Conditions: Relapsed/Refractory Large B-cell Lymphoma
Keywords: Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) GM-CSF antibody Chimeric Antigen Receptor (CAR) CD19
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 6
Healthy volunteers: no

Brief summary:
The primary objectives of this study are:

Phase 1: To evaluate the safety of sequenced therapy with lenzilumab and axicabtagene ciloleucel in participants with relapsed or refractory large B-cell lymphoma and identify the most appropriate dose of lenzilumab for Phase 2.

Phase 2: To evaluate the incidence of neurologic events with sequenced therapy given at the recommended Phase 2 dose (RP2D) of lenzilumab in participants with relapsed or refractory large B-cell lymphoma.

Detailed description:
This study was intended to be a Phase 1/2, but the planned Phase 2 part has been canceled.

All participants who received an infusion of lenzilumab and axicabtagene ciloleucel will be provided the opportunity to transition to a separate long-term follow-up (LTFU) study, KT-US-982-5968.

Arms:
arm 1: Phase 1: Participants will receive cyclophosphamide and fludarabine lymphodepleting chemotherapy followed by sequenced therapy of lenzilumab and axicabtagene ciloleucel on Day 0 to determine a recommended Phase 2 dose (RP2D) of lenzilumab. Phase 2: Participants will receive cyclophosphamide and fludarabine lymphodepleting chemotherapy followed by sequenced therapy of lenzilumab, at the RP2D, and axicabtagene ciloleucel on Day 0.

Interventions: intervention 1: Cyclophosphamide intervention 2: Fludarabine intervention 3: Lenzilumab intervention 4: Axicabtagene Ciloleucel
Intervention descriptions: intervention 1: Administered according to package insert intervention 2: Administered according to package insert intervention 3: Administered as an IV infusion intervention 4: A single infusion of chimeric antigen receptor (CAR) transduced autologous T cells administered intravenously.

Protocol document:
SAP_002.pdf: 
 
TRANSLATIONAL STATISTICAL ANALYSIS PLAN KT-US-471-0119 
 
Sponsor: 
Kite Pharma, Inc. 
2400 Broadway 
Santa Monica, CA 90404 
United States of America 
Product Name: 
KTE-C19 
Protocol: 
KT-US-471-0119 (ZUMA-19) 
A Phase 1/2 Open-label, Multicenter Study of Lenzilumab and 
Axicabtagene Ciloleucel in Subjects with Relapsed or 
Refractory Large B-cell Lymphoma (ZUMA-19) 
Protocol Version Number 
and Date: 
Amendment 1, 16 September 2019 
TSAP Release Date: 
26 May 2021 
Replaces Previous 
Version(s): 
 
 
 
 
 
 
 
 
CONFIDENTIALITY NOTICE 
This document contains confidential information of Kite Pharma Inc., a wholly owned subsidiary 
of Gilead Sciences Inc.  This document must not be disclosed to anyone other than the site 
research staff and members of the Institutional Review Board/Independent Ethics Committee, a 
scientific review board or an equivalent.  The information in this document cannot be used for 
any purpose other than the conduct of the clinical investigation without the prior written consent 
of Kite Pharma Inc.  Questions regarding how this document should be used or the conduct of 
the clinical trial should be directed to the key sponsor contacts. 
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TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
LIST OF TABLES......................................................................................................................................................... 3 
1. 
INTRODUCTION ................................................................................................................................................ 5 
2. 
OBJECTIVES ....................................................................................................................................................... 6 
2.1. 
Objectives ................................................................................................................................................. 6 
2.2. 
Hypothesis ................................................................................................................................................ 6 
3. 
ENDPOINTS, SUBGROUPS AND COVARIATES ........................................................................................... 7 
3.1. 
Biomarker datasets ................................................................................................................................... 7 
3.2. 
Endpoints ................................................................................................................................................. 7 
4. 
DEFINITIONS ...................................................................................................................................................... 9 
4.1. 
General ..................................................................................................................................................... 9 
4.2. 
Key Measurements of Pharmacokinetics: ................................................................................................ 9 
4.2.1. 
Anti-CD19 CAR+ T-Cell ....................................................................................................... 9 
4.2.2. 
Lenzilumab Pharmacokinetics.............................................................................................. 10 
4.3. 
Key Measurements of Pharmacodynamics: Serum Analytes ................................................................. 10 
4.4. 
Key Measurements of CSF Analytes ..................................................................................................... 10 
4.5. 
Key Measurements of Product Characteristics ....................................................................................... 11 
5. 
ANALYSIS SETS............................................................................................................................................... 12 
5.1. 
Modified Intent-to-treat Analysis Set (mITT) ........................................................................................ 12 
5.2. 
Safety Analysis Set ................................................................................................................................ 12 
6. 
STATISTICAL ANALYSIS ............................................................................................................................... 13 
6.1. 
General Methods .................................................................................................................................... 13 
6.2. 
Analysis .................................................................................................................................................. 13 
6.2.1. 
Characterize the anti-CD19 CAR T cell expansion (pharmacokinetics) 
and serum analyte (pharmacodynamics) profiles ................................................................. 13 
6.2.2. 
Characterize the product attributes ....................................................................................... 14 
6.2.3. 
Characterize lenzilumab pharmacokinetics and soluble GM-CSF levels ............................. 14 
6.2.4. 
Characterize analytes, CAR-T cells and other cell subsets in CSF ...................................... 14 
7. 
REFERENCES ................................................................................................................................................... 15 
8. 
APPENDIX ......................................................................................................................................................... 16 
8.1. 
Analytic Visit Windows for CAR T Cells in Blood ............................................................................... 16 
8.2. 
Analytic Visit Windows for Lenzilumab Pharmacokinetics .................................................................. 16 
8.3. 
Analytic Visit Windows for Pharmacodynamics Key Measurements (serum analytes) ........................ 16 
8.4. 
Immune cell subsets in CSF (FLOW) .................................................................................................... 17 
8.5. 
Using Trapezoidal Rule to Approximate the AUC ................................................................................ 17 
 
 
 


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LIST OF TABLES 
Table 3-1. 
Data overview on assay methods and biomarker lists .............................................................. 7 
Table 8-1. 
Visit window for blood draw for PBMC ................................................................................ 16 
Table 8-2. 
Visit window for blood draw for Lenzilumab (Phase 1) ........................................................ 16 
Table 8-3. 
Visit window for blood draw for serum analytes ................................................................... 16 
Table 8-4. 
Visit window for CSF samples ............................................................................................... 17 
Table 8-5. 
CSF T-cell analytes ................................................................................................................ 17 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
Adverse event 
AUC 
Area under the curve 
Axicabtagene ciloleucel / 
KTE-C19 
Autologous T cells transduced with retroviral vector containing anti-CD19 
CD28/CD3 zeta chimeric antigen receptor 
CAR 
Chimeric antigen receptor 
CR 
Complete response   
CRS 
Cytokine release syndrome 
CSF 
Cerebrospinal fluid 
mITT 
Modified intent-to-treat 
NE 
Neurologic event  
ORR 
Objective response rate 
PBMC 
Peripheral blood mononuclear cells 
PD 
Progressive disease 
PR 
Partial response  
SD 
Stable disease 
SOA 
Schedule of assessments 
RP2D 
Recommended Phase 2 Dose 
qPCR 
Quantitative PCR 
 


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1. 
INTRODUCTION 
This supplemental statistical analysis plan outlines the analyses of pharmacokinetics/ 
pharmacodynamics, product characteristics, and other biomarkers in support of the end of study 
for sequenced therapy with lenzilumab and axicabtagene ciloleucel (KTE-C19) in subjects with 
relapsed or refractory large B-cell lymphoma. The analysis will be conducted for biomarker data 
within protocol KT-US-471-0119 (ZUMA-19) Amendment 1 on 16 September 2019. 


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2. 
OBJECTIVES 
2.1. 
Objectives 
• Characterize the presence, expansion, persistence and clearance of anti-CD19 CAR T cell in 
blood (cells/µL) (pharmacokinetics), and serum analytes (pharmacodynamics) profiles 
• Characterize the KTE-C19 product attributes 
• Characterize lenzilumab pharmacokinetics and soluble GM-CSF levels 
• Characterize soluble analytes, CAR-T cells and other cell subsets in CSF 
2.2. 
Hypothesis 
The analyses outlined in this TSAP are exploratory and no formal pre-specified hypothesis will 
be tested. 


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3. 
ENDPOINTS, SUBGROUPS AND COVARIATES 
3.1. 
Biomarker datasets 
Table 3-1. 
Data overview on assay methods and biomarker lists 
Data type 
Assay method/Sample 
type 
Biomarker set 
Pharmacokinetics 
data (CAR T) 
qPCR/PBMCs 
• Number of CAR T cells (/µL) 
• %PBMC 
Pharmacokinetics 
data (lenzilumab) 
Immunoassays/serum 
samples 
Serum lenzilumab  
Pharmacodynamics 
data (serum 
analytes) 
Serum analyte assays/serum 
samples 
• Proinflammatory, homeostatic, and immune-modulating 
cytokines: IL-5, IL-6, IL-15, IL-17a, IL-10, tumor 
necrosis factor-α, GM-CSF, G-CSF, IFN-γ, IL-
12p40/p70, and IL-13;  
• Immune effector molecules: granzymes A and B and 
perforin; 
• Correlates of acute phase response: SAA, CRP and 
ferritin; chemokines MIP-1α, MIP-1β, MCP-1, CXCL-
10, and IL-8.  In addition, IL-1Ra, IL-2Rα 
CSF Biomarkers 
• Serum analyte 
assays/CSF samples 
• Flow cytometry/CSF 
samples 
• Biomarkers listed in the Pharmacodynamics analytes 
• Infiltration of CAR T cells  
• Infiltration of myeloid cells (CD14+) 
Appendix 8.4 
Product attributes 
Flow cytometry/Product 
Total number of T cells, total number of CAR T cells, 
transduction rate (%), vector copy number, CD3 cells (% 
and #), CD4 cells (% and #), CD8 cells (% and #), 
CD4/CD8 ratio, T naïve/CM/EM/EFF cells (% and #), 
(% Tnaive + % T central memory) / (% T effector memory 
+ % T effector cells), % viability, IFN-gamma production 
in Co-culture (normalized and not-normalized) 
 
3.2. 
Endpoints 
All definitions are generally applied to pharmacokinetics and/or pharmacodynamics. Detailed 
definitions can be found in Section 4. 
• Fold change from baseline at Day X 
• Peak 
• AUC 
• Time to peak 


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All measurable biomarker values at each visit will be used as main endpoints for all biomarkers 
listed in Table 3-1 as follows: 
• Levels of anti-CD19 CAR T cells in blood samples measured as number of anti-CD19 CAR+ 
cells/µL by visit, peak, Day 0-28 AUC, and time to peak 
• Levels of serum analytes by visit, fold change from baseline, fold change from Day 0, peak, 
Day 0-28 AUC, and time to peak 
• Product characteristics measurements after product manufacturing and prior to dosing 
• Levels of analytes in CSF pre- and post-infusion 
• Levels of CAR-T and other cell subsets in CSF pre- and post-infusion 


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4. 
DEFINITIONS 
4.1. 
General 
All definitions are generally applied to pharmacokinetics and pharmacodynamics. 
Study day 0 is defined as the day the subject receives the first KTE-C19 infusion. 
Baseline is generally defined as the last non-missing value measured on or prior to conditioning 
chemotherapy (starting at day −5 for serum analyte markers). 
4.2. 
Key Measurements of Pharmacokinetics: 
4.2.1. 
Anti-CD19 CAR+ T-Cell 
The presence, expansion and persistence of anti-CD19 CAR T cells in peripheral blood will be 
monitored by qPCR analysis. 
Scheduled blood draw for anti-CD19 CAR T cell 
This TSAP will focus on the anti-CD19 CAR T cell data collected as per planned assessment. 
The schedule of assessments and the analytic visit windows are defined in Appendix 8.1. 
 
 
Baseline number of anti-CD19 CAR T (cells/ µL) is defined as 0 since the axicabtagene 
ciloleucel infused in day 0, and number of CAR T (cell/µL) will not be derived. 
Peak of anti-CD19 CAR T cell (cells/ µL blood) is defined as the maximum absolute number 
of anti-CD19 CAR T cells in serum attained after Day 0. 
Time-to-Peak of CAR T cell (days) is defined as “Peak Date – KTE-C19 Dosing Date + 1”. 
Area-Under-Curve (AUC) of levels of anti-CD19 CAR T cell (cells/ µL ▪ days) is defined as 
the area under the curve in a plot of levels of anti-CD19 CAR T cells against scheduled visits 
from Day 0 to Day 28. This AUC measures the total levels of anti-CD19 CAR T cells overtime. 
Given the anti-CD19 CAR+ T cell is measured at certain discrete time points, the trapezoidal 
rule (Appendix 8.5) will be used to estimate the AUCs. 
Anti-CD19 CAR T peak/tumor burden: ratio of CAR T peak and baseline tumor burden local 
(investigator’s assessment) will be assessed. 
Pharmacokinetic anlaytes (nCART, nCAR T Peak, or nCAR T AUC)  
Baseline Tumor Burden (SPD) (mm^2) from local lab
 
CCI


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4.2.2. 
Lenzilumab Pharmacokinetics 
Serum samples will be assayed for lenzilumab concentration (µg/mL) with the use of a validated 
analytical method. 
Blood draws for lenzilumab pharmacokinetics will be performed at different intervals by study 
phase (Appendix 8.2). 
• Phase 1, blood draws will occur at baseline prior to infusion and 30 minutes and 1, 3, 6, 9, 
and 12 hours after infusion on Day 0, then every 12 hours on Days 1 to 5 and daily on Days 6 
and 7, then at Week 2 and Week 4. 
4.3. 
Key Measurements of Pharmacodynamics: Serum Analytes 
Scheduled blood draw for serum analytes: Within approximately 5 days of eligibility 
confirmation (Enrollment/Leukapheresis) at baseline, Day 0, twice daily from Day 1 to Day 5, 
daily on Day 6 and Day 7, and Week 2 and Week 4. This TSAP will focus on the serum analyte 
data collected from baseline to Day 28. The SOA and analytic visit window is defined in 
Appendix 8.3. 
Baseline of serum analytes is defined as the last value measured prior to lymphodepleting 
chemotherapy. 
Fold change from baseline at Day X is defined as 
Analyte level at Day X
Analyte level at Baseline 
Peak of serum analytes post baseline is defined as the maximum level of analyte in serum 
attained after baseline up to Day 28. 
Time to peak of serum analyte post KTE-C19 infusion is defined as “Peak Date – KTE-C19 
Dosing Date + 1”. 
Area-Under-Curve (AUC) of analyte levels from baseline to Day 28: is defined as the area 
under the curve in a plot of levels of analyte against scheduled visits from baseline to Day 28. 
This AUC measures the total levels of analyte overtime. Given the serum analyte is measured at 
certain discrete time points, the trapezoidal rule will be used to estimate the AUCs. 
4.4. 
Key Measurements of CSF Analytes 
CSF analytes are similar to the serum ones used in pharmacodynamics profiling. Peak and AUC 
analyses are not applied to CSF analytes. 
CSF T cells are listed in Appendix 8.4. The T-cell analyte level normalized to CSF volume or 
CD45 cells will be used in analysis. 
CSF sample collection scheduled assessment visits: Baseline, Day 5, and Day 28 (Month 1) 


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4.5. 
Key Measurements of Product Characteristics 
All product characteristics as listed in Table 3-1 will be summarized individually and also for the 
correlative analysis with anti-CD19 CAR T levels in blood, serum analyte levels, and clinical 
outcome endpoints. 


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5. 
ANALYSIS SETS 
5.1. 
Modified Intent-to-treat Analysis Set (mITT) 
The modified intent-to-treat set will consist of all subjects enrolled and treated with axicabtagene 
ciloleucel at a minimum dose of 1.0 x 106 anti-CD19 CAR T cells/kg (or a minimum dose of 
1.0  x 108 anti-CD19 CAR T cells for subjects who weigh more than 100 kg) prior to 
axicabtagene ciloleucel infusion. This analysis set will be used for all efficacy analyses. 
5.2. 
Safety Analysis Set 
The safety set is defined as all subjects treated with any dose of axicabtagene ciloleucel and/or 
any dose of lenzilumab. This analysis set will be used for all safety analyses except for the 
primary endpoint analysis. 


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6. 
STATISTICAL ANALYSIS 
6.1. 
General Methods 
The following methods will be applied to the data analysis when applicable. All p-values 
generated will be descriptive. 
1) Summary statistics 
Summary statistics will be generated in frequency (N, %) and quartile range (Minimum, 1st 
quartile (Q1), Median, 3rd quartile (Q3), Maximum) in overall and by cohort. 
2) Simple linear Regression 
Simple linear regression will be conducted to explore relationships between biomarkers with 
continuous numbers {Gelman 2006}. The estimated slope and its 95% confidence interval with 
the unadjusted p-value will be reported. 
3) Non-parametric Wilcoxon rank sum tests 
Non-parametric Wilcoxon rank sum tests {Siegel 1956, Wilcoxon 1945} will be utilized to 
explore the associations between pharmacokinetics/pharmacodynamics profiles, product 
characteristics by clinical outcomes subgroups. Unadjusted p-values will be reported. The 
multiplicity adjustment (Holm-Bonferroni step-down method, {Holm 1979, Hommel 1988} may 
be implemented when further characterization of potential association are identified and adjusted 
p-values will be reported. Median fold change will be utilized to describe the differences in the 
outcome. 
4) Non-parametric Kruskal-Wallis test 
Non-parametric Kruskal-Wallis test {Kruskal 1952} will be conducted for three or more-group 
comparison followed by pairwise comparisons using Dunn’s test with Holm’s adjustment 
method {Dunn 1964}. 
5) Clopper Pearson Method 
Will be used to calculate exact 95% confidence intervals for ORR and complete response rate 
{Brown 2002}. 
6.2. 
Analysis 
6.2.1. 
Characterize the anti-CD19 CAR T cell expansion (pharmacokinetics) and 
serum analyte (pharmacodynamics) profiles 
• mITT and safety analysis sets will be used 


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• Individual line plot or median line plot over time with interquartile range will be produced by 
target doses within each study cohort and overall. 
• Anti-CD19 CAR T cell profile (pharmacokinetics) overtime will be summarized using 
summary statistics described in Section 6.1 by cohort and overall. 
• Similarly, pharmacodynamics profile as measured by serum analyte levels overtime will be 
summarized using summary statistics described in Section 6.1 by cohort and overall. 
 Pre-selected key analytes as listed in Table 3-1 will be presented in the Clinical 
Pharmacology report. 
6.2.2. 
Characterize the product attributes 
• Safety analysis sets will be used to summarize the product attributes 
• Summary statistics for product characteristics will be generated by cohort and overall. 
• Additional summaries may be generated by baseline characteristics subgroups, if applicable. 
6.2.3. 
Characterize lenzilumab pharmacokinetics and soluble GM-CSF levels 
• Safety analysis set will be used for lenzilumab pharmacokinetics and GM-CSF analysis with 
summary statistics (Section 6.1) in by cohort and overall 
• Over time individual line plot or median profile plots will be provided by cohort for serum 
lenzilumab concentration (µg/mL) both in linear scale 
6.2.4. 
Characterize analytes, CAR-T cells and other cell subsets in CSF 
• Safety analysis sets will be used to summarize the analytes in CSF 
• Summary statistics for CSF biomarkers will be generated for pre- and post-infusion 


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7. 
REFERENCES 
Brown LD, Cai TT, DasGupta A. Confidence Intervals for a Binomial Proportion and 
Asymptotic Expansions. The Annals of Statistics 2002;30 (1):160-201. 
Dunn OJ. Multiple Comparisons Using Rank Sums. Technometrics 1964;6 (3):241-52. 
Gelman A, Hill J. Linear regression. In: Gelman A, Hill J, eds.  Data Analysis Using Regression 
and Multilevel/Hierarchical Models. 5th ed. New York: Cambridge University 
Press; 2006: 31-77.  
Holm S. A Simple Sequentially Rejective Multiple Test Procedure. Scandinavian Journal of 
Statistics 1979;6 (2):65-70. 
Hommel G. A Stagewise Rejective Multiple Test Procedure Based on a Modified Bonferroni 
Test. Biometrika 1988;75 (2):383-6. 
Kruskal WH, Wallis WA. Use of Ranks in One-Criterion Variance Analysis. Journal of the 
American Statistical Association 1952;47 (260):583-621. 
Siegel S. The One-Sample Runs Test. In: Morgan CT, ed.  Nonparametric Statistics: For the 
Behavioral Sciences. New York: McGraw-Hill Book Company, Inc.; 1956: 75-
83.  
Wilcoxon F. Individual Comparisons by Ranking Methods. Biometrics Bulletin 1945;1 (6):80-3. 
 


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8. 
APPENDIX 
8.1. 
Analytic Visit Windows for CAR T Cells in Blood 
Table 8-1. 
Visit window for blood draw for PBMC 
 
8.2. 
Analytic Visit Windows for Lenzilumab Pharmacokinetics 
Table 8-2. 
Visit window for blood draw for Lenzilumab (Phase 1) 
 
 
*Blood draw twice daily on Day 1 to Day 5 
8.3. 
Analytic Visit Windows for Pharmacodynamics Key Measurements (serum 
analytes) 
Table 8-3. 
Visit window for blood draw for serum analytes 
 
 
Analytic Visit 
Baseline 
Day 0 
Day 1 
Day 3 
Day 5 
Day 7 
Week 2 
Week 4 
Month 3 
Target Day 
Baseline 
0 
1 
3 
5 
7 
14 
28 
90 
Lab Window 
≤ 0 
 [0, 0] 
[1, 1] 
[2, 4] 
[5, 6] 
[7, 10] 
[11, 21] 
[22, 59] 
[60, 97] 
Analytic 
Visit 
Day 0 
Baseline 
Day 0 
0.5 h 
Day 0 
1 h 
Day 0 
3 h 
Day 0 
6 h 
Day 0 
9 h 
Day 0 
12 h 
Target time 
0 
30 min 
1 h 
3 h 
6 h 
9 h 
12 h 
Lab Window 
 < 0 min 
[0, 45] min 
(45, 120] min (120, 270] min (270, 450] min (450, 630] min (630, 1080] min 
Analytic Visit 
*Day 1 
*Day 2 
*Day 3 
*Day 4 
*Day 5 
Target Day 
AM 
PM 
AM 
PM 
AM 
PM 
AM 
PM 
AM 
PM 
Lab Window 
[0, 12] h  (12, 24] h [0, 12] h  (12, 24] h [0, 12] h  (12, 24] h [0, 12] h  (12, 24] h [0, 12] h  (12, 24] h 
Analytic Visit 
Day 6 
Day 7 
Week 2 
Week 4 
Target Day 
6 
7 
14 
28 
Lab Window 
[6, 6] day 
[7, 10] day 
[11, 21] day 
[22, 59] day 
Analytic 
Visit 
Baseline Day 0 
*Day 1 
*Day 2 
*Day 3 
*Day 4 
*Day 5 
Target Day 
Baseline 
0 
AM 
PM 
AM 
PM 
AM 
PM 
AM 
PM 
AM 
PM 
Lab Window 
≤ -5 
[0, 0] [0, 12] h (12, 24] 
h 
[0, 12] h (12, 24] 
h 
[0, 12] h (12, 24] 
h 
[0, 12] h (12, 24] h [0, 12] h (12, 24] h 
Analytic Visit 
Day 6 
Day 7 
Week 2 
Week 4 
Target Day 
6 
7 
14 
28 
Lab Window 
[6, 6] day 
[7, 10] day 
[11, 21] day 
[22, 59] day 
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8.4. 
Immune cell subsets in CSF (FLOW) 
Table 8-4. 
Visit window for CSF samples 
 
Table 8-5. 
CSF T-cell analytes 
Number 
Name of the analyte (cells/Volume unit) 
1 
CD14 (#, gated on CD45+) 
2 
CD19 (#, gated on CD45+/66b/14-) 
3 
CD3 (#, gated on CD45+/66b/14-) 
4 
CD3 CAR+ (#, gated on CD 45+/66b/14-/3+) 
5 
CD4 (#, gated of CD45+/66b/14-/3+) 
6 
CD4 CAR+ (#, gated on CD45+/66b/14-/3+/4+) 
7 
CD45 (#, gated on viable singlets cells) 
8 
CD56+CD3- (#, gated on CD45+/66b/14-) 
9 
CD56+CD3+(#, gated onCD45+/66b/14-) 
10 
CD66b (#, gated on CD45+) 
11 
CD8 (#, gated on CD45+/66b/14-/3+) 
12 
CD8 CAR+ (#, gated on CD45+/66b/14-/3+/8+) 
13 
CSF Volume 
14 
Viability (# Total Cells, Gated on Singlets) 
15 
Viability (# Viable Cells, Gated on Singlets) 
 
8.5. 
Using Trapezoidal Rule to Approximate the AUC 
 
AUC ≈1
2 (𝑦𝑦0 + 𝑦𝑦1) ∙Δ𝑥𝑥+ 1
2 (𝑦𝑦1 + 𝑦𝑦2) ∙Δ𝑥𝑥+ 1
2 (𝑦𝑦2 + 𝑦𝑦3) ∙Δ𝑥𝑥+ ⋯ 
 
Analytic Visit 
Screening/baseline  
Day 5 
Week 4 
Target Day 
Screening/baseline 
5 
28 
Lab Window 
≤ -5 
[0, 14] day 
[15, 45] day 
Yo 
Y1 Y2 Y3 Y4 Ys 

Prot_000.pdf: 
Protocol Title: 
Protocol Number: 
IND Number: 
EudraCT Number: 
Clinical Study Sponsor: 
Key Sponsor Contacts: 
Version: 
Original Protocol Date: 
Kite 
A GILEAD Corrpa·,y 
CLINICAL STUDY PROTOCOL 
A Phase 1/2 Open-label, Multi.center Study ofLen.zilumab 
and Axicabtagene Ciloleucel in Subjects with Relapsed or 
Refractory Large B-cell Lymphoma (ZUMA-19) 
KT-US-471-0119 (ZUMA-19) 
016278 - Axicabtagene Ciloleucel 
122950- Lenzilumab 
2015-005007-86 
Kite Phanna, Inc. 
2400 Broadway 
Santa Monica, CA 90404 
United States of America 
Meru.cal Director, Clinical Development 
Kite Phanna, Inc. 
2400 Broadway 
Santa Monica, CA 90404 
Phone: IPPD 
Email:PPD 
PPD 
Clinical Program Manager, Clinical Operations 
Kite Phanna, Inc. 
199 E Blaine St 
Seattle, WA 98102 
Phone: IPPD 
Email: PPD 
----------
Amendment 2 03 August 2021 
Amendment 116 September 2019 
05 August 2019 
CONFIDENTIALITY NOTICE 
This document contains confidential information of Kite Phanna, Inc., a wholly owned 
subsidiary of Gilead Sciences, Inc. This document must not be disclosed to anyone other than the 
site research staff, collaborators, and members of the Institutional Review Board/Independent 
Ethics Committee, a scientific review board, or an equivalent. The information in this document 
cannot be used for any purpose other than the conduct of the clinical investigation without the 
prior written consent of Kite Pharma, Inc. Questions regarding how this document should be 
used or the conduct of the clinical trial should be directed to the key sponsor contacts. 


Axicabtagene ciloleucel 
Kite Pharma, Inc. 
Clinical Protocol: KT-US-471-0119 
Amendment 2 
CONFIDENTIAL 
Page 2 
 
03 August 2021 
Sponsor and Investigator Signature Page 
KITE PHARMA, INC. 
2400 BROADWAY 
SANTA MONICA, CA 90404 
 
STUDY ACKNOWLEDGMENT 
 
A Phase 1/2 Open-label, Multicenter Study of Lenzilumab and Axicabtagene Ciloleucel in 
Subjects with Relapsed or Refractory Large B-cell Lymphoma (ZUMA-19) 
Amendment 2.0, 03 August 2021 
This protocol has been approved by Kite Pharma, Inc  The following signature documents this 
approval: 
 
Kite Medical Monitor Name (Printed)  
 
 
 
 
Date 
 
 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I agree to comply with the International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use (ICH) Harmonised Tripartite Guideline on Good Clinical 
Practice and applicable national or regional regulations and guidelines. I will provide all study 
personnel under my supervision copies of the protocol and access to all information provided by 
Kite Pharma, Inc. I will discuss this material with them to ensure that they are fully informed 
about the investigational product and the study. 
I agree and will ensure that financial disclosure statements will be completed by: 
x Me (including, if applicable, my spouse, legal partner and dependent children) 
x Subinvestigators (including, if applicable, their spouse, legal partner, and dependent 
children) at the start of the study and for up to one year after the study is completed. 
 
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the conduct of the clinical investigation without prior written consent 
from Kite Pharma, Inc. 
 
 
 
Principal Investigator Name (Printed) 
 
Signature 
 
 
 
Date 
 
Site Number 
    		 
 
PPD
PPD


Axicabtagene ciloleucel
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Clinical Protocol: KT-US-471-0119
Amendment 2
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PROTOCOL SYNOPSIS
Title
A Phase 1/2 Open-label, Multicenter Study of Lenzilumab and 
Axicabtagene Ciloleucel in Subjects with Relapsed or Refractory 
Large B-cell Lymphoma (ZUMA-19)
Indication
Relapsed or refractory large B-cell lymphoma after 2 or more lines of 
systemic therapy, including diffuse large B-cell lymphoma (DLBCL) 
not otherwise specified, primary mediastinal large B-cell lymphoma, 
high-grade B-cell lymphoma, and DLBCL arising from follicular 
lymphoma.
Study Design
This is a Phase 1/2, open-label, multicenter study evaluating 
lenzilumab use to prevent axicabtagene ciloleucel treatment-related 
toxicities in subjects with relapsed or refractory large B-cell 
lymphoma. The addition of lenzilumab to the approved axicabtagene 
ciloleucel treatment regimen will hereafter be referred to as sequenced 
therapy.
In Phase 1, a 3+3 design will be used to determine the recommended 
Phase 2 dose (RP2D) of lenzilumab within sequenced therapy for 
large B-cell lymphoma. The RP2D of lenzilumab will be determined 
primarily by clinical assessment of the incidence of dose-limiting 
toxicity (DLT) related to sequenced therapy. In addition to evaluation 
of DLT incidence, the extent of granulocyte macrophage-colony 
stimulating factor (GM-CSF) axis suppression as assessed by 
translational analysis may be assessed in defining the RP2D.
Once the RP2D is determined, the study will convert to Phase 2 and 
assume a Simon 2-stage design. After 14 subjects have been treated 
with sequenced therapy at the RP2D of lenzilumab and followed for 
28 days across Phase 1 and Phase 2, futility of sequenced therapy to 
demonstrate a significant decrease, compared to historical controls, in 
the incidence of Grade 2 or higher neurologic events will be assessed. 
If the futility threshold is not met, an additional 16 subjects will be 
treated with sequenced therapy at the RP2D of lenzilumab to complete 
accrual.
In total, approximately 36 subjects will be enrolled and treated during 
the study.
In Phase 1, a Safety Review Team (SRT) will pause enrollment to 
review safety data after 3 and 6 (as needed) subjects have been 
followed for 28 days after sequenced therapy in each dose escalation 
cohort. At the conclusion of dose escalation, the SRT will determine 
the RP2D of lenzilumab and conversion to Phase 2. The SRT can 
meet more often if needed.


Axicabtagene ciloleucel
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Once the study converts to Phase 2, the SRT will convene after a total 
of 14 subjects have been treated at the RP2D across Phase 1 and Phase 
2, and have been followed for at least 28 days after axicabtagene 
ciloleucel administration. At this time, enrollment will be paused for 
safety data review and interim/futility analysis. If the SRT determines 
that the study does not meet criteria for futility, an additional 16 
subjects will be enrolled to complete accrual.
Study Objectives
In Phase 1, the primary objective of the study is to evaluate the safety 
of sequenced therapy with lenzilumab and axicabtagene ciloleucel in 
subjects with refractory large B-cell lymphoma.
In Phase 2, the primary objective is to evaluate the incidence of 
Grade 2 or higher neurologic events with sequenced therapy given at 
the RP2D of lenzilumab in subjects with relapsed or refractory large 
B-cell lymphoma. The secondary objectives are to evaluate the safety 
and efficacy of sequenced therapy, the extent of GM-CSF axis 
suppression in the blood, and the levels of chimeric antigen receptor 
(CAR) T cells and cytokines in the blood
Study Hypothesis 
No formal hypothesis will be tested in Phase 1 of this study. In the 
Phase 2, this study is designed to differentiate between a treatment 
that has a Grade 2 or higher neurologic event rate of 45%, as seen in 
ZUMA-1 Cohorts 1 and 2, and a treatment with a Grade 2 or higher 
neurologic event rate of 20% or less. The hypothesis is that the 
Grade 2 or higher neurologic event rate for subjects treated with 
sequenced therapy at the RP2D of lenzilumab is significantly less than 
45%.
Primary Endpoints 

Phase 1: Incidence of DLTs related to sequenced therapy with 
lenzilumab and axicabtagene ciloleucel

Phase 2: Incidence of Grade 2 or higher neurologic events within 
28 days of axicabtagene ciloleucel administration
Secondary 
Endpoints

Safety of sequenced therapy, as measured by the incidence of 
adverse events (AE) and serious AEs, including cytokine release 
syndrome and neurologic events

Efficacy of sequenced therapy, as measured by analysis of 
objective response rate (complete response [CR] + partial 
response), CR rate, duration of response, overall survival, and 
progression-free survival

Levels of anti-CD19 CAR T cells in blood 

Levels of cytokines (including free GM-CSF) in blood


Axicabtagene ciloleucel 
Kite Pha1ma, Inc. 
Clinical Protocol: KT-US-471-0119 
Amendment2 
Sample Size 
Study Eligibility 
Treatment 
CONFIDENTIAL 
I 
I 
I 
I 
Approximately 36 subjects: 
• 
Phase 1: approximately 3 to 12 subjects 
• 
Phase 2: approximately 8 to 24 subjects 
Refer to Section 5 for a complete and detailed list of inclusion and 
exclusion criteria for both phases of the study. 
Lymphodepleting chemotherapy: 
• 
Lymphodepleting chemotherapy consisting of cyclophosphamide 
500 mg/tn2/ day and fludarabine 30 mg/m2/day will be 
administered for 3 days, prior to axicabtagene ciloleucel infusion. 
Investigational product ti·eatments: 
• 
Lenzilumab h'eatment consists of an inh'avenous (IV) infusion on 
Day 0, 6 hours prior to axicabtagene ciloleucel, in the following 
dose coho1is: 
Coho1i 1 : 600 mg IV administered on Day 0 
Coho1i 2: 1800 mg IV administered on Day 0 
• 
Axicabtagene ciloleucel ti·eatment consists of a single infusion of 
CAR ti·ansduced autologous T cells administered IV on Day 0 at a 
target dose of 2 x 106 anti-CD19 CART cells/kg. 
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Axicabtagene ciloleucel 
Kite Pha1ma, Inc. 
Clinical Protocol: KT-US-471-0119 
Amendment2 
Procedures 
At specific time points as outlined in the schedule of assessments 
(SOA), subjects will undergo the following assessments/procedures: 
collection of info1med consent, general medical histo1y including 
previous treatments for non-Hodgkin's lymphoma, physical 
examinations (including vital signs and perfonnance status), 
neurologic assessments, blood draws for complete blood count, 
chemistiy panels, cytokine levels, C-reactive protein, lymphocyte 
subsets, anti-axicabtagene ciloleucel antibodies, replication-competent 
reti·ovims, and anti-CD19 CART-cell analysis. Women of 
childbearing potential will undergo a urine or semm pregnancy test. 
Subjects will also undergo a baseline electi·ocardiogram, 
echocardiogram, brain magnetic resonance image, a positi·on emission 
tomography-computed tomography, and possible bone maITow 
aspirate or biopsy prior to enrolhnent and associated leukapheresis. 
Subjects will have lumbar punctures perfonned for the collection of 
CSF (see Section 7.9 and SOA) before and after axicabtagene 
ciloleucel infusion. 
Routinely throughout the conduct of the study, subjects will be asked 
to repo1i concomitant medications and AEs and will have their disease 
assessed. 
Safety Review T earn 
The SR T will be specifically chaiiered to review safety data during the 
dose escalation portion of the study and make recommendations on 
further study conduct based on the incidence of DLTs, AEs, and 
ti·anslational assessment of GM-CSF axis suppression. In Phase 1, the 
SRT will meet after the first 3 and 6 subjects ai·e u-eated in each dose 
escalation coho1i with axicabtagene ciloleucel and lenzilumab and 
have had the opportunity to be followed for 28 days after the last 
axicabtagene ciloleucel dose. The SRT can meet more often if needed. 
In Phase 2, the SRT will meet to assess safety data and futility of 
sequenced therapy with lenzilumab and axicabtagene ciloleucel to 
significantly reduce the incidence of Grade 2 or higher neurologic 
events after axicabtagene ciloleucel ti·eatment once 14 subjects have 
been ti·eated at the RP2D and have been followed for 28 days after the 
last axicabtagene ciloleucel dose, through an interim analysis. 
Statistical 
The primaiy endpoint for Phase 1 is the incidence of DLTs related to 
Considerations 
sequenced therapy with lenzilumab and axicabtagene ciloleucel. 
CONFIDENTIAL 
The primaiy endpoint for Phase 2 is the incidence of Grade 2 or higher 
neurologic events 28 days after administi·ation of axicabtagene 
ciloleucel. This endpoint will be based on a primaiy objective analysis 
set consisting of all subjects enrolled in the RP2D coho1i and ti·eated 
with axicabtagene ciloleucel at a minimum dose of 
anti-
CD 19 CAR T cells/kg 
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03 August 2021 


Axicabtagene ciloleucel
Kite Pharma, Inc.
Clinical Protocol: KT-US-471-0119
Amendment 2
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 and any dose 
of lenzilumab prior to axicabtagene ciloleucel infusion.
In Phase 2, this study uses a Simon 2-stage design to evaluate the 
incidence of Grade 2 or higher neurologic events in this study 
compared with the incidence observed in the pivotal study of 
axicabtagene ciloleucel (ZUMA-1 Cohorts 1 and 2). This study has an 
80% power to distinguish a therapy with a ≤ 20% rate of Grade 2 or 
higher neurologic events from a therapy with a ≥45% rate of Grade 2 
or higher neurologic events (the rate seen in ZUMA-1 Cohorts 1 and 
2) with a 1-sided alpha level of 0.025. At primary analysis, the null 
hypothesis will be rejected if ≤ 8 subjects experience Grade 2 or 
higher neurologic events are observed in 30 subjects.
Prior to primary analysis, a futility analysis will be conducted at the 
conclusion of Stage 1 of Phase 2, when 14 subjects have been treated 
at the RP2D and followed for 28 days after axicabtagene ciloleucel 
treatment. If ≥ 5 of the initial 14 subjects had Grade 2 or higher 
neurologic events, the study may be stopped for futility at the 
discretion of the SRT. This assessment has an 83.28% chance of 
stopping when no treatment effect is likely to be seen.
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Amendment 2
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STUDY GLOSSARY
Abbreviation or Term
Definition/Explanation
AE
Adverse event
ALL
Acute lymphoblastic leukemia
ANC
Absolute neutrophil count
BBB
Blood brain barrier
CAR
Chimeric antigen receptor 
CBC
Complete blood count
CMML
Chronic myelomonocytic leukemia
CNS
Central nervous system
CPF
Cell processing facility
CR
Complete response
CRP
C-reactive protein
CRS
Cytokine release syndrome
CSF
Cerebrospinal fluid
CTCAE
Common Terminology Criteria for Adverse Events
DLBCL
Diffuse large B-cell lymphoma
DLT
Dose-limiting toxicity
DOR
Duration of response
eACT™
Engineered autologous cell therapy 
ECG
Electrocardiogram
ECHO
Echocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic case report form
FAS
Full analysis set
FL
Follicular lymphoma 
GCP
Good Clinical Practice
GM-CSF
Granulocyte macrophage-colony stimulating factor
HGBL
High-grade B-cell lymphoma 
HLH
Hemophagocytic lymphohistiocytosis
IB
Investigator’s Brochure
ICE
Immune effector cell-associated encephalopathy
ICF
Informed consent form
ICH
International Conference on Harmonisation 
ID
Identification
IFN-γ
Interferon-gamma
IP
Investigational product
IPM
Investigational Product Manual
IRB/IEC
Institutional Review Board/Independent Ethics Committee
IV
Intravenous(ly)


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IWG
International Working Group 
LDH
Lactate dehydrogenase
LTFU
Long-term follow-up
MCP-1
Monocyte chemoattractant protein-1
MIP-1α
Macrophage inflammatory protein-1α
MRI
Magnetic resonance imaging
NCI
National Cancer Institute
NHL
Non-Hodgkin lymphoma
ORR
Objective response rate
OS
Overall survival
PAP
pulmonary alveolar proteinosis
PET-CT
Positron emission tomography–computed tomography
PBMC
Peripheral blood mononuclear cell
PCR
polymerase chain reaction
PD
Progressive disease
PFS
Progression-free survival
PK
Pharmacokinetic(s)
PMBCL
Primary mediastinal large B-cell lymphoma 
PR
Partial response
R-CHOP
Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone
RCR 
Replication-competent retrovirus
RP2D
Recommended Phase 2 dose
r/r
relapsed/refractory 
SAE
Serious adverse event
SCT
Stem cell transplant
SD
Stable disease
SEER
Surveillance, Epidemiology, and End Results 
SOA
Schedule of assessments
SRT
Safety Review Team
TFL
Transformed follicular lymphoma
WBC
White blood cell


Axicabtagene ciloleucel
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Clinical Protocol: KT-US-471-0119
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Figure 1.
Study Schema (Phase 1 and Phase 2)

Collection of peripheral blood mononuclear cells from the subjects will occur through leukapheresis performed at study enrollment.

Lymphodepleting chemotherapy consists of administration of fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days (Day -5 through Day -3).

Investigational Products: Lenzilumab will be administered on Day 0 at a dose determined by dose cohort as above 6 hours prior to axicabtagene ciloleucel infusion. 
Axicabtagene ciloleucel consists of a single IV infusion of a target of 2  106 anti-CD19 transduced autologous CAR T cells/kg 
 administered on Day 0.
*After the end of KT-US-471-0119, subjects who received an infusion of axicabtagene ciloleucel will complete the remainder of the 15-year follow-up assessments in a 
separate Long-term Follow-up study, KT-US-982-5968. 
Abbreviations: CAR, chimeric antigen receptor; IP, Investigational Product; IV, intravenous.
Screening
Long-term Follow-up Period*
Lymphodepleting 
Chemotherapy
(Day -5 to Day -3)
Fludarabine 
30 mg/m2/day
Cyclophosphamide 
500 mg/m2/day
Administered daily x 3
Post-treatment Assessment Period
Enrollment
IP infusion: Axicabtagene Ciloleucel 
(Day 0)
Subject is hospitalized prior to treatment 
with axicabtagene ciloleucel
IP Infusion: Lenzilumab 
(Day 0)
Cohort 1: 
    600 mg IV infusion over 1 hour
Cohort 2: 
    1800 mg IV infusion over 2 hours
 
 
 
 
 
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TABLE OF CONTENTS
PROTOCOL SYNOPSIS................................................................................................................................................3
STUDY GLOSSARY .....................................................................................................................................................8
TABLE OF CONTENTS..............................................................................................................................................11
LIST OF IN-TEXT TABLES .......................................................................................................................................13
LIST OF IN-TEXT FIGURES......................................................................................................................................13
1.
OBJECTIVES.......................................................................................................................................................14
1.1.
Primary Objective....................................................................................................................................14
1.2.
Secondary Objectives ..............................................................................................................................14
2.
DISEASE BACKGROUND AND RATIONALE...............................................................................................15
2.1.
Disease Background ................................................................................................................................15
2.2.
Axicabtagene Ciloleucel..........................................................................................................................16
2.2.1.
Product Description...............................................................................................................16
2.2.2.
Axicabtagene Ciloleucel Approval........................................................................................16
2.2.3.
Strategies to Mitigate Risks Associated With Axicabtagene Ciloleucel...............................17
2.3.
Prior Anti-CD19 CAR T-cell Study Designs and Results.......................................................................18
2.4.
Rationale for GM-CSF Neutralization With CAR T-cell Therapy .........................................................18
2.4.1.
GM-CSF Level Correlation With CAR T-cell Therapy-related Toxicities...........................18
2.4.2.
GM-CSF Neutralization in Preclinical Models of CAR T-cell Toxicity ..............................19
2.5.
Lenzilumab..............................................................................................................................................20
2.5.1.
Product Description...............................................................................................................20
2.5.2.
Summary of Clinical Studies for Lenzilumab.......................................................................20
3.
STUDY DESIGN.................................................................................................................................................22
3.1.
General Study Design..............................................................................................................................22
3.2.
Participating Sites....................................................................................................................................25
3.3.
Number of Subjects .................................................................................................................................25
3.4.
Replacement of Subjects .........................................................................................................................25
3.5.
Study Duration.........................................................................................................................................25
3.5.1.
Study Duration for Individual Subjects.................................................................................25
3.5.2.
Completion of Study..............................................................................................................25
3.5.3.
Long-term Follow-up ............................................................................................................25
4.
SUBJECT IDENTIFICATION ASSIGNMENT .................................................................................................27
5.
SUBJECT ELIGIBILITY.....................................................................................................................................28
5.1.
Inclusion Criteria.....................................................................................................................................28
5.2.
Exclusion Criteria....................................................................................................................................30
6.
PROTOCOL TREATMENT................................................................................................................................32
6.1.
Study Treatment ......................................................................................................................................32
6.1.1.
Leukapheresis........................................................................................................................32
6.1.3.
Lymphodepleting Chemotherapy ..........................................................................................32
6.1.4.
Lenzilumab............................................................................................................................33
6.1.5.
Axicabtagene Ciloleucel........................................................................................................34
6.1.6.
Concomitant Therapy ............................................................................................................34
6.1.7.
Excluded Medications ...........................................................................................................35
6.1.8.
Subsequent Therapy ..............................................................................................................36
6.1.9.
Toxicity Management............................................................................................................36
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6.2.
Study Treatment Schedule.......................................................................................................................36
6.2.1.
Leukapheresis (Within Approximately 5 Days of Eligibility 
Confirmation)........................................................................................................................36
6.2.2.
Study Treatment ....................................................................................................................37
6.2.3.
Rationale for Study Treatment Dosing..................................................................................38
6.2.4.
Study Treatment by Agent and Phase ...................................................................................39
7.
STUDY PROCEDURES......................................................................................................................................41
7.1.
Informed Consent ....................................................................................................................................41
7.2.
Demographic Data...................................................................................................................................41
7.3.
Medical and Treatment History...............................................................................................................41
7.4.
Physical Examination, Vital Signs, Performance Status.........................................................................42
7.5.
Neurological Assessment ........................................................................................................................42
7.6.
Cardiac Function .....................................................................................................................................42
7.7.
Magnetic Resonance Imaging .................................................................................................................43
7.8.
Bone Marrow Aspirate and Biopsy .........................................................................................................43
7.9.
Lumbar Puncture .....................................................................................................................................43
7.10.
Disease Response Assessment ................................................................................................................43
7.11.
Laboratory ...............................................................................................................................................44
7.13.
Description of Study Periods...................................................................................................................47
7.13.1.
Screening ...............................................................................................................................47
7.13.2.
Rescreening ...........................................................................................................................48
7.13.3.
Enrollment/Leukapheresis.....................................................................................................49
7.13.5.
Lymphodepleting Chemotherapy Period...............................................................................50
7.13.6.
Investigational Products Treatment Period ...........................................................................52
7.13.7.
Post-treatment Assessment Period ........................................................................................55
7.13.8.
Long-term Follow-up Period.................................................................................................57
7.13.9.
Retreatment............................................................................................................................59
7.14.
Summary of Scheduled Assessments ......................................................................................................59
8.
SUBJECT WITHDRAWAL ................................................................................................................................65
8.1.
Reasons for Removal From Treatment....................................................................................................65
8.2.
Reasons for Removal From Study...........................................................................................................66
9.
SAFETY REPORTING........................................................................................................................................67
9.1.
Adverse Events........................................................................................................................................67
9.2.
Reporting of Adverse Events...................................................................................................................67
9.2.1.
Reporting Abnormal Laboratory Findings ............................................................................68
9.3.
Definition of Serious Adverse Events .....................................................................................................69
9.4.
Reporting of Serious Adverse Events and Nonserious CRS Events Grade ≥ 3 ......................................69
9.5.
Reporting Deaths.....................................................................................................................................70
9.6.
Diagnosis Versus Signs and Symptoms ..................................................................................................71
9.7.
Pregnancy and Lactation .........................................................................................................................71
9.8.
Hospitalization and Prolonged Hospitalization.......................................................................................72
9.9.
Abnormal Vital Sign Values ...................................................................................................................72
9.10.
Safety Review Team and Dose-limiting Toxicity...................................................................................73
10.
STATISTICAL CONSIDERATIONS.................................................................................................................75
10.1.
Hypothesis ...............................................................................................................................................75
10.2.
Study Endpoints.......................................................................................................................................75
10.2.1.
Primary ..................................................................................................................................75
10.2.2.
Secondary ..............................................................................................................................75
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10.3.
Sample Size Considerations ....................................................................................................................76
10.4.
Access to Individual Subject Treatment Assignments ............................................................................77
10.5.
Interim Analysis and Early Stopping Guidelines ....................................................................................77
10.6.
Analysis Subsets......................................................................................................................................78
10.7.
Planned Method of Analysis ...................................................................................................................79
10.7.1.
Grade 2 or Higher Neurologic Events Rate...........................................................................79
10.7.2.
Safety.....................................................................................................................................79
10.7.3.
Objective Response Rate.......................................................................................................79
10.7.4.
Complete Response Rate.......................................................................................................79
10.7.5.
Duration of Response ............................................................................................................79
10.7.6.
Progression-free Survival ......................................................................................................79
10.7.7.
Overall Survival.....................................................................................................................80
10.7.9.
Long-term Data Analysis ......................................................................................................80
11.
REGULATORY OBLIGATIONS.......................................................................................................................81
11.1.
Independent Review Board/Independent Ethics Committee...................................................................81
11.2.
Subject Confidentiality............................................................................................................................81
11.3.
Investigator Signatory Obligations..........................................................................................................81
12.
PROTOCOL AMENDMENTS AND TERMINATION .....................................................................................82
13.
STUDY DOCUMENTATION AND ARCHIVE ................................................................................................83
14.
STUDY MONITORING AND DATA COLLECTION......................................................................................84
15.
PUBLICATION ...................................................................................................................................................85
16.
COMPENSATION...............................................................................................................................................86
17.
REFERENCES.....................................................................................................................................................87
18.
APPENDICES......................................................................................................................................................92
LIST OF IN-TEXT TABLES
Table 1.
Clinical Experience With Lenzilumab.....................................................................................20
Table 3.
Schedule of Assessments.........................................................................................................60
Table 4.
Schedule of Assessments (Long-term Follow-up Period).......................................................64
Table 5.
Simon’s Two-stage Design for RP2D1 Cohort........................................................................77
LIST OF IN-TEXT FIGURES
Figure 1.
Study Schema (Phase 1 and Phase 2) ......................................................................................10
Figure 2.
Correlation Between CAR T-cell Expansion, Efficacy, and Safety........................................18
Figure 3.
Schematic of Study Design......................................................................................................23
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1.
OBJECTIVES
1.1.
Primary Objective

The primary objective of Phase 1 of the study is to evaluate the safety of sequenced therapy 
with lenzilumab and axicabtagene ciloleucel in subjects with relapsed or refractory large 
B-cell lymphoma.

In Phase 2, the primary objective is to evaluate the incidence of Grade 2 or higher neurologic 
events with sequenced therapy given at the recommended Phase 2 dose (RP2D) of 
lenzilumab in subjects with relapsed or refractory large B-cell lymphoma.
1.2.
Secondary Objectives

Secondary objectives will include evaluating the safety and efficacy of sequenced therapy, 
the extent of granulocyte macrophage-colony stimulating factor (GM-CSF) axis suppression 
in the blood, and the levels of chimeric antigen receptor (CAR) T cells and cytokines in the 
blood.


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2.
DISEASE BACKGROUND AND RATIONALE
2.1.
Disease Background
Non-Hodgkin lymphoma (NHL) is a heterogeneous group of cancers originating in 
B lymphocytes and, to a lesser extent, in T lymphocytes or natural killer cells. For 2019, the 
United States Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program 
estimated that there will be 74,200 new cases of NHL and over 19,970 deaths related to the 
disease. NHL is the most prevalent hematological malignancy and is the seventh leading site of 
new cancers among men and women, accounting for 4% of all new cancer cases and 
approximately 3% of deaths related to cancer {Howlader 2017}.
Diffuse large B-cell lymphoma (DLBCL) is an aggressive NHL subtype that accounts for 
approximately 30% of NHL cases worldwide {Al-Hamadani 2015, Perry 2016, Rodriguez-Abreu 
2007, Teras 2016}. Incidence varies by region, with age-adjusted incidence of 5.6 cases 
per 100,000 persons reported by the SEER program and 3.13 per 100,000 persons reported from 
cancer registries in the EU {National Cancer Institute (NIH) 2019, Sant 2010}. The addition of 
rituximab into combination therapies for DLBCL, such as R-CHOP (rituximab, 
cyclophosphamide, doxorubicin, vincristine, prednisone), has greatly improved patient 
outcomes. However, it is estimated that 30% to 40% of patients are refractory to R-CHOP, and 
these patients have a particularly dire prognosis {Coiffier 2016, Flowers 2010}.
Other aggressive NHL subtypes include primary mediastinal large B-cell lymphoma (PMBCL), 
transformed follicular lymphoma (TFL), and high-grade B-cell lymphoma (HGBL). PMBCL 
accounts for < 3% of all B-cell lymphomas and is thought to arise from thymic (medullary) 
B cells, with histology similar to DLBCL and a gene-expression pattern similar to classical 
Hodgkin lymphoma {National Comprehensive Cancer Network 2019, The Non-Hodgkin's 
Lymphoma Classification Project 1997}. TFL arises from follicular lymphoma (FL), the most 
common indolent form of NHL (approximately 20% to 30%), with histological transformation to 
DLBCL at an annual rate of approximately 3% for 15 years and decreasing in subsequent years. 
HGBL is a very aggressive lymphoma phenotypically intermediate between DLBCL and 
Burkitt’s lymphoma. HGBL includes lymphomas with MYC and BCL2 and/or BCL6 
rearrangements (previously termed double- or triple-hit lymphomas) that have poor outcome 
compared with DLBCL. While R-CHOP is a first-line therapy option for PMBCL and TFL, it is 
generally an ineffective therapy for HGBL. Patients with relapsed/refractory (r/r) HGBL, 
PMBCL, and TFL have a similar or worse prognosis relative to those with refractory DLBCL, 
although no large prospective studies have been conducted in r/r PMBCL or r/r TFL {Kuruvilla 
2008, National Comprehensive Cancer Network 2019}.
SCHOLAR-1, a large multicenter, patient-level retrospective study, examined outcomes of 
refractory DLBCL, PMBCL, and TFL using pooled data from 2 randomized Phase 3 clinical 
trials (Lymphoma Academic Research Organization-CORAL and Canadian Cancer Trials Group 
LY.12) and 2 observational cohorts (MD Anderson Cancer Center and University of Iowa/Mayo 
Clinic Lymphoma Specialized Program of Research Excellence). For the study, refractory 
DLBCL was defined as progressive disease (PD) or stable disease (SD) as the best response at 


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any point during chemotherapy (≥ 4 cycles of first-line or 2 cycles of later-line therapy) or 
relapsed ≤ 12 months of autologous stem cell transplantation. The study highlighted the poor 
prognosis of patients affected with refractory DLBCL, reporting that the pooled patient 
population with refractory disease (N = 636) had an objective response rate (ORR) to the next 
line of therapy of 26% (complete response [CR], 7%), and a median overall survival (OS) of 
only 6.3 months {Crump 2017}.
These discouraging results demonstrate that new treatment options are needed for patients whose 
tumors do not respond to chemotherapy. The recently approved anti-CD19 CAR T-cell products 
are a promising treatment option for patients with relapsed or refractory large B-cell lymphoma.
2.2.
Axicabtagene Ciloleucel
2.2.1.
Product Description
Axicabtagene ciloleucel is a CD19-directed, genetically modified, autologous T-cell 
immunotherapy. For this therapy, a patient’s T cells are genetically modified to produce a 
chimeric antigen receptor (CAR) protein, allowing the T cells to identify and eliminate 
CD19-expressing normal and malignant cells. CD19 is expressed by most B-cell malignancies 
{Leonard 2001, Olejniczak 2006, Rodriguez 1994, Uckun 1988}, as well as normal B 
lymphocytes in peripheral blood and the spleen, but not by granulocytes, monocytes, platelets, 
erythrocytes, and T lymphocytes {Uckun 1988}. Briefly, the anti-CD19 CAR transgene 
comprises the following key domains: 1) an extracellular antihuman CD19 single-chain variable 
region fragment derived from the monoclonal antibody FMC63; 2) the transmembrane 
costimulatory domain CD28; and 3) the cytoplasmic portion of human CD3ζ that includes the 
signaling domains {Nicholson 1997}. Following CAR engagement with CD19+ target cells, the 
costimulatory domains activate a downstream signaling cascade that leads to T-cell activation, 
proliferation, and acquisition of effector function.
2.2.2.
Axicabtagene Ciloleucel Approval
On 18 October 2017, the Food and Drug Administration (FDA) approved axicabtagene 
ciloleucel for the treatment of adult patients with relapsed or refractory large B-cell lymphoma 
after 2 or more lines of systemic therapy, including DLBCL not otherwise specified, PMBCL, 
HGBL, and TFL {YESCARTA 2019}.
FDA approval was based on ZUMA-1 (Cohorts 1 and 2), a single-arm, multicenter study of 
108 adult subjects with relapsed or refractory aggressive large B-cell NHL {Neelapu 2017}. In 
the 101 subjects treated in Phase 2, the ORR was 83%, and the CR rate was 58%. At a median 
follow-up of 27.1 months, 37% of subjects remained in remission, highlighting the durability of 
responses achieved with axicabtagene ciloleucel over time. Median OS was not reached and 
50.5% of subjects remained alive at 24 months {Locke 2019}. The most common Grade 3 or 
higher adverse events (AEs) in all 108 subjects (incidence of ≥ 10%) were febrile neutropenia, 
fever, cytokine release syndrome (CRS), encephalopathy, infections (pathogen unspecified), 
hypotension, hypoxia, and lung infections. Serious adverse reactions occurred in 52% of subjects 
and included, but were not limited to, encephalopathy, fever, febrile neutropenia, and serious 
infections. Grade 3 or higher CRS and neurologic events were reported for 13% and 31% of 


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subjects, respectively {YESCARTA 2019}, and 1 fatal case of CRS occurred {Locke 2019}. 
FDA approved axicabtagene ciloleucel with a Risk Evaluation and Mitigation Strategy to 
mitigate the risk of CRS and neurologic events {YESCARTA 2019}.
The dose of axicabtagene ciloleucel is a single intravenous (IV) infusion with a target of 2 x 106 
CAR -positive viable T cells per kg body weight (maximum 2 x 108), preceded by 
cyclophosphamide and fludarabine lymphodepleting chemotherapy {YESCARTA 2019}. 
Additional details regarding the mechanism of action and clinical results of axicabtagene 
ciloleucel can be found in the Investigator’s Brochure (IB).
2.2.3.
Strategies to Mitigate Risks Associated With Axicabtagene Ciloleucel
Despite the success of axicabtagene ciloleucel, patients may require intensive care to mitigate 
morbidity and mortality caused by CRS and neurologic events. In many cases, CRS can be 
ameliorated by administration of the interleukin-6 (IL-6) receptor antagonist antibody 
tocilizumab, but case studies and retrospective analysis suggest neurologic events may be 
unaffected by tocilizumab treatment {Gust 2017, Lee 2014, Santomasso 2018}. Furthermore, 
ZUMA-1 cohort 3 demonstrated that prophylactic tocilizumab alone possibly worsens the 
incidence of neurologic events {Locke 2017a}.
There are no approved therapies available for the prevention or the treatment of neurologic 
events associated with CAR T-cell therapy. Identification of mitigation strategies is complicated 
by a statistically significant association between CAR T-cell expansion and both the likelihood 
of objective response and with the likelihood of observing a Grade 3 or higher neurologic event 
in the ZUMA-1 study. This finding suggests a direct correlation between efficacy and toxicity 
with anti-CD19 CAR T-cell therapy (Figure 2) {Neelapu 2017}. Systemic corticosteroids are 
currently used to treat neurologic events through broad suppression of the immune system. 
Whether corticosteroid treatment therefore blunts the clinical activity of CAR T-cells is as yet 
unresolved; clinical trials assessing this important question are underway. However, alternative 
strategies to improve the safety profile of CAR T-cell therapy without negatively impacting 
efficacy should be investigated.


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Figure 2. 
Correlation Between CART-cell Expansion, Efficacy, and Safety 
104 
Objective Response Rate 
Peak factor, 4.0 
l0-1..,__P_=_0._00_2 ____ 
_ 
Objective 
No Objective 
Response 
Response 
Rate 
Rate 
(N-83) 
(N-18) 
}03 
Neurologic Events 
Peak factor, 2.1 
l 0-1..,__P_=_O._Ol _____ 
_ 
Grade ~3 
Grade 0-2 
(N-28) 
(N-73) 
104 
101 
Cytokine Release Syndrome 
Peak factor, l.l 
l O-l 
P=0.28 
Grade ~3 
Grade 0-2 
(N-13) 
(N-88) 
CAR, chimeric antigen receptor. 
2.3. 
Prior Anti-CD19 CART-cell Study Designs and Results 
The design and rationale of this study is in paii derived from prior experience with axicabtagene 
ciloleucel on other Kite Phaim a, Inc.-sponsored studies, including ZUMA-1. Refer to the cmTent 
axicabtagene ciloleucel IB for the most cmTent anti-CD19 CAR T-cell nonclinical and clinical 
info1mation. 
2.4. 
2.4.1. 
Rationale for GM-CSF Neutralization With CART-cell Therapy 
GM-CSF Level Correlation With CART-cell Therapy-related Toxicities 
Much has been learned regarding the possible mechanisms and pathophysiology of nemologic 
events related to CART-cell therapy, including the role of myeloid cells and proinflammato1y 
cytokines. In ZUMA-1, several cytokines were significantly associated with Grade 3 or higher 
nemologic events, including GM-CSF, a soluble immune-modulating cytokine {Locke 2017b, 
Neelapu 2017}. However, there was no direct association between GM-CSF levels and overall 
response {Rossi 2016}, suggesting that GM-CSF inhibition may have the potential to decouple 
toxicity from efficacy of anti-CD19 CART cells. Increased GM-CSF levels have also been 
associated with CRS. In a study of 51 subjects with r/r acute lymphoblastic leukeinia, Grade 4 or 
higher CRS was associated with increased levels of several cytokines and chemokines including 
interferon-gamma (IFN-y), IL-6, IL-8, CCL2 (monocyte chemoattractant protein 1 [MCP-1]), 
CCL3 (macrophage inflammato1y protein-la [MIP-la]), and GM-CSF {Teachey 2016}. 
Generally considered a myeloid inflammato1y factor, GM-CSF serves as a communication 
conduit between activated lymphocytes that express GM-CSF and nonspecific inflammato1y 
myeloid cells that express the GM-CSF receptor. Outside the context of inflammation, animals 
lacking either GM-CSF or its receptor display no severe pe1imbation in myelopoiesis or the 
myeloid system generally, with the exception of alveolar macrophage dysfunction {Becher 
2016}. Preclinical models demonstrate that GM-CSF signaling drives numerous functions of 
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mature tissue macrophages, such as cell adhesion, expression of pathogen recognition receptors, 
and proinflammatory cytokines (tumor necrosis factor-α, IL-12, IL-18, IL-6, MCP-1, and 
macrophage colony stimulating factor-1), phagocytosis, and microbial killing {Shibata 2001}. 
Recent preclinical models of CAR T-cell therapy-related CRS and neurologic events indicate 
that CAR T cells produce GM-CSF upon tumor challenge in vitro and in vivo, and monocytes 
are the primary source of toxicity-related proinflammatory cytokines, such as IL-1, IL-6, and 
IL-8 {Barrett 2016, Giavridis 2018, Norelli 2018, Sterner 2019}.
GM-CSF levels are elevated within 1 day after CAR T-cell infusion and peak in 2 to 3 days 
{Roberts 2018, Rossi 2016}, suggesting its role as an initiator of an inflammatory cascade. Other 
cytokines have been associated with Grade 3 or higher neurologic events, including IL-15, IL-6, 
IL-1Ra, IL-2α, IFN-γ, IL-10, IL-8, MCP-1 {Locke 2017b}; however, many of these cytokines 
peak later after CAR T-cell infusion or are directly related to T-cell expansion {Roberts 2018}. 
Once activated by T cell-derived GM-CSF, myeloid cells are capable of expansion, trafficking, 
and cytokine production that fosters further myeloid cell recruitment, which exacerbates the 
inflammatory cascade {Spath 2017}. It is possible that once initiated, this inflammatory cascade 
can become a self-perpetuating “storm,” resulting in further activation, expansion, and 
trafficking of myeloid cells, abnormally high levels of inflammatory cytokines, endothelial cell 
activation, vascular permeability, and ultimately neurologic events. As such, inhibition of a key 
early driver of the inflammatory cascade may be more effective in reducing both the frequency 
and severity of neurologic events.
2.4.2.
GM-CSF Neutralization in Preclinical Models of CAR T-cell Toxicity
Preclinically, GM-CSF neutralization with the anti-GM-CSF antibody lenzilumab, has 
demonstrated that toxicities related to anti-CD19 CAR T-cell therapy can be effectively 
prevented in vivo {Sterner 2019}. Blood-brain-barrier (BBB) disruption, allowing the infiltration 
of immune cells and proinflammatory cytokines into the central nervous system (CNS), has been 
shown to be an important factor in the pathogenesis of neurologic events related to CAR T-cell 
therapy. Both preclinical in vivo studies and clinical trials have demonstrated BBB impairment 
following CAR T-cell therapy, enabling both immune cell neuroinfiltration and marked elevation 
of inflammatory cytokines in the CNS {Santomasso 2018, Sterner 2019, Taraseviciute 2018}. In 
the preclinical model of sequenced lenzilumab and CAR T-cell therapy, quantification of 
magnetic resonance imaging (MRI) gadolinium-enhanced T1 hyperintensities showed a 75% 
decrease in neuroinflammation and BBB impairment when lenzilumab was added to anti-CD19 
CAR T-cell therapy versus anti-CD19 CAR T-cell therapy alone. When lenzilumab was added to 
anti-CD19 CAR T-cell therapy, body weight and cytokine levels were more similar to that seen 
in mice infused with untransduced T cells, suggesting CRS was prevented. Despite the 
improvement in toxicities related to anti-CD19 CAR T-cell therapy, disease control was not 
impaired by the addition of lenzilumab to anti-CD19 CAR T-cell therapy in vivo. Furthermore, 
GM-CSF neutralization with lenzilumab may even enhance efficacy of anti-CD19 CAR T 
therapy by reducing the rate of relapse and improving the durability of response, as demonstrated 
in this model {Sterner 2019}. Taken together, these preclinical findings suggest that the addition 
of lenzilumab to anti-CD19 CAR T-cell therapy has the potential to improve safety, without 
harming anti-CD19 CAR T-cell therapy efficacy, breaking the link between efficacy and toxicity 
observed with anti-CD19 CAR T-cell therapy.


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2.5.
Lenzilumab
2.5.1.
Product Description
Lenzilumab is a first-in-class Humaneered® recombinant monoclonal antibody targeting soluble 
human GM-CSF, with potential immunomodulating activity, high binding affinity in the pM 
range, and 94% specificity to the human germline, which reduces immunogenicity. Upon 
administration, lenzilumab binds to and neutralizes GM-CSF. This prevents GM-CSF binding to 
the GM-CSF receptor, which is a heterodimeric protein expressed on myeloid progenitor cells, 
and prevents GM-CSF-mediated signaling.
2.5.2.
Summary of Clinical Studies for Lenzilumab
Clinical experience to date with lenzilumab is summarized in Table 1. As of July 2019, 
lenzilumab has been administered to a total of 114 subjects at various dose levels in 4 studies.
Table 1.
Clinical Experience With Lenzilumab
Protocol
Title
Subjects
Status
HGEN003-01
Single-dose Lenzilumab in Healthy Adult Volunteers
12
Completed
HGEN003-02
Study of Lenzilumab in Biologics-Inadequate Rheumatoid 
Arthritis
9
Terminated
HGEN003-04
Effect of Lenzilumab in Subjects with Asthma Inadequately 
Controlled by Corticosteroids
160
Completed
HGEN003-05
Study of Lenzilumab in Subjects with Relapsed or 
Refractory Chronic Myelomonocytic Leukemia (CMML)
15
Ongoing
Study HGEN003-01 was a Phase 1 dose escalation study assessing 1, 3, or 10 mg/kg of 
lenzilumab in healthy subjects. Nine subjects received lenzilumab (3 subjects per dose), and 
3 subjects received placebo. The regimen was well tolerated with no observed dose-limiting 
toxicities (DLTs). All 7 observed treatment-emergent AEs (TEAEs) were Grade 1 in severity, 
with 1 TEAE considered possibly related to study treatment (hot flush that resolved within 
1 hour without treatment). Study HGEN003-02 assessed lenzilumab in subjects with rheumatoid 
arthritis and was terminated after the safety run-in was complete due to changes in corporate 
direction. The safety run-in included 7 subjects who received 600 mg lenzilumab IV and 
2 subjects who received placebo on Weeks 0, 2, 4, 8, and 12. All TEAEs observed were Grade 1 
or Grade 2 in severity and similar to those reported with placebo.
Study HGEN003-04 was a Phase 2 randomized, double-blind, placebo-controlled study of 
lenzilumab in subjects with asthma inadequately controlled with long-acting bronchodilators and 
inhaled/oral corticosteroids. Subjects received 400 mg lenzilumab IV (n = 78) or placebo 
(n = 82) at Weeks 0, 2, 4, 8, 12, 16, and 20. Forty-eight subjects (61.5%) who received 
lenzilumab and 41 subjects (50.0%) who received placebo had ≥ 1 TEAE. TEAEs reported to 
occur with an overall incidence rate > 5% were nasopharyngitis, upper respiratory tract infection, 
and headache; these events were all considered Grade 1 or Grade 2 in severity and occurred at a 
similar rate to the placebo group. Six serious AEs (SAEs) were reported for 5 of 78 subjects 


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(6.4%) who received lenzilumab and 4 SAEs were reported for 2 of 82 subjects (2.4%) who 
received placebo. For subjects who received lenzilumab, SAEs included 2 cases of pneumonia 
and 1 case each of acute myocardial infarction, appendicitis, suicide attempt, and hypoxia; for 
subjects who received placebo, SAEs included 1 case each of diarrhea, thrombosis in device, 
anaphylactic reaction, and bacterial arthritis. No SAEs were considered as possibly related to 
treatment. Sixteen Grade 1 and Grade 2 infusion-related reactions were reported (6 events in 
4 subjects who received lenzilumab and 10 events in 2 subjects in the placebo group), but all 
were either self-limiting or resolved upon treatment with no sequelae {Molfino 2016}.
HGEN003-05 is a multicenter Phase 1 study designed to evaluate the safety and determine the 
RP2D of lenzilumab in subjects with chronic myelomonocytic leukemia (CMML). Dose 
escalation proceeded using a standard 3+3 study design to determine the maximum tolerated 
dose. Three dose cohorts included 200, 400, and 600 mg, given IV on Day 1 and 15 of cycle 1 
and then only on Day 1 of subsequent 28-day cycles. Three subjects were enrolled at each dose 
level and an additional 6 subjects were enrolled at 600 mg as planned. No DLTs were identified, 
and no treatment-emergent Grade 3 or 4 toxicities were reported. Pharmacokinetic analysis and 
pharmacodynamics were also evaluated. The mean duration on therapy was 221.8 days 
(range: 14 to 787 days).  Durable clinical benefit was achieved in 33% of subjects and 1 subject 
was bridged to allogenic transplant, providing proof of concept that GM-CSF neutralization has 
activity in CMML. The median age at study entry was 74 years (range: 62 to 85 years), and 80% 
were male. Nine subjects were classified as CMML-0, 3 as CMML-1, and 3 as CMML-2. Nine 
subjects were previously treated with hypomethylating agents and/or experimental therapies, 
4 were treated with hydroxyurea, and 3 were untreated. The mean hemoglobin was 9.7g/dL 
(range: 7.6 to 14g/dL), the mean platelet count was 147 x 103 cells/dL (range: 16 to 
942 x103 cells/dL), and 66% of cases were myeloproliferative neoplasms-CMML by the 
French-American-British classification at study entry. The safety profile of lenzilumab was 
consistent with that reported in prior studies.
One theoretical concern regarding GM-CSF neutralization as a therapeutic strategy was the 
potential for pulmonary alveolar proteinosis (PAP) development. Autoimmune PAP can be 
caused by a disruption of GM-CSF signaling in alveolar macrophages, leading to surfactant 
accumulation in the bronchioles and gas exchange impairment {Trapnell 2019}. Patients with 
autoimmune PAP typically have high levels of polyclonal GM-CSF neutralizing auto-antibodies 
compared with healthy individuals {Inoue 2008, Kitamura 1999, Uchida 2009}. Across the 
3 studies of lenzilumab, no evidence of PAP was detected as assessed by surfactant protein D 
levels, lactate dehydrogenase levels, oxygen saturation, chest X-rays, and pulmonary function. 
The risk of PAP is theorized to be reduced for a monoclonal antibody versus polyclonal 
antibodies directed towards GM-CSF, since the monoclonal antibody off-rate could allow for a 
basal level of GM-CSF signaling by alveolar macrophages.
As a single agent, lenzilumab is well tolerated, with only mild to moderate AEs reported in 
114 subjects treated in Phase 1 and 2 clinical trials. No identified risks or important potential 
risks were associated with lenzilumab in clinical studies. Overall, the specificity of GM-CSF 
neutralization toward suppression of a myeloid-driven inflammatory cascade, combined with the 
favorable safety profile of lenzilumab provides a rationale for adding lenzilumab to the 
axicabtagene ciloleucel treatment regimen. Rationale specific to the dosing of lenzilumab is 
described in Section 6.2.3.


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3.
STUDY DESIGN
3.1.
General Study Design
ZUMA-19 is a Phase 1/2, open-label, multicenter study evaluating lenzilumab use to prevent 
axicabtagene ciloleucel treatment-related toxicity in subjects with relapsed or refractory large 
B-cell lymphoma. The addition of lenzilumab to the approved axicabtagene ciloleucel treatment 
regimen will hereafter be referred to as sequenced therapy.
ZUMA-19 will be separated into 2 distinct phases designated as the Phase 1 study and Phase 2 
study.
In Phase 1, a 3+3 design will be used to determine the RP2D of lenzilumab within sequenced 
therapy for large B-cell lymphoma. There will be 2 dose escalation cohorts. The RP2D of 
lenzilumab will be determined primarily by clinical assessment of the incidence of DLTs related 
to sequenced therapy. In addition to evaluation of DLT incidence, the extent of GM-CSF axis 
suppression as assessed by translational analysis may be assessed in defining the RP2D.
During Phase 1, a Safety Review Team (SRT) will pause enrollment to review safety data after 
3 and 6 (as needed) subjects have been followed for 28 days after axicabtagene ciloleucel 
administration in each dose escalation cohort. At the conclusion of dose escalation, the SRT will 
determine the RP2D and study conversion to Phase 2. The SRT can meet more often if needed.
In Phase 2, the study will assume a Simon 2-stage design. After 14 subjects have been treated 
with sequenced therapy at the RP2D of lenzilumab and followed for 28 days across Phase 1 and 
Phase 2, futility of sequenced therapy to demonstrate a significant decrease, compared to 
historical controls, in the incidence of Grade 2 or higher neurologic events will be assessed. If 
the futility threshold is not met, an additional 16 subjects will be treated with sequenced therapy 
at the RP2D of lenzilumab to complete accrual.
In total, this Phase 1/2 study will enroll approximately 36 subjects to evaluate the incidence of 
Grade 2 or higher neurologic events related to sequenced therapy.


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Figure 3.
Schematic of Study Design
A) Phase 1
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
  
 
 
 
 


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B) Phase 2
Abbreviations: CAR, chimeric antigen receptor; DLT, dose-limiting toxicity; RP2D, recommended Phase 2 dose.
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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3.2.
Participating Sites
Approximately 12 centers located in North America and Europe will participate in this study. 
During the conduct of the study, additional regions, countries, or sites may be added as 
necessary.
3.3.
Number of Subjects
Participants in this study will be referred to as “subjects.” The study intends to enroll 
approximately 36 evaluable subjects in total over Phase 1 and Phase 2.
It should be noted that Kite may choose to close enrollment at any time. Please refer to the 
statistical considerations section of the protocol for sample size estimations.
3.4.
Replacement of Subjects
Subjects will continue to be enrolled until the specified number of evaluable subjects are attained 
in Phase 1 and Phase 2. Subjects who have not received the target dose of lenzilumab and 
axicabtagene ciloleucel will be retained in the analyses of disposition and safety, where 
appropriate (Section 10.6).
3.5.
Study Duration
3.5.1.
Study Duration for Individual Subjects
The duration of the study for individual subjects will vary depending on a subject’s screening 
requirements, response to treatment, survival, and if applicable, timing of transitions to the 
separate Long-term Follow-up (LTFU) study, KT-US-982-5968 (discussed in section 3.5.3).
The need for prolonged follow-up is based on concerns about late safety events. Subjects will be 
followed for potential persistence of CAR T cells, secondary expansion events, and gene transfer 
vector elements in treated subjects manifesting as secondary malignancy and other clinically 
relevant outcomes.
3.5.2.
Completion of Study
Completion of the study is defined as the time at which the last subject completes 6 months of 
assessments. 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. The primary analyses will be 
conducted when 30 subjects in the primary objective analysis set have completed a 6-month 
disease-response assessment, are lost to follow-up, withdraw from the study, or die, whichever 
occurs first.
3.5.3.
Long-term Follow-up
All subjects who received an infusion of lenzilumab and axicabtagene ciloleucel will be provided 
the opportunity to transition to a separate LTFU study, KT-US-982-5968, where they will be 
monitored for occurrence of late-onset targeted AEs/SAEs suspected to be possibly related to 


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lenzilumab and axicabtagene ciloleucel as defined in KT-US-982-5968, presence of replication-
competent retrovirus (RCR), and/or insertional mutagenesis for up to 15 years from the time of 
lenzilumab and axicabtagene ciloleucel infusion (also refer to Section 7.13.8).
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/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 timepoints in this study.
In some circumstances, subjects may be eligible to receive a second course of treatment after 
enrolling in the LTFU rollover study. Retreatment eligibility criteria are described in the KT-US-
982-5968 protocol.


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4.
SUBJECT IDENTIFICATION ASSIGNMENT
Each subject who enters the screening period, which starts when the subject signs the informed 
consent form (ICF), will receive a unique subject identification (ID) number. This number will 
be used to identify the subject throughout the study and must be used on all study documentation 
related to the subject. The subject ID number will never be changed even if the subject is 
rescreened.


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5.
SUBJECT ELIGIBILITY
5.1.
Inclusion Criteria
1) Adult subjects with large B-cell lymphoma, including DLBCL not otherwise specified, 
PMBCL, HGBL, and DLBCL arising from FL
2) Subjects must have relapsed disease after 2 or more lines of systemic therapy, OR 
chemorefractory disease defined as the following:

No response to first-line therapy, including the following:
PD as best response to first therapy
SD as best response after ≥ 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP), 
with SD duration no longer than 6 months from the last dose of therapy
Note: Subjects who are intolerant to first-line chemotherapy are excluded
OR

No response to ≥ 2 lines of therapy, including the following:
PD as best response to most recent therapy
SD as best response after ≥ 2 cycles of last line of therapy
3) Subjects must have received adequate prior therapy including at a minimum:

Anti-CD20 monoclonal antibody unless investigator determines that tumor is 
CD20 negative, and

An anthracycline-containing chemotherapy regimen

Subjects with transformed FL must have chemorefractory disease after transformation to 
DLBCL
4) At least 1 measurable lesion according to the International Working Group (IWG) Lugano 
Classification {Cheson 2014}. Lesions that have been previously irradiated will be 
considered measurable only if progression has been documented following completion of 
radiation therapy.
5) Magnetic resonance imaging of the brain showing no evidence of CNS lymphoma


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6) At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior 
systemic therapy at the time the subject is planned for leukapheresis, except for systemic 
inhibitory/stimulatory immune checkpoint therapy. At least 3 half-lives must have elapsed 
from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the 
time the subject is planned for leukapheresis (eg, ipilimumab, nivolumab, pembrolizumab, 
atezolizumab, OX40 agonists, 4-1BB agonists).
7) Toxicities due to prior therapy must be stable and recovered to Grade ≤ 1 (except for 
clinically nonsignificant toxicities such as alopecia)
8) Age 18 or older
9) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
10) Subjects with a known medical history of tuberculosis or a risk for tuberculosis exposure 
require negative tuberculosis testing by either tuberculin skin test or interferon gamma 
release assay.
11) Adequate bone marrow function as evidenced by:

Absolute neutrophil count ≥ 1000/µL

Platelets ≥ 75,000/µL

Absolute lymphocyte count ≥ 100/µL
12) Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:

Creatinine clearance (Cockcroft-Gault) ≥ 60 mL/min

Serum alanine aminotransferase or aspartate aminotransferase ≤ 2.5 upper limit of normal

Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert’s Syndrome

Cardiac ejection fraction ≥ 50% with no evidence of clinically significant pericardial 
effusion as determined by echocardiogram (ECHO), and no clinically significant 
electrocardiogram (ECG) findings

No clinically significant pleural effusion

Baseline oxygen saturation > 92% on room air
13) Females of childbearing potential must have a negative serum or urine pregnancy test 
(females who have undergone surgical sterilization or who have been postmenopausal for at 
least 2 years are not considered to be of childbearing potential)


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5.2.
Exclusion Criteria
1) History of malignancy other than nonmelanoma skin cancer or carcinoma in situ 
(eg, cervix, bladder, breast) or FL unless disease free for at least 3 years
2) History of Richter’s transformation of chronic lymphocytic leukemia
3) Autologous stem cell transplant (SCT) within 6 weeks of planned axicabtagene ciloleucel 
infusion
4) History of allogeneic stem cell transplantation
5) Prior CD19 targeted therapy or prior CAR T cell therapy.
6) History of PAP
7) History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
8) Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring 
intravenous antimicrobials for management. Simple urinary tract infection and 
uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after 
consultation with the Kite medical monitor.
9) Known history of human immunodeficiency virus (HIV) infection, hepatitis B (HBsAg 
positive) or hepatitis C (anti-HCV positive) infection. A history of hepatitis B or hepatitis C 
infection is permitted if the viral load is undetectable per quantitative polymerase chain 
reaction (PCR) and/or nucleic acid testing.
10) Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling 
Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central 
venous access catheter such as a Port-A-Cath or Hickman catheter are permitted
11) Subjects with detectable CSF malignant cells, or brain metastases, or with a history of CNS 
lymphoma, CSF malignant cells or brain metastases
12) History or presence of CNS disorder such as seizure disorder, cerebrovascular 
ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS 
involvement
13) Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
14) History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other 
clinically significant cardiac disease within 12 months of enrollment
15) Requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic 
emergency (eg, tumor mass effect, tumor lysis syndrome)
16) Primary immunodeficiency


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17) History of deep vein thrombosis or pulmonary embolism within 6 months of enrollment
18) Any medical condition likely to interfere with assessment of safety or efficacy of study 
treatment
19) History of severe hypersensitivity reaction to any of the agents used in this study
20) Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen
21) Women of childbearing potential who are pregnant or breastfeeding because of the 
potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females 
who have undergone surgical sterilization or who have been postmenopausal for at least 
2 years are not considered to be of childbearing potential
22) Subjects of both genders who are not willing to practice birth control from the time of 
consent through 6 months after the completion of lenzilumab and axicabtagene ciloleucel
23) In the investigator’s judgment, the subject is unlikely to complete all protocol-required study 
visits or procedures, including follow-up visits, or comply with the study requirements for 
participation
24) History of autoimmune disease (eg, Crohn’s, rheumatoid arthritis, systemic lupus) resulting 
in end organ injury or requiring systemic immunosuppression/systemic disease modifying 
agents within the last 2 years


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6.
PROTOCOL TREATMENT
6.1.
Study Treatment

The investigational products for this study are named lenzilumab and axicabtagene 
ciloleucel,which will be administered as sequenced therapy.

The term study treatment refers to all protocol-required therapies.
6.1.1.
Leukapheresis
Leukapheresis refers to the procedure for collecting peripheral blood mononuclear cells 
(PBMCs) that are used to manufacture the subject-specific axicabtagene ciloleucel. Subjects will 
undergo leukapheresis to obtain T cells for the manufacturing of axicabtagene ciloleucel.  
Leukapheresed cells obtained at participating centers will be shipped to the sponsor’s 
manufacturing facility as described in the Investigational Product Manual (IPM).
6.1.3.
Lymphodepleting Chemotherapy
Lymphodepleting chemotherapy refers to fludarabine and cyclophosphamide used for 
lymphodepletion prior to administration of axicabtagene ciloleucel.
Lymphodepleting chemotherapy will be supplied by the investigative site unless otherwise noted.
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Refer to the current product label for guidance on packaging, storage, preparation, 
administration, and toxicity management associated with the administration of chemotherapy 
agents.
6.1.3.1.
Fludarabine
Fludarabine phosphate (hereafter, fludarabine) is a synthetic purine nucleoside that differs from 
physiologic nucleosides in that the sugar moiety is arabinose instead of ribose or deoxyribose.  
Fludarabine is a purine antagonist antimetabolite.
Refer to the most recent version of the package insert for specific details surrounding the 
administration of fludarabine.
6.1.3.2.
Cyclophosphamide
Cyclophosphamide is a nitrogen mustard-derivative alkylating agent following conversion to 
active metabolites in the liver and has potent immunosuppressive activity. The serum half-life 
after IV administration ranges from 3 to 12 hours; the drug and/or its metabolites can be detected 
in the serum for up to 72 hours after administration.
Refer to the most recent version of the package insert for specific details surrounding the 
administration of cyclophosphamide.
6.1.3.3.
Mesna
Mesna is a detoxifying agent used to inhibit the hemorrhagic cystitis induced by chemotherapy.  
The active ingredient in mesna is a synthetic sulfhydryl compound designated as 
sodium-2-mercaptoethane sulfonate with a molecular formula of C2H5NaO3S2.
Mesna should be administered per institutional guidelines. Refer to the most recent version of the 
package insert for specific details surrounding the administration of mesna.
6.1.4.
Lenzilumab
Lenzilumab is one of the investigational products for this study.
Lenzilumab is an anti-GM-CSF antibody with the ability to neutralize GM-CSF. It is formulated 
as a sterile, clear, colorless to slightly yellow liquid for IV administration and supplied in 
single-use, 10-mL vials.  Each vial contains 100 mg of lenzilumab at a concentration of 
10 mg/mL.  Lenzilumab is provided as open-label bulk supply cartons containing 6 vials per 
carton. Vials should not be removed from the carton prior to dose preparation and are to be 
stored in the refrigerator (2°C to 8°C).
Refer to the IPM protocol supplement for details and instruction on storage and administration of 
lenzilumab.
To date, 114 subjects have received doses of lenzilumab IV ranging from 200 mg to 600 mg. 
There have been no instances of accidental overdose of subjects.


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If any problems related to the use of lenzilumab or any products that support the administration 
of lenzilumab are identified, research staff should report the problem per the instructions in the 
IPM protocol supplement.
6.1.5.
Axicabtagene Ciloleucel
Axicabtagene ciloleucel is one of the investigational products for this study.
Axicabtagene ciloleucel is supplied cryopreserved in cryostorage bags. The product in the bag is 
slightly cloudy and cream to yellow. The cryostorage bag containing axicabtagene ciloleucel 
arrives frozen in a liquid nitrogen dry shipper. The bag must be stored in vapor phase of liquid 
nitrogen and remain frozen until the subject is ready for treatment to assure that viable live 
autologous cells are administered to the subject. Several inactive ingredients are added to the 
product to assure viability and stability of the live cells through the freezing, thawing, and 
infusion process.
Axicabtagene ciloleucel is a subject-specific product. The product is labelled per local 
regulations with the subject’s unique subject ID number assigned at the time of screening. Upon 
receipt, verification that the product and subject-specific labels match the subject’s information 
(eg, subject ID number) is essential. Do not infuse the product if the information on the 
subject-specific label does not match the intended subject. The volume of axicabtagene 
ciloleucel infused, the thaw start/stop time, and axicabtagene ciloleucel administration start/stop 
time will all be noted in the subject’s medical record. The product must not be thawed until the 
subject is ready for the infusion. Refer to the IPM for details and instruction on storage, thawing, 
and administration of axicabtagene ciloleucel.
There have been no instances of accidental overdose of subjects in this program to date. In case 
of accidental overdose, treatment should be supportive. Corticosteroid therapy may be 
considered if any dose is associated with severe toxicity.
If any problems related to the use of axicabtagene ciloleucel or any products that support the 
management of axicabtagene ciloleucel (eg, cryostorage bags, subject ID labels) are identified, 
research staff should report the problem per the instructions in the IPM.
6.1.6.
Concomitant Therapy
Concomitant therapy refers to treatment that subjects receive during the conduct of the study.
During the course of the study, investigators may prescribe any concomitant medications or 
treatment deemed necessary to provide adequate supportive care except those medications listed 
in Section 6.1.7.
All concurrent therapies, including medications, intubation, dialysis, oxygen, and blood products, 
will be recorded.
For subjects who go on to receive protocol-permitted consolidative therapy (eg, SCT), only 
concomitant medications related to a sequenced therapy-related SAE will be recorded.  


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Reporting of these concomitant medications will commence at the time the preparative regimen 
of the therapy commences.
For subjects who receive study drug:

Concomitant therapies will be recorded from the date of the informed consent through 
3 months after completing treatment with axicabtagene ciloleucel.

After this 3-month follow-up period, only targeted concomitant medication will be collected 
for 12 months after axicabtagene ciloleucel infusion or until disease progression, whichever 
occurs first. Targeted concomitant medications include gammaglobulin, immunosuppressive 
drugs, anti-infective drugs, and vaccinations.
For subjects who are enrolled but not dosed with axicabtagene ciloleucel, concomitant therapies 
will only be recorded from the date of the informed consent through 30 days after the last 
study- specific procedure (eg, leukapheresis, lymphodepleting chemotherapy, lenzilumab 
administration) or until the initiation of new anticancer therapy, whichever occurs first.
For subjects who are not enrolled (eg, screen failure or not leukapheresed), only concurrent 
therapies related to any SAE(s) will be recorded.
Specific concomitant medication collection requirements and instructions are included in the 
electronic case report form (eCRF) completion guidelines.
6.1.7.
Excluded Medications
Excluded medications refer to treatment that is not to be administered, unless otherwise 
specified, during the conduct of the study.
Corticosteroid therapy at a pharmacologic dose (≥ 5 mg/day of prednisone or equivalent doses of 
other corticosteroids) and other immunosuppressive drugs must be avoided for 7 days prior to 
leukapheresis, and 5 days prior to axicabtagene ciloleucel administration.
Systemic corticosteroids may not be administered as premedication to subjects for whom 
CT scans with contrast are contraindicated (ie, subjects with contrast allergy or impaired renal 
clearance).  Such subjects should undergo noncontrast CT scans instead.
Corticosteroids and other immunosuppressive drugs should also be avoided for 3 months after 
axicabtagene ciloleucel administration, unless used to manage axicabtagene ciloleucel-related 
toxicities.  Other medications that might interfere with the evaluation of axicabtagene ciloleucel, 
such as nonsteroidal anti-inflammatory agents, should also be avoided for the same period unless 
medically necessary.
GM-CSF stimulating agents (ie, sargramostim) should be avoided for 2 months after lenzilumab 
administration, unless used to manage PAP.


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Therapeutic doses of systemic anticoagulants, such as unfractionated heparin and low-molecular 
weight heparin, should be avoided anytime subjects are at risk of bleeding due to 
thrombocytopenia when possible.
Treatments for lymphoma such as chemotherapy, immunotherapy, targeted agents, radiation, and 
high-dose corticosteroids (other than defined/allowed in this protocol), and other investigational 
agents are prohibited, except as needed for treatment of disease progression after axicabtagene 
ciloleucel infusion.
If permissibility of a specific medication/treatment is in question, please contact the Kite medical 
monitor.
6.1.8.
Subsequent Therapy
Subsequent therapy refers to treatment administered after axicabtagene ciloleucel infusion or 
standard of care that is necessary to treat a subject’s disease.
Subsequent therapy administered after axicabtagene ciloleucel infusion that is necessary to treat 
a subject’s LBCL, such as non-study-specified chemotherapy, immunotherapy, targeted agents, 
SCT, 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 axicabtagene ciloleucel infusion, any additional 
anticancer 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, whichever occurs first.
6.1.9.
Toxicity Management
To date, the following risks have been identified with axicabtagene ciloleucel/KTE-C19:  CRS, 
neurologic events, infections, and cytopenias. Refer to Section 6 of the current IB for details 
regarding these events and management guidance
6.2.
Study Treatment Schedule
6.2.1.
Leukapheresis (Within Approximately 5 Days of Eligibility Confirmation)
Subjects will undergo leukapheresis to obtain leukocytes (white blood cells) for the 
manufacturing of axicabtagene ciloleucel. Leukapheresed cells obtained at participating centers 
will be shipped to the cell processing facility (CPF) overnight as described in the IPM. Once a 
subject commences leukapheresis, the subject is considered enrolled in the study.
Mononuclear cells will be obtained by leukapheresis (12-15 liters by apheresis with a goal to 
target approximately 5 to 10 x 109 mononuclear cells). The leukapheresed cells are then 
packaged for expedited shipment to the CPF as described in the IPM.


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Upon arrival at the CPF, each subject’s leukapheresed product will be processed to enrich for the 
T-cell-containing PBMC fraction. T cells are then stimulated to expand and transduced with a 
retroviral vector to introduce the CAR gene. The T cells are then expanded and cryopreserved to 
generate the investigational product per CPF standard operating procedures.  Once the product 
has passed certain release tests, it will be shipped back to the treating facility. Following 
completion of each subject’s lymphodepleting chemotherapy regimen, subjects will receive their 
respective axicabtagene ciloleucel infusion.
6.2.2.
Study Treatment
6.2.2.1.
Chemotherapy General Instructions
Subjects will receive a nonmyeloablative conditioning regimen consisting of cyclophosphamide 
and fludarabine in order to induce lymphocyte depletion and create an optimal environment for 
expansion of axicabtagene ciloleucel in vivo. Subjects will initiate lymphodepleting 
chemotherapy with cyclophosphamide and fludarabine beginning on Day -5 through Day -3. The 
3-day lymphodepleting chemotherapy regimen may be administered in an outpatient setting.
Subjects will be instructed to drink plenty of liquids during and for 24 hours following the 
chemotherapy.  In general, subjects should be kept well hydrated but closely monitored to 
prevent fluid overload.
6.2.2.2.
Lenzilumab General Instructions
Subjects will receive lenzilumab infusion at a healthcare facility on the day of axicabtagene 
ciloleucel infusion, Day 0. Infusion should be initiated at least 6 hours prior to axicabtagene 
ciloleucel administration. Lenzilumab will be infused over 1 hour at doses of 600 mg and over 
2 hours at doses of 1800 mg. Rate of infusion may be modified at the investigator’s discretion for 
subject safety.
The following medications should be administered approximately 1 hour prior to lenzilumab 
infusion to prevent infusion reactions. Alternatives to the recommendations below should be 
discussed with the medical monitor.

Acetaminophen 500 to 1000 mg PO or equivalent

Diphenhydramine 12.5 to 25 mg IV, or 25 mg PO or equivalent
6.2.2.3.
Axicabtagene Ciloleucel General Instructions
All subjects will receive axicabtagene ciloleucel infusion at a healthcare facility, followed by 
daily or more frequent monitoring at a healthcare facility for at least 7 days unless otherwise 
required by country regulatory agencies to monitor for signs and symptoms of CRS and 
neurologic toxicities. Subjects should be instructed to remain within proximity of the clinical 
study site for at least 4 weeks following axicabtagene ciloleucel 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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Alternatively, subjects may be hospitalized to receive their axicabtagene ciloleucel infusion and 
be observed for CRS and neurologic events in the hospital setting, if deemed appropriate by the 
investigator.
If subjects are hospitalized, subjects should not be discharged from the hospital until all 
sequenced therapy-related nonhematological toxicities resolve to ≤ Grade 1 or return to baseline. 
Subjects may be discharged with noncritical and clinically stable or improving toxicities 
(eg, renal insufficiency) even if > Grade 1, if deemed appropriate by the investigator. Subjects 
should remain in a hospital for ongoing sequenced therapy-related fever, hypotension, hypoxia, 
or neurologic toxicities > Grade 1, or if deemed necessary by the investigator.
The following medications should be administered approximately 1 hour prior to axicabtagene 
ciloleucel infusion and at least 6 hours after the last dose of each received. Alternatives to the 
recommendations below should be discussed with the medical monitor.

Acetaminophen 500 to 1000 mg PO or equivalent

Diphenhydramine 12.5 to 25 mg IV, or 25 mg PO or equivalent
Central venous access, such as a port or a peripherally inserted central catheter, is required for 
the administration of axicabtagene ciloleucel. Catheter care, per institutional guidelines, should 
be followed. Materials and instructions for the thawing, timing, and administering of 
axicabtagene ciloleucel are outlined in the IPM. The IPM must be reviewed prior to 
administration of axicabtagene ciloleucel.
Research sites should follow institutional guidelines for the infusion of cell products.
There is no requirement to initiate levetiracetam prophylaxis of seizures with administration of 
axicabtagene ciloleucel. Investigators may follow their own institutional standards in regard to 
levetiracetam use. Previous experience from Cohorts 1 and 2 of ZUMA-1 indicates that those 
patients who started levetiracetam seizure prophylaxis with axicabtagene ciloleucel 
administration and those who either never received levetiracetam or started only after the 
initiation of signs and symptoms of neurologic events had comparable rates of neurologic events 
and no improvement in incidence of seizures.
6.2.3.
Rationale for Study Treatment Dosing
6.2.3.1.
Rationale for Lenzilumab Dosing in Cohorts 1 and 2
Lenzilumab has been tested extensively in 114 human subjects from doses of 
, up 
to 600 mg in the setting of repeated dosing. Following single-dose administration at 600 mg, 
serum concentrations declined below the therapeutic threshold following 3 days of 
administration. Steady-state pharmacokinetic (PK) data revealed a terminal half-life of 28 days 
and as described in Section 2.5.2, no Grade 3 or Grade 4 treatment-emergent AEs have been 
reported (see the IB). There was no evidence of an increase in infections or the development of 
PAP at these doses.
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The goal of lenzilumab therapy is to neutralize the GM-CSF burst seen after infusion of 
anti-CD19 CAR T cells and prevent the recruitment of myeloid cells and the initiation of the 
inflammatory cascade that may lead to neurologic toxicities and CRS. This suggests that 
lenzilumab will be required to suppress GM-CSF signaling for at least 7 days after axicabtagene 
ciloleucel administration.
Though 600 mg is a dose known to be safe, it may not be sufficient to entirely abrogate the 
GM-CSF elaborated in the serum and tissues after the anti-CD19 CAR T-cell infusion. 
Additional unpublished analyses suggest that a higher serum concentration of lenzilumab may be 
required to fully neutralize GM-CSF in the tissues. Therefore, in Cohort 2 an 1800 mg dose will 
be utilized to fully neutralize GM-CSF in the tissues after anti-CD19 CAR T-cell infusion. 
Pharmacokinetic analysis performed in Phase 1 will provide first-in-human data related to 
lenzilumab PK at this previously untested dose. Translational assessment of GM-CSF 
neutralization and downstream mediators of inflammation will help determine the extent of 
GM-CSF axis suppression in the serum and tissues at the respective doses.
6.2.4.
Study Treatment by Agent and Phase
6.2.4.1.
Lymphodepleting Chemotherapy
Phase 1 and 2:
Provided the criteria for lymphodepleting chemotherapy are met, outlined in Section 7.13.5.1., 
the 3-day conditioning regimen of fludarabine and cyclophosphamide will be administered in 
accordance with the following daily dosing instructions:

IV hydration with a balanced crystalloid according to institutional guidelines prior to 
administration of cyclophosphamide on the day of infusion

Cyclophosphamide 500 mg/m2 /day IV over approximately 30-60 minutes

Fludarabine 30 mg/m2/day IV over approximately 30 minutes

Additional IV hydration with a balanced crystalloid according to institutional guidelines to be 
administered upon completion of the cyclophosphamide infusion

Mesna to be administered per institutional guidelines
6.2.4.2.
Lenzilumab
Phase 1:
Cohort 1: Subjects will receive a single IV dose:

Lenzilumab 600 mg IV over approximately 60 minutes on Day 0, initiated approximately 
6 hours prior to axicabtagene ciloleucel infusion


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Coho1i 2: Subjects will receive a single IV dose: 
• 
Lenzilumab 1800 mg IV over approximately 120 minutes on Day 0, initiated approximately 
6 hours prior to axicabtagene ciloleucel infusion. 
• 
The infusion rate of lenzilumab may be adjusted at the discretion of the investigator for 
subject safety. 
An additional dose coho1i may be added as required to enhance safety of sequenced therapy. 
This decision would be made by the SR T. 
Phase 2: 
Based on the DLT rate and if necessaiy the translational assessment of GM-CSF axis 
suppression seen in Phase 1, an RP2D oflenzilumab will be determined by the SRT to be used in 
Phase 2. 
6.2.4.3. 
Axicabtagene Ciloleucel 
Phases 1 and 2: 
Subjects will receive axicabtagene ciloleucel treatment consisting of a single infusion of 
CAR transduced autolo ous T cells administered IV at a tai· et dose of 2 x 106 anti-CD19 CAR 
T cells/k 
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7.
STUDY PROCEDURES
Research staff should refer to the schedule of assessments (SOA) for an outline of the procedures 
required.
The visit schedule is calculated from axicabtagene ciloleucel infusion on Day 0.
An overview of study assessments/procedures is outlined below. A description for each period of 
the study is provided in Section 7. Refer to the eCRF completion guidelines for data collection 
requirements and documentation of study procedures.
7.1.
Informed Consent
Before a subject’s participation in the clinical study, the investigator is responsible for obtaining 
written informed consent from the subject after adequate explanation of the study design, 
anticipated benefits, and the potential risks. Subjects must sign the most current Institutional 
Review Board/Independent Ethics Committee (IRB/IEC)-approved ICF prior to any 
study-specific activity or procedure is performed.
The consent process and the subject’s agreement or refusal to participate in the study is to be 
documented in the subject’s medical records. If the subject agrees to participate, the ICF is to be 
signed and personally dated by the subject and by the person who conducted the informed 
consent discussion. The original signed ICF will be retained in accordance with institution policy 
and IRB/IEC requirements with a copy of the ICF provided to the subject.
All subjects who are enrolled into the study should be reconsented with any updated version of 
the IRB/IEC-approved ICF if relevant to their participation in the study.
7.2.
Demographic Data
Demographic data will be collected as per country and local regulations and guidelines. Where 
applicable, demographic data will include sex, year of birth, race, ethnicity, and country of 
enrollment to study a possible association between these variables and subject safety and 
treatment effectiveness.
7.3.
Medical and Treatment History
Relevant medical history prior to the start of AE reporting will be collected.  Relevant medical 
history is defined as data on the subject’s concurrent medical condition that would be typically 
shared in a referral letter. All findings will be recorded in the eCRFs.
In addition to the medical history, all history related to the subject’s disease, treatment, and 
response to treatment will be collected and must date back to the original diagnosis.
For subjects who are being referred from another clinic or institution to the participating research 
center, copies from the subject’s chart should be obtained.


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GM-CSF suppression may increase the risk for tuberculosis re-activation. Subjects with a 
medical history of tuberculosis or with risk of tuberculosis exposure should be evaluated for 
tuberculosis by either tuberculin skin testing or interferon gamma release assay. Risk assessment 
and testing methodology to be determined at the investigator’s discretion or based on 
institutional standards of care. A negative test within 3 months of anticipated lenzilumab 
administration is acceptable.
7.4.
Physical Examination, Vital Signs, Performance Status
Physical examinations will be performed during screening and at times noted in the SOA.  
Changes noted in subsequent examinations when compared to the baseline examination will be 
reported as an AE.
During investigational product administration, vital signs including blood pressure, heart rate, 
oxygen saturation, and temperature will be monitored before and after the lenzilumab and 
axicabtagene ciloleucel infusion and then routinely per institutional guidelines. If the subject has 
a fever (temperature 38.3oC or greater), vital signs will be monitored more frequently as 
clinically indicated.
Performance status, as measured by the ECOG scale, will be performed to quantify the subject’s 
general well-being and ability to perform activities of daily life.
7.5.
Neurological Assessment
Neurological assessments will be standardized by using the Immune Effector Cell-Associated 
Encephalopathy (ICE) score {Lee 2019}. ICE is a 10-point, 5-question evaluation that covers 
orientation, naming, following commands, writing, and attention. Please refer to Appendix 3 for 
the exact scoring criteria.
A full neurological assessment will be completed during screening to establish a baseline.  
Subsequent assessments will be performed before administration of sequenced therapy on Day 0, 
and daily during the 7-day post-infusion period, and any period of ongoing Grade 2 or higher 
neurologic event, as well as the Week 2, Week 4, and Month 3 visits.
7.6.
Cardiac Function
Each subject’s cardiac function, as measured by an ECHO, will be assessed during the screening 
period to confirm study eligibility. Both left ventricular ejection fraction and pericardial effusion 
will be assessed prior to study entrance by an ECHO. An ECHO performed following the 
subjects last chemotherapy treatment and within 28 days prior to signing the consent may be 
used for confirmation of eligibility.
To establish a baseline, an ECG will also be performed during the screening period.


Axicabtagene ciloleucel 
Kite Pha1ma, Inc. 
Clinical Protocol: KTE-US-471-0119 
Amendment2 
7.7. 
Magnetic Resonance Imaging 
Each subject will undergo a screening brain MRI, with contrast whenever possible or without 
contrast in case of contraindication, to rnle out CNS metastasis during the screening period of the 
study. A brain MRI perfo1med 28 days before signing the consent may be used for 
confinnation of eligibility. 
Evaluation of any new onset of Grade 2 or higher neurologic events should include a brain MRI. 
7.8. 
Bone Marrow Aspirate and Biopsy 
Bone manow aspirate and biopsy may be perfonned at screening at the discretion of the 
investigator. For subjects with a potential CR to axicabtagene ciloleucel, a follow-up bone 
manow aspirate and biopsy may be perfo1med in subjects presenting with bone maITow 
involvement prior to therapy or if new abnonnalities in the peripheral blood counts or blood 
smear cause clinical suspicion of bone manow involvement with 1 
homa after treatment. A 
bone manow as irate and bio s is not re uired to confmn a CR. 
Appendix 1 for treatment response assessment requirements per the IWG Lugano Classification. 
Bone manow aspirate and biopsy should also be considered to evaluate hemophagocytic 
lymphohistiocytosis (HLH) as indicated in the IB. A po1iion of the bone manow sample 
collected to evaluate HLH or other toxicities should be submitted to the central laborato1y as 
outlined in the central laborato1y manual. 
7.9. 
Lumbar Puncture 
Subjects with symptoms of CNS malignancy such as new onset severe headaches, neck stiffness, 
or any focal neurologic findings on physical examination will have a lumbar puncture (LP) 
perfo1med at the screening visit for examination of CSF. In addition, the LP will be perfo1med at 
Day 5 after axicabtagene ciloleucel infusion as per the SOA or for subjects with new onset of 
Grade 2 or higher neurologic events after sequenced therapy. Opening pressures should be 
measured and recorded in the sub·ect's site chaii with each LP whenever ossible 
Adequate platelet suppo1i should be provided prior to perfonning an LP ( eg, platelet > 
50,000/mm3). The medical monitor should be contacted in the event a Day 5 LP is not attainable 
related to subject status. 
7.10. 
Disease Response Assessment 
Subjects will be evaluated for disease response by the site investigator at times indicated in the 
SOA. Disease assessments will be evaluated per the IWG Lugano Classification {Cheson 2014} 
(Appendix 1). Flow cytometric and moleculai· or cytogenetic studies will not be used to 
dete1mine response. 
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Baseline positron emission tomography – computed tomography (PET-CT) scans of the neck, 
chest, abdomen, and pelvis, along with the appropriate imaging of all other sites of disease are 
required. Subjects will undergo additional PET-CT tumor assessments after their axicabtagene 
ciloleucel infusion. The first of these post-treatment PET-CT tumor assessments will occur 
4 weeks after infusion; subsequent assessments will occur at regular intervals throughout the 
post-treatment and long-term follow-up portions of the study, as highlighted in the SOA.
After axicabtagene ciloleucel administration, disease assessments will be used to determine the 
time when PD occurs. Subjects with symptoms suggestive of disease progression should be 
evaluated for progression at the time symptoms occur even if it is off schedule as per the SOA.
7.11.
Laboratory
The following samples will be collected at the time points indicated in the SOA. Additional 
samples (eg, blood, urine, CSF, tissue) may be collected as needed for further safety testing.
Local laboratory analysis:

Sodium, potassium, chloride, total CO2 (bicarbonate), creatinine, glucose, blood urea 
nitrogen or urea (if blood urea nitrogen test cannot be analyzed by the local laboratory), 
albumin, calcium total, magnesium total, inorganic phosphorus, alkaline phosphatase, alanine 
aminotransferase/glutamic-pyruvic transaminase, aspartate 
aminotransferase/glutamic-oxaloacetic transaminase, total bilirubin, direct bilirubin, lactate 
dehydrogenase (LDH), uric acid

C-reactive protein (CRP), ferritin

Complete blood count (CBC) with differential

A urine or serum sample will be collected and assessed locally for females of childbearing 
potential. If the screening pregnancy test is positive, the subjects should not be enrolled. If a 
standard of care pregnancy test is collected during the course of the study, and the result is 
positive, the investigator should contact the Kite medical monitor for instructions. If a female 
partner of a male subject becomes pregnant during the conduct of the study, the pregnancy 
must be reported by contacting the Kite medical monitor for instructions. See Section 9.7 for 
pregnancy reporting.

For EU sites, a serology (eg, HIV, hepatitis B, hepatitis C, syphilis) test will be carried out 
per institutional guidelines and EU regulations. This may be administered within the 30 days 
prior to leukapheresis and/or on the day of leukapheresis.
Central laboratory analysis:

Blood draws for PBMC (lymphocyte subsets, replication-competent retrovirus [RCR], and 
anti-CD19 CAR T-cell levels) and cytokine analysis will be performed at intervals outlined 
in the SOA.  With each PBMC submission, also draw and include a CBC with differential to 
facilitate centrally the calculation of anti-CD19 CAR T-cell levels.


Axicabtagene ciloleucel 
Kite Pha1ma, Inc. 
Clinical Protocol: KTE-US-471-0119 
Amendment2 
• 
Blood draws for lenzilumab PK will be perfo1med at different intervals by study phase. 
I 
I 
Lenzilumab PK will be assessed with blood draws from a line not used for infusion of the 
related investigational product. In Phase 1, blood draws will occur at baseline prior to 
lenzilumab infusion and then after completion of lenzilumab infusion at 30 minutes and 
1, 3, 6, 9, 12, and 24 hours later. Thereafter, blood draws for PK will coincide with cytokine 
draws from Days 1 to 7, specifically eve1y 12 hours after infusion on Days 1 to 5, and then 
daily on Days 6 and 7. Fmther PK draws will occur at Weeks 2 and 4 in conjunction with 
other blood draws. In Phase 2, lenzilumab PK will be assessed at baseline prior to 
lenzilumab infusion and then after completion of lenzilumab infusion at 12 
hours; thereafter, PK samples will be drawn twice daily from Day 1 to Day 5 and daily on 
Days 6 and 7 to coincide with cytokine blood draws. Fmther PK draws will occur at Weeks 2 
and 4 in conjunction with other blood draws for these scheduled visits. 
sam les will also be collected and 
s outlined in the SOA. 
. -
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Axicabtagene ciloleucel 
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Clinical Protocol: KTE-US-471-0119 
Amendment2 
7.13. 
Description of Study Periods 
Investigative sites will maintain a log of all screened subjects who were reviewed and evaluated 
for study paiiicipation. Infonnation collected on the screening log should include limited 
infonnation, such as the date of screening, date the subject was enrolled, or the reason for why 
the subject failed screening. 
7.13.1. 
Screening 
The screening period begins on the date the subject signs the IRB/IEC-approved ICF and 
continues through confnmation of enrollment. Info1med consent must be obtained before 
completion of any nonstandai·d of care study-specific procedures. Procedures that ai·e pa1i of 
standard of care ai·e not considered study-specific procedures and may be perfonned prior to 
obtaining consent and used to confnm eligibility. Confinnation of these data must occur within 
the time allowance as outlined below and in the SOA. 
After written infonned consent has been obtained, subjects will be screened to confnm study 
eligibility and paii icipation. Only subjects who meet the eligibility criteria listed in Section 5 and 
who commence leukapheresis will be enrolled in the study. If at any time prior to enrollment the 
subject fails to meet the eligibility criteria, the subject should be designated as a screen failure on 
the subject screening log with the reasons for failing screening. 
The following assessments/procedures are to be completed during the screening period at the 
time points outlined in the SOA: 
• 
Medical histo1y and disease assessment 
• 
Physical examination including height and weight 
• 
Subjects with symptoms of CNS malignancy such as new onset severe headaches, neck 
stiffness, or any focal neurologic findings on physical examination will have an LP for 
examination of CSF and for assessment of opening pressure. 
• 
Vital signs, including blood pressure, heaii rate, oxygen saturation, and temperature 
• 
ECOG perfo1mance sta.tus 
• 
Neurological assessment including ICE 
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Clinical Protocol: KTE-US-471-0119 
Amendment2 
• 
ECG 
• 
ECHO for left ventricular ejection fraction and pericardial effusion assessment (an ECHO 
perfo1med following the subjects last chemotherapy treatment and within 28 days prior to 
signing the consent may be used for confinnation of eligibility) 
• 
Imaging studies 
I 
-
Brain MRI 
-
Baseline PET-CT of the neck, chest, abdomen, and pelvis 
PET-CT perfo1med following the subjects last line of therapy and prior to signing the 
consent may be used for confomation of eligibility. 
If PET-CT is perfo1med > 28 days prior to the initiation of lymphodepleting 
chemotherapy or if subject receives any anticancer therapy between screening and 
lymphodepleting chemotherapy, the scans must be repeated to establish a new 
baseline. PET-CT should be perfonned as close to enrollment as possible. 
• 
Tuberculosis screening in relevant subjects based on medical histo1y as per Section 7.3 
• 
Laborato1y tests 
-
Chemistry panel 
-
CBC with differential 
-
~-human chorionic gonadou-ophin pregnancy test (sennn or urine) for all women of 
childbearing potential 
-
Blood draw for RCR 
• 
AE/SAE repo1ting (refer to Section 9 for safety repo1ting guidelines) 
• 
Concomitant medications documentation and previous cancer ti·eatment histo1y 
I 
• 
Lumbar puncture for collection of CSF samples to be perfo1med after eligibility confmned 
and prior to stait of lymphodepleting chemotherapy 
7.13.2. 
Rescreening 
Subjects who ai·e unable to complete or meet the eligibility criteria during the 28-day screening 
period will be pe1mitted to rescreen 1 time. Subjects will retain the saine subject ID number 
assigned at the original screening. If rescreening occurs within 28 days of the signing of the 
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original informed consent, only the procedure(s)/assessment(s) that did not originally meet the 
eligibility criteria needs to be repeated; all other initial screening procedures/assessments do not 
need to be repeated. If rescreening occurs, or leukapheresis is delayed, more than 28 days from 
the signing of the original informed consent, subjects must be reconsented and repeat all 
screening procedures/assessments.
7.13.3.
Enrollment/Leukapheresis
If any screening assessments or procedures are repeated between confirmation of eligibility and 
the start of leukapheresis and results are outside the eligibility criteria listed in Section 5, contact 
the Kite medical monitor prior to proceeding with leukapheresis.
Before leukapheresis commences, the following criteria must be met. If criteria are not met, 
leukapheresis must be delayed until the event resolves. If leukapheresis is delayed beyond 
5 days, baseline CBC with differential and chemistry panel must be repeated. If results are 
outside eligibility criteria listed in Section 5, contact the Kite medical monitor prior to 
proceeding with leukapheresis.

No evidence or suspicion of an infection

Corticosteroid therapy at a pharmacologic dose (≥ 5 mg/day of prednisone or equivalent 
doses of other corticosteroids) and other immunosuppressive drugs must be avoided for 
7 days prior to leukapheresis.
Once a subject commences leukapheresis, the subject will be considered enrolled into the study.
The following procedures/requirements will occur on the leukapheresis collection day and as 
outlined in the SOA:

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature

Weight

Laboratory tests (to be drawn prior to leukapheresis, on the day of or day before 
leukapheresis)
Chemistry panel with LDH
CBC with differential
CRP and ferritin; if CRP is ≥ 100 mg/L, a call must be made to the Kite medical monitor 
before proceeding with lymphodepleting chemotherapy
Anti-CD19 CAR T cells
Lymphocyte subsets
Cytokine levels


Axicabtagene ciloleucel 
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Clinical Protocol: KTE-US-471-0119 
Amendment2 
• 
Leukapheresis 
• 
AE/SAE repo1iing 
• 
Concomitant medications documentation 
-
7.13.5. 
Lymphodepleting Chemotherapy Period 
If any screening assessments or procedures are repeated between screening and the staii of 
lymphodepleting chemotherapy and results ai·e outside the eligibility criteria (Section 5), contact 
the Kite medical monitor for approval prior to proceeding with lymphodepleting chemotherapy. 
The investigational product (axicabtagene ciloleucel) must be available before initiation of 
lymphodepleting chemotherapy. 
7.13.5.1. 
Requirements for Initiating Lymphodepleting Chemotherapy 
Administration of anti-CD19 CART cells to subjects with ongoing infection or inflammation, 
even if such processes ai·e asymptomatic, increases the risk of high-grade and fatal toxicity. All 
effo1is should be made to rnle out such conditions prior to cell infusion. Signs, symptoms, or 
abnonnal laborato1y results attributed to the malignancy ( eg "tumor fever," elevated CRP) are 
diagnoses of exclusion that require a documented workup to establish a malignancy. 
Lymphodepleting chemotherapy and axicabtagene ciloleucel infusion should only be initiated 
after it is reasonably assured that cell infusion can safely proceed. 
If any of the following criteria ai·e met prior to initiation of lymphodepleting chemotherapy, then 
the workup listed in Section 7.13.6.3 must be perfonned to detennine the potential cause ifthere 
is no identified source of infection. 
• 
Temperature > 38°C within 72 hours oflymphodepleting chemotherapy 
• 
CRP > 100 mg/L anytime between emollment to sta1i of lymphodepleting chemotherapy 
• 
White blood cell (WBC) count or WBC differential that is suggestive of infectious process 
and is observed between emollment and the initiation of lymphodepleting chemotherapy 
(eg WBC > 20,000/µL, rapidly increasing WBC, or differential with high percentage of 
segments/bands) 
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Additionally:

If any screening assessments or procedures are repeated between confirmation of eligibility 
and the start of lymphodepleting chemotherapy and the results are outside the eligibility 
criteria listed in Section 5, then the condition must resolve prior to proceeding with 
lymphodepleting chemotherapy.

Complete history and physical examination, including head, ears, eyes, nose, and throat 
examination, cardiac, vascular, respiratory, gastrointestinal, integumentary, and neurological 
systems, must not reveal evidence of infection/inflammation.

The subject must not have received systemic antimicrobials for the treatment of known or 
suspected infection within 48 hours before lymphodepleting chemotherapy (prophylactic use 
of antimicrobials 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 the subject is confirmed to have an infectious process for which antimicrobials are not 
available (eg, viral pneumonia), the infection must be clinically resolved as determined by 
the investigator and in consultation with infectious disease service (if applicable).

The most recently collected blood, urine, or other body fluid cultures must show no growth 
for at least 48 hours, and any other infectious workup performed (eg, bacterial, viral 
serologies, PCR, stood studies, imaging studies) must be negative. If clinical suspicion is for 
an infection for which cultures are unlikely to be positive within 48 hours (eg, fungal 
infection), adequate time must be allowed for cultures to become positive.
Once the above criteria are met, then the subject can proceed with lymphodepleting 
chemotherapy.
7.13.5.2.
Lymphodepleting Chemotherapy Administration
The following procedures will be completed during Day -5 to Day -3 at the time points outlined 
in the SOA:

Physical Examination

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature

Laboratory tests (to be drawn prior to chemotherapy)
Chemistry panel 
CBC with differential


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
Fludarabine and cyclophosphamide administration

AE/SAE reporting

Concomitant medications documentation
7.13.6.
Investigational Products Treatment Period
7.13.6.1.
Requirements for Initiating Lenzilumab and Axicabtagene Ciloleucel Infusion
If any of the following criteria are met prior to the initiation of lenzilumab or axicabtagene 
ciloleucel infusion on Day 0, then the workup listed in Section 7.13.6.3 must be performed to 
determine the potential cause if there is no identified source of infection.

Temperature > 38°C within 72 hours of axicabtagene ciloleucel infusion.

CRP > 100 mg/L anytime between enrollment to start of lymphodepleting chemotherapy

WBC count or WBC differential, that is suggestive of infectious process, and is observed 
between enrollment and the initiation of axicabtagene ciloleucel infusion 
(eg, WBC > 20,000/µL, rapidly increasing WBC, or differential with high percentage or 
segments/bands)
Additionally: If any screening assessments or procedures are repeated between confirmation 
of eligibility and the start of axicabtagene ciloleucel infusion and the results are outside the 
eligibility criteria listed in Section 5, then the condition must resolve prior to proceeding with 
axicabtagene ciloleucel infusion (except for peripheral blood cell counts that have been 
impacted by lymphodepleting chemotherapy)

Complete history and physical examination including head, ears, eyes, nose, and throat 
examination, cardiac, vascular, respiratory, gastrointestinal, integumentary, and neurological 
systems must not reveal evidence of infection/inflammation

The subject must not have received systemic antimicrobials for the treatment of a known or 
suspected infection within 48 hours before axicabtagene ciloleucel infusion (prophylactic use 
of antimicrobials 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 (eg, 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 (eg, bacterial, viral serologies, 


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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 (eg, fungal infection), adequate 
time must be allowed for cultures to become positive.
After the above criteria are met, then the subject can proceed with administration of sequenced 
therapy.
If the axicabtagene ciloleucel infusion is delayed > 2 weeks, protocol guidelines should be 
followed regarding the need for repeat lymphodepleting chemotherapy.
7.13.6.2.
Monitoring After Axicabtagene Ciloleucel Infusion
All subjects will receive axicabtagene ciloleucel infusion at a healthcare facility followed by 
daily monitoring at a healthcare facility for at least 7 days unless otherwise required by country 
regulatory agencies to monitor for signs and symptoms of CRS and neurologic toxicities.  
Alternatively, subjects may be hospitalized to receive their axicabtagene ciloleucel infusion and 
be observed for CRS and neurologic toxicities in the hospital setting, if deemed appropriate by 
the investigator.
If subjects are hospitalized, subjects should not be discharged from the hospital until all 
axicabtagene ciloleucel-related nonhematological toxicities return to ≤ Grade 1 or return to 
baseline. Subjects may be discharged with noncritical and clinically stable or improving 
toxicities (eg, renal insufficiency) even if > Grade 1, if deemed appropriate by the investigator.  
Subjects should remain in the hospital for ongoing axicabtagene ciloleucel-related fever, 
hypotension, hypoxia, or ongoing central neurologic toxicities > 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 axicabtagene ciloleucel infusion. Subjects and their family 
members/caregivers should be educated on potential CRS and neurologic symptoms, such as 
fever, dyspnea, confusion, aphasia, dysphagia, somnolence, encephalopathy, ataxia, or tremor.  
Subjects or their family members/caregivers should be instructed to immediately contact the 
treating investigator or seek immediate medical attention if any of these symptoms develop.
During this period, the following procedures will be completed at the time points outlined in the 
SOA:

Neurological assessment by ICE {Lee 2019}. ICE will be administered before treatment with 
axicabtagene ciloleucel on Day 0, and then daily from Day 1 through the 7-day postinfusion 
monitoring period.

Vital signs including blood pressure, heart rate, oxygen saturation, and temperature, daily at a 
healthcare facility for at least 7 days

Laboratory tests (before lenzilumab and axicabtagene ciloleucel infusion, and after as 
described in the SOA)


Axicabtagene ciloleucel 
Kite Pha1ma, Inc. 
Clinical Protocol: KTE-US-471-0119 
Amendment2 
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Chemistry panel with LDH 
-
CBC with differential 
-
Lymphocyte subsets 
-
Cytokine levels 
-
Anti-CD19 CART cells 
-
RCR analysis 
-
Lenzilumab PK (refer to Section 7 .11 for directions based on Phase 1 and Phase 2) 
• 
Infusion of lenzilumab on Day O initiated at least 6 hours prior to axicabtagene ciloleucel 
• 
Infusion of axicabtagene ciloleucel on Day 0 
• 
Lumbar puncture for collection of CSF samples at Day 5 (± 3 days) 
I 
I 
• 
AE/SAE repo1ting (refer to Section 9 for safety repo1ting guidelines) 
• 
Concomitant medications documentation 
Monitoring of CRP, fenitin, and LDH (only ifLDH is elevated at baseline) levels may assist 
with the diagnosis and define the clinical course in regards to CRS/neurologic toxicities. It is, 
therefore, recommended that CRP, fenitin, and LDH (if elevated at baseline) be monitored daily 
staiting at Day O and for at least 7 days at a healthcai·e facility. In addition, lactate should be 
monitored as clinically indicated. 
7.13.6.3. 
Requirements for Workup Potential Infectious and/or Inflammato1y States 
In the absence of an identified source of infection (eg, line infection, pneumonia on chest x-ray), 
the minimum workup to be perfo1med prior to adminisu-ation of lymphodepleting chemotherapy 
and/or axicabtagene ciloleucel consists of the following: 
• 
Call Kite medical monitor 
• 
Infectious disease service consult (if available) 
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
CT imaging of the neck, chest, abdomen, and pelvis with IV contrast. If there is a medical 
contraindication to contrast, then noncontrast CT is allowed.

The following must be performed (prior to the initiation of antimicrobials if clinically 
feasible):
Blood cultures (aerobic and anaerobic x 2 bottles each) and urinalysis and urine culture. 
Deep/induced sputum culture if clinically indicated.
 All indwelling lines, such as central venous catheters, should be examined for any signs 
of infection and additional cultures should be drawn from the line
Nasopharyngeal-throat swab or equivalent assay for viral infection such as influenza A/B 
(including H1N1), parainfluenza 1/2/3, adenovirus, respiratory syncytial virus, 
coronavirus, metapneumovirus
Collection of fungal cultures and markers as appropriate (eg, galactomannan, Fungitell®)
Collection of appropriate serum viral studies (eg, cytomegalovirus)

If a CNS process is suspected, appropriate brain imaging and subsequent LP with cytology, 
culture, Gram stain, and viral PCR should be performed.

Any additional sign or symptom-directed investigation should be performed as clinically 
indicated.
Prior to proceeding with lymphodepleting chemotherapy and/or axicabtagene ciloleucel infusion, 
the above workup must not suggest the presence of an active infection and all requirements for 
lymphodepleting chemotherapy and/or axicabtagene ciloleucel infusion must be satisfied. If the 
axicabtagene ciloleucel infusion is delayed > 2 weeks following lymphodepleting chemotherapy, 
protocol guidelines should be followed regarding the need for repeat lymphodepleting 
chemotherapy.
If the above workup was triggered due to CRP > 100 mg/L, CRP should be repeated. If CRP 
continues to increase significantly, an evaluation should be performed for any other potential 
infectious or inflammatory condition that was not previously evaluated.
7.13.7.
Post-treatment Assessment Period
After completing axicabtagene ciloleucel infusion and completing the minimum 7-day 
observation period, all subjects will be followed in the post-treatment assessment period.  
Counting from Day 0 (axicabtagene ciloleucel infusion), subjects will return to the clinic at the 
following intervals.

Week 2 (± 2 days)

Week 4 (± 3 days)

Month 3 (± 1 week)


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Subject will allow key sponsor contacts to continue to access medical records so that information 
related to the subject’s health condition and initial treatment response may be obtained. The 
following procedures will be completed for subjects as outlined in the SOA:

Neurological assessment including ICE

PET-CT for disease assessment:  If the PET-CT is not of high enough resolution, the scan 
must be repeated.  Refer to the imaging charter for detailed instructions.

Bone marrow aspirate and biopsy as needed

Physical examination

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature

Laboratory tests
Chemistry panel
CBC with differential
β-human chorionic gonadotrophin pregnancy test (serum or urine) for all women of 
childbearing potential
Cytokine levels
Lymphocyte subsets
Anti-CD19 CAR T cells
RCR analysis
Lenzilumab PK

Lumbar puncture with opening pressure for collection of CSF samples at Week 4 (± 3 days)

AE/SAE reporting (refer to Section 9 for safety reporting guidelines)

Concomitant medications documentation
If a subject is admitted to the hospital during the 7-day observation period, discharged, and is 
subsequently re-admitted to the hospital with any axicabtagene ciloleucel-related AE(s), the 
following laboratory tests will be collected on the day of hospital re-admission and then weekly 
through and including on the day of discharge:

PBMCs (anti-CD19 CAR T cells)


Axicabtagene ciloleucel 
Kite Pha1ma, Inc. 
Clinical Protocol: KTE-US-471-0119 
Amendment2 
• 
Cytokines 
• 
Lenzilumab PK 
At any time during the post-ti·eatment assessment period, if a subject progresses and is either not 
eligible for reu-eatment or chooses not to pursue reti·eatment, the subject will proceed directly to 
the Month 3 visit and be followed for survival, subsequent therapy, and disease outcomes in the 
long-te1m follow-up period. A PBMC (for anti-CD19 CART cells) and sernm sample 
(for cytokine evaluation) should be collected at the time of progression, prior to staiiing any 
subsequent anticancer therapy. 
7.13.8. 
Long-term Follow-up Period 
• 
All enrolled subjects will be followed in the long-te1m follow-up period for survival and 
disease status, if applicable. Subjects will begin the long-te1m follow-up period after they 
have completed the Month 3 visit of the post-ti·eatment assessment period (whether they have 
responded to ti·eatment or went sti·aight to the Month 3 visit due to disease progression). 
Eve1y 3 months ( ± 2 weeks) through Month 12 
• 
Eve1y 12 months(± 3 months) between Month 24 - 15 yeai·s 
The following procedures will be completed for subjects who ai·e enrolled and receive sequenced 
therapy at the time points outlined in the SOA: 
• 
Physical examination 
• 
PET-CT/Disease assessment through 12 months or until disease progression, whichever 
occurs first. If subject's disease has not progressed by Month 12, disease assessments will 
continue to be perfo1med per institutional standard of cai·e. 
• 
Survival status 
• 
Laborato1y tests 
-
CBC with differential 
-
Lymphocyte subsets 
-
Anti-CD19 CART-cell levels 
-
RCR analysis 
• 
Subsequent therapy for the ti·eatment of NHL 
CONFIDENTIAL 
Page 57 
03 August 2021 


Axicabtagene ciloleucel 
Kite Pha1ma, Inc. 
Clinical Protocol: KTE-US-471-0119 
Amendment2 
• 
Refer to Sections 9.2 and 9.4 for targeted AE/SAE repo1i ing 
-
Including neurological, hematological, and autoimmune disorders, and infections and 
secondaiy malignancies 
• 
Targeted concomitant medication documentation (for 12 months or until disease progression, 
whichever occurs first) 
-
Including gammaglobulins, immunosuppressive diugs, anti-infectives, and vaccinations 
Subjects may be conta.cted by telephone to confom survival status and report targeted 
concomitant medication use. 
All subjects, subjects who received an infusion of axicabtagene ciloleucel will be given the 
oppo1iunity to transition to a separate LTFU study, KT-US-982-5968, after providing info1med 
consent. 
If a subject progresses in the long-te1m follow-up phase, the subject will continue to be followed 
for survival status and subsequent therapy for the treatment of NHL. A PBMC sample (for 
anti-CD19 CART cells) and sernm (for cytokine evaluation) should be collected at the time of 
progression, prior to staiiing any subsequent anticancer therapy. 
Subjects who are emolled, but do not receive axicabtagene ciloleucel treatment, will be followed 
only until the end of this study and will undergo the following assessments at the time points 
outlined in the SOA: 
• 
Subsequent therapy for the treatment of NHL 
• 
Survival status 
• 
Disease assessment per standard of care 
• 
AE/SAE repo1i ing and concomitant medication documentation until 30 days after last 
procedure (eg, leukapheresis, lymphodepleting chemotherapy) 
Should the subject fail to return to the clinic for a scheduled protocol-specific visit, sites will 
need to make 2 attempts by a combination of telephone and mail to contact the subject. Sites 
must document both attempts to contact the subject. If a subject does not respond within 
1 month after the second conta.ct the subject will be considered lost to follow-up and no 
additional contact will be required. 
CONFIDENTIAL 
Page 58 
03 August 2021 


Axicabtagene ciloleucel
Kite Pharma, Inc.
Clinical Protocol:  KTE-US-471-0119
Amendment 2
CONFIDENTIAL
Page 59
03 August 2021
7.13.9.
Retreatment
Subjects who achieve a partial response (PR) or complete response (CR) have an option to 
receive a second course of lymphodepleting chemotherapy and axicabtagene ciloleucel without 
lenzilumab under the following conditions:

Subject had a documented PR or CR to sequenced therapy

Subject’s disease subsequently progresses

CD19 tumor expression confirmed locally by immunohistochemistry or flow cytometry on a 
representative progression biopsy

Subject would meet study eligibility requirements for treatment with axicabtagene ciloleucel, 
except regarding prior CD19 targeted therapy or prior CAR T cell therapy.  Screening 
assessments should be repeated if clinically indicated, as determined by the investigator and 
Kite medical monitor, to confirm said eligibility.

Subject has not received any subsequent therapy for the treatment of lymphoma

Subject did not experience a DLT in Phase 1 or a comparable toxicity in Phase 2

Toxicities related to lymphodepleting chemotherapy (fludarabine and cyclophosphamide), 
with the exception of alopecia, have resolved to ≤ Grade 1 or returned to baseline prior to 
retreatment

Subject would not require additional leukapheresis for retreatment
The decision to administer retreatment should be made in consultation with the Kite medical 
monitor.  Retreatment will be considered a subsequent therapy. Retreated subjects will follow the 
schedule of assessments as specified in section 7.14 during and after retreatment, excluding 
assessments solely related to lenzilumab. Further adjustments to the schedule of assessments 
must be discussed with the Kite medical monitor.
7.14.
Summary of Scheduled Assessments
The SOA and the long-term follow-up assessments are provided in Table 3 and Table 4, 
respectively.


Axicabtagene ciloleucel 
Kite Pha1ma, Inc. 
Clinical Protocol: KT-US-471-0119 
Amendment2 
Table 3. 
Schedule of Assessments 
Procedures 
Day 
Medical history2 
ECOG 
performance status 
Neurological 
assessment 
including immune 
effector cell-
associated 
encephalopathy 
score3 
Electrocardiogram 
I 
• 
I 
1,:_, • U 
: 
• 
I 
I' 
PET-CT/ disease 
assessment6 
Physical 
examination 
Vital signs (BP, 
HR, 02 saturation, 
temperature) 
CONFIDENTIAL 
Enrollment / 
Screening Leukapheresis 
Within 
28 days of 
enrollment 
X 
X 
X 
X 
X 
X 
X 
Within 
- 5 days of 
eligibility 
confirm ation 
X 
Lymphodepleting 
Chemotherapy 
IP 
Pe1·iod 
Adm in 
Post-treatment Intensive Monitoring Pe1iod 
Post-tr eatment Follow-up 
Week 
Month 
-4 
-3 
0 
1 
2 
3 
4 
5 
7 
2 
Week 4 
3 
I 
AM 
PM AM PM AM PM A1'\i PM A1'\i PM 
(± 2 
(± 1 
days) (± 3 days) 
week) 
• 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
• . - - - - - - - - - - - - - - -
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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03 August 2021 


Axicabtagene ciloleucel 
Clinical Protocol: KT-US-471-0119 
Procedures 
Day 
Weight (plus 
height at 
screening) 
1 
· ,:_..1 . 1 
• 
: . . . . . . 
chemistry panel 
Blood draw for 
CBC with 
differentia18 
Serology (EU 
sites)9 
Blood draw for 
C-reactive protein 
(CRP)/ferritin 
Blood draw for 
lenzilumab PK12 
Enrollment / 
Screening Leukapheresis 
Within 
28 days of 
enrollment 
X -
X 
X 
X 
Within 
- 5 days of 
eligibility 
confirmation 
X 
X 
X 
X 
X 
CONFIDENTIAL 
Kite Pha1ma, Inc. 
Amendment2 
Lymphodepleting 
Chemotherapy 
IP 
Pe1·iod 
Adm in 
Post-treatment Intensive Monitoring Pe1iod 
Post-treatment Follow-up 
Week 
Month 
-5 
-4 
-3 
0 
1 
2 
3 
4 
5 
7 
2 
Week 4 
3 
(± 2 
(± 1 
AM 
PM AM PM AM PM A1'\i PM A1'\i PM 
days) (± 3 days) 
week) 
X 
----
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
XS 
xs 
X 
X 
xs 
xs xs 
xs 
xs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
XXX 
X 
XXXX 
X 
X 
X 
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Axicabtagene ciloleucel 
Clinical Protocol: KT-US-471-0119 
Procedures 
Day 
Axicabtagene 
ciloleucel infusion 
IV 
Lenzilumab 
infusion IV 
AEs/ Concomitant 
medication 
Enrollment / 
Screening Leukapheresis 
Within 
28 days of 
enrollment 
X 
Within 
- 5 days of 
eligibility 
confirmation 
X 
Lymphodepleting 
Chemotherapy 
IP 
Pe1·iod 
Adm in 
-4 
-3 
0 
1 
AM 
X 
X 
X 
X 
X 
X 
X 
X 
Kite Pha1ma, Inc. 
Amendment2 
Post-treatment Intensive Monitoring Pe1iod 
Post-treatment Follow-up 
Week 
Month 
2 
3 
4 
5 
7 
2 
Week4 
3 
(± 2 
(± 1 
PM AM PM AM PM A1'\i PM A1'\i PM 
days) 
(± 3 days) week) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: BP, blood presstu·e; CBC, complete blood count; CSF, cerebrospinal fluid; ECOG, Eastem Cooperative Oncology Group; EU, Etu·opean Union; HR, heait rate; IP, 
investigational product; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; PBMC, peripheral blood mononuclear cell; PK, pharmacokinetics; PET-CT, positron 
h -com uted tomogra h ; RCR, r lication-com etent retrovims; IV, intravenous. 
2. 
u ercu os1s testrng s 1ou 
e pe1fo1med in subjects with a history of tuberculosis and for those subjects at high risk for tuberculosis exposure related to medical history. 
Testing may include either the tuberculin skin test or interferon gamma release assay, at the investigators discretion, and must have been performed within 3 months of 
anticipated lenzihunab administration. 
3. 
Pe1fo1m scoring according to Appendix 3, as described in Section 7. 5. Scoring should be continued daily during any period of Grade 2 or higher neurologic events as per 
Section 7.5. 
I 
5. 
etion of the investigator. Bone ma!l'ow samples may also be collected and 
analyzed centrally for subjects who develop toxicities after sequenced therapy (see Section 7.12). 
CONFIDENTIAL 
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Axicabtagene ciloleucel 
Kite Pha1ma, Inc. 
Clinical Protocol: KT-US-471-0119 
Amendment2 
6. 
PET-CT (neck, chest, abdomen, and pelvis)/disease assessment pe1fo1med following last line of therapy (>28 days from enrollment) may be used for confomation of 
eligibility. If PET-CT pe1fo1med > 28 days prior to the initiation oflymphodepleting chemotherapy or if subject receives any anticancer therapy between screening and 
lymphodepleting chemotherapy, baseline scans must be repeated. Screening PET-CT should be completed as close to enrollment as possible. Baseline scans should be 
provided to the central imaging review for evaluation of disease burden. 
7. 
Pregnancy test (serum or mine) for EU sites: A pregnancy test will be completed within 7 days prior to both leukapheresis and lymphodepleting chemotherapy for females of 
childbea,ing potential. 
8. 
At the time of PBMC collection, collect CBC with differential for central submission to allow for a more rapid analysis of anti-CD19 CART-cell levels in the blood. 
9. 
Viral testing for EU sites: A viral serologic tests (eg, HIV, Hepatitis B, and Hepatitis C) will be carried out per institution guidelines and EU regulations. Testing may be done 
within the 30 da s rior to leuka heresis and/or on the da of leuka heresis. 
. 
ws will occm· at 
baseline, 30 minutes and 1, 3, 6, 9, 12, and 24 hours after infusion oflenzilumab. Thereafter, blood draws will coincide with remaining cytokine blood draws from Days 1-7 
and Weeks 2 and 4. In Phase 2, blood draws will occur at baseline and at 12 hours after infusion, before coinciding with remaining cytokine blood draws from Days 1-7 and 
Weeks 2 and 4. Please refer to Section 7.11 for fiuiher information. 
CONFIDENTIAL 
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Axicabtagene ciloleucel 
Clinical Protocol: KT-US-471-0119 
Table 4. 
Schedule of Assessments (Long-term Follow-up Period) 
Long-te1·m Follow-up Pe1iod 9 
Procedure 
(Each visit calculated from Day 0) 
Month 6 
Month 9 
Month 12 
Visit Frequency 
(± 2 weeks) 
(± 2 weeks) 
(± 2 weeks) 
Physical examination1 
X 
X 
X 
PET-CT/disease assessment2 
X 
X 
X 
Survival status 
X 
X 
X 
Blood draw for CBC with differential 4 
X 
X 
X 
Blood draw for PBMc4 
X 
X 
X 
Blood draw for RCR analysis 4,5 
X 
X 
Targeted AE/SAEs 6 
X 
X 
X 
Targeted concomitant medication 7 
X 
X 
X 
Subsequent therapy for NHL8 
X 
X 
X 
Month 24 and Annually 
Thereafter 
(±3 months) 
X 
X 
X 
Kite Pha1ma, Inc. 
Amendment2 
At Time of 
Progression 
X 
X 
X 
X 
Abbreviations: AE, adverse event; CBC, complete blood count; NHL, non-Hodgkin's lymphoma; PBMC, peripheral blood mononuclear cell; PET-CT, positron emission 
tomography-computed tomography; SAE, serious adverse event; RCR, replication-competent retrovims. 
1. 
Physical examinations will continue through Month 12 and then can be performed as per institutional standard of care. 
2. 
PET-CT scans/disease assessments will continue through Month 12 or until disease progression, whichever comes first. If subject's disease has not progressed by Month 12, 
disease assessments will continue to be e1fo1med er institutional standard of care. 
I 
4. 
u 3ects w, contmue to prov, e samp es or centra ana ys1s o 
C with differential and PBMC to allow for evaluation oflymphocyte subsets and anti-CD19 CART cells 
through Month 12. On days where PBMC is drawn, an RCR blood draw does not need to be pe1fo1med separately. 
5. 
RCR samples: Collected and measured at Months 3, 6, and 12, then collected yearly for up to 15 years. Yearly samples will only be analyzed if positive at Month 3, 6, or 12. 
6. 
Targeted AEs/SAEs will be collected for 12 months or 1mtil disease progression (whichever occurs first) 
7. 
Targeted concomitant medications will be collected for 12 months or until disease progression (whichever occurs first) 
8. 
Subsequent therapy administered after axicabtagene ciloleucel infusion for a subjects' disease, such as nonstudy specified chemotherapy, immunotherapy, targeted agents, as 
well as stem cell transplant and radiation therapy, must be collected until the subject completes the long-term follow-up period, is considered lost to follow-up, withdraws 
consent, or dies. Subjects may be contacted by telephone to collect info,mation about subsequent therapy for NHL and to assess survival status. 
9. 
After completion of at least 6 months of assessments in the KT-US-471-0119 study, subjects who received an infusion of axicabtagene ciloleucel will be provided the 
opportunity to transition to a LTFU study (KT-US-982-5968) after providing signed informed consent to complete the remainder of their L TFU period. 
CONFIDENTIAL 
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Kite Pharma, Inc.
Clinical Protocol: KT-US-471-0119
Amendment 2
CONFIDENTIAL
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03 August 2021
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 but continue 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 investigational product, study treatment, or other 
protocol-required therapies and must 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 or undergo procedures and the subject does not wish to continue 
further study follow-up. Subject data collected up to withdrawal of consent will be retained and 
included in the analysis of the study, and where permitted by local regulations, publically 
available data (death records) can be included after withdrawal of consent. 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 be also 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 or 
at any time prior to study completion.
8.1.
Reasons for Removal From Treatment
Reasons for removal from protocol-required investigational products or procedures include any 
of the following:

Adverse event

Subject request

Product not available

Lost to follow-up

Death

Decision by sponsor


Axicabtagene ciloleucel
Kite Pharma, Inc.
Clinical Protocol: KT-US-471-0119
Amendment 2
CONFIDENTIAL
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03 August 2021
8.2.
Reasons for Removal From Study
Reasons for removal of a subject from the study are as follows:

Subject withdrawal of consent from further follow-up

Investigator decision

Lost to follow-up 

Death


Axicabtagene ciloleucel
Kite Pharma, Inc.
Clinical Protocol: KT-US-471-0119
Amendment 2
CONFIDENTIAL
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03 August 2021
9.
SAFETY REPORTING
9.1.
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 AEs 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. A pre-existing condition that has not 
worsened during the study or interventions for pre-existing conditions, such as elective cosmetic 
surgery, or medical procedures 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 (eg, B-cell lymphoma).
For situations when an AE or SAE is due to the disease under investigation, the signs and 
symptoms should be reported. Worsening of signs and symptoms of the malignancy under study 
should also be reported as AEs in the appropriate section of the eCRF.
The investigator’s clinical judgment is used to determine whether a subject is to be removed 
from treatment due to an AE. In the event a subject requests to withdraw from protocol-required 
therapies or the study due to an AE, the subject should undergo the procedures outlined in the 
Month 3 visit of the SOA.
9.2.
Reporting of Adverse Events
The investigator is responsible for ensuring that all AEs observed by the investigator or reported 
by the subject that occur from enrollment (ie, commencement of leukapheresis) through 
3 months after treatment with lenzilumab and axicabtagene ciloleucel infusion are monitored and 
reported. After 3 months, targeted AEs, including, for example, neurological, hematological, 
autoimmune disorders, infections, and secondary malignancies, will be monitored and reported 
for 12 months after treatment with the sequenced therapy or until disease progression, whichever 
occurs first.
For subjects who are enrolled, but do not receive axicabtagene ciloleucel, the AE reporting 
period ends 30 days after the last study-specific procedure (eg, leukapheresis, lymphodepleting 
chemotherapy, lenzilumab).


Axicabtagene ciloleucel
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Clinical Protocol: KT-US-471-0119
Amendment 2
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The investigator must address the following for AEs:

Adverse event diagnosis or syndrome (if not known, signs or symptoms)

Dates of onset and resolution

Severity

Assessment of relatedness to investigational product, lymphodepleting chemotherapy, or 
study procedures

Action taken
The AE grading scale used will be the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) version 4.03 to match the criteria used in Cohorts 1 and 2 
of ZUMA-1. A copy of the grading scale can be downloaded from the Cancer Therapy 
Evaluation Program home page (http://ctep.cancer.gov). For neurologic events, in addition to 
grading by the CTCAE v4.03 investigator’s should provide a narrative report of each incident, 
including onset, evolution of symptoms, treatment employed, and resolution, if any by the D28 
visit. Cytokine release syndrome events will also be reported using the grading scale outlined in 
the IB.
In reviewing AEs, investigators must assess whether the AE is possibly related to 
1) the investigational products (lenzilumab and/or axicabtagene ciloleucel), 
2) lymphodepleting chemotherapy, or 3) any protocol-required study procedure.  The 
relationship is indicated by a yes or no response and entered into the eCRF. 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 eCRFs.
The investigator is expected to follow reported AEs until stabilization or resolution.  If a subject 
begins a new anticancer therapy, the AE reporting period for nonserious AEs ends at the time the 
new treatment is started.
9.2.1.
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.


Axicabtagene ciloleucel
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Clinical Protocol: KT-US-471-0119
Amendment 2
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An abnormal laboratory test result must be reported as an AE if it is a change from baseline and 
meets any of the following criteria:

Associated with clinical symptoms

Results in a medical intervention (eg, potassium supplementation for hypokalemia or iron 
replacement therapy for anemia) or a change in concomitant therapy

Clinically significant in the investigator’s judgment 
9.3.
Definition of Serious Adverse Events
An SAE is defined as an AE that meets at least one of the following serious criteria:

Fatal

Life-threatening (places the subject at immediate risk of death)

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity

Congenital anomaly/birth defect

Other medically important serious event
An AE would meet the criterion of “requires hospitalization” if the event necessitated an 
admission to a healthcare facility (eg, 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 or if that event resulted in a prolongation of the existing 
planned hospitalization.
If an investigator considers an event to be clinically important, but it does not meet any of the 
serious criteria, the event could be classified as an SAE with the criterion of “other medically 
important serious event.”
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an AE 
according to NCI CTCAE; the event itself may be of relatively minor medical significance and, 
therefore, may not meet the seriousness criteria. Severity and seriousness need to be 
independently assessed for each AE recorded in the eCRF.
9.4.
Reporting of Serious Adverse Events and Nonserious CRS Events Grade ≥ 3
The investigator is responsible for reporting all SAEs observed by the investigator or reported by 
the subject that occur after the signing of the consent through 30 days after completing the final 
dose of lenzilumab or 3 months after the axicabtagene ciloleucel infusion, whichever is longer. 


Axicabtagene ciloleucel
Kite Pharma, Inc.
Clinical Protocol: KT-US-471-0119
Amendment 2
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Once this follow-up period has been completed, only serious targeted AEs (eg, neurological, 
hematological, autoimmune disorders, infections, and secondary malignancies) observed by the 
investigator or reported by the subject will be reported for 24 months after axicabtagene 
ciloleucel infusion or until disease progression, whichever occurs first.  For subjects who fail 
screening or are enrolled but do not receive either investigational product, the reporting period 
for SAEs ends 30 days after the last procedure (eg, screening procedure, leukapheresis, 
lymphodepleting chemotherapy).
Serious AEs that the investigator assesses as related to the investigational products, lenzilumab, 
and/or axicabtagene ciloleucel should be reported regardless of the study period.
All SAEs must be submitted to Kite via the eSAE system within 24 hours of the investigator’s 
knowledge of the event. If the eSAE system is unavailable (eg, system outage), then the SAE 
must be submitted using the SAE Report Form and sent via email to the SAE reporting mailbox: 
Subsequently, all SAEs will be reported to the health authorities per local reporting guidelines.
Progression of the malignancy during the study should not be reported as an SAE. Adverse 
events associated with disease progression may be reported as an SAE.  If the malignancy has a 
fatal outcome within 3 months of the last day of the conditioning therapy, lenzilumab, or 
axicabtagene ciloleucel, then the event leading to death must be recorded as an SAE with an NCI 
CTCAE of Grade 5.
Death must be reported if it occurs during the SAE reporting period, irrespective of any 
intervening treatment.
Any death occurring after the first dose of chemotherapy, for the purpose of preconditioning, and 
within 30 days of the last lenzilumab infusion or 3 months of the axicabtagene ciloleucel 
infusion, regardless of attribution to treatment, requires expedited reporting within 24 hours.  
Any death occurring greater than 3 months after the lenzilumab and axicabtagene ciloleucel 
infusions requires expedited reporting within 24 hours only if it is considered related to 
treatment.
Following completion of KT-US-471-0119, any relevant information on ongoing SAEs must be 
submitted to 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: 
9.5.
Reporting Deaths
Deaths that occur during the protocol-specified AE reporting period that are attributed by the 
investigator solely to progression of underlying lymphoma should be recorded as SAEs with the 
preferred term “B-cell lymphoma” 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. The term “unexplained death” should be captured 
if the cause of death is not known. However, every effort should be made to capture the 
PPD
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established cause of death, which may become available later on (eg, after autopsy). Deaths 
during the poststudy survival follow-up due to underlying cancer should be recorded only in the 
Survival Status section of the eCRF.
9.6.
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 both CRS and neurologic events where the diagnosis and 
signs and symptoms must be captured on the eCRF 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.
9.7.
Pregnancy and Lactation
There is no relevant clinical experience with axicabtagene ciloleucel 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. 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 
lymphodepleting chemotherapy dosing or the administration of axicabtagene ciloleucel, 
whichever is longer. Male subjects are recommended to not father a child for at least 6 months 
after the lymphodepleting chemotherapy dosing or the administration of axicabtagene ciloleucel, 
whichever is longer. Refer to Appendix 2 for a complete list of highly effective contraception 
methods.
If a pregnancy occurs in either a female subject enrolled into the study or a female partner of a 
male subject within 6 months of completing lymphodepleting chemotherapy or the 
administration of axicabtagene ciloleucel, whichever is longer, the pregnancy must be reported to 
Gilead PVE (
 or fax 
 using the pregnancy report form 
within 24 hours. Refer to Section 9 of the protocol (Safety Reporting) and the eCRF completion 
guidelines for full instructions on the mechanism of pregnancy reporting. Information regarding 
the pregnancy and/or the outcome will be requested by the sponsor. The pregnancy itself is not 
considered an AE nor is an induced elective abortion to terminate a pregnancy without medical 
reasons. Any premature termination of pregnancy (eg, a spontaneous abortion, an induced 
therapeutic abortion due to complications or other medical reasons) must be reported within 
24 hours as an SAE. The underlying medical reason for this procedure should be recorded as the 
AE term.
A spontaneous abortion is always considered to be an SAE and should be reported as described 
in Section 9.4 of the protocol (SAE Reporting). Furthermore, any SAE occurring as an adverse 
pregnancy outcome post study must be reported to Gilead PVE (
 or 
fax: 
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The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead PVE 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 Gilead PVE. Gilead PVE contact information is as follows: 
email: 
 and fax: 
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead PVE using the 
pregnancy and pregnancy outcome forms within 24 hours. If the end of the pregnancy occurs 
after the study has been completed, the outcome should be reported directly to Gilead PVE, 
fax number 
 or email 
If a lactation case occurs in a female in the study, report the lactation case to Gilead PVE 
(
 using the lactation reporting form within 24 hours of the investigator’s 
knowledge of the event. In addition to reporting a lactation case during the study, investigators 
should monitor for pregnancy and lactation cases for 15 years after the administration of 
axicabtagene ciloleucel dosing.
9.8.
Hospitalization and Prolonged Hospitalization
Any AE that results in hospitalization or prolonged hospitalization should be documented and 
reported as an SAE as described in Section 9.4.
The following hospitalization scenarios are not considered to be SAEs:

Hospitalization for palliative care or hospice care

Planned hospitalization required by the protocol (eg, for monitoring of the subject or to 
perform an efficacy measurement for the study)

Planned hospitalization for a pre-existing condition

Hospitalization due to progression of the underlying cancer
9.9.
Abnormal Vital Sign Values
Not all vital sign abnormalities qualify as an AE. A vital sign result must be reported as an AE if 
it is a change from baseline and meets any of the following criteria:

Is accompanied by clinical symptoms

Results in a medical intervention or a change in concomitant therapy

Is clinically significant in the investigator’s judgment
PPD
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It is the investigator’s responsibility to review all vital sign findings. Medical and scientific 
judgment should be exercised in deciding whether an isolated vital sign abnormality should be 
classified as an AE. However, if a clinically significant vital sign abnormality is a sign of a 
disease or syndrome (eg, high blood pressure), only the diagnosis (ie, hypertension) should be 
recorded in the eCRF.
9.10.
Safety Review Team and Dose-limiting Toxicity
Phase 1
The SRT will be specifically chartered to review safety data during Phase 1 of the study and 
make recommendations on further study conduct in Phase 1 and progression to Phase 2 based on 
the incidence of DLTs with sequenced therapy, review of SAEs, and translational data.   
Dose-limiting toxicity is defined as the following sequenced therapy-related events with onset 
within the first 28 days following axicabtagene ciloleucel infusion:

Grade 4 neutropenia lasting longer than 21 days from the day of cell transfer

Grade 4 thrombocytopenia lasting longer than 28 days from the day of cell transfer

Any sequenced therapy-related AE requiring intubation, including Grade 4 encephalopathy 
requiring intubation for airway protection, is considered to be a DLT

Any sequenced therapy-related Grade 5 event

All other clinically significant Grade 3 toxicities lasting more than 3 days and all Grade 4 
toxicities, with the exception of the following conditions which are not considered DLT’s:
Encephalopathy that resolves to at worst Grade 1 within 2 weeks and to baseline within 
4 weeks
Grade 3 fever 
Myelosuppression (includes bleeding in the setting of platelet count < 50 x109/L and 
documented bacterial infections in the setting of neutropenia), defined as lymphopenia, 
decreased hemoglobin, neutropenia, and thrombocytopenia unless neutropenia and 
thrombocytopenia meet the DLT definition described above
Immediate hypersensitivity reactions occurring within 2 hours of cell or lenzilumab 
infusion that are reversible to Grade 2 or less within 24 hours of administration with 
standard therapy
Renal toxicity which requires dialysis for ≤ 7 days 
Tumor lysis syndrome including associated manifestations attributable to tumor lysis 
syndrome (eg, electrolyte abnormalities, renal function, hyperuricemia)


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Grade 3 transaminase, alkaline phosphatase, bilirubin or other liver function test 
elevation, provided there is resolution to ≤ Grade 2 within 14 days
Grade 4 transient serum hepatic enzyme abnormalities provided there is resolution to 
≤ Grade 3 within < 72 hours
Grade 3 or 4 hypogammaglobulinemia
Grade 3 nausea or anorexia 
CRS will be graded according to a revised grading system {Lee 2014}, as described in the 
current axicabtagene ciloleucel IB. Adverse events attributed to CRS will be mapped to the 
overall CRS grading assessment for the determination of DLT. If Grade 3 or 4 CRS per Lee 2014 
is due to one of the exceptions above, the event will not be considered a DLT.
During Phase 1, approximately 3 to 12 subjects with DLBCL, PMBCL, or TFL will be enrolled 
to evaluate the safety of the sequenced therapy.
Subjects in each cohort will be evaluated for DLTs within the first 30 days following the 
completion of axicabtagene ciloleucel infusions. The analysis of DLTs will be based on the DLT 
evaluable set as defined in Section 10.6. The SRT will make recommendations based on the 
incidence of DLT and overall safety profile of sequenced therapy with lenzilumab and 
axicabtagene ciloleucel. If the subject incidence of DLT is ≤ 1 of 6 subjects in Cohort 1 and 2, 
the RP2D will be selected by the SRT and the study can proceed to Phase 2. This decision will 
be based on overall benefit/risk assessment of adding lenzilumab to the axicabtagene ciloleucel 
regimen and available translational data.
However, if 2 of the 6 enrolled subjects present with a protocol-defined DLT during Phase 1, the 
SRT may recommend enrolling additional subjects at the relevant cohorts for further safety 
review and translational assessment (up to 12 subjects in total).
If the subject incidence of DLT is > 2/6, > 3/9, or > 4/12 subjects, other lenzilumab dosing 
regimens may be explored. The same DLT rules apply as above.
Phase 2
The SRT will meet to review the interim analysis once a total of 14 subjects have been treated at 
the RP2D and have been followed for 28 days after treatment with sequenced therapy across 
Phase 1 and Phase 2. In addition, the SRT will review futility according to the statistical analysis 
plan as in Section 10.5.The SRT may meet more often as needed during Phase 2 of the study.


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10.
STATISTICAL CONSIDERATIONS
10.1.
Hypothesis
This study is designed to differentiate between a treatment that has a true event rate of 20% or 
less and a treatment with a true event rate of 45% or more. The hypothesis is that the Grade 2 or 
higher neurologic event rate related to sequenced therapy is significantly less than 45%. No 
hypothesis will be tested during Phase 1 of the study.
10.2.
Study Endpoints
10.2.1.
Primary
Phase 1: Incidence of DLT related to sequenced therapy with lenzilumab and axicabtagene 
ciloleucel
Phase 2: Incidence of Grade 2 or higher neurologic events within 28 days of axicabtagene 
ciloleucel administration
10.2.2.
Secondary
The secondary endpoints include:

The incidence AEs and SAEs, including CRS and neurologic events

ORR: defined as the incidence of either a CR or a PR per the IWG Lugano Classification 
{Cheson 2014} as determined by the study investigators. All subjects who do not meet the 
criteria for an objective response by the analysis cutoff date will be considered 
nonresponders.

CR rate: defined as the incidence of CR per the IWG Lugano Classification {Cheson 2014} 
as determined by the study investigators

DOR: among subjects who experience an objective response, DOR is defined as the date of 
their first objective response to disease progression per the IWG Lugano Classification 
{Cheson 2014} as determined by study investigators or death from any cause. Subjects not 
meeting the criteria for disease progression or death by the analysis cutoff date will be 
censored at their last evaluable disease assessment date and their response will be noted as 
ongoing. Subjects who receive additional anticancer therapy in the absence of documented 
disease progression will be censored at the last evaluable disease assessment prior to the 
additional therapy. Subjects who receive an SCT in the absence of documented disease 
progression will be censored at the last evaluable disease assessment prior to the date of the 
SCT. A sensitivity analysis will be conducted in which disease assessments obtained after the 
SCT while in axicabtagene ciloleucel-induced remission are included in the derivation of the 
DOR.


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• 
PFS: defined as the time from the axicabtagene ciloleucel infusion date to the date of disease 
progression per the IWG Lugano Classification { Cheson 2014} as detennined by study 
investigators or death from any cause. Subjects not meeting the criteria for disease 
progression or death by the analysis data cutoff date will be censored at their last evaluable 
disease assessment date. Subjects who receive additional anticancer therapy in the absence of 
documented disease progression will be censored at the last evaluable disease assessment 
prior to the additional therapy. Subjects who receive an SCT in the absence of documented 
disease progression will be censored at the last evaluable disease assessment prior to the date 
of the SCT. A sensitivity analysis will be conducted in which disease assessments obtained 
after the SCT while in axicabtagene ciloleucel-induced remission are included in the 
derivation of PFS. 
• 
OS: defined as the time from axicabtagene ciloleucel infusion to the date of death. Subjects 
who have not died by the analysis data cutoff date will be censored at their last date known as 
alive or the data cutoff date, whichever is earlier. 
• 
Axicabtagene ciloleucel phaimacodynamics: levels of cytokines (including free GM-CSF) in 
blood 
• 
Axicabtagene ciloleucel PK: levels of anti-CD19 CART cells in blood 
-
I 
I 
I 
10.3. 
Sample Size Considerations 
The anticipated enrollment in this study is approximately 3 to 36 subjects. 
Up to 6 subjects in each coho1i will be enrolled and treated in Phase 1 of this study. 
If the study proceeds to the Phase 2, up to an additional 24 subjects will be enrolled at the RP2D 
for assessment of the reduction in the incidence of Grade 2 or higher neurologic event seen by 
adding lenzilumab to the axicabtagene ciloleucel regimen. 
Simon's 2-stage design {Simon 1989} is used to calculate the sample size for the RP2D 
coho1i . The null hypothesis that the trne event rate is 45% will be tested against a I-sided 
alternative. In the first stage, 14 subjects will be accrned and treated at the RP2D (including 
subjects treated at the RP2D under both Phase 1 and Phase 2). If there are 5 or more subjects 
with Grade 2 or above neurologic events in these 14 Stage 1 subjects, the study will be stopped 
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for futility at the discretion of the SRT. Othe1wise, 16 additional subjects will be accrned and 
treated at the RP2D for a total of 30. The null hypothesis will be rejected if 8 or fewer subjects 
with Grade 2 or above neurologic events are observed in the 30 subjects. This design yields a 
I-sided type I eITor rate of 0.025 and power of 80% when the hue event rate is 20% or less. The 
robabili of earl sto in when the null h 
othesis is hue is 0.8328. 
Table 5. 
Simon's Two-stage Design for RP2D1 Cohort 
Stages 
Total Number of Subjects 
Target Number of Subjects with Events 
Stage 1 
14 
< 5 
Stage 2 
30 
< 9 
RP2D: recollllllended phase 2 dose 
All analyses for the incidence of Grade 2 or higher neurologic event in Phase 1 and Phase 2 
po1iions of the study will be based on a prima1y objective anal sis set consisting of all subjects 
who receive axicabta ene ciloleucel at a minimum dose of 
anti-CD19 CAR T cells/kg 
Inferential testing will be perfo1med only for the primaiy endpoint in Phase 2 of the study. 
10.4. 
Access to Individual Subject Treatment Assignments 
This is a single-ann, open-label study. Subjects and investigators will be awai·e of the h·eatinent 
received. Data handling procedures for the study will be devised to reduce potential sources of 
bias and maintain the validity and credibility of the study. These procedures will be outlined in 
the study statistical plan. 
10.5. 
Interim Analysis and Early Stopping Guidelines 
During Phase 1, the SRT will review safety data after 3 and 6 (as needed) subjects have been 
followed for 28 days after their axicabtagene ciloleucel adminisu-ation in each dose escalation 
coho1i and will make recommendations on fuither study conduct and progression of the study as 
outlined in Section 9.10. At the conclusion of dose escalation, the SRT will detennine the RP2D 
and conversion to Phase 2. 
During Phase 2, the SRT will assess safety and futility through an interim analysis once 
14 subjects ai·e enrolled and h·eated with axicabta ene ciloleucel at a minimum dose of 1.6 x 106 
anti-CD19 CART cells/k 
and lenzilumab at the RP2D (including Phase 1 and Phase 2) prior 
to ax1ca tagene c1 o euce m sion, and have had the opportunity to be followed for 28 days after 
the axicabtagene ciloleucel dose. According to Simon's 2-stage design, if there ai·e 5 or more 
subjects with events in the 14 Stage 1 subjects, the study will be stopped at the discretion of the 
SRT. This timing will coincide with an interim analysis. 
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10.6. 
Analysis Subsets 
• 
Full analysis set (FAS): The full analysis set will consist of all enrolled subjects and will be 
used for the summaiy of subject disposition. 
• 
Primaiy objective analysis set: The primaiy objective analysis set will consist of all subjects 
enrolled and ti·eated with axicabta ene ciloleucel at a minimum dose of 1.6 x 106 anti-CD19 
CAR Tcells/k 
Phase 2) prior to axicabtagene ciloleucel infusion. This analysis set will be used for the 
primaiy endpoint analysis. 
• 
Modified intent-to-ti-eat set: The modified intent-to-ti·eat set will consist of all subjects 
enrolled and ti·eated with axicabta ene ciloleucel at a minimum dose of 
anti-CD19 
CAR T cells/k 
and any dose of lenzilumab at the RP2D (including Phase 1 and 
P ase 2 pnor to ax1ca tagene ciloleucel infusion. This analysis set will be used for all 
efficacy analyses. 
• 
Safety set: The safety set is defined as all subjects ti·eated with any dose of axicabtagene 
ciloleucel and/or any dose of lenzilumab. This analysis set will be used for all safety analyses 
except for the primaiy endpoint analysis. 
• 
Sensitivity analysis for some key secondaiy endpoints (eg, incidence rate by severity of CRS, 
incidence rate by severity of neurologic events) may be perfonned based on the primaiy 
objective analysis set. 
DLT evaluable set (Phase 1 only): defined for each dosing coho1i in Phase 1, will include 
subjects ti·eated in the Phase 1 dosing coho1i who: 
• 
Received the tai·get dose of lenzilumab and axicabtagene ciloleucel and were followed for at 
least 28 days after the anti-CD19 CART cell infusion; or 
• 
Received a dose oflenzilumab lower than the target for that coho1i and experienced a DLT 
during the 28-day postinfusion period. 
Depending on the dosing coho1i and results of the Phase 1 po1iion of the study, lenzilumab may 
be: 
• 
Administered as a single IV infusion at a tai·get dose 600 m 
of 2 x 106 anti-CD19 CART cells/kg(± 20%) 
or 
• 
Administered as a single IV infusion at a tai·get dose 1800 mg on Day 0 prior to 
administi·ation of2 x 106 anti-CD19 CART cells/kg(± 20%); or 
• 
If needed, more subjects will be enrolled to achieve 6 DLT evaluable subjects at the tai·get 
dose for each coho1i . 
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10.7.
Planned Method of Analysis
The primary analysis will be performed after 30 subjects in the primary objective analysis set 
have had the opportunity to be evaluated for response 6 months after the axicabtagene ciloleucel 
infusion. The final analysis will occur when all subjects have completed the study. Additional 
analyses of safety and efficacy may occur at any time after the primary analysis.
10.7.1.
Grade 2 or Higher Neurologic Events Rate
The primary endpoint of incidence of Grade 2 or higher neurologic event for all analyses 
(futility, interim, and primary) will be based on investigator review of neurologic assessments, 
signs and symptoms in the primary objective analysis set. The incidence of Grade 2 or higher 
neurologic events and the exact 2-sided 95% confidence interval will be generated.  An exact 
binomial test will be used to compare the observed event rate to an event rate of 45%.
10.7.2.
Safety
Subject incidence rates of AEs including all, serious, fatal, and NCI CTCAE version 4.03 
Grade 3 or higher, and treatment-related AEs reported throughout the conduct of the study will 
be tabulated by preferred term and system organ class.  Identified and potential risks of 
axicabtagene ciloleucel and lenzilumab infusions will be summarized. Changes in laboratory 
values and vital signs will be summarized with descriptive statistics. The incidence of 
concomitant medications will be summarized.
Tables and/or narratives of deaths through long-term follow-up and treatment-related SAEs will 
be provided.
10.7.3.
Objective Response Rate
The incidence of ORR and exact 2-sided 95% confidence intervals will be generated.
10.7.4.
Complete Response Rate
The incidence of CR rate and exact 2-sided 95% confidence intervals will be generated.
10.7.5.
Duration of Response
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for DOR. 
Estimates of the proportion of subjects alive and in response at 3-month intervals will be 
provided.
10.7.6.
Progression-free Survival
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for PFS.  
Estimates of the proportion of subjects alive and in response at 3-month intervals will be 
provided.


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10.7.7. 
Overall Survival 
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for OS. 
Estimates of the propo1i ion of subjects alive at 3-month intervals will be provided. 
-
10.7.9. 
Long-term Data Analysis 
All subjects will be followed for smvival status for up to 15 years after receiving axicabtagene 
ciloleucel. LTFU data analysis will be perfonned on subjects in this study and after transition to 
the KT-US-982-5968 LTFU study. No fonnal hypothesis testing will be perfo1med based on data 
obtained after the cutoff for the primaiy analysis. 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 sites respective IRB/IEC for approval. Once 
approval is obtained from the IRB/IEC, all documents must be provided to the key sponsor 
contact before subject recruitment can begin.
The investigator must also receive IRB/IEC approval for all protocol and ICF changes or 
amendments. Investigators must ensure that ongoing/continuous IRB/IEC approval 
(ie, annual approval) is provided throughout the conduct of the study. Copies of 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

Date of birth or year of birth/age at time of enrollment will be reported according to local 
laws and regulations
For the reporting of SAEs, subjects will be identified by their respective subject ID number, 
initials, and data of birth or year of birth (as per their local reporting requirements for both 
initials and date of birth).
Per federal regulations and International Conference on Harmonisation Good Clinical Practice 
(ICH GCP) guidelines, investigators and institutions are required to permit authorization to the 
sponsor, contract research organization, 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 
personal information.
11.3.
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 are to be submitted to the key sponsor contact.
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 contract research organization with a copy of the correspondence.
Kite reserves the unilateral right, at is sole discretion, to determine whether to manufacture 
axicabtagene ciloleucel 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 who are authorized to fulfil these responsibilities should be outlined 
and included in the Delegation of Authority Form.
Source documents are original documents, data, and records for which the study data are 
collected and verified. Example of such source documents may include, but are not limited to, 
hospital records and subject charts; laboratory, pharmacy, radiology and records; subject diaries; 
microfiches; correspondence; and death registries. Case report form entries may be considered as 
source data if the site of the original data collection is not available. However, use of the eCRFs 
as source documentation as a routine practice is not recommended.
The investigator and study staff are responsible for maintaining a comprehensive and centralize 
filing system of all subject records that are readily retrieved to be monitored and or audited at 
any time by the key sponsor contact, regulatory authorities, and IRB/IECs. The filing system will 
include at a minimum the following:

Subject content including ICFs and subject ID lists

Protocols and protocol amendments, IB, copies of prestudy 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 eCRFs must be maintained at the site and 
readily available upon request. No study documents should be discarded without prior written 
agreement between Kite and the investigator. Should storage no longer be available to archive 
source documents or must be moved to an alternative location, the research staff should notify 
the key sponsor contact prior to the shipping the documents.


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14.
STUDY MONITORING AND DATA COLLECTION
The key sponsor contact, monitors, auditors, and regulatory inspectors are responsible for 
contacting and visiting the investigator for the purpose of inspecting the facilities and verifying 
source documents and records assuring that subject confidentially is respected.
The monitor is responsible for source document verification of eCRF data at regular intervals 
during the study. Protocol adherence, accuracy, and consistency of study conduct and data 
collection with respect to local regulations will be confirmed. 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 eCRF system. All entries must be completed in English and 
concomitant medications should be identified by tradenames. For further details surrounding the 
completion of eCRFs, please refer to the eCRF completion guidelines.


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15.
PUBLICATION
Authorship of publications from data generated in study ZUMA-19 will be determined based on 
the uniform requirements for manuscripts submitted to biomedical journals as outlined in the 
International Committee of Medical Journal Editors {International Committee of Medical 
Journal Editors 2018}, which states that authorship should be based on the following criteria:

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 
individuals who accept direct responsibility for the manuscript. This individual should fully meet 
the criteria for authorship defined above.
Funding, collecting data, or general supervising 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 between the institution, principal investigation, 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.
REFERENCES
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Lymphoma Subtype Distribution, Geodemographic Patterns, and Survival in the 
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Barrett DM, Singh N, Hofmann TJ, Gershenson Z, Grupp SA. Interleukin 6 Is Not Made By 
Chimeric Antigen Receptor T Cells and Does Not Impact Their Function 
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Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. 
Recommendations for initial evaluation, staging, and response assessment of 
Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 
2014;32 (27):3059-68.
Coiffier B, Sarkozy C. Diffuse Large B-Cell Lymphoma: R-CHOP Failure-What To Do? 
Hematology Am Soc Hematol Educ Program 2016:366-78.
Crump M, Neelapu SS, Farooq U, Van Den Neste E, Kuruvilla J, Westin J, et al. Outcomes in 
refractory diffuse large B-cell lymphoma: results from the international 
SCHOLAR-1 study. Blood 2017;130 (16):1800-8.
Flowers CR, Sinha R, Vose JM. Improving outcomes for patients with diffuse large B-cell 
lymphoma. CA Cancer J Clin 2010;60 (6):393-408.
Giavridis T, van der Stegen SJC, Eyquem J, Hamieh M, Piersigilli A, Sadelain M. CAR T Cell-
Induced Cytokine Release Syndrome is Mediated by Macrophages and Abated by 
IL-1 Blockade. Nat Med 2018;24:731-8.
Gust J, Hay KA, Hanafi LA, Li D, Myerson D, Gonzalez-Cuyar LF, et al. Endothelial Activation 
and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive 
Immunotherapy with CD19 CAR-T Cells. Cancer Discov 2017;7 (12):1404-19.
Howlader N, Noone A, Krapcho M, Miller D, Bishop K, Kosary C, et al. SEER Cancer Statistics 
Review, 1975-2014. National Cancer Institute. Bethesda, MD, 
https://seer.cancer.gov/csr/1975_2014/, based on November 2016 SEER data 
submission, posted to the SEER web site, April 2017 2017.
Inoue Y, Trapnell BC, Tazawa R, Arai T, Takada T, Hizawa N, et al. Characteristics of a Large 
Cohort of Patients with Autoimmune Pulmonary Alveolar Proteinosis in Japan. 
Am J Respir Crit Care Med 2008;177:752-62.


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International Committee of Medical Journal Editors. Recommendations for the Conduct, 
Reporting, Editing, and Publication of Scholarly Work in Medical Journals. 
Updated: December.  2018:
Kitamura T, Tanaka N, Watanabe J, Uchida, Kanegasaki S, Yamada Y, et al. Idiopathic 
Pulmonary Alveolar Proteinosis as an Autoimmune Disease with Neutralizing 
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Kuruvilla J, Pintilie M, Tsang R, Nagy T, Keating A, Crump M. Salvage chemotherapy and 
autologous stem cell transplantation are inferior for relapsed or refractory primary 
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lymphoma. Leuk Lymphoma 2008;49 (7):1329-36.
Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the 
diagnosis and management of cytokine release syndrome. Blood 2014;124 
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Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT 
Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity 
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Leonard JP, Schattner EJ, Coleman M. Biology and management of mantle cell lymphoma. Curr 
Opin Oncol 2001;13 (5):342-7.
Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, et al. Long-Term 
Safety and Activity of Axicabtagene Ciloleucel in Refractory Large B-Cell 
Lymphoma (ZUMA-1): A Single-Arm, Multicentre, Phase 1-2 Trial. Lancet 
Oncol 2019;20:31-42.
Locke FL, Neelapu SS, Bartlett NL, Lekakis LJ, Jacobson CA, Braunschweig I, et al. 
Preliminary Results of Prophylactic Tocilizumab after Axicabtageneciloleucel 
(axi-cel; KTE-C19) Treatment for Patients with Refractory,Aggressive Non-
Hodgkin Lymphoma (NHL). Blood 2017a;130 (Suppl 1):1547-.
Locke FL, Rossi J, Xue A, Neelapu SS, Ryan DH, Ghobadi A, et al. Immune Signatures of 
Cytokine Release Syndrome and Neurologic Events in a Multicenter 
Registrational Trial (ZUMA-1) in Subjects With Refractory Non-Hodgkin 
Lymphoma Treated With Axicabtagene Ciloleucel (KTE-C19) [Presentation 
CT020]. AACR Annual Meeting; 2017b 01-05; Washington, D. C. 
Molfino NA, Kuna P, Leff JA, Oh CK, Singh D, Chernow M, et al. Phase 2, randomised 
placebo-controlled trial to evaluate the efficacy and safety of an anti-GM-CSF 
antibody (KB003) in patients with inadequately controlled asthma. BMJ Open 
2016;6 (1):e007709.


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National Cancer Institute (NIH). SEER Cancer Stat Facts: NHL - Diffuse Large B-Cell 
Lymphoma (DLBCL). Available at: 
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(NCCN Guidelines) B-Cell Lymphomas. Version 2.2019. 06 March.  2019.
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene 
Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J 
Med 2017;377 (26):2531-44.
Nicholson IC, Lenton KA, Little DJ, Decorso T, Lee FT, Scott AM, et al. Construction and 
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Neurotoxicity Due to CAR T Cells. Nat Med 2018;24:739-48.
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the International Non-Hodgkin Lymphoma Classification Project. Haematologica 
2016;101 (10):1244-50.
Roberts ZJ, Better M, Bot A, Roberts MR, Ribas A. Axicabtagene ciloleucel, a first-in-class 
CAR T cell therapy for aggressive NHL. Leuk Lymphoma 2018;59 (8):1785-96.
Rodriguez-Abreu D, Bordoni A, Zucca E. Epidemiology of Hematological Malignancies. Ann 
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Rodriguez J, Pugh WC, Romaguera JE, Cabanillas F. Primary mediastinal large cell lymphoma. 
Hematological Oncology 1994;12 (4):175-84.
Rossi JM, Sherman M, Xue A, wei-Shen Y, Navale L, Rosenberg SA, et al. Levels of IL-15 and 
GM-CSF Are Elevated One Day After Anti-CD19 CAR T Cell Infusion in 
Patients Who Had an Objective Response or Experienced a Grade ≥3 Neurologic 
AE [Presentation]. EMA Workshop; 2016 15-16 November; London, England. 
Sant M, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Visser O, et al. Incidence of 
hematologic malignancies in Europe by morphologic subtype: results of the 
HAEMACARE project. Blood 2010;116 (19):3724-34.


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Santomasso BD, Park JH, Salloum D, Riviere I, Flynn J, Mead E, et al. Clinical and Biological 
Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with 
B-cell Acute Lymphoblastic Leukemia. Cancer Discov 2018:958-71.
Shibata Y, Berclaz PY, Chroneos ZC, Yoshida M, Whitsett JA, Trapnell BC. GM-CSF 
Regulates Alveolar Macrophage Differentiation and Innate Immunity in the Lung 
through PU.1. Immunity 2001;15 (4):557-67.
Simon R. Optimal Two-Stage Designs for Phase II Clinical Trials. Control Clin Trials 1989;10 
(1):1-10.
Spath S, Komuczki J, Hermann M, Pelczar P, Mair F, Schreiner B, et al. Dysregulation of the 
Cytokine GM-CSF Induces Spontaneous Phagocyte Invasion and 
Immunopathology in the Central Nervous System. Immunity 2017;46:245-60.
Sterner RM, Sakemura R, Cox MJ, Yang N, Khadka RH, Forsman CL, et al. GM-CSF Inhibition 
Reduces Cytokine Release Syndrome and Neuroinflammation But Enhances 
CAR-T Cell Function in Xenografts. Blood 2019;133 (7):697-709.
Taraseviciute A, Tkachev V, Ponce R, Turtle CJ, Snyder JM, Liggitt HD, et al. Chimeric 
Antigen Receptor T Cell-Mediated Neurotoxicity in Nonhuman Primates. Cancer 
Discov 2018:750-63.
Teachey DT, Lacey SF, Shaw PA, Melenhorst JJ, Maude SL, Frey N, et al. Identification of 
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YESCARTA, Kite Pharma Inc. YESCARTA® (axicabtagene ciloleucel) Suspension for 
Intravenous Infusion. U. S. Prescribing Information. Santa Monica, CA. Revised: 
May.  2019:


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18.
APPENDICES
Appendix 1.
International Working Group Lugano Classification {Cheson 2014}
Appendix 2.
Birth Control Methods Which May Be Considered as Highly Effective
Appendix 3.
Immune Effector Cell-associated Encephalopathy (ICE) Score
Appendix 4.
European regulatory agency requirements


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Appendix 1.
International Working Group Lugano Classification {Cheson 2014}
Score
Description
1
No uptake above background
2
Uptake ≤ mediastinum
3
Uptake > mediastinum but ≤ liver
4
Uptake moderately higher than liver
5
Uptake markedly higher than liver and/or new lesions
X
New areas of uptake unlikely to be related to lymphoma
Complete Remission:
Complete Metabolic Response for Positron Emission Tomography–Computed 
Tomography-Based Response
The designation of complete metabolic response requires all of the following:

A 5PS (5-point scale) score of 1, 2, or 3, with or without a residual mass.
In Waldeyer’s ring or extranodal sites with high physiologic uptake or with activation 
within spleen or marrow, uptake may be greater than normal in the mediastinum and/or 
liver. In this circumstance, complete metabolic response may be inferred if uptake at sites 
of initial involvement is no greater than surrounding normal tissue even if the tissue has 
high physiologic uptake.

No new sites of disease should be observed

No evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow
Complete Radiologic Response for Computed Tomography-Based Response
The designation of complete radiologic response requires all of the following:

Target nodes/nodal masses must regress to ≤ 1.5 cm in longest transverse diameter (LDi) of a 
lesion

No extra lymphatic sites of disease

Absent nonmeasured lesion

Organ enlargement regress to normal

No new sites of disease should be observed

Bone marrow normal by morphology; if indeterminate, immunohistochemistry negative


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Partial Remission:
Partial Metabolic Response for Positron Emission Tomography–Computed Tomography-Based 
Response
The designation of partial metabolic response requires all of the following:

A 5PS score of 4 or 5, with reduced uptake compared to baseline (screening), and residual 
mass (es) of any size.
Note:
At interim, these findings suggest responding disease.
At end of treatment, these findings suggest residual disease.

No new sites of disease should be observed

Residual uptake is higher than uptake in normal bone marrow but reduced compared with 
baseline (diffuse uptake is compatible with reactive changes from chemotherapy allowed).
If there are persistent focal changes in the marrow in the context of a nodal response, 
consideration should be given to further evaluation with magnetic resonance imaging or biopsy 
or an interval scan.
Partial Radiologic Response for Computed Tomography-Based Response
The designation of partial radiologic response requires all of the following:

≥ 50% decrease in sum of the product of the perpendicular diameters of up to 6 target 
measurable nodes and extranodal sites.
When a lesion is too small to measure on a computed tomography scan, assign 5 mm x 
5 mm as the default value
When no longer visible, 0 x 0 mm
For a node > 5 mm x 5 mm, but smaller than normal, use actual measurement for 
calculation

Absent/normal, regressed, but no increase of nonmeasured lesions

Spleen must have regressed by > 50% in length beyond normal

No new sites of disease should be observed


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Stable Disease:
No Metabolic Response for Positron Emission Tomography–Computed Tomography-Based 
Response
The designation of no metabolic response requires all of the following:

A 5PS score of 4 or 5, with no significant change in FDG uptake compared to baseline 
(screening) at an interim time point or end of treatment

No new sites of disease should be observed

No change from baseline in bone marrow
Stable Radiologic Disease for Computed Tomography-Based Response
The designation of stable radiologic disease requires all of the following:

< 50% decrease from baseline in the sum of the product of the perpendicular diameters of up 
to 6 dominant, measurable nodes and extranodal sites; no criteria for progressive disease are 
met

No increase consistent with progression in nonmeasured lesion and organ enlargement

No new sites of disease should be observed.
Progressive Disease:
Progressive Metabolic Disease for Positron Emission Tomography–Computed 
Tomography-Based Response
The designation of progressive metabolic disease requires at least one of the following:

A 5PS score 4 or 5 with an increase in intensity of uptake from baseline nadir and/or

New FDG-avid foci consistent with lymphoma at interim or end of treatment assessment

New FDG-avid foci consistent with lymphoma rather than another etiology 
(eg, infection, inflammation). If uncertain regarding etiology of new lesions, biopsy or 
interval scan may be considered

New or recurrent FDG-avid foci in bone marrow


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Progressive Radiologic Disease for Computed Tomography-Based Response
The designation of progressive radiologic disease requires at least one of the following:

An individual node/lesion must be abnormal with:
LDi > 1.5 cm and
Increase by ≥ 50% from cross product of LDi and perpendicular diameter nadir and
An increase in LDi or shortest transverse diameter, shortest axis perpendicular to the LDi, 
(shortest transverse diameter) from nadir
■
0.5 cm for lesions ≤ 2 cm
■
cm for lesions > 2 cm
In the setting of splenomegaly, the splenic length must increase by > 50% of the extent of 
its prior increase beyond baseline (eg, a 15-cm spleen must increase to > 16 cm). If no 
prior splenomegaly, spleen must increase by at least 2 cm from baseline;
New or recurrent splenomegaly

New or clear progression of preexisting nonmeasured lesions

New lesion
Regrowth of previously resolved lesions
A new node > 1.5 cm in any axis
o A new extranodal site > 1.0 cm in any axis; if < 1.0 cm in any axis, its presence must be 
unequivocal and must be attributable to lymphoma
Assessable disease of any size unequivocally attributable to lymphoma

New or recurrent bone marrow involvement


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Appendix 2.
Birth Control Methods Which May Be Considered as Highly Effective
For the purpose of this guidance, 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.1  
Such methods include:

Combined (estrogen and progesterone containing) hormonal contraception associated with 
inhibition of ovulation2:
Oral
Intravaginal
Transdermal

Progestogen-only hormonal contraception associated with inhibition of ovulation2:
Oral
Injectable
Implantable3

Intrauterine device3

Intrauterine hormone-releasing system3

Bilateral tubal occlusion3

Vasectomized partner 3,4

Sexual abstinence5
1
2014 clinical trial facilitation and coordination group contraception guidance
2
Hormonal contraception may be susceptible to interaction with the investigational product, which may reduce the efficacy of 
the contraception method.
3
Contraception methods that in the context of this guidance are considered to have low user dependency.
4
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.
5
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 3.
Immune Effector Cell-associated Encephalopathy (ICE) Score 
ICE1
Orientation: orientation to year, month, city, hospital: 4 points
Naming: ability to name 3 objects (eg, point to clock, pen, button): 3 points
Following commands: ability to follow simple commands (eg, “Show me 2 fingers” or “Close your eyes and stick 
out your tongue”): 1 point
Writing: ability to write a standard sentence (eg, “Our national bird is thebald eagle”): 1 point
Attention: ability to count backwards from 100 by 10: 1 point
1
ICE score as developed by the American Society for Transplantation and Cellular Therapy consensus grading for cytokine 
release syndrome and neurologic toxicity associated with immune effector cells (2019) {Lee 2019}


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Appendix 4.
European regulatory agency requirements
The post-infusion monitoring of subjects (described in Section 6.2.2.3 and Section 7.13.6.2 of 
this protocol) will be extended by monitoring on Day 8, Day 9, and Day 10, according to 
procedures outlined in Table 3, column “IP Admin, D1 to 7”. 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 (see Section 7.4), blood draw for chemistry panel 
with CRP, blood draw for CBC w/differential, and neurological assessment (see Section 7.11). 
Any observed toxicity will be managed according to Section 6.1.9 of this protocol.

SAP_001.pdf: 
Sponsor:
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
United States of America
Company Code:
KTE-C19
USAN Name:
Axicabtagene ciloleucel
Lenzilumab
Protocol
A Phase 1/2 Open-label, Multicenter Study of Lenzilumab and 
Axicabtagene Ciloleucel in Subjects with Relapsed or Refractory Large B-
cell Lymphoma (ZUMA-19)
Version Number:
1.0
Release Date:
12 June 2020
Replaces Previous Version(s):
NA
CONFIDENTIALITY NOTICE
This document contains confidential information of Kite Pharma Inc., a wholly owned subsidiary 
of Gilead Sciences, Inc.    This document must not be disclosed to anyone other than the site 
research staff and members of the institutional review board/independent ethics committee, a 
scientific review board, or an equivalent.  The information in this document cannot be used for 
any purpose other than the conduct of the clinical investigation without the prior written consent 
of Kite Pharma, Inc.  Questions regarding how this document should be used or the conduct of 
the clinical trial should be directed to the key sponsor contacts.
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KT-US-471-0119
Version 1.0
Statistical Analysis Plan
Kite Pharma, Inc.
Confidential
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12 June 2020
TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF TABLES.........................................................................................................................................................3
LIST OF FIGURES.......................................................................................................................................................3
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS................................................................................4
1.
INTRODUCTION ................................................................................................................................................6
2.
OBJECTIVES.......................................................................................................................................................7
3.
STUDY DESIGN..................................................................................................................................................8
3.1.
Overview..................................................................................................................................................8
3.2.
Hypothesis..............................................................................................................................................11
3.3.
Sample Size Consideration.....................................................................................................................11
4.
STUDY ENDPOINTS AND COVARIATES ....................................................................................................12
4.1.
Endpoints ...............................................................................................................................................12
4.1.1.
Primary Endpoint .................................................................................................................12
4.1.2.
Secondary Endpoints............................................................................................................12
4.2.
Subgroups and Covariates......................................................................................................................12
5.
DEFINITIONS....................................................................................................................................................14
5.1.
General...................................................................................................................................................14
5.2.
Safety .....................................................................................................................................................15
5.3.
Efficacy..................................................................................................................................................19
6.
ANALYSIS SETS...............................................................................................................................................20
6.1.
Full Analysis Set ....................................................................................................................................20
6.2.
Primary Objective Analysis Set .............................................................................................................20
6.3.
Modified Intent-to-treat Analysis Set.....................................................................................................20
6.4.
Safety Analysis Set ................................................................................................................................20
6.5.
DLT Evaluable Set.................................................................................................................................20
7.
INTERIM ANALYSIS AND EARLY STOPPING GUIDELINES...................................................................21
8.
DATA SCREENING AND ACCEPTANCE......................................................................................................22
8.1.
General Principles ..................................................................................................................................22
8.2.
Electronic Transfer and Archiving of Data ............................................................................................22
8.3.
Handling of Missing and Incomplete Data.............................................................................................22
8.3.1.
Efficacy ................................................................................................................................22
8.3.2.
Safety....................................................................................................................................22
8.4.
Detection of Bias....................................................................................................................................22
8.5.
Outliers...................................................................................................................................................22
8.6.
Distributional Characteristics.................................................................................................................23
8.7.
Validation and Configuration Management ...........................................................................................23
9.
STATISTICAL METHODS OF ANALYSIS ....................................................................................................24
9.1.
General Principles ..................................................................................................................................24
9.2.
Subject Accountability...........................................................................................................................24
9.3.
Important Protocol Deviations ...............................................................................................................24
9.4.
Demographic and Baseline Characteristics............................................................................................24
9.5.
Grade 2 or Higher Neurologic Events Rate............................................................................................25
9.6.
Safety Analyses......................................................................................................................................26


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9.7. 
9.8. 
9.9. 
9.10. 
9.11. 
9.12. 
9.13. 
9.14. 
9 .6.1. 
Adverse Events ..................................................................................................................... 26 
9.6.2. 
Neurological Assessment ..................................................................................................... 27 
9.6.3. 
Laboratory Test Results ........................................................................................................ 27 
9.6.4. 
Replication Competent Retrovirus ....................................................................................... 27 
Efficacy Analyses ................................................................................................................................... 27 
9.7.1. 
Complete Response and Objective Response ....................................................................... 28 
9.7.2. 
Duration of Response ........................................................................................................... 28 
9.7.3. 
Progression Free Survival .................................................................................................... 28 
9.7.4. 
Overall Survival ................................................................................................................... 28 
9.7.5. 
Tumor Burden ...................................................................................................................... 28 
Exposure to Study Treatments and Product Characteristics ................................................................... 29 
Exposure to Concomitant Medications and Procedures ......................................................................... 29 
Subsequent Anti-Cancer Therapy and Subsequent Stem Cell Transplant .............................................. 30 
Duration Metrics .................................................................................................................................... 30 
Axicabtagene Ciloleucel Delivery Time ................................................................................................ 30 
Hospitalization and Health Care Facility Use ........................................................................................ 30 
Additional Anal sis ................................................................................................................................ 30 
10. CHANGES FROM PROTOCOL SPECIFIED ANALYSES ............................................................................. 32 
11. 
REFERENCES ................................................................................................................................................... 33 
12. APP ENDICES .................................................................................................................................................... 34 
Appendix I. 
Appendix 2. 
Appendix 3. 
Table I 
Table 2. 
Table 3. 
Table 4. 
Table 5. 
Table 6. 
Table 7. 
Figure I. 
Confidential 
Conventions for Clinical Data That Require Imputation for Partial or Missing Dates ........... 35 
Derivation of Time to Event Endpoints .................................................................................. 37 
Derivation of Last date known to be alive .............................................................................. 40 
LIST OF TABLES 
Simon's Two-stage Design for RP2D1 Cohort ....................................................................... 11 
Imputation Rules for Partial or Missing Start Dates ............................................................... 35 
Primmy Analysis of DOR ...................................................................................................... 37 
Sensitivity Analysis of DOR .................................................................................................. 38 
Primmy Analysis of PFS ........................................................................................................ 38 
Sensitivity Analysis of PFS .................................................................................................... 39 
Imputation Rule of OS Event/Censoring Date ....................................................................... 39 
LIST OF FIGURES 
Schematic of Study Design ...................................................................................................... 9 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Definition
ADaM
Analysis data model
AE
Adverse event
ASCT
Autologous stem cell transplant
BSA
Body surface area
CAR
Chimeric antigen receptor
CNS
Central nerve system
CR
Complete response 
CRF
Case report form
CRS
Cytokine release syndrome
CTCAE
Common terminology criteria for adverse event
DLBCL
Diffuse large B-cell lymphoma
DOR
Duration of response 
ECOG
Eastern Cooperative Oncology Group
HLGT
High-level group term
GM-CSF
Granulocyte macrophage-colony stimulating factor
ICANS
Immune Effector Cell-Associated neurotoxicity syndrome
ICE
Immune effector cell –associated encephalopathy
IPD
Important protocol deviations
MedDRA
Medical Dictionary for Regulatory Activities
mITT
Modified intent-to-treat 
NCI
National Cancer Institute
NHL
Non-Hodgkin lymphoma
ORR
Objective response rate 
PD
Progressive disease 
PFS
Progression free survival 
PK
Pharmacokinetics
PR
Partial response
RCR
Replication-competent retrovirus
RP2D
Recommended Phase 2 Dose
OS
Overall survival 


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Abbreviation
Definition
SAE
Serious adverse event
SAP
Statistical analysis plan
SCT
Stem cell transplant
SD
Stable disease
SDTM
Study data tabulation model 
SMQ
Standardized MedDRA query 
SOC
System organ class
SOP
Standard operating procedure
SPD
Sum of the product of the diameters 
SRT
Safety review team
TEAE
Treatment-emergent adverse event
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) sets forth prospectively the details of statistical analyses that 
are outlined in protocol KT-US-471-0119 entitled “A Phase 1/2 Open-label, Multicenter Study 
of Lenzilumab and Axicabtagene Ciloleucel in Subjects with Relapsed or Refractory Large B-
cell Lymphoma (ZUMA-19)”.


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2.
OBJECTIVES
The primary objective of Phase 1 of the study is to evaluate the safety of sequenced therapy with 
lenzilumab and axicabtagene ciloleucel in subjects with relapsed or refractory large B-cell 
lymphoma. 
In Phase 2, the primary objective is to evaluate the incidence of Grade 2 or higher neurologic 
events with sequenced therapy given at the recommended Phase 2 dose (RP2D) of lenzilumab in 
subjects with relapsed or refractory large B-cell lymphoma. 
Secondary objectives will include evaluating the safety and efficacy of sequenced therapy, the 
extent of granulocyte macrophage-colony stimulating factor (GM-CSF) axis suppression in the 
blood, and the levels of chimeric antigen receptor (CAR) T cells and cytokines in the blood. 


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3.
STUDY DESIGN
3.1.
Overview
This is a Phase 1/2, open-label, multicenter study evaluating lenzilumab use to prevent 
axicabtagene ciloleucel treatment-related toxicities in subjects with relapsed or refractory large 
B-cell lymphoma. The addition of lenzilumab to the approved axicabtagene ciloleucel treatment 
regimen will hereafter be referred to as sequenced therapy.  
In Phase 1, a 3+3 design will be used to determine the RP2D of lenzilumab within sequenced 
therapy for large B-cell lymphoma. The RP2D of lenzilumab will be determined primarily by 
clinical assessment of the incidence of dose-limiting toxicity (DLT) related to sequenced 
therapy. In addition to evaluation of DLT incidence, the extent of GM-CSF axis suppression as 
assessed by translational analysis may be assessed in defining the RP2D.  
Once the RP2D is determined, the study will convert to Phase 2 and assume a Simon 2-stage 
design. After 14 subjects have been treated with sequenced therapy at the RP2D of lenzilumab 
and followed for 28 days across Phase 1 and Phase 2, futility of sequenced therapy to 
demonstrate a significant decrease, compared to historical controls as seen in ZUMA 1 Cohorts 1 
and 2, in the incidence of Grade 2 or higher neurologic events will be assessed. If the futility 
threshold is not met, an additional 16 subjects will be treated with sequenced therapy at the 
RP2D of lenzilumab to complete accrual.
In total, approximately 36 subjects will be enrolled and treated during the study.
In Phase 1, a Safety Review Team (SRT) will pause enrollment to review safety data after 3 and 
6 (as needed) subjects have been followed for 28 days after sequenced therapy in each dose 
escalation cohort. At the conclusion of dose escalation, the SRT will determine the RP2D of 
lenzilumab and conversion to Phase 2. The SRT can meet more often if needed.
Once the study converts to Phase 2, the SRT will convene after a total of 14 subjects have been 
treated at the RP2D across Phase 1 and Phase 2, and have been followed for at least 28 days after 
axicabtagene ciloleucel administration. At this time, enrollment will be paused for safety data 
review and interim/futility analysis. If the SRT determines that the study does not meet criteria 
for futility, an additional 16 subjects will be enrolled to complete accrual.


Figure 1.
Schematic of Study Design
A) Phase 1
Assess Safety 
:!: 2/3 DLTs 
Evaluation: 
Safety 
(n=3) 
1/3 
DLTs 
0/3 DLT 
Cohort2 
1800 mg 
I :!: 2/6 DLTs 
Evaluation: 
Safety 
(N =6) 
S1/6DLT 
r -
-
I ::: 2 
I DLTs 
I 
Evaluation: 
Safety 
(n=3) 
1< 2 DLTs 
I 
I 
Evaluation of Safety and 
Translational 
Assessment: Cohort 1 
(N =6) 
I :!: 2/6 DLT 
I 
Lower DL T rate 
1/6 DL T inconsistent 
with CAR therapy 
Evaluation: 
RP2D 
600 mg 
Translational Assessment: 
GM-CSF Axis Suppression to 
Inform RP2D Selection 
Safety 
(N =6) 
1ffi DL T<oo,o,rernwlth 
-
CAR therapy 
• • • 
: 11 
t 
I 
I 0/6DLT 
-·• 
-----------
: 11 
• 


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B) Phase 2
Abbreviations: CAR, chimeric antigen receptor; DLT, dose limiting toxicity; RP2D, recommended Phase 2 dose.
Evaluation: 
Safety and 
Futility in 
RP2D Treated 
Subjects 
N=14 
Futile 
. .  
•. 
I 
-
-
-
-
,f 
Complete 
Accrual: 
.. 
RP2D Treated 
Subjects 
(N=30) 
Primary analysis 
of RP2D Treated 
Subjects6 
months after 
treatment 


3.2. 
Hypothesis 
This Phase 2 portion of the study is designed to differentiate between a treatment that has a true 
event rate of 20% or less and a treatment with an event rate of 45% or more. The hypothesis is 
that the Grade 2 or higher neurologic event rate related to sequenced therapy is significantly less 
than 45%. No hypothesis will be tested during Phase 1 of the study. 
3.3. 
Sample Size Consideration 
The anticipated enrollment in this study is approximately 3 to 36 subjects. 
Up to 6 subjects in each cohort will be enrolled and treated in Phase 1 of this study. 
If the study proceeds to the Phase 2, up to an additional 24 subjects will be enrolled at the RP2D 
for assessment of the reduction in the incidence of Grade 2 or higher neurologic event seen by 
adding lenzilumab to the axicabtagene ciloleucel regimen. 
Simon's 2-stage design {Simon 1989} is used to calculate the sample size for the RP2D 
cohort. The null hypothesis that the event rate is 45% will be tested against the alternative 
hypothesis that the event rate is 20% or less at 1-sided alpha of 2.5%. In Stage 1, 14 subjects will 
be accrued and treated at the RP2D (including subjects treated at the RP2D under both Phase 1 
and Phase 2). If there are 5 or more subjects with Grade 2 or above neurologic events in these 14 
Stage 1 subjects, the study will be stopped for futility at the discretion of the SRT. Otherwise, 16 
additional subjects will be accrued and treated at the RP2D for a total of 30. The null hypothesis 
will be rejected if 8 or fewer subjects with Grade 2 or above neurologic events are observed in 
the 30 subjects. This design yields a 1-sided type I error rate of 0.025 for rejecting true null 
hypothesis and power of 80% when the true event rate is 20% or less. The robabili of early 
sto 
in when the null h 
othesis is true is 0.8328 
Table 1 
Simon's Two-stage Design for RP2D1 Cohort 
Stages 
Total Number of Subjects 
Target Number of Subjects with Events 
Stage I 
14 
< 5 
Stage 2 
30 
< 9 
1RP20 : recommended phase 2 dose 
All analyses for the incidence of Grade 2 or higher neurologic event in Phase 1 and Phase 2 
portions of the study will be based on a primary objective analysis set consisting of all subjects 
who receive axicabtagene ciloleucel at a minimum dose of 1.6 x 106 anti-CD 19 CAR T cells/kg 
(or a minimum dose of 1.6 x 108 anti-CD19 CAR T cells for subjects who weigh more than 
100 kg) and target dose of lenzilumab. 
Inferential testing will be perfonned only for the primary endpoint in Phase 2 of the study. 


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4.
STUDY ENDPOINTS AND COVARIATES
4.1.
Endpoints
4.1.1.
Primary Endpoint
Phase 1: Incidence of DLT related to sequenced therapy with lenzilumab and axicabtagene 
ciloleucel
Phase 2: Incidence of Grade 2 or higher neurologic events within 28 days of axicabtagene 
ciloleucel administration 
4.1.2.
Secondary Endpoints
Phase 1 and 2:

The incidence AEs and SAEs, including CRS and neurologic events

Objective Response Rate (complete response [CR] + partial response [PR]) per the Lugano 
Classification (Cheson et al, 2014), as determined by study investigators

Complete Response rate per the Lugano Classification (Cheson et al, 2014), as determined by 
study investigators

Axicabtagene ciloleucel pharmacodynamics: levels of cytokines (including free GM-CSF) in 
blood

Axicabtagene ciloleucel pharmacokinetics (PK): levels of anti-CD19 CAR T cells in blood
Phase 2:

Duration of Response (DOR), as determined by study investigators

Progression Free Survival (PFS), as determined by study investigators 

Overall Survival (OS)
4.2.
Subgroups and Covariates
The following variables may be used to examine efficacy results in subgroups analyses, as well 
as safety analyses. Analyses might be subject to restrictions due to small sample size.

Eastern Cooperative Oncology Group (ECOG) performance status (0, 1)

Age at baseline (<65 years, ≥65 years)


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
Race

Gender

Histologically proven diffuse large B-cell lymphoma (DLBCL) type  

Cell of origin

Double/Triple hit status

Disease stage at screening

Age-adjusted International Prognostic Index (IPI) total score at screening

Relapse/refractory subgroup 

Lines of prior therapies for the study disease

Bulky disease (at least one lesion with largest diameter ≥10 cm))  

Tumor burden at baseline, as measured by the sum of the product of the diameters (SPD) of 
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5.
DEFINITIONS
5.1.
General
Study enrollment: Study enrollment occurs when subject commences leukapheresis. 
Study Day 0: Defined as the day the subject receives the first axicabtagene ciloleucel infusion. 
The day prior to Day 0 will be study day -1. Any days prior to Day 0 will be sequential and 
negative integer-valued. 
Baseline: Defined as the last non-missing value measured on or prior to conditioning 
chemotherapy, unless specified otherwise.
Relapse/refractory Subgroup at Baseline: 

Primary refractory:  A subject is considered to be primary refractory if the subject 
experienced disease progression as best response to first line therapy or had stable disease
(SD) after at least 4 cycles of first line therapy with duration of SD no longer than 6 months 
from the last dose of therapy.

Refractory to 2nd or greater line therapy:  A subject is considered to be refractory to 2nd or 
greater line therapy if the patient experienced progressive disease (PD) as best response to 
the most recent therapy regimen or experienced SD after at least 2 cycles of therapy with 
duration of SD no longer than 6 months. 

Relapsed to 2nd or greater line therapy: A subject is considered to be relapsed to 2nd or greater 
line therapy if the patient experienced PR/CR as best response to the most recent therapy 
regimen and then subsequently had PD.

Relapse post ASCT:  A subject is considered to be relapsed post-ASCT if the subject 
experienced relapse ≤ 12 months of ASCT.
In case a subject may meet the criteria for multiple refractory subgroups, this subject will be 
assigned to the subgroup based on the hierarchy of priority of Refractory post ASCT > 
Refractory/relapse to second or greater line of therapy > Primary refractory disease.  

Actual follow-up time:  Actual follow-up time among all subjects treated with axicabtagene 
ciloleucel is calculated as the time from the axicabtagene ciloleucel infusion to the date of 
death, last date known to be alive, lost to follow-up, or full withdrawal of consent, whichever 
is later.

Potential follow-up time:  Potential follow-up time is defined as the time from the 
axicabtagene ciloleucel infusion to the data cutoff date for the analysis.


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5.2.
Safety
Treatment-emergent adverse event (TEAE):  any adverse event with onset on or after 
lenzilumab administration.
Deaths: Any death occurring after the leukapheresis up through the end of study.
Adverse events of interest: The following AEs are of interest for the treatments of axicabtagene 
ciloleucel in combination with lenzilumab:  
Identified risks: 

Cytokine-release syndrome (CRS) 

Neurologic events

Cytopenias 

Infections

Hypogammaglobulinemia
Potential risks: 

Secondary malignancy

Replication competent retrovirus (RCR)

Autoimmune disorders
CRS: CRS is identified via collection of the syndrome on a case report from (CRF) specifically 
designed to collect CRS. Specific individual symptoms of CRS (eg, fever) collected on the AE 
log are coded using MedDRA and linked to the corresponding CRS episode. Individual 
symptoms of CRS are graded per the latest version of Common Terminology Criteria for 
Adverse Events (CTCAE), and CRS as a syndrome is graded per modified Lee criteria (Lee et al, 
2014). In the modified grading scale, neurologic AEs are not reported as part of the CRS 
syndrome as they will be reported separately with the neurologic events category and graded per 
the latest version of CTCAE v4.03.
Neurologic events: Neurologic adverse events are identified with a search strategy based on 
known neurologic toxicities associated with anti-CD19 immunotherapy (Topp et al, 2015).  The 
search strategy focuses on central nervous system toxicity, without regard to temporal 
relationship or concomitant conditions (e.g. CRS).   This method will be used to identify 
neurologic AEs for primary endpoint. Additionally, the MedDRA system organ classes (SOCs) 
of Psychiatric Disorders and Nervous System Disorders will be reviewed for additional events; 
these events will then be evaluated for potential inclusion as neurologic AEs.


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Cytopenias:  Cytopenias (neutropenia, anemia, and thrombocytopenia) are identified as: 

Neutropenia is identified using the latest version of MedDRA search terms (MST) 
documented prior to each analysis.

Anemia (including aplastic anemia) is identified using the standardized MedDRA query 
(SMQ) haematopoietic erythropenia (broad search).

Thrombocytopenia is identified using the SMQ haematopoietic thrombocytopenia (narrow
search).
Longest consecutive period with cytopenias is calculated as the greatest number of consecutive 
days (without gaps between events) that subjects experiencing the AE of interest without gaps 
between events.  For subjects who have AEs without reported ending dates, the longest 
consecutive period will be calculated with the ending dates of such AEs imputed using the 
earliest date of the data extraction date (or the data cutoff date, if applicable), study 
discontinuation date and the death date (if applicable). Prolonged cytopenias (neutropenia or 
thrombocytopenia or anemia) will be summarized separately by the three blood cell lineages. 
Infections:  Infections are identified as AEs within the MedDRA SOC of Infections and 
Infestations that occur after treatment with anti-CD19 CAR T cells. Subtypes of infections are 
identified using MedDRA high level group terms (HLGT) that capture events of: 

Bacterial infection, encompassing the MedDRA HLGTs of 
Bacterial infectious disorders 
Chlamydial infectious disorders

Viral infection, encompassing the MedDRA HLGT of viral infectious disorders

Opportunistic infections, encompassing the MedDRA HLGTs of 
Fungal infectious disorders
Mycobacterial infectious disorders

Other infections, encompassing the MedDRA HLGT of Infections pathogen unspecified 
Hypogammaglobulinemia: Hypogammaglobulinemia will be identified using a MST search 
strategy defined by Kite.  
Secondary malignancy:  Secondary malignancies are identified via collection on a case report 
form in which the investigator classifies the event as a secondary malignancy.  Additionally, 
adverse events that are coded into the SOC of Neoplasms benign, malignant, and unspecified 
(including cysts and polyps) with the exception of preferred terms containing “B-cell” or “B 
cell” and “Lymphoma”  will be reviewed to identify other potential events.  


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Autoimmune disorders: Autoimmune disorders are identified via collection on a case report 
form in which the investigator classifies the event as an autoimmune disorder. Additionally, 
adverse events that are coded into the MedDRA HGLT of auto-immune disorders within the 
immune system disorders SOC will be reviewed to identify other potential events.
Study day of onset of event/syndrome: Study day of onset of an event/syndrome is defined as 
the study day of the first occurrence of the event/syndrome. Study day of Onset of Grade 3 or 
Higher Events/Syndromes are defined in the same way, but restricted to Grade 3 or higher 
events/syndromes.
Study day of resolution of an event/syndrome: Study day of resolution of an event/syndrome 
is the last study day the event is present. If multiple events occur after axicabtagene ciloleucel 
infusion, the study day of resolution is the last day of the multiple events presented. Study day of 
resolution will not be calculated for events that are ongoing at the time of the data cutoff date or 
death.  
Duration of an AE of interest: The duration of an AE of interest may be derived only among 
subjects for whom all events of the class have resolved by the analysis data cutoff date. The 
duration is defined as the time from the earliest onset date of the AEs in the event class of 
interest through the resolution date of the last AEs in the event class, regardless of the gaps of the 
days between multiple events, ie, the resolution date of the last AE in the event class the start 
date of the first AE in the event class + 1.  
DLT: DLT is defined as the following sequenced therapy-related events with onset within the 
first 28 days following axicabtagene ciloleucel infusion:

Grade 4 neutropenia lasting longer than 21 days from the day of cell transfer

Grade 4 thrombocytopenia lasting longer than 28 days from the day of cell transfer

Any sequenced therapy-related AE requiring intubation, including Grade 4 encephalopathy 
requiring intubation for airway protection, is considered to be a DLT

Any sequenced therapy-related Grade 5 event

All other clinically significant Grade 3 toxicities lasting more than 3 days and all Grade 4 
toxicities, with the exception of the following conditions which are not considered DLT’s:
Encephalopathy that resolves to at worst Grade 1 within 2 weeks and to baseline within 4 
weeks
Grade 3 fever 
Myelosuppression (includes bleeding in the setting of platelet count < 50 x109/L and 
documented bacterial infections in the setting of neutropenia), defined as lymphopenia, 
decreased hemoglobin, neutropenia, and thrombocytopenia unless neutropenia and 
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Immediate hypersensitivity reactions occurring within 2 hours of cell or lenzilumab 
infusion that are reversible to Grade 2 or less within 24 hours of administration with 
standard therapy
Renal toxicity which requires dialysis for ≤ 7 days 
Tumor lysis syndrome including associated manifestations attributable to tumor lysis 
syndrome (eg, electrolyte abnormalities, renal function, hyperuricemia)
Grade 3 transaminase, alkaline phosphatase, bilirubin or other liver function test 
elevation, provided there is resolution to ≤ Grade 2 within 14 days
Grade 4 transient serum hepatic enzyme abnormalities provided there is resolution to 
≤Grade 3 within < 72 hours
Grade 3 or 4 hypogammaglobulinemia
Grade 3 nausea or anorexia 
CRS will be graded according to a revised grading system {Lee 2014}, as described in the 
current axicabtagene ciloleucel IB. Adverse events attributed to CRS will be mapped to the 
overall CRS grading assessment for the determination of DLT. If Grade 3 or 4 CRS per Lee 2014 
is due to one of the exceptions above, the event will not be considered a DLT.


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5.3.
Efficacy
Complete Response Rate (CRR):  The proportion of subjects with a CR while after treatment 
with axicabtagene ciloleucel and prior to any subsequent anti-lymphoma therapy. Subjects who 
do not meet the criteria for CR by the analysis cutoff date will be considered non-CR. The 
derivation of this endpoint will only include response assessments obtained after axicabtagene 
ciloleucel infusion, and prior to any subsequent therapies for non-Hodgkin lymphoma (NHL)
(including stem cell transplant [SCT]).  Responses will be assessed per the Lugano Classification 
(Cheson et al, 2014), as determined by the study investigators.
Objective Response Rate (ORR):  The proportion of subjects with a CR or PR while after 
treatment with axicabtagene ciloleucel and prior to any subsequent anti-lymphoma therapy. 
Subjects who do not meet the criteria for objective response by the analysis cutoff date will be 
considered non-responders.  The derivation of this endpoint will only include response 
assessments obtained after axicabtagene ciloleucel infusion, and prior to any subsequent 
therapies for NHL (including SCT).  Responses will be assessed per the Lugano Classification 
(Cheson et al, 2014), as determined by the study investigators. 
Duration of response (DOR): DOR is defined only for subjects who experience an objective 
response (CR or PR) and is the time from the first objective response to disease progression per 
the Lugano Classification (Cheson et al, 2014) as determined by study investigators or death due 
to any reason. 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. Subjects who receive subsequent anti-cancer therapy in the absence of 
documented progression will be censored at the last evaluable disease assessment prior to the 
subsequent therapy. Subjects who receive an SCT in the absence of documented progression will 
be censored at the last evaluable disease assessment prior to the date of the SCT. A sensitivity 
analysis will be conducted in which disease assessments obtained after SCT while in 
axicabtagene ciloleucel induced remission are included in the derivation of DOR. Additional 
details on the derivation of DOR are provided in Appendix 2. 
Progression-free Survival (PFS): PFS is defined as the time from the axicabtagene ciloleucel 
infusion date to the date of disease progression per the Lugano Classification (Cheson et al, 
2014) as determined by study investigators or death from any 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. The PFS for subjects who undergo SCT while in remission 
will be censored at the last evaluable disease assessment prior to the date of SCT; the PFS for 
subjects who undergo other new anti-cancer therapies in the absence of documented relapse will 
be censored at the last evaluable disease assessment prior to the new anti-cancer therapies. A 
sensitivity analysis will be conducted in which disease assessments obtained after SCT while in 
axicabtagene ciloleucel induced remission are included in the derivation of PFS. Additional
details on the derivation of PFS are provided in Appendix 2.
Overall Survival (OS): OS is defined as the time from the axicabtagene ciloleucel infusion to 
the date of death. Subjects who have not died by the analysis data cutoff date will be censored at 
their last date known to be alive or the data cutoff date, whichever is earlier.  Further details on 
the derivation of OS and the specific data modules that will be used to derive the last date known 
to be alive are provided in Appendix 2.   


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6. 
ANALYSIS SETS 
The following analyses sets are defined for this study. 
6.1. 
Full Analysis Set 
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Kite Pharma, Inc. 
The full analysis set (FAS) will consist of all enrolled subjects (i.e., c01mnences leukapheresis) 
and will be used for the smmnary of subject disposition and list of death. 
6.2. 
Primary Objective Analysis Set 
The primary objective analysis set will consist of all subjects enrolled and treated with 
axicabta ene ciloleucel at a minimmn dose of 
anti-CD19 CART cells/k 
and target dose of lenzilumab at the reco1mnended phase 2 dose (RP2D) (including Phase 1 and 
Phase 2) prior to axicabtagene ciloleucel infusion. This analysis set will be used for the primary 
endpoint analysis. Sensitivity analysis for neurologic events/assessments, CRS, and SAE may be 
perfonned using primary objective analysis set. 
6.3. 
Modified Intent-to-treat Analysis Set 
The modified intent-to-treat set will consist of all subjects enrolled and treated with axicabta ene 
ciloleucel at a minimum dose of 
anti-CD 19 CAR T cells/k 
-
and target dose of 
lenzilmnab at the RP2D (including Phase 1 and Phase 2) prior to axicabtagene ciloleucel 
infusion. This analysis set will be used for all efficacy analyses. 
6.4. 
Safety Analysis Set 
Safety analysis set is defined as all subjects treated with any dose of axicabtagene ciloleucel 
and/or any dose of lenzilmnab. This analysis set will be used for all safety analyses except for the 
primary endpoint. 
6.5. 
DL T Evaluable Set 
DLT evaluable set defined for each dosing cohort in Phase 1, will include subjects treated in the 
Phase 1 dosing cohort who: 
• 
Received the target dose of lenzilumab (within ±10% of the planned dose) and axicabtagene 
ciloleucel (within ±20% of the planned dose) and were followed for at least 28 days after the 
anti-CD19 CART cell infusion; or 
• 
Received a dose of lenzilmnab lower than the target for that cohort and experienced a DL T 
during the 28-day after the anti-CD 19 CART cell infusion. 
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7. 
INTERIM ANALYSIS AND EARLY STOPPING GUIDELINES 
During Phase 1, the Safety Review Team (SRT) will review safety data after 3 and 6 (as needed) 
subjects have been followed for 28 days after their axicabtagene ciloleucel administration in each 
dose escalation cohort and will make reco1mnendations on further study conduct and progression 
of the study. At the conclusion of dose escalation, the SRT will detennine the RP2D and 
conversion to Phase 2. 
During Phase 2, the SRT will assess safety and futility through an interim analysis once 
14 subjects are enrolled and treated with axicabta ene ciloleucel at a minimmn dose o 
anti-CD19 CART cells/k 
and lenzilumab at the RP2D (including Phase 1 and Phase 2) prior 
to ax1ca tagene c1 o euce m sion, and have had the opportunity to be followed for 28 days after 
the axicabtagene ciloleucel dose. According to Simon's optimal 2-stage design, if there are 5 or 
more subjects with events in the 14 Stage 1 subjects, the study will be stopped at the discretion 
of the SRT. This timing will coincide with an interim analysis. 
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8.
DATA SCREENING AND ACCEPTANCE
8.1.
General Principles
The database will be subject to the edit checks outlined in the Data Management Plan and 
additional manual data reviews defined by the study team. Data inconsistencies will be reviewed 
and resolved before the database snapshot for the interim analysis, primary analysis and the final 
database lock.
8.2.
Electronic Transfer and Archiving of Data
The Medidata Rave system will be used to collect the data in this study. Raw data extracted from 
Medidata Rave will be archived prior to further dataset creation, maintenance, and analysis. 
Datasets (raw data, study data tabulation model [SDTM] data, and/or analysis data model 
[ADaM] data) for planned analyses will be archived. Any additional unplanned analyses that 
occur after the primary analysis and prior to the final analysis will also be archived. Key data 
external to the clinical study database will be included in the relevant SDTM and ADaM 
modules when the external data are available.
8.3.
Handling of Missing and Incomplete Data
8.3.1.
Efficacy
The method for handling missing data is described in the definition for each efficacy endpoint. 
Every effort will be made to obtain complete dates for deaths. In the event of a partial or missing 
death date and the corresponding censoring date for survival, the algorithm in Appendix 1
(Section 12) will be used.
8.3.2.
Safety
Partial AE start dates will be imputed. If dates are missing or incomplete for adverse event start 
dates, the algorithm defined in Appendix 1 (Section 12) will be used. Completely missing death 
dates or death dates with only a year reported will not be imputed.
8.4.
Detection of Bias
A listing of subjects with important protocol deviations (IPD) will be generated. The deviations 
included in this list will include, but not be limited to, violations of eligibility criteria and use of 
exclusionary medication during the study. Lack of protocol compliance will be evaluated by 
summarizing the subject incidence of IPD. High rates of IPD may indicate bias.
8.5.
Outliers
Descriptive statistics may be used to identify potential outliers in any key variables analyzed. 
Suspected outliers will be included in all analyses unless there is sufficient scientific justification 
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8.6.
Distributional Characteristics
The primary analysis of the primary endpoint is an exact binomial test used to compare the 
Grade 2 or higher neurologic events rate in the primary objective analysis set to an event rate of 
45%.  This test assumes only the independence of the individual subject events.  
An exact 95% confidence interval will be generated about the event rate. The Clopper-Pearson 
(an exact interval) method is used to generate this interval. While the Clopper-Pearson interval 
provides adequate coverage probability, it is commonly wider than necessary (Brown et al, 
2002), leading to overly conservative estimates of the lower bound of event rate.
8.7.
Validation and Configuration Management
Programs for the development of the SDTM and ADaM datasets and the generation of the tables, 
figures, and listings will be developed and maintained according to Kite Pharma’s Standard 
Operating Procedures (SOPs) if applicable. The software and version used to generate analyses 
will be indicated in the archived documentation.


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9.
STATISTICAL METHODS OF ANALYSIS
9.1.
General Principles
The primary analysis will be performed after 30 subjects in the primary objective analysis set 
have had the opportunity to be evaluated for response 6 months after the axicabtagene ciloleucel 
infusion. The final analysis will occur when all subjects have completed the study. Additional 
analyses of safety and efficacy may occur at any time after the primary analysis. 
9.2.
Subject Accountability
The number of subjects screened, enrolled, treated with conditioning chemotherapy, treated with 
investigational treatments will be summarized. The reasons for discontinuing treatment and 
discontinuing study will be summarized.
Summaries of actual and potential follow-up time from axicabtagene ciloleucel infusion will be 
provided.
The number of subjects enrolled by site will be summarized.
The number of subjects in each analysis set along with reasons for exclusion will be provided if 
data are available.
9.3.
Important Protocol Deviations
The clinical study team will define IPD categories and review all potential IPD at minimum, 
prior to the database snapshot for the primary efficacy analysis. Important protocol deviations 
will be categorized by deviation type (eg, entry eligibility, use of excluded medication). The 
subject incidence of IPDs will be summarized overall and by deviation category.
9.4.
Demographic and Baseline Characteristics
Statistics and frequencies for the following demographic and baseline characteristics will be 
tabulated:

Age (in years) at baseline and by category (< 65, ≥ 65)

Sex

Ethnicity and race

Weight at leukapheresis

ECOG performance status at baseline

Number of prior chemotherapy regimens and best overall response to the last prior regimen


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
Prior ASCT and best overall response corresponding to the ASCT

Refractory subgroup

Tumor burden, as measured by the SPD of selected nodes or lesions at baseline

Disease stage at screening (I, II, III, IV)

Cell of origin

Histologically proven DLBCL type

Disease extent (presence of B symptoms, S [splenic involvement], E [extranodal disease], X 
[bulky disease], bone marrow involvement) as determined by the investigator at screening

Double/Triple Hit Status

Age-adjusted International Prognostic Index Total Score at screening
9.5.
Grade 2 or Higher Neurologic Events Rate
The primary endpoint of incidence of Grade 2 or higher neurologic event within 28 days of 
axicabtagene ciloleucel infusion will be based on investigator review of neurologic assessments,
signs, and symptoms in the primary objective analysis set. Neurologic events are identified with 
a search strategy based on known neurologic toxicities associated with anti-CD19 
immunotherapy {Topp 2015}. The search strategy focuses on central nervous system (CNS)
toxicity, without regard to temporal relationship and concomitant conditions (eg, CRS). 
The hypothesis testing for the event rate will be based on the exact binomial distribution. The 
incidence of Grade 2 or higher neurologic events and the exact 2-sided 95% confidence interval 
will be generated using Clopper-Pearson method. 
Additional analyses for Grade 2 or higher neurologic events may be performed:

Including all the Grade 2 or higher neurologic events with onset after axicabtagene 
ciloleucel infusion 

Using safety analysis set. 

Including all the Grade 2 or higher neurologic events with onset after axicabtagene 
ciloleucel infusion that are related to axicabtagene ciloleucel

If there are subjects who receive axicabtagene ciloleucel that is out of specification (e.g., 
low viability), each case will be reviewed and a sensitivity analysis may be performed to 
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9.6.
Safety Analyses
The incidence of DLT in the Phase 1 portion of the study will be summarized using DLT-
evaluable set. All other safety analyses will be conducted on the safety analysis set. The primary 
analysis of safety data will summarize all TEAEs and laboratory values. 
AEs will be coded with the latest version of MedDRA. The severity of adverse events will be 
graded using the version 4.03 of National Cancer Institute (NCI) Common Terminology Criteria 
for Adverse Events (CTCAE). The incidence and severity of Cytokine release syndrome (CRS) 
will be graded using a revised CRS grading scale developed by Lee and colleagues (Lee et al, 
2014). Individual symptoms associated with CRS will be graded per the latest version of 
CTCAE.
Subjects enrolled, but not received investigational treatments, will be followed for AEs for 30 
days after the last study procedure. AEs reported in these subjects will be archived in the study 
database and available in SDTM and ADaM datasets, but will not be tabulated in adverse event 
summaries.
9.6.1.
Adverse Events 
The subject incidence of the following TEAEs will be tabulated: 

Summary of adverse events (any, worst severity, serious, related) 

All AEs 

All SAEs 

All axicabtagene ciloleucel and/or Lenzilumab related AEs/SAEs 

All Grade 3 or higher AEs 

All Grade 3 or higher axicabtagene ciloleucel and/or Lenzilumab related AEs 

AEs of interest, including identified risks and potential risks 

Other clinically important adverse reactions 

Death (through the long term follow-up and treatment related SAEs)
Subjects with prolonged cytopenias (neutropenia or thrombocytopenia or anemia) will be 
identified with the following method:

Subjects with cytopenias (neutropenia or thrombocytopenia or anemia) present on or after 
Day 30 post axicabtagene ciloleucel infusion 


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Summary statistics for the study day of onset, the study day of resolution, and the duration of 
AEs of interest will be provided. A subject listing of deaths and SAEs (including narratives) will 
be provided by overall and by treatment period. 
Subgroup analyses of AEs may be generated using the covariates listed in Section 4.2 if 
applicable.
9.6.2.
Neurological Assessment
The Immune Effector Cell-Associated Encephalopathy (ICE) score will be collected at 
screening, pre-infusion on Day 0, daily during the 7-day post-infusion period, and daily during 
any period of ongoing Grade 2 or higher neurologic event, as well as the Week 2, Week 4, and 
Month 3 visits.  Descriptive summary for the values and change from baseline values will be 
provided for baseline, Day 0, best value during 7-day post-infusion period, worst value during 7-
day post-infusion period, Week 2, Week 4, and Month 3. Overall worst value during the study 
and change from baseline will also be summarized using safety analysis set. The same analysis 
may be repeated using primary objective analysis set. 
Immune Effector Cell-associated neurotoxicity syndromes (ICANS) and its associated AEs will 
be summarized by worst grade. 
Subject listings will be provided for both ICE score and ICANS with grade. 
9.6.3.
Laboratory Test Results 
Laboratory results will be graded according to the latest version of CTCAE. Laboratory data 
collected at baseline and through the treatment and follow-up periods will be summarized. The 
incidence of worst CTCAE grade post-infusion by grade for selected analytes will be provided. 
Additional lab tables for subjects who had worsening grade change from the last assessment 
prior to infusion to post-infusion may be generated by the worst post-infusion CTCAE grade. 
9.6.4.
Replication Competent Retrovirus   
The subject incidence of RCR detected in blood samples will be tabulated overall and by 
assessment time. The persistence of RCR over time will be summarized.
9.7.
Efficacy Analyses
Efficacy analyses will be conducted on the mITT analysis set, and the investigator assessment of 
disease status per the Lugano Classification (Cheson et al, 2014) will be used for disease 
response related analyses. The same analyses may be repeated using primary objective analysis 
set.


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9.7.1.
Complete Response and Objective Response
9.7.1.1.
Analyses of Response Rate
The subject incidence of CR and objective response (CR+PR) will be calculated. Two-sided 95% 
Confidence Intervals will be generated using the Clopper-Pearson (an exact interval) method.
The number and percentage of subjects who initially do not attain CR and who subsequently 
attain a CR will be summarized. 
9.7.1.2.
Subgroup Analyses 
The response rates and exact 2-sided 95% confidence intervals will be generated for subgroups 
of the mITT analysis set based on but not limited to the covariates defined in Section 4.2. A 
forest plot of the proportion of responders for each of these groups will be generated.
9.7.2.
Duration of Response
The Kaplan-Meier approach will be used to estimate DOR. The number of subjects censored and 
the reasons for censoring will be summarized. The reverse Kaplan-Meier approach (Schemper 
and Smith 1996) will be used to estimate the follow-up time for DOR.    
DOR may be summarized in subgroups defined by the best response attained on study.
9.7.3.
Progression Free Survival 
Kaplan-Meier plots, estimates and 2-sided 95% confidence intervals will be generated for PFS.  
Estimates of the proportion of subjects alive and progression-free at 3 month intervals will be 
provided.  The number of subjects censored or having events, and the reasons for censoring or 
type of events (PD or death) will be summarized. 
PFS may be summarized in subgroups defined by the best response attained on study.
9.7.4.
Overall Survival
The analysis of overall survival will use the same methods as the analysis of PFS. The reverse 
Kaplan-Meier approach (Schemper and Smith 1996) will be used to estimate the follow up time 
for overall survival. 
OS may be summarized in subgroups defined by the best response attained on study.
9.7.5.
Tumor Burden
The change in tumor burden, as measured by the SPD of the selected lesions, from baseline to 
post-baseline nadir will be summarized in absolute numbers (mm2) and percentage.  A graphical 
summary of this change will be presented in a vertical bar chart with each subject’s change from 
baseline to nadir displayed as a vertical bar, with color coding that indicates best response 
attained (“waterfall” plot).  Summary statistics will be provided for this change. Data collected 
after new anti-cancer therapy (including SCT) will not be included for the analyses.


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9.8.
Exposure to Study Treatments and Product Characteristics
Summary statistics and subject listings will be provided for the following:

Total body surface area (BSA)-adjusted dose of cyclophosphamide 

Total BSA-adjusted dose of fludarabine 

Weight-adjusted dose of axicabtagene ciloleucel    

Total CAR T cells of the axicabtagene ciloleucel infusion

Total T cells of the axicabtagene ciloleucel infusion

Transduction percentage 

Ratio of CD4 and CD8 T cells 

Percentages of T cell memory phenotypes 

Interferon gamma (IFN-γ) production in co-cultures of axicabtagene ciloleucel product

Total dose of Lenzilumab administered
9.9.
Exposure to Concomitant Medications and Procedures
The subject incidence of concomitant medications will be provided and summarized by 
medication category (general, immunosuppressive, anti-infective, vasopressor, corticosteroid, 
and tocilizumab) and WHO Drug coded term. The subject incidence of procedures will be 
tabulated.
The following summaries related to systemic steroid use and tocilizumab use may be performed:

Number of subjects who received systemic steroid as treatment for neurological events or 
CRS

Number of subjects who received tocilizumab as treatment for neurological events or 
CRS

Time to first systemic steroid use

Time to first tocilizumab use

Duration of systemic steroid use

Duration of tocilizumab use


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
Cumulative systemic steroid use 
9.10.
Subsequent Anti-Cancer Therapy and Subsequent Stem Cell Transplant
The incidence and type (by WHO Drug coded term and categories) of subsequent anti-cancer 
therapy and stem cell transplant (autologous, allogeneic) will be summarized. 
9.11.
Duration Metrics 
Summary statistics will be provided for the following durations:

Days from leukapheresis to commencement of conditioning chemotherapy

Days from leukapheresis to administration of axicabtagene ciloleucel 

Days from conditioning chemotherapy to administration of axicabtagene ciloleucel 

Duration of hospitalization for the axicabtagene ciloleucel infusion
9.12.
Axicabtagene Ciloleucel Delivery Time
Summary statistics will be provided for the following delivery time:

Days from leukapheresis to axicabtagene ciloleucel release 

Days from leukapheresis to delivery of axicabtagene ciloleucel at study site among dosed 
subjects
9.13.
Hospitalization and Health Care Facility Use
Summary statistics may be provided for the following health care facility use:

Incidence and duration of hospitalization for axicabtagene ciloleucel administration

Incidence and duration of intensive care unit (ICU) use 
9.14.
Additional Analysis
Descriptive statistics for disease characteristics at baseline will be evaluated against the available 
descriptive statistics from existing DLBCL studies (e.g., ZUMA 1 cohort 1 and 2). If different 
distributions are identified for some characteristics, additional analysis may be explored. Key 
safety and efficacy endpoints may be evaluated based on some matching method. 
CCI• 


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10.
CHANGES FROM PROTOCOL SPECIFIED ANALYSES
Not applicable.


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11.
REFERENCES
Brown LD, Cai TT, DasGupta A. Confidence Intervals for a Binomial Proportion and 
Asymptotic Expansions. The Annals of Statistics. 2002;30(1):160-201.
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA. 
Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-
Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059-68.
Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL. 
Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 
2014;124(2):188-95.
Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin 
Trials. 1996;17(4):343-6.
Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, et al. Safety and activity 
of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic 
leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncology. 2015;16(1):57-66.


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12.
APPENDICES
Appendix 1.
Conventions for Clinical Data That Require Imputation for Partial or Missing Dates
Appendix 2.
Derivation of Time to Event Endpoints
Appendix 3.
Derivation of Last date known to be alive


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Appendix 1.
Conventions for Clinical Data That Require Imputation for Partial or 
Missing Dates
The following data will be imputed using the algorithm shown in Table 2 below:

Adverse event start dates 

Deaths (please see exceptions below) 

Concomitant start dates
Table 2.
Imputation Rules for Partial or Missing Start Dates
Start Date
Stop Date
Complete:  
yyyymmdd
Partial:  yyyymm
Partial:  yyyy
Missing
< day 0
≥ day 0
< day 0 
yyyymm
≥ day 0
yyyymm
< day 0 
yyyy
≥ day 0
yyyy
Partial
yyyymm
= day 0
yyyymm
2
1
2
1
n/a
1
1
≠ day 0
yyyymm
2
2
2
2
2
Partial
yyyy
= day 0
yyyy
3
1
3
1
n/a
1
1
≠ day 0 
yyyy
3
3
3
3
3
Missing
4
1
4
1
4
1
1
1  impute the date of day 0
2  impute the first of the month
3  impute January 1 of the year
4  impute January 1 of the stop year
Note:  if the start date imputation leads to a start date that is after the stop date, then do not impute the start date.
Imputation rules for partial or missing death dates:
1. If death year and month are available but day is missing:

If mmyyyy for the last contact date  mmyyyy for death date, set death date to the day after 
the last date known to be alive.

If mmyyyy for the last date known to be alive < mmyyyy for death date, set death date to the 
first day of the death month.

If mmyyyy for last date known to be alive > mmyyyy for death date, data error and do not 
impute.


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2. If both month and day are missing for death date or a death date is completely missing, do 
not impute and censor the subject survival time at the last date known to be alive.
Imputation rules for original date of diagnosis: 
1. If year and month are available but day is missing, then impute the first day of the month.  
2. If year is available but month and day are missing, then impute January 1 of the year.


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Derivation of Time to Event Endpoints 
Version 1.0 
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The derivations of Duration of Response (DOR), Progression-free Survival (PFS), and Overall 
Survival (OS) are provided below. 
Duration of Response 
Table 3. 
Primary Analysis of DOR 
Circumstance 
Event/ Censored 
Date of Event / Censoring 
Disease progression prior to initiation of new anti-
Event 
Progression date 
cancer therapy (including SCT) , and prior to data 
cutoff for analysis 
Death without disease progression and without new 
Event 
Death date 
anti-cancer therapy (including SCT) prior to data 
cutoff for analysis 
New anti-cancer therapy (including SCT) started 
Censored 
Date of last evaluable disease 
before disease progression or death, and prior to 
assessment prior to initiation of 
data cutoff for analysis 
new therapy or SCT, whichever 
is earlier. 
Disease progression or death documented after data 
Censored 
Date of last evaluable disease 
cutoff for analysis 
assessment prior to data cutoff 
for analysis 
Remain in response without new anti-cancer 
Censored 
Date of last evaluable disease 
therapy (including SCT) through the 
assessment prior to the 
discontinuation of study, and prior to data cutoff 
discontinuation of study, or 
for analysis 
prior to data cutoff for analysis, 
whichever earlier 
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Table 4. 
Sensitivity Analysis of DOR 
Circumstance* 
Event/ Censored 
Date of Event / Censoring 
Disease progression after initiation of SCT, but 
Event 
Progression date 
prior to other new anti-cancer therapy 
Death after SCT without disease progression or 
Event 
Death date 
other new anti-cancer therapy 
Remain in response after SCT without other new 
Censored 
Last evaluable disease 
anti-cancer therapy 
assessment date 
Remain in response after SCT prior to other 
Censored 
last evaluable disease 
initiated new anti-cancer therapy 
assessment prior to other 
initiated new anti-cancer 
therapy 
Death without disease progression and without new 
Censored 
Last evaluable disease 
anti-cancer therapy (including SCT) prior to data 
assessment date before death 
cutoff for analysis 
date 
*For data from SCT after axicabtagene ciloleuc.el infusion. For all the other circumstances, follow the imputation mies described 
in Table 3. 
Progression-free Survival (PFS): 
Table 5. 
Primary Analysis of PFS 
Circumstance 
Event/ Censored 
Date of Event / Censoring 
Disease progression prior to initiation of 
Event 
Progression date 
new anti-cancer therapy (including SCT) , 
or prior to the data cutoff for analysis 
Death without disease progression and 
Event 
Death date 
without new anti-cancer therapy (including 
SCT) prior to the data cutoff for analysis 
New anti-cancer therapy (including SCT) 
Censored 
Date of last evaluable disease assessment 
started before disease progression or death, 
prior to initiation of new therapy or SCT, 
or prior to the data cutoff for analysis 
whichever is earlier 
Disease progression or death documented 
Censored 
Date of last evaluable disease assessment 
after data cutoff for analysis 
prior to data cutoff for analysis 
No disease progression through the 
Censored 
Date of last evaluable disease assessment 
discontinuation of study, or prior to data 
prior to the discontinuation of study, or 
cutoff for analysis 
prior to data cutoff for analysis, whichever 
is earlier 
No disease assessment done after 
Censored 
Axicabtagene ciloleucel infusion date 
axicabtagene ciloleucel infusion by the 
cutoff date 
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Table 6. 
Sensitivity Analysis of PFS 
Circumstance* 
Event/ Censored 
Date of Event / Censoring 
Disease progression after initiation of SCT, 
Event 
Progression date 
but prior to other new anti-cancer therapy 
Death after SCT without disease 
Event 
Death date 
progression or other new anti-cancer 
therapy 
Remain no disease progression after SCT 
Censored 
Last evaluable disease assessment date 
without other new anti-cancer therapy 
Remain no disease progression after SCT 
Censored 
last evaluable disease assessment prior to 
prior to other initiated new anti-cancer 
other initiated new anti-cancer therapy 
therapy 
*For data from SCT after axicabtagene ciloleuc.el infusion. For all the other circumstances, follow the imputation mies described 
in Table 5. 
Overall Survival (OS): 
Table 7. 
Imputation Rule of OS Event/Censoring Date 
Circumstance 
Event/ Censored 
Date of Event / Censoring 
Death before data cutoff date for analysis 
Event 
Date of death 
Death after data cutoff date for analysis 
Censored 
Data cutoff date 
Known to be alive after data cutoff date for 
Censored 
Data cutoff date 
analysis 
Alive up through the discontinuation of 
Censored 
last date known to be alive date up 
study, or data cutoff date and no further 
through the date of discontinuation of 
information available afterwards 
study, or data cutoff date, whichever is 
earlier 
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Statistical Analysis Plan
Kite Pharma, Inc.
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Appendix 3.
Derivation of Last date known to be alive
The last date known to be alive will be derived by obtaining the maximum complete date among 
the following data modules:

Start date and stop date of AE (including targeted AE)

Start date and stop date of concomitant medication

Start date and stop date of new anti-cancer therapy

Subsequent SCT date

Leukapheresis date

Conditioning chemo admin date

axicabtagene ciloleucel infusion date (including retreatment date)

Lenzilumab infusion date for Cohort 1

CT scan date

PET scan date

Target lesion assessment date

Non-target lesion assessment date

New lesion assessment date

Disease response assessment date

Long term follow up subject status date where status  ‘alive’

End of treatment disposition where status is not equal to death or lost to follow up

End of post-treatment assessment period where status is not equal to death or lost to follow 
up

End of study data where end of study reason is not equal to death or lost to follow up