local reporting guidelines.
For reporting of targeted concomitant medications and AEs, see Section 6.8 and Section 9.2.
9.6.
Pregnancy and Lactation
There is no relevant clinical experience with KITE-439 in pregnant or lactating women, and 
animal reproductive studies have not been performed.  Women of childbearing potential must 
have a negative pregnancy test prior to enrollment because of the potentially dangerous effects of 
the preparative chemotherapy on the fetus.  Women of childbearing potential should be 
monitored according to local and country-specific regulations. Refer to Appendix 3 for the 
definition of childbearing potential. This experimental therapy should not be administered to 
pregnant women or women who are breastfeeding.
Female subjects and female partners of male subjects are recommended to use highly effective 
contraception (method must achieve an annual failure rate of < 1%) for at least 6 months after 
conditioning chemotherapy dosing.  Male subjects are recommended to not father a child for 
6 months after the conditioning chemotherapy dosing. Please refer to main study informed 
consent form for recommended methods of highly-effective contraception.
Any pregnancy in a female subject enrolled into the study must be reported, regardless of the 
time after KITE-439 infusion.  If the pregnancy occurs in a female partner of a male subject 
within 6 months after completing lymphodepleting chemotherapy or the administration of 
KITE-439, whichever is longer, the pregnancy must be reported.  All such pregnancies must be 
reported to Kite Pharmacovigilance and Epidemiology using the Pregnancy Report Form within 
24 hours after becoming aware of the pregnancy. The outcome should be reported to Kite 
Pharmacovigilance and Epidemiology 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 Pharmacovigilance and Epidemiology. Pregnancy report forms should be reported to 
Kite Pharmacovigilance and Epidemiology at 
 or fax: 
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 (e.g., 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 post study must be reported to Kite Pharmacovigilance and Epidemiology.
If a lactation case occurs in a female subject in the study, the lactation case must be reported to 
Kite Pharmacovigilance and Epidemiology within 24 hours after the investigator’s awareness of 
the event using the Special Situations Reporting Form. Report the lactation case and Special 
Situations report forms to Kite Pharmacovigilance and Epidemiology at 
 
or fax: 
Sponsor Reporting Requirement (Includes Reporting of SAEs and Deaths)
PPD
PPD
PPD
PPD

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9.7.2.
Safety Review Team
A SRT will make recommendations on the conduct of the study.  The SRT membership includes 
the study sponsor and at least one Phase 1 investigator with an enrolled and dosed subject in the 
study.  The SRT will assess overall safety and DLTs in Phase 1A as well as pausing criteria in 
Phase 1A and Phase 1B.  The SRT will also review subject-level safety and efficacy data on an 
ongoing basis in Phase 1B.
The SRT, which is internal to the study sponsor and in collaboration with at least one study 
investigator with an enrolled and dosed subject, will be specifically chartered to review safety 
data during the Phase 1 component of the study and make recommendations on further study 
conduct and progression of the study based on the incidence of KITE-439 related DLTs and 
review of serious adverse events. The SRT safety review outcome will be communicated to the 
active clinical study sites after the SRT safety review meeting.
9.7.2.1.
Dose Escalation Criteria
During Phase 1A, the study will employ a single-subject dose escalation scheme for the first 4 of 
the planned 6 dose cohorts (see Section 3.1.1).  Subjects will be monitored for the occurrence of 
DLTs within the first 21 days after receiving the KITE-439 infusion (see Section 9.7.1 for DLT 
criteria).  If the subject does not experience a DLT during the DLT window, then the next subject 
will be dosed at the next higher dose cohort for the first 4 of the planned 6 dose cohorts. Once 
the highest dose cohort is reached, it will follow a 3+3 design, (noted as Cohort 5 and 6 (n=3+3) 
below). If the subject does experience a DLT, then the rules as outlined below will apply.  
Enrollment in the dose cohorts will proceed as follows based on the incidence of DLTs:

If there are no DLTs in any dose cohort from Cohort 1 to Cohort 6, enrollment will proceed 
as follows:
Cohort 1 (n = 1):  1 x 106 E7 TCR T cells/kg 
Cohort 2 (n = 1):  3 x 106 E7 TCR T cells/kg
Cohort 3 (n = 1):  1 x 107 E7 TCR T cells/kg
Cohort 4 (n = 1):  3 x 107 E7 TCR T cells/kg
Cohort 5 (n = 3 + 3):  1 x 108 E7 TCR T cells/kg
Cohort 6* (n = 3+3):  1 x 108 E7 TCR T cells/kg
*  For Cohort 6, the target dose is 1 x 108 E7 TCR T cells/kg and the total number of cells will be calculated 
based on weight. The minimally acceptable dose for patients above 60 kg will be 6 x 109 E7 TCR T cells. 
The maximum total number of cells in this cohort will be 1 x 1010 E7 TCR T cells.
In single-subject dose escalation/de-escalation design,

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
If the initial subject had DLT in Cohort 1, Cohort 1 will be expanded to 6 subjects.  If the 
incidence of DLT is < 33% after the expansion, then enrollment will continue to the next 
dose cohort with all subsequent cohorts being expanded to 3 + 3.  If there are ≥ 2 DLTs in 
Cohort 1, the study may explore a lower KITE-439 dose (Cohort –1).

If the first subject in dose cohort 2, 3 or 4 experiences a DLT, enrollment will proceed as 
follows:
The previous dose cohort will be expanded to 3 + 3.  If there are < 33% DLTs in the 
previous dose cohort after the expansion or if the previous dose cohort had already been 
expanded, then the current dose cohort will be expanded to 6 subjects.
■
If there are < 33% DLTs in the expanded cohort, then enrollment will continue to the 
next dose cohort.
■
All subsequent dose cohorts will be expanded to 3 + 3.
■
If the incidence of DLTs remains < 33%, then enrollment will continue with this 
approach until the highest dose cohort is reached.
The highest dose cohort in which the incidence of DLTs is < 33% will be designated the 
MTD.

If there are ≥ 2 DLTs in any dose cohort after the first dose cohort, enrollment will proceed 
as follows:
The previous dose cohort will be expanded to 3 + 3, unless it was already expanded in 
which case the dose tested in the previous cohort will be designated the MTD.
■
If there is 0 or 1 DLT (i.e., 0 DLT in 3 subjects or 1 DLT in 6 subjects) in the 
previous cohort, then that dose cohort will be designated the MTD.
■
If there are ≥ 2 DLTs (i.e., ≥ 2 DLTs in 6 subjects) in the previous cohort, then the 
cohort before the previous cohort will be expanded to 3 + 3 and so on.
The highest dose cohort in which the incidence of DLTs is < 33% will be designated the 
MTD.
At any time, when ≥ 2 DLTs have been observed prior to completing dosing of the planned 
number of subjects in a cohort, enrollment and dosing of additional subjects in that cohort will be 
stopped, and the cohort will be deemed unsafe.
In 3+3 study design,

If there is no DLT observed among the first 3 subjects of Cohort 5, then the enrollment will 
continue to Cohort 6.

If there is a DLT observed among the first 3 subjects, then an additional 3 subjects will be 
enrolled into the same cohort.

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
If there is no DLT among the additional 3 subjects in Cohort 5, then the enrollment will 
continue to Cohort 6.

If there are ≥ 2 DLTs among the first 3 subjects or at least 1 DLT among the additional 3 
subjects in Cohort 5, then follow the single-subject dose escalation/de-escalation process 
described in the “If there are ≥ 2 DLTs in any dose cohort after the first dose cohort” above.

Cohort 6 will follow the same process as Cohort 5, except
If there is no DLT in the first 3 subjects or 1 DLT in the first 6 subjects, Cohort 6 may be 
designated as MTD.
Otherwise Cohort 5 may be designated as MTD.
Based on the incidence of DLTs and other accumulating data, such as AEs and objective 
response outcomes, each disease type will be evaluated to proceed to the Phase 1B portion of the 
study.  Kite/sponsor reserves the right to recommend one or more doses to be evaluated in Phase 
1B, provided that each dose is at or below the MTD.
The decision to proceed with a specific dose or doses of KITE-439 to Phase 1B will be made by 
Kite and formally communicated to participating sites in a separate communication.
9.7.2.2.
Criteria to Pause Enrollment
As part of its oversight of the study, the SRT will assess criteria to pause enrollment during the 
study.
Enrollment will be paused if the following KITE-439-related AEs are observed:

After 15 and 30 subjects enrolled in the study (including both Phase 1A and Phase 1B, 
respectively) have been treated with KITE-439 and have had the opportunity to be followed 
for 21 days, the incidence of Grade 4 CRS is greater than 25%

Any Grade 4 infusion reaction/hypersensitivity

Any Grade 4 cardiac event

Any Grade 4 neurologic toxicity

Any Grade 5 SAE after KITE-439 infusion at least possibly related to KITE-439
Applicable Regulatory Agencies will be notified within applicable safety reporting timelines if 
any of these pausing rules occur.
In the event that the enrollment is paused after the pausing criteria have been met, overall 
assessment of the benefit/risk ratio will be conducted. If the overall assessment of the benefit/risk 

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ratio is favorable, the study can resume enrollment. Restart of the study may require prior 
approval if required by applicable regulatory requirements or mandated by country specific 
Regulatory Agency.

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10.
STATISTICAL CONSIDERATIONS
10.1.
Hypothesis
Phase 1A:  KITE-439 at one of the dose levels planned will be considered safe as determined by 
the incidence of DLTs.
Phase 1B:  A formal hypothesis will not be tested.  The clinical hypothesis is that KITE-439 will 
have clinically meaningful anti-tumor activity, as measured by ORR, in adult subjects with 
relapsed/refractory HPV16+ cancers.  The Phase 1B portion of the study is designed to estimate 
the ORR.
10.2.
Study Endpoints
10.2.1.
Primary
Phase 1A:  Incidence of AEs defined as DLTs
Phase 1B:  ORR (complete response [CR] + partial response [PR]) per modified RECIST v1.1 
(Appendix 1)
10.2.2.
Secondary

Duration of response (DOR):  For subjects who experience an objective response, DOR is 
defined as the time from the date of their first objective response to the date of disease 
progression per modified RECIST v1.1 (Appendix 1) or death regardless of cause.  Subjects 
not meeting the criteria for progression 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.

PFS is defined as the time from the KITE-439 infusion date to the date of disease progression 
per modified RECIST v1.1 (Appendix 1) or death from any cause.  Subjects not meeting the 
criteria for progression by the analysis data cutoff date will be censored at their last evaluable 
disease assessment date.

OS is defined as the time from KITE-439 infusion to the date of death.  Subjects who have 
not died by the analysis data cutoff date will be censored at their last contact date.

Incidence of AEs

Incidence of anti-KITE-439 antibodies, and incidence of RCR

Levels of E7 TCR T cells

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10.3.
Sample Size Considerations
The anticipated enrollment in this study is approximately 2 to 71 subjects.
Approximately 2 to 36 subjects will be enrolled into the Phase 1A portion of this study.
If the study proceeds to Phase 1B, including subjects from Phase 1A, subjects will enroll into 1 
of 2 Phase 1B cohorts (n = 15 subjects total for the HPV16+ squamous cell cancer of the head 
and neck cohort and n = 20 subjects total for the HPV16+ tumors other than squamous cell 
carcinoma of the head and neck cohort).
The primary efficacy endpoint and all analyses based on the objective response (objective 
response, DOR, PFS) of the study will be based on a mITT population consisting of all subjects 
who receive any dose of KITE-439 and with measurable disease after completion of bridging 
chemotherapy (if applicable) and prior to administration of conditioning chemotherapy.
The Phase 1B uses a single-arm design to estimate response rate in each of the 2 cohorts (n = 15 
for  the HPV16+ squamous cell carcinoma of the head and neck cohort, n = 20 for the HPV16+ 
tumors other than squamous cell carcinoma of the head and neck cohort ) and in all Phase 1B 
cohorts combined (n = 35).  With the planned sample size in the two cohorts, the ORR can be 
estimated with a standard error not greater than 13% (HPV16+ squamous cell cancer of the head 
and neck cohort) and 11% (other HPV16+ tumors cohort).  Assuming an observed ORR of 40%, 
the lower bound of the 95% CI for the estimated ORR will exclude values less than 16% 
(HPV16+ squamous cell cancer of the head and neck cohort) and 19% (other HPV16+ tumors 
cohort).  With a planned total sample size of 35 for all Phase 1B cohorts combined, the ORR can 
be estimated with a standard error no greater than 8%.  Assuming an observed ORR of 40%, the 
lower bound of the 95% CI for the estimated ORR will exclude values less than 24%.
One primary analysis is planned for each of the Phase 1B cohorts and will be performed after all 
subjects accrued for a specific cohort to the study have had the opportunity to be assessed for 
response 3 months after the KITE-439 infusion.  If an individual cohort takes > 24 months to 
accrue from the initiation of Phase 1B, the primary analysis would occur with < 15 subjects 
accrued for the HPV16+ squamous cell carcinoma of the head and neck cohort and < 20 subjects 
accrued for the other HPV16+ tumors cohort.  If the primary analysis for 2 cohorts is projected to 
occur within 3 months of each other, the cohorts may be combined and carried out at the same 
time.  No formal hypothesis testing will be performed.  However, within the HPV16+ squamous 
cell carcinoma of the head and neck cohort and compared to a control of 20% ORR, 5 or more 
responses would indicate an improvement in response with p-value of 0.164 or smaller; 6 or 
more responses would indicate a significant improvement in response with p-value of 0.061 or 
smaller. Within the other HPV16+ cohort excluding squamous cell carcinoma of the head and 
neck and compared to a control of 20% ORR, 7 or more responses would indicate an 
improvement in response with p-value of 0.087 or smaller; 8 or more responses would indicate a 
CCI

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significant improvement in response with p-value of 0.032 or smaller, by exact binomial test. 
The CIs of the objective response and p-values will be presented for descriptive purpose.  These 
may be used as guidance for decision of further development of KITE-439.
Statistical software R version 3.2.0 and EAST version 6.3 were used to calculate the sample sizes 
and evaluate the operational characteristics of this design.
10.4.
Analysis Subsets

The DLT evaluable set (Phase 1A only) will include subjects treated in the Phase 1A portion 
who:
Received the target dose (± 20%) and had the opportunity to be followed for at least 
21 days after the KITE-439 infusion; or
Received a dose of KITE-439 lower than the target dose and experienced a DLT within 
21 days after the KITE-439 infusion

mITT:  The mITT set will consist of all subjects enrolled and treated with Phase 1B target 
dose of KITE-439 and with measurable disease after completion of bridging chemotherapy 
(if applicable) and prior to administration of conditioning chemotherapy.  This analysis set 
will be used for all analyses of objective response and endpoints based on objective response 
(objective response, DOR, PFS).

Safety analysis set:  The safety analysis set is defined as all subjects treated with any dose of 
KITE-439.

Full analysis set (FAS):  The full analysis set will consist of all enrolled subjects and will be 
used for the summary of subject disposition.
10.5.
Access to Individual Subject Treatment Assignments
This is a single-arm, open-label study, and subjects and investigators will be aware of treatment 
received.
10.6.
Safety Review and Interim Analysis
10.6.1.
Phase 1A Safety Review
The SRT will be chartered to review safety during Phase 1A of the study only and make 
recommendations on further study conduct in Phase 1A (see details in Section 9.7).

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10.6.2.
Efficacy Interim Analysis
No formal interim analysis is planned for the Phase 1B part of the study.  However, the SRT will 
review subject-level safety and efficacy data on an ongoing basis to monitor subject safety and 
ensure data quality.  Informal safety and efficacy analyses may be done with accumulating data 
when such a need arises during the study.  Within the Phase 1B HPV16+ squamous cell cancer of 
the head and neck cohort, if no response is observed in the first 7 subjects treated with the target 
dose after a minimum of 1 month of follow-up, the sponsor may consider stopping enrollment 
for this cohort. Within the other Phase 1B HPV16+ tumors cohort, if no response is observed in 
the first 10 subjects treated with the target dose after a minimum of 1 month of follow-up, the 
sponsor may consider stopping enrollment for this cohort.
10.7.
Planned Method of Analysis
The primary efficacy analysis of each cohort in Phase 1B will be performed when all enrolled 
subjects in each cohort have had the opportunity to be evaluated for response 3 months after the 
KITE-439 infusion.  Additional analyses may occur after the primary analysis has been 
completed.  The final analysis will occur when all subjects have completed the study.
Analyses of efficacy endpoints will be summarized by cohort and overall.  Analyses of safety 
endpoints will be evaluated by cohort and overall.
10.7.1.
Objective Response Rate
The incidence of objective response and exact 2-sided 95% CIs will be generated.  An exact 
binomial test will be used to compare the observed response rate to a response rate of 20%.  The 
p-values from such tests will be for descriptive purposes only.
10.7.2.
Duration of Response
Kaplan-Meier estimates and 2-sided 95% CIs will be generated for DOR.
10.7.3.
Progression-free Survival
Kaplan-Meier estimates and 2-sided 95% CIs will be generated for PFS time.
10.7.4.
Overall Survival
Kaplan-Meier estimates and 2-sided 95% CIs will be generated for OS.
10.7.5.
Safety
Subject incidence rates of AEs, including all, serious, fatal, CTCAE Grade 3 or higher, and 
treatment -related AEs reported throughout the conduct of the study, will be tabulated by system 
organ class and preferred terms.  The incidence of concomitant medications will be summarized.

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Tables and/or narratives of deaths through the LTFU and treatment-related SAEs will be 
provided.
MMSE at baseline and change from baseline will be summarized.
10.7.6.
Long-term Data Analysis
All subjects will be followed for survival for up to approximately 15 years after the last subject is 
enrolled.  Descriptive estimates of key efficacy and safety analyses may be updated to assess the 
overall treatment profile.

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11.
REGULATORY OBLIGATIONS
11.1.
Independent Review Board/Independent Ethics Committee
A copy of the protocol, ICF, and any additional subject or trial information, such as subject 
recruitment materials, must be submitted to each site’s respective IRB/IEC for approval.  After 
approval is obtained from the IRB/IEC, all documents must be provided to the key sponsor 
contact before subject recruitment can begin.
The investigator must also receive IRB/IEC approval for all protocol and ICF changes or 
amendments.  Investigators must ensure that ongoing/continuous IRB/IEC approval (i.e., annual 
approval) is provided throughout the conduct of the study.  Copies of IRB/IEC approval are to be 
forwarded to the key sponsor contact for archiving.
During the course of the study, investigators are to submit site-specific and study 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.
11.2.
Subject Confidentiality
Subject confidentiality must be contained for all material submitted to the key sponsor contact.  
The following rules are to be applied:

Subjects will be identified by a unique ID number.

Year of birth will be reported according to local laws and regulations.

Age at the time of enrollment
For reporting of SAEs, subjects will be identified by their respective subject ID number, initials, 
and year of birth (as per their local reporting requirements for both initials and year of birth).
Per federal regulations and International Conference on Harmonization/Good Clinical Practice 
(ICH/GCP) guidelines, investigators and institutions are required to permit authorization to the 
sponsor, Contract Research Organization (CRO), IRB/IEC, and regulatory agencies to subject’s 
original source documents for verification of study data.  The investigator is responsible for 
informing potential subjects that such individuals will have access to their medical records, 
which includes access to personal information.
11.2.1.
Investigator Signatory Obligations
Each clinical study report will be signed by the coordinating investigator.  The coordinating 
investigator will be identified by Kite under the following criteria:

A recognized expert in the disease setting

Provided significant contributions to the design or analysis of study data

Participated in the study and enrolled a high number of eligible subjects

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12.
PROTOCOL AMENDMENTS AND TERMINATION
If the protocol is amended, the investigator’s agreement with the amendment and the IRB/IEC 
approval of the amendment must be obtained.  Documentation acknowledging approval from 
both parties is to be submitted to the key sponsor contact.
Kite reserves the right to terminate the study at any time.  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 and provide the CRO with a copy of the 
correspondence.
Kite reserves the unilateral right, at its sole discretion, to determine whether to manufacture 
KITE-439 T cells and provide them to sites and subjects after the completion of the study and 
before treatment becomes commercially available.

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13.
STUDY DOCUMENTATION AND ARCHIVE
The investigator will maintain a list of qualified staff to whom study responsibilities have been 
delegated.  These individuals authorized to fulfil these responsibilities are 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.  Examples of such source documents may include, but are not limited to, 
hospital records and subject charts; laboratory, pharmacy, radiology, and records; subject diaries; 
microfiches; correspondence; and death registries.  CRF entries may be considered as source data 
if the site of the original data collection is not available.  However, use of the CRFs as source 
documentation as a routine practice is not recommended.
The investigator and study staff are responsible for maintaining a comprehensive and centralized 
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 minimum:

Subject content including ICFs and subject ID lists

Protocols and protocol amendments, IB, copies of pre-study documentation, and all IRB/IEC 
and sponsor communication

Proof of receipt, experimental treatment flow records, and experimental product-related 
correspondence
Original source documents supporting entries into CRFs 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.  If storage is no longer available to archive source 
documents or must be moved to an alternative location, the research staff should notify the key 
sponsor contact prior to the shipping of the documents.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject ID

Documentation that subject meets eligibility criteria (i.e., medical history, physical 
examination, and confirmation of diagnosis [to support inclusion and exclusion criteria])

Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number/name)

Study discussed and date of informed consent

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
Dates of all visits

Documentation that protocol-specific procedures were performed

Results of efficacy parameters, as required by the protocol

Start and end date (including dose regimen) of IP, including start and stop times of KITE-439 
administration 

Record of all AEs and other safety parameters (start and end date, and including causality 
and severity), and documentation that adequate medical care has been provided for any AE

Concomitant medication (including start and end date, dose if relevant, and dose changes)

Date of study completion and reason for early discontinuation, if it occurs
Traceability records for the product, from procurement through manufacture to the 
administration of the product, should be kept by each relevant party (e.g., 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, whilst 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.

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14.
STUDY MONITORING AND DATA COLLECTION
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 CRF 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.  Monitors will have access to 
subject records as identified in Section 13.
By signing the investigator agreement, the investigator agrees to cooperate with the monitor to 
address and resolve issues identified during monitoring visits.
In accordance with ICH GCP and the audit plan, a site may be chosen for a site audit.  A 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.
All data will be collected in an electronic CRF system.  All entries must be completed in English, 
and concomitant medications should be identified by trade names.  For additional details 
surrounding the completion of CRFs, refer to the CRF completion guidelines.

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15.
PUBLICATION
Authorship of publications from data generated in this study will be determined based on the 
uniform requirements for manuscripts submitted to biomedical journals (as outlined in the 
International Committee of Medical Journal Editors December 2013), which states authorship 
should be based on:

Substantial contributions to the conception or design of the work; acquisition of data, 
analysis, or interpretation of data for the work; and

Drafting the article or revising it critically for important intellectual content; and

Final approval of the version to be published; and

Agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated or resolved
When a large, multicenter group has conducted the work, the group should identify the 
individual who accepts direct responsibility for the manuscript.  This individual should fully 
meet the criteria for authorship defined above.
Funding, collection of data, or general supervision of the research alone or in combination does 
not qualify an individual for authorship.
Any publication, in any form, that is derived from this study must be submitted to Kite for 
review and approval.  The study contract among the institution, principal investigator, and Kite 
or its delegate will outline the requirements for publication review.

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16.
COMPENSATION
Kite will provide compensation for study-related illness or injury pursuant to the information 
outlined in the injury section of the ICF.

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17.
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Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC, Hughes MS, et al. Gene therapy 
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Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, et al. Phase III 
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regression in patients after transfer of genetically engineered lymphocytes. 
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cells. Proc Natl Acad Sci U S A 2002;99 (25):16168-73.

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18.
APPENDICES
Appendix 1.
Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines Version 1.1 
with Modifications
Appendix 2.
Practical Body Weight Calculation for Subjects Whose BMI is > 35
Appendix 3.
Childbearing Potential and Birth Control
Appendix 4.
Country-specific Regulatory Agency Requirements

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Appendix 1.
Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines 
Version 1.1 with Modifications
These guidelines provide a standard approach to solid tumor measurement and definitions for 
objective assessments of change in tumor size and are based on guidelines developed and 
published by {Eisenhauer 2009}.  Modifications to the guidelines are listed in Table 13.
Eligibility
Per protocol, subjects must have at least 1 measurable lesion per modified RECIST v1.1 (see 
Table 13) on the most recent computed tomography (CT) or magnetic resonance imaging (MRI) 
staging evaluation.
Method
CT scans (or MRI scans) of the neck (if applicable), chest, abdomen, pelvis, and all other sites of 
disease will be performed to evaluate tumor response.  Lesions identified on chest x-ray should 
be imaged by CT or MRI scan.  Ultrasound (US) and F-flurodeoxyglucose positron emission 
tomographic (FDG-PET) alone cannot be used to measure objective tumor response or 
progressive disease (PD).
Measurability of lesions on CT scan is based on the assumption that CT slice thickness is 5 mm 
or less.  When CT scans have slice thickness greater than 5 mm, the minimum size for a 
measurable lesion should be the greater of either at least 10 mm or twice the slice thickness.
MRI is acceptable to assess disease extent if used throughout the study.
At baseline and throughout the study, images should be performed using the same method of 
assessment, and the same technique should be used to characterize each identified and reported 
lesion.  A switch from CT to MRI (or vice versa) is considered the only acceptable change in 
modality.  It should not preclude response assessment if, in the judgement of the site radiologist, 
there is no significant difference in the assessment by changing modalities.  This may occur if a 
subject has developed a medical contraindication to intravenous (IV) contrast for CT scans while 
on trial.  If this happens, contact the Kite medical monitor to discuss the change in modality on a 
per subject basis.
For this protocol, a response of complete response (CR), partial response (PR), or stable disease 
(SD) will be determined as assessed by cross-sectional imaging techniques (CT or MRI).
FDG-PET will not contribute to the assessment of response.  It is sometimes reasonable to 
incorporate the use of FDG-PET scanning to complement CT scanning in assessment of 
progression.  For the determination of PD, FDG-PET could be used to identify new lesions as 
follows:

Negative FDG-PET at baseline, with a positive FDG-PET at follow-up, is a sign of PD if a 
new lesion is identified.

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
No FDG-PET at baseline and a positive FDG-PET at follow-up:
If the positive FDG-PET at follow-up corresponds to a new location of disease, confirm 
by CT (or MRI) this is the PD.
If the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT (or 
MRI), additional follow-up CT (or MRI) scans are needed to determine if there is truly 
progression occurring at that site (if so, the date of PD will be the date of the initial 
abnormal FDG-PET scan).
If the positive FDG-PET at follow-up corresponds to a pre-existing site of disease on CT 
(or MRI) that is not progressing on the basis of the anatomic images, this is not PD.
If a combined FDG-PET/CT scan is performed at the discretion of the investigator, the CT 
portion of that exam should not be substituted for the dedicated CT exams required by this 
protocol for Response Evaluation Criteria in Solid Tumor (RECIST) measurements unless the 
site can document that the CT performed as part of the FDG PET-CT is of identical diagnostic 
quality to a diagnostic CT.  Tumor markers alone cannot be used to assess objective tumor 
response.
Physical exam cannot be used to quantify tumor measurements other than in the case of 
cutaneous or palpable subcutaneous lesions.
Definitions of “Measurable” and “Non-measurable”
All measurements will be determined using a ruler or calipers and reported in metric notation 
(mm) and will be recorded unidimensionally.
At baseline, tumor lesions/pathologic lymph nodes are categorized as measurable or non-
measurable according to the following definitions:

Measurable or target lesions:
Measurable target lesions are defined at baselines as lesions that can be accurately 
measured in at least 1 dimension (longest diameter to be recorded) with a minimum size 
of 10 mm by CT scan (CT scan slice thickness no greater than 5 mm).
To be considered pathologically enlarged and measurable, a lymph node must be 
≥ 15 mm in short axis diameter when assessed by CT scan.

Non-measurable or non-target lesions:
All other lesions that were not chosen as target lesions, including lesions too small to 
measure (longest diameter < 10 mm, lymph nodes with ≥ 10 or < 15 mm short axis 
diameter), and other truly non-measurable lesions are considered non-measurable and 
characterized as non-target lesions.

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Other examples of non-measurable lesions include:
■
Some bone lesions
■
Inflammatory breast disease
The following examples should not be followed as lesions for assessment of disease:

Nodes that have short axis < 10 mm are considered non-pathological and should not be 
recorded or followed.

Ascites or pleural effusions are not considered non-measurable for this study.
Baseline Documentation of “Target” and “Non-target” Lesions
Baseline images will be used to prospectively identify all sites of disease present as close as 
possible to the start of treatment and never more than 35 days before enrollment/leukapheresis.
Site of disease will be characterized as either target or non-target lesions.

Target lesions
Up to 5 target lesions (a maximum of 2 per organ) meeting the target lesion definition 
above will be chosen to measure at baseline and over the course of the study.
Target lesions should be selected on the basis of their size and suitability for accurate 
repeated measurements by imaging techniques.
Target lesions must not be chosen from a previously irradiated field unless there has been 
documented tumor progression in that field prior to enrollment.
The distribution of these target lesions should be representative of the subject’s overall 
disease status.
A sum of the diameters (longest for non-nodal lesions, short axis diameter for nodal 
lesions) for all target lesions will be calculated and reported as the baseline sum 
diameters.  The baseline sum diameters will be used as reference by which to characterize 
the objective tumor response.

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
Non-target lesions
All other lesions (or sites of disease) meeting the non-target lesion definition above 
should be identified as non-target lesions.
Non-target lesions should be recorded and assessed qualitatively over the course of 
therapy.  These lesions should be followed as “present,” “absent,” or, in rare cases, 
“unequivocal progression.”
It is possible to record multiple non-target lesions involving the same organ as a single 
item on the case report form (CRF) (e.g., multiple enlarged pelvic lymph nodes or 
multiple liver metastases).
Response Criteria
The subject’s overall tumor response will be assessed based on the response of the target lesions 
(Table 10), the response of the non-target lesions (Table 11), and the presence or absence of new 
lesions.
Evaluation of Target Lesions
Table 10.
Evaluation of Target Lesions at Each Assessment Point
Response
Criteria
Complete response (CR):
Disappearance of all target lesions
Any pathological lymph nodes (whether target or non-target) must have 
reduction in short axis to < 10 mm.
Partial response (PR): 
At least a 30% decrease in the sum of diametersa of all target lesions, taking as 
a reference the baseline sum diametersa
Progressive disease (PD):
At least a 20% increase in the sum of diametersa of all target lesions, taking as 
a reference the nadir (i.e., smallest sum of the diametersa since receiving 
KITE-439) 
The sum must also demonstrate an absolute increase of at least 5 mm above 
the same reference (i.e., nadir).
Stable disease (SD):
Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify 
for PD, taking as a reference the nadir (i.e., smallest sum of diametersa since 
receiving KITE-439)
Inevaluable (NE):
Scans were not performed, were incomplete, or were inevaluable due to poor 
scan quality at this time point and did not permit the measurement of all or 
some target lesions.
a
Diameters used:
For nodal disease, shortest axis.
For non-nodal disease, sum of longest diameters.

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While on study, all target lesions (nodal and non-nodal) recorded at baselines should have their 
actual measurements recorded at each subsequent evaluation.  The conventions will be used that 
if a lesion being measured is faintly seen and/or too small to measure, a value of 5 mm will be 
assigned.  If a lesion disappears, a measurement of “0” mm should be recorded.
Lymph nodes identified as target lesions should always have the actual short axis measurement 
recorded even if the nodes regress to below 10 mm on study.  When lymph nodes are included as 
target lesions, the “sum” of target lesions may not be 0 even if CR criteria are met because a 
normal lymph node is defined as having a short axis < 10 mm.  For CR, each node must achieve 
a short axis < 10 mm.  For PR, SD, and PD, the actual short axis measurement of the nodes is to 
be included in the sum of target lesions.
Evaluation of Non-target Lesions
Table 11.
Evaluation of Non-target Lesions at Each Assessment Point
Response
Criteria
Complete response (CR)
Disappearance of all non-target lesions 
All lymph nodes must be non-pathological in size (< 10 mm short axis). 
Non-CR/Non-PD
Persistence of 1 or more non-target lesions 
Progressive disease (PD):
Unequivocal progression of existing non-target lesions, or 
Appearance of 1 or more new lesions
Not applicable (NA):
No non-target lesions identified at baseline
Inevaluable (NE):
Scans were not performed, were incomplete, or were inevaluable due to poor 
scan quality at this time point and did not permit the assessment of all or some 
non-target lesions. 
When the subject also has measurable disease, to achieve an unequivocal progression, there must 
be an overall level of substantial worsening in non-target disease such that even in the presence 
of SD or PR in target disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy.  When the subject has only non-measurable disease, the increase of 
non-measurable disease should be comparable in magnitude to the increase required to declare 
PD for measurable disease (e.g., equivalent to a 20% increase in sum of diameters of all 
measurable lesions).
Evaluation of Best Overall Response
Table 12 provides a summary of the overall response status calculation at each time point for 
subjects who have measurable disease.

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Table 12.
Time Point Response in Subjects with Target (± non-target) Disease
Target Lesions 
(response)
Non-target Lesions
(response)
New Lesions
(Yes or No)
Overall Response
CR
CR
No
CR
CR
Non-CR/non-PD
No
PR
CR
NE
No
PR
PR
Non-PD or NE
No
PR
SD
Non-PD or NE
No
SD
NE
Non-PD
No
NE
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
PR
NA*
No
PR
CR
NA*
No
CR
SD
NA*
No
SD
NE
NA*
No
NE
Abbreviations:  CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; NE, inevaluable; 
NA*, no non-target lesions identified at baseline.
Non-CR/non-PD is preferred over “stable disease” for non-target disease because SD is 
increasingly used as endpoint for assessment of efficacy in some trials so to assign this category 
when no lesions can be measured, is not advised.
For equivocal findings (e.g., very small and uncertain new lesions; cystic changes, or necrosis in 
existing lesions), if progression is confirmed, the date of progression should be the earlier date 
when progression was suspected.
Response Confirmation
For a subject to be assigned an overall best response of PR or CR, the responses of PR or CR 
must be confirmed by performing additional radiological exams no less than 28 days after the 
initial criteria for response are first met.
For a subject to be assigned an overall best response of SD or better, the response must be 
documented ≥ 28 days after the KITE-439 infusion; otherwise the overall response will be 
inevaluable (NE).

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Appendix 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.
A. Definition of Childbearing Potential
A woman is considered of childbearing potential (i.e., 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 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 women 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.
B. 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
C. 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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Appendix 4.
Country-specific Regulatory Agency Requirements
A. France, Italy, and Germany
The post-infusion monitoring of subjects, described in Section 7.5.4 of this protocol, will be 
extended by monitoring on Day 8, Day 9, and Day 10, according to procedures outlined in the 
Schedule of Assessments (Table 5), “Post-treatment Follow-up” column. The subject may stay 
hospitalized or return to the clinic daily for this extended monitoring at the discretion of the 
investigator. The daily monitoring will include vital signs (refer to Table 5), blood draw for 
chemistry panel with C-reactive protein, blood draw for complete blood count with differential, 
and neurological assessment (refer to Section 6.11). Any observed toxicity will be managed 
according to Section 7.8 of this protocol.