Conditions: Relapsed/Refractory Multiple Myeloma
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 17
Healthy volunteers: no

Brief summary:
The primary objective of the study is to evaluate the safety and tolerability of KITE-585, an autologous engineered chimeric antigen receptor (CAR) T-cell product targeting a protein commonly found on myeloma cells called B-cell maturation antigen (BCMA), as measured by the incidence of dose-limiting toxicities (DLTs). Participants will be given a 3 day course of conditioning chemotherapy followed by a single infusion of KITE-585.

Detailed description:
Participants with relapsed/refractory multiple myeloma can participate if all eligibility criteria are met. Tests required to determine eligibility include disease assessments, a physical exam, ECG and echocardiogram of the heart, brain MRI, and blood draws. Eligible participants have white blood cells collected by leukapheresis. These cells are genetically modified to make the experimental treatment KITE-585. Participants receive conditioning chemotherapy prior to the KITE-585 infusion. After the KITE-585 infusion, participants will be followed for side effects and effect of KITE-585 on their myeloma. Study procedures may be performed while hospitalized and/or in the outpatient setting. Participants who received an infusion of KITE-585 will complete the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968

Arms:
arm 1: Participants with relapsed/refractory multiple myeloma (RRMM), will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m\^2/day and fludarabine 30 mg/m\^2/day intravenous (IV) infusion for 3 days followed by a single infusion of KITE-585 at a dose of 3 x 10\^7 autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively. arm 2: Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m\^2/day and fludarabine 30 mg/m\^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a dose of 1 x 10\^8 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively. arm 3: Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m\^2/day and fludarabine 30 mg/m\^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a dose of 3 x 10\^8 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively. arm 4: Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m\^2/day and fludarabine 30 mg/m\^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a dose of 1 x 10\^9 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively. arm 5: RRMM participants with moderate renal impairment (creatinine clearance 30 to 59 mL/min \[Grade 2 chronic kidney disease\]) will receive a conditioning chemotherapy consisting of cyclophosphamide 300 mg/m\^2/day and fludarabine 24 mg/m\^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a tolerable dose of 3 x 10\^7 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants then had a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.

Interventions: intervention 1: KITE-585 intervention 2: Cyclophosphamide intervention 3: Fludarabine
Intervention descriptions: intervention 1: A single infusion of KITE-585 autologous anti-BCMA CAR T cells intervention 2: Administered intravenously intervention 3: Administered intravenously

Protocol document:
Prot_002.pdf: 



























































































































































































Prot_000.pdf: 
KITE-585 
                           Kite Pharma, Inc. 
Clinical Protocol 
 
KITE-585-501  
11 September 2017 
 
Confidential 
Page 1 of 82 
 
 
 
CLINICAL STUDY PROTOCOL 
Protocol Title: 
A Phase 1 Multicenter Study of KITE-585, an Autologous Anti-BCMA 
CAR T-Cell Therapy, in Subjects with Relapsed/Refractory Multiple 
Myeloma  
Protocol Number:  
KITE-585-501  
USAN/INN 
Not applicable 
Company Code 
KITE-585 
IND Number:  
17619 
Clinical Study Sponsor:  
Kite Pharma, Inc. 
2225 Colorado Avenue 
Santa Monica, CA 90404 
Key Sponsor Contacts: 
 
Senior Director, Clinical Development 
Kite Pharma, Inc. 
2225 Colorado Avenue 
Santa Monica, CA 90404 
Phone: 
 
email: 
 
 
Study Manager, Clinical Operations 
Kite Pharma, Inc.  
2225 Colorado Avenue 
Santa Monica, CA 90404 
Phone: 
 
Email: 
  
Amendment Number and Date: 
Supersedes Amendment Number 
and Date: 
2.0, 11 September 2017 
1.0, 27 July 2017 
 
 
CONFIDENTIALITY NOTICE 
This document contains confidential information of Kite Pharma 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.  
 
PPD
PPD
PPD
PPD
PPD
PPD
.
Kite Pharma 


KITE-585 
                           Kite Pharma, Inc. 
Clinical Protocol 
 
KITE-585-501  
11 September 2017 
 
Confidential 
Page 2 of 82 
 
 
INVESTIGATORS AGREEMENT 
Protocol Title:  A Phase 1 Multicenter Study of KITE-585, an Autologous Anti-BCMA CAR T-Cell 
Therapy, in Subjects with Relapsed/Refractory Multiple Myeloma  
Protocol Date:  11 September 2017 
I agree to comply with the International Conference on Harmonisation Tripartite Guideline on Good 
Clinical Practice and applicable national or regional regulations and guidelines and agree to abide by all 
provisions set forth therein.  
I agree and will ensure that financial disclosure statements will be completed by: 
 
Me (including, if applicable, my spouse, legal partner, and dependent children) 
 
Sub-investigators (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. 
 
 
 
 
 
____________________________________ 
Signature 
 
____________________________________ 
Name of investigator 
 
____________________________________ 
Date 
 
 
 


KITE-585 
                           Kite Pharma, Inc. 
Clinical Protocol 
 
KITE-585-501  
11 September 2017 
 
Confidential 
Page 3 of 82 
 
 
PROTOCOL SYNOPSIS 
Title: 
A Phase 1 Multicenter Study of KITE-585, an Autologous Anti-BCMA CAR T-Cell 
Therapy, in Subjects with Relapsed/Refractory Multiple Myeloma 
Indication: 
The treatment of patients with relapsed/refractory multiple myeloma (MM) that has 
progressed within 60 days after the last dose of prior therapy and who have received at least 
3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory 
agent, or who are refractory to both a proteasome inhibitor and an immunomodulatory agent 
(ie, dual-refractory). 
Study Design: 
Study KITE-585-501 is a Phase 1, multicenter, open-label study evaluating the safety and 
efficacy of KITE-585 in subjects with relapsed/refractory multiple myeloma (RRMM).   
Approximately 6 to 24 subjects will be enrolled in a standard 3 + 3 dose escalation to 
evaluate the safety of KITE-585 regimens.  Following enrollment and treatment with 
cyclophosphamide and fludarabine conditioning chemotherapy, subjects will be assigned to 
one of the following cohorts at a fixed dose (see Sections 3.1 and 6.5.1).  
Dose Level 
Total Anti-BCMA CAR T-cell Dose† 
-1* 
 
 
1 
3 x 107 
2 
 
 
3 
 
 
4 
 
 
*If the incidence of dose-limiting toxicities (DLTs) in Cohort 1 is ≥ 2 of 6 subjects treated, the sponsor 
may, in consultation with the safety review team, choose to decrease to the dose shown for Cohort -1. 
† Dose is calculated based on CAR-expressing transduced T cells. Subjects weighing less than 53 
kg at enrollment will receive a cell dose that is reduced by 33%.  See Section 6.5.1 for additional 
information.  
Safety within each cohort will be assessed by the incidence of dose-limiting toxicities 
(DLTs).  Enrollment in each cohort will continue to occur sequentially until a maximum 
tolerated dose (MTD) is reached (see Section 9.6). 
A safety review team (SRT), internal to the study sponsor and including at least 1 study 
investigator, will review the safety data and make recommendations on further study 
conduct as outlined in Section 9.6.  
The sponsor may, in consultation with the SRT, choose to treat up to 40 additional subjects 
at any dose deemed safe by the SRT up to, and including, the MTD in Expansion Cohort 1 
and Cohort 2 to further characterize benefit/risk.  Expansion Cohort 1 will be comprised of 
approximately 20 subjects who meet all eligibility criteria specified for the dose escalation 
portion of the study.  Expansion Cohort 2 will be comprised of up to approximately 
20 subjects who meet all eligibility criteria specified for the dose escalation criteria with the 
exception that they will have moderate renal impairment (creatinine clearance 30 to 59 
mL/min by Cockcroft-Gault estimation [Grade 2 chronic kidney disease]).   
All subjects enrolled in the study will follow the same study treatment schedule and 
procedural requirements.  Each subject will proceed through the following study periods: 
 
Screening  
 
Enrollment/leukapheresis  
 
Bridging therapy (at the discretion of the treating investigator) 
CCI
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CCI
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KITE-585 
                           Kite Pharma, Inc. 
Clinical Protocol 
 
KITE-585-501  
11 September 2017 
 
Confidential 
Page 4 of 82 
 
 
 
Conditioning chemotherapy  
 
KITE-585 treatment (Day 0 through Week 2) 
 
Post-treatment assessment (Week 2 through Month 3) 
 
Long-term follow-up (Month 3 through Year 15) 
Study 
Objectives:  
Primary Objective: 
The primary objective of this study is to evaluate the safety and tolerability of KITE-585, as 
measured by the incidence of DLTs, as outlined in Section 9.6.1.    
Secondary Objectives: 
The secondary objective of this study is to gain insight into additional features of safety, 
tolerability, and efficacy of KITE-585 in subjects with both intact and moderately impaired 
renal function, including depth and durability of response, minimal residual disease (MRD), 
survival, and toxicity of the regimen. 
Hypothesis: 
KITE-585 at one of the planned dose levels will be considered safe as determined by the 
incidence of DLTs. 
Primary 
Endpoint: 
Incidence of adverse events defined as DLTs 
Secondary 
Endpoint(s): 
 
Objective response rate (partial response [PR] + very good PR (VGPR) + complete 
response [CR] + stringent CR [sCR]), as determined by study investigators, 
according to International Myeloma Working Group (IMWG) Consensus Panel 1 
Criteria (see Appendix 1) 
 
Duration of response (DOR) 
 
Progression-free survival (PFS) 
 
Time to next treatment (TTNT) 
 
Overall survival (OS) 
 
Incidence of adverse events and clinically significant changes in laboratory values 
in subjects treated with KITE-585 
Exploratory 
Endpoint(s):  
Sample Size:  Approximately 6 to 64 subjects overall will be enrolled and treated as follows:  
 
6 to 24 subjects in the initial dose escalation portion 
 
Up to approximately 20 additional subjects with creatinine clearance ≥ 60 mL/min 
by Cockcroft-Gault estimation  
(Expansion Cohort 1)  
 
Up to approximately 20 subjects with moderate renal impairment (creatinine 
clearance 30 to 59 mL/min by Cockcroft-Gault estimation [Grade 2 chronic kidney 
disease])  
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KITE-585 
                           Kite Pharma, Inc. 
Clinical Protocol 
 
KITE-585-501  
11 September 2017 
 
Confidential 
Page 5 of 82 
 
 
(Expansion Cohort 2)  
Study 
Eligibility 
Refer to Section 5 for a complete and detailed list of inclusion and exclusion criteria.  
Treatment 
Bridging Therapy (optional): 
 
 
. 
Conditioning Chemotherapy Treatment: 
KITE-585 is administered after a conditioning chemotherapy regimen consisting of 
fludarabine 30 mg/m2/day and cyclophosphamide 300 mg/m2/day, administered daily for 
3 days.  Refer to Section 6.4 and Section 7.3.4 for chemotherapy treatment details. 
Investigational Product: 
KITE-585 treatment consists of a single infusion of autologous anti-BCMA CAR T cells 
administered intravenously.  Refer to Sections 6.5 and 7.3.5 for treatment details. 
Procedures: 
At specific time points as outlined in the schedule of assessments, subjects will undergo the 
following procedures:  
 
Collection of informed consent and general medical history, including previous 
treatments for MM 
 
Physical exam, including vital signs, weight, and performance status 
 
Neurologic assessment 
 
Baseline electrocardiogram (ECG) and echocardiogram (ECHO) 
 
Brain magnetic resonance imaging (MRI) 
 
Disease staging and assessments by serum and urine biomarkers, bone marrow 
aspirate, and biopsy and positron emission tomography–computed tomography 
(PET CT) 
 
 
 
Blood draw for local laboratory:  complete blood count (CBC), chemistry panels, 
C-reactive protein (CRP), and serum/urine pregnancy test for women of 
childbearing potential 
 
Blood draw for central laboratory:  serum cytokines, peripheral blood mononuclear 
cells (PBMCs; lymphocyte subsets, replication-competent lentivirus [RCL], and 
anti-BCMA CAR T cells), and 
 
 
Bone marrow aspirate and biopsy for evaluation of MRD and other biomarkers 
 
Lumbar puncture (LP) for collection of cerebrospinal fluid (CSF) as applicable 
 
Leukapheresis 
 
Bridging therapy (at discretion of treating investigator) 
 
Conditioning chemotherapy (fludarabine and cyclophosphamide) 
 
Hospitalization for KITE-585 infusion 
 
KITE-585 infusion 
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KITE-585 
                           Kite Pharma, Inc. 
Clinical Protocol 
 
KITE-585-501  
11 September 2017 
 
Confidential 
Page 6 of 82 
 
 
Safety Review 
Team: 
A SRT that is internal to the study sponsor, and including at least 1 study investigator, will 
review safety data and make recommendations on further study conduct as depicted in 
Section 3.1, Figure 4, and outlined in Section 9.6.  
Statistical 
Considerations: 
The primary endpoint is the incidence of DLTs. 
All subjects treated with KITE-585 will be included in the safety analysis.  Subject 
incidence of adverse events and abnormalities in clinical laboratory will be summarized.  
Demographics, baseline characteristics, pharmacokinetic and pharmacodynamic parameters, 
and other biomarkers will be analyzed in descriptive statistics.  Disease assessments will be 
evaluated locally per the IMWG Consensus Panel 1 (Rajkumar et al, 2011).  MRD will be 
assessed by IMWG criteria (Kumar et al, 2016).  See detailed methods in Section 10.  
Analysis to support the clinical study report (CSR) will occur after all enrolled subjects 
have had the opportunity to complete 6 months of protocol-specified visits, have died, or 
have withdrawn from the study. 


KITE-585 
                                                 Kite Pharma, Inc. 
Clinical Protocol 
KITE-585-501 
11 September 2017
 
Confidential  
 
Page 7 of 82 
Figure 1. 
Study Schema 
Screening 
Conditioning 
Chemotherapy 
Period 
(Day -5 to Day -3) 
 
Fludarabine 
30 mg/m2/day,  
Cyclophosphamide 
300 mg/m2/day  
administered daily x 3 
days  
Investigational 
Product (IP) 
Treatment Period  
(Day 0) 
 
Subject is 
hospitalized prior to 
treatment with KITE-
585 
 
KITE-585 at a target 
dose (± 20%) 
anti-BCMA CAR 
T cells to be infused 
intravenously 
Post-Treatment Assessment Period  
Long-term Follow-up Period 
Enrollment/Leukapheresis 
Study KITE-585-501 is a Phase 1, single-arm, open-label, multicenter study evaluating the safety and efficacy of KITE-585, an autologous anti-BCMA CAR T-cell 
therapy, in subjects with RRMM.  
During Phase 1, approximately 6 to 24 subjects with RRMM will be enrolled to evaluate the safety of KITE-585 regimens.  Cell dose will be delivered in a single 
infusion and escalated in a standard 3 + 3 fashion (Section 3.1).  Dose is calculated based on CAR-expressing transduced T cells.  Dosing groups will be as follows 
with an option to go to a lower dose (Section 3.1, Table 1): 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Upon completion of enrollment and KITE-585 infusion, a safety review team (SRT), internal to the study sponsor and in collaboration with at least 1 study investigator, 
will review the safety data for each dosing group and will make recommendations on further study conduct as depicted in Table 7, Figure 4, and outlined in Section 9.6.   
Each subject will follow the same study treatment schedule and procedural requirements.  Each subject will follow through the following study periods:  a screening 
period, an enrollment/leukapheresis period, a conditioning chemotherapy period, an IP treatment period, a post-treatment assessment period, and a long-term follow-up 
period. 
Bridging Therapy 
(optional) 
 
(
 
 
 
 
 
 
 
) 
CCI
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i 
i 
i 
t 
1111 
1111 
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KITE-585 
Kite Pharma, Inc. 
Clinical Protocol 
 
KITE-585-501 
11 September 2017 
 
Confidential 
Page 8 of 82 
 
 
TABLE OF CONTENTS 
INVESTIGATORS AGREEMENT ............................................................................................. 2 
PROTOCOL SYNOPSIS .............................................................................................................. 3 
TABLE OF CONTENTS .............................................................................................................. 8 
LIST OF TABLES ....................................................................................................................... 10 
LIST OF FIGURES ..................................................................................................................... 10 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ............................................. 11 
1. 
OBJECTIVES ...................................................................................................................... 15 
1.1. 
Primary Objective ........................................................................................................... 15 
1.2. 
Secondary Objectives...................................................................................................... 15 
2. 
DISEASE BACKGROUND AND RATIONALE .............................................................. 15 
2.1. 
Study Rationale ............................................................................................................... 18 
2.1.1. Rationale for Treatment of Subjects with Moderate Renal Impairment ............. 19 
2.2. 
KITE-585 Anti-BCMA CAR T Cells ............................................................................ 19 
2.2.1. BCMA Background and Tissue Expression ............................................................ 19 
2.2.2. Anti-BCMA CAR T-cell Product ............................................................................. 20 
2.3. 
Nonclinical Experience ................................................................................................... 21 
2.3.1. Safety ........................................................................................................................... 21 
2.3.2. Efficacy ....................................................................................................................... 22 
2.4. 
Prior Human Experience ............................................................................................... 23 
3. 
STUDY DESIGN .................................................................................................................. 24 
3.1. 
General Study Design ..................................................................................................... 24 
3.2. 
Participating Sites ........................................................................................................... 26 
3.3. 
Number of Subjects......................................................................................................... 26 
3.4. 
Replacement of Subjects ................................................................................................. 26 
3.5. 
Study Duration ................................................................................................................ 27 
3.5.1. Study Duration for Individual Subjects................................................................... 27 
3.5.2. Completion of Study .................................................................................................. 27 
4. 
SUBJECT SCREENING AND ENROLLMENT.............................................................. 27 
5. 
SUBJECT ELIGIBILITY ................................................................................................... 27 
5.1. 
Inclusion Criteria ............................................................................................................ 27 
5.2. 
Exclusion Criteria ........................................................................................................... 28 
6. 
PROTOCOL TREATMENT .............................................................................................. 30 
6.1. 
Treatment Terminology ................................................................................................. 30 
6.2. 
Leukapheresis .................................................................................................................. 31 
6.3. 
Bridging Therapy ............................................................................................................ 31 
6.4. 
Conditioning Chemotherapy .......................................................................................... 32 
6.4.1. Rationale for Conditioning Chemotherapy ............................................................. 32 
6.5. 
Investigational Product KITE-585 ................................................................................ 33 
6.5.1. Rationale for KITE-585 Dose ................................................................................... 34 
6.6. 
Concomitant Therapy ..................................................................................................... 35 
6.7. 
Excluded Medications ..................................................................................................... 36 
6.8. 
Subsequent Therapy ....................................................................................................... 36 
6.9. 
Toxicity Management ..................................................................................................... 36 
7. 
STUDY PROCEDURES ...................................................................................................... 37 
7.1. 
Laboratory ....................................................................................................................... 37 
7.2. 
Baseline Disease and Treatment Response Assessments ............................................. 38 
7.2.1. Disease Staging ........................................................................................................... 38 
7.2.2. Local Serum and Urine Assessments ....................................................................... 38 


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Kite Pharma, Inc. 
Clinical Protocol 
 
KITE-585-501 
11 September 2017 
 
Confidential 
Page 9 of 82 
 
 
7.2.3. Bone Marrow Evaluations ........................................................................................ 39 
7.2.4. Imaging Requirements .............................................................................................. 40 
7.3. 
Procedures by Study Period ........................................................................................... 41 
7.3.1. Screening .................................................................................................................... 41 
7.3.2. Enrollment/Leukapheresis ........................................................................................ 43 
7.3.3. Bridging Therapy ...................................................................................................... 44 
7.3.4. Conditioning Chemotherapy .................................................................................... 44 
7.3.5. KITE-585 Treatment ................................................................................................. 47 
7.3.6. Post-treatment Follow-up Period ............................................................................. 50 
7.3.7. Long-term Follow-up Period .................................................................................... 51 
7.4. 
Biomarkers ...................................................................................................................... 53 
8. 
SUBJECT WITHDRAWAL ............................................................................................... 58 
8.1. 
Reasons for Removal from Treatment .......................................................................... 58 
8.2. 
Reasons for Removal from Study .................................................................................. 59 
9. 
SAFETY REPORTING ....................................................................................................... 59 
9.1. 
Adverse Events ................................................................................................................ 59 
9.2. 
Reporting of Adverse Events ......................................................................................... 60 
9.3. 
Definition of Serious Adverse Events ............................................................................ 61 
9.4. 
Reporting of Serious Adverse Events and Non-serious ≥ Grade 4 CRS Events, 
Neurologic Events, and Product Infusion Reactions  .................................................. 62 
9.5. 
Pregnancy and Lactation ............................................................................................... 63 
9.6. 
Safety Review Team and Dose-limiting Toxicity ......................................................... 63 
9.6.1. Dose-limiting Toxicity ............................................................................................... 63 
9.6.2. Criteria to Pause Enrollment .................................................................................... 65 
10. STATISTICAL CONSIDERATIONS ............................................................................... 66 
10.1. Hypothesis ........................................................................................................................ 66 
10.2. Study Endpoints .............................................................................................................. 66 
10.2.1. Primary ....................................................................................................................... 66 
10.2.2. Secondary ................................................................................................................... 66 
10.2.3. Exploratory ................................................................................................................ 67 
10.2.4. Covariates ................................................................................................................... 67 
10.3. Handling of Missing Data ............................................................................................... 67 
10.4. Sample Size Considerations ........................................................................................... 67 
10.5. Analysis Subsets .............................................................................................................. 68 
10.6. Access to Individual Subject Treatment Assignments ................................................. 68 
10.7. Interim Analysis .............................................................................................................. 68 
10.7.1. Safety Analysis ........................................................................................................... 68 
10.8. Planned Method of Analysis .......................................................................................... 69 
10.8.1. Clinical Response Rate .............................................................................................. 69 
10.8.2. Progression-free Survival .......................................................................................... 69 
10.8.3. Overall Survival ......................................................................................................... 69 
10.8.4. Time to Next Treatment ............................................................................................ 69 
10.8.5. Safety Analysis ........................................................................................................... 69 
10.8.6. Long-term Data Analysis .......................................................................................... 70 
11. REGULATORY OBLIGATIONS ...................................................................................... 70 
11.1. Independent Review Board/Independent Ethics Committee ...................................... 70 
11.2. Subject Confidentiality ................................................................................................... 70 
11.3. Investigator Signatory Obligations ............................................................................... 71 
12. PROTOCOL AMENDMENTS AND TERMINATION................................................... 71 
13. STUDY DOCUMENTATION AND ARCHIVE ............................................................... 71 


KITE-585 
Kite Pharma, Inc. 
Clinical Protocol 
 
KITE-585-501 
11 September 2017 
 
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Page 10 of 82 
 
 
14. STUDY MONITORING AND DATA COLLECTION .................................................... 72 
15. PUBLICATION ................................................................................................................... 72 
16. COMPENSATION ............................................................................................................... 73 
17. REFERENCES ..................................................................................................................... 74 
APPENDIX 1 ................................................................................................................................ 81 
 
LIST OF TABLES 
Table 1. 
Dosing Cohorts ......................................................................................................... 24 
Table 2. 
Relationship of Cell Dose to Grade ≥ 3 CRS in Two Anti-BCMA CAR T-cell 
Studies ....................................................................................................................... 34 
Table 3. 
Local and Central Laboratory Samples and Analysis .......................................... 37 
Table 4. 
Schedule of Assessments .......................................................................................... 54 
Table 5. 
Schedule of Assessment (Long-term Follow-up Period) ....................................... 55 
Table 6. 
Dose-limiting Toxicities ............................................................................................ 64 
Table 7. 
Recommendations Based on DLTs ......................................................................... 65 
 
LIST OF FIGURES 
Figure 1. 
Study Schema .............................................................................................................. 7 
Figure 2. 
KITE-585 Construct and Mechanism of Action .................................................... 20 
Figure 3. 
Anti-BCMA CAR Construct ................................................................................... 21 
Figure 4. 
Study Design ............................................................................................................. 26 
 


KITE-585 
Kite Pharma, Inc. 
Clinical Protocol 
 
KITE-585-501 
11 September 2017 
 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation/Term 
Definition 
AE 
Adverse event 
ALL 
Acute lymphoblastic leukemia 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
ASCT 
Autologous stem cell transplant 
AST 
Aspartate aminotransferase 
BCMA 
B-cell maturation antigen 
BMMNC 
Bone marrow mononuclear cell 
KITE-585  
Autologous T cells transduced with a lentiviral vector containing anti-BCMA 
CD28/CD3 zeta chimeric antigen receptor 
CAR 
Chimeric antigen receptor  
CBC 
Complete blood count 
CI 
Confidence interval 
CLL 
Chronic lymphocytic leukemia 
CNS 
Central nervous system 
CPK 
Creatine phosphokinase 
CR 
Complete response 
CRF 
Case report form 
CRO 
Contract Research Organization 
CRP 
C-reactive protein  
CRS 
Cytokine release syndrome 
CSF 
Cerebrospinal fluid 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
Dose-limiting toxicity 
DOR 
Duration of response 
DVT 
Deep vein thrombosis 
ECG 
Electrocardiodiogram 
ECHO 
Echocardiodiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 


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Clinical Protocol 
 
KITE-585-501 
11 September 2017 
 
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Abbreviation/Term 
Definition 
EDC 
Electronic data capture  
End of study for 
individual subject 
Defined as when the last day that the protocol specified assessments are conducted for 
an individual subject 
End of study (primary 
completion) 
Defined as when the last subject is assessed or received an intervention for the 
purposes of final collection of data for the primary endpoint at Day 140 
End of study (end of 
trial) 
Defined as when the last subject is assessed or received an intervention for evaluation 
in the study, including survival assessments  
FAS 
Full analysis set 
FFPE 
Formalin-fixed paraffin embedded block 
FISH 
Florescent in-situ hybridization 
FLC 
Free light chain 
GCP 
Good Clinical Practice  
GPI 
Glycophosphatidylinositol 
HCG 
Human chorionic gonadotropin 
HIV 
Human immunodeficiency syndrome 
HLH 
Hemophagocytic lymphohistiocytosis 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
ICU 
Intensive care unit 
IFM 
Intergroupe Francophone du Myélome 
IFN 
Interferon 
IHC 
Immunohistochemistry 
IMiD 
Immunomodulatory drug 
IMWG 
International Myeloma Working Group  
IP 
Investigational product 
IPM 
Investigational Product Manual 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
ISS 
International Staging System  
IV 
Intravenous 
KITLG 
Kit ligand 
LDH 
Lactate dehydrogenase 


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Abbreviation/Term 
Definition 
LMWH 
Low molecular weight heparin 
LP 
Lumbar puncture 
LTFU 
Long-term follow-up 
MGUS 
Monoclonal gammopathy of undetermined significance 
MM 
Multiple myeloma 
MR 
Minimal response 
MRD 
Minimal residual disease  
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose 
NCI 
National Cancer Institute 
nCR 
Near complete response 
NE 
Neurologic event 
NHL 
Non-Hodgkin lymphoma 
OR 
Objective response 
ORR 
Objective response rate 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cell 
PCR 
Polymerase chain reaction 
PD 
Progressive disease 
PET-CT 
Positron emission tomography-computed tomography 
PFS 
Progression-free survival  
PI 
Proteasome inhibitor 
PPAS 
Per protocol analysis set 
PR 
Partial response 
RCL 
Replication-competent lentivirus 
RRMM 
Relapsed/refractory multiple myeloma 
SAE 
Serious adverse event 
scFv 
Single-chain variable fragment 
sCR 
Stringent complete response 
SCT 
Stem cell transplant 
SIFE 
Serum protein immunofixation electrophoresis 
SIN 
Self-inactivating 


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Abbreviation/Term 
Definition 
SOA 
Schedule of assessment 
SOC 
Standard of care 
SPEP 
Serum protein electrophoresis 
SRT 
Safety review team 
Study Day 0 
Defined as the first day that KITE-585 is administered to the subject 
TEAE 
Treatment-emergent adverse event 
TNF 
Tumor necrosis factor 
TTNT 
Time to next treatment 
UIFE 
Urine protein immunofixation electrophoresis 
ULN 
Upper limit of normal 
UPEP 
Urine protein electrophoresis 
VGPR 
Very good partial response 
WBC 
White blood cell 
 
 
 


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1. OBJECTIVES 
1.1. Primary Objective 
The primary objective of this study is to evaluate the safety and tolerability of KITE-585 as measured by 
the incidence of dose-limiting toxicities (DLTs) as outlined in Section 9.6.  
1.2. Secondary Objectives 
The secondary objective of this study is to gain insight into additional features of safety, tolerability, and 
efficacy of KITE-585 in subjects with intact (creatinine clearance ≥ 60 mL/min by Cockcroft-Gault 
estimation) and moderately impaired renal function (creatinine clearance 30-59 mL/min by Cockcroft-
Gault), including depth and durability of response, including minimal residual disease (MRD), survival, 
and toxicity of the regimen.  
2. DISEASE BACKGROUND AND RATIONALE 
Multiple myeloma (MM) is a disease of neoplastic proliferation of antibody-producing plasma cells in the 
bone marrow.  Approximately 86,000 cases of MM occur annually worldwide (Becker 2011), and MM 
accounts for about 1% of all malignancy and about 10% of hematologic malignancy in the US.  Median 
age of diagnosis is ~70 years (Howlader et al, 2015).  Diagnosis of MM is usually made in one of two 
distinct manners.  Subclinical clonal proliferation of plasma cells may precede the formal diagnosis of 
MM by several years and is usually discovered via the incidental finding of an elevated level of 
monoclonal antibody concentration in serum, the M-spike, during a workup for unrelated signs or 
symptoms.  This elevation of so-called paraprotein is measured by a serum- or urine protein 
electrophoresis (SPEP or UPEP, respectively), and represents, in the absence of clinical signs and 
symptoms of end-organ damage related to MM, a precursor state of either monoclonal gammopathy of 
undetermined significance (MGUS) or smoldering MM (Landgren 2013).  Alternatively, patients may 
present with full-blown MM, which is characterized by neoplastic plasma cell proliferation in the setting 
of one of the following clinical hallmarks of MM:  hypercalcemia, renal insufficiency, anemia, or 
pathological bone disease.  Formal histopathologic diagnosis is made upon examination of a bone marrow 
aspirate and core biopsy in which ≥ 10% of cells are clonal plasma cells, which classically contain a 
nucleus that appears as a “clock face” and contains no nucleoli.  Immunophenotypically, the cells will 
either be kappa or lambda light chain-restricted and display surface expression of CD79a, VS38c, CD138, 
and CD38 (Swerdlow et al, 2008).  
Choices for induction and consolidation strategies are based on both patient-based factors, such as fitness 
and eligibility for high-dose therapy, followed by autologous stem cell transplantation (ASCT) and 
disease-based factors, such as tumor cell cytogenetics.  Thus, workup for a new case of MM involves an 
overall health assessment, as well as fluorescent in-situ hybridization (FISH), or conventional 
cytogenetics.  FISH analysis for t(11;14), t(4;14), t(6;14), t(14;16), t(14;20), del17p13, 1q+, and trisomy 
of odd numbered chromosomes and conventional cytogenetics for del 13, monosomy 13, or hypodiploidy 
will provide sufficient risk-stratification for clinical decision-making.  High-risk disease characteristics 
include clinical features, such as lactose dehydrogenase (LDH) ≥ 2 times the upper limit of normal (ULN) 
and the following cytogenetic abnormalities:  del 17p, t(14;16), and t(14;20) (Rajkumar 2012).  


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Initial therapy for MM has changed considerably over the last 15 years.  Recent randomized clinical trials 
have demonstrated that regimens containing novel agents, such as the proteasome inhibitor (PI) 
bortezomib, and immunomodulatory agents, such as thalidomide or lenalidomide, administered in 2- or 3-
drug combinations, have dramatically improved efficacy and safety profiles over older regimens built 
around cytotoxic chemotherapy backbones (Cavo et al, 2010; Harousseau et al, 2010; Moreau et al, 2011; 
Kumar et al, 2012; Rosinol et al, 2012; Sonneveld et al, 2013).  In the Intergroupe Francophone du 
Myélome (IFM) cooperative group Phase 3 trial IFM 2005-01, post-induction overall response rates were 
defined as a very good partial response (VGPR) or better, in subjects treated with bortezomib plus 
dexamethasone (78.5%) vs vincristine/doxorubicin/dexamethasone (62.8%).  Post-induction near-
complete responses (nCR), defined as 100% reduction in M-spike, but detectable disease by 
immunofixation, were seen in 14.8% of subjects treated with bortezomib/dexamethasone vs 6.4% of 
subjects treated with vincristine/doxorubicin/dexamethasone.  Following ASCT and consolidation with 
cyclophosphamide, etoposide, and cisplatin, progression-free survival (PFS) was improved to 36 months 
in subjects who received bortezomib vs 29.7 months in those treated in the control arm (Harousseau et al, 
2010).   
Addition of the immunomodulatory agent thalidomide to bortezomib in the front-line setting led to further 
improvements in responses.  The GIMEMA Italian Multiple Myeloma Network randomized Phase 3 
study in nearly 500 patients demonstrated that the combination of bortezomib, thalidomide, and 
dexamethasone led to a significantly improved objective response rate (ORR) rate vs thalidomide and 
dexamethasone alone.  After post-induction therapy, 62% and 31% of patients treated with the triple 
therapy achieved a VGPR or nCR or better, respectively, as compared to the thalidomide/dexamethasone 
only arm in which patients achieved VGPR and nCR rates of 28% and 11%, respectively (Cavo et al, 
2010). 
More recently, use of the thalidomide analogue lenalidomide in 2- or 3-agent containing regimens with 
dexamethasone and bortezomib has further improved outcomes.  The randomized Phase 2 EVOLUTION 
trial was designed to evaluate various combinations of bortezomib, lenalidomide, and cyclophosphamide 
and showed rates of VGPR or better and complete response (CR) (defined as nCR with negative 
immunofixation) in 51% and 24% of patients, respectively (Kumar et al, 2012).  As a result of these and 
other studies, bortezomib and the immunomodulatory (IMiD) drugs thalidomide and lenalidomide are 
part of several category 1 recommendations for first-line treatment of newly-diagnosed MM (Kumar et al, 
2017). 
Unfortunately, in spite of these impressive improvements in durable responses following induction 
therapy as well as routine use ASCT and prolonged maintenance therapy with either bortezomib or an 
IMiD in all eligible patients, nearly all patients will eventually relapse.  In the first salvage setting, a 
number of options are available to clinicians and patients, including re-challenge with the original 
induction regimen, introduction of a different anti-myeloma therapy, ASCT or allogeneic stem cell 
transplant (SCT), or enrollment in a clinical trial of a novel agent.  The original studies of lenalidomide 
were performed in heavily pretreated patients with MM.  Lenalidomide plus dexamethasone received 
FDA approval for treatment of patients with relapsed MM who had received at least 1 prior therapy, 
based on 2 randomized studies that enrolled a combined total of 704 subjects.  In the MM-009 trial and 
MM-010 studies, subjects were randomized to receive lenalidomide plus dexamethasone or 


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dexamethasone alone (Dimopoulos et al, 2007; Weber et al, 2007).  The results of these studies were 
pooled and, at a median follow-up of 48 months, the overall survival (OS) for the 
lenalidomide/dexamethasone arms was 38 months compared to 31.6 months in the dexamethasone-only 
arms (p = 0.045) despite crossover after disease progression or unblinding among 47.6% of subjects 
(Dimopoulos et al, 2009).  
Furthermore, combination of lenalidomide with cytotoxic chemotherapy, monoclonal antibodies (eg, 
elotuzumab and daratumumab), or PI (bortezomib or carfilzomib, a recently FDA-approved second-
generation PI) have increased the ORR from 65% to 95% (Baz et al, 2006; Plesner et al, 2012; 
Richardson et al, 2012; Wang et al, 2013; Richardson et al, 2014; Reece et al, 2015).  Carfilzomib and, 
more recently, ixazomib, an orally-available PI, have produced clinically meaningful responses in patients 
who have received 1 to 3 prior lines of treatment, including a PI and an IMiD.  A randomized Phase 3 
trial of carfilzomib, lenalidomide, and dexamethasone vs lenalidomide and dexamethasone in 792 patients 
(ASPIRE) showed a median PFS (primary endpoint) of 26.3 months and 17.6 months, respectively, and a 
hazard ratio for progression or death of 0.69 (p = 0.0001) (Stewart et al, 2015).  
Next-generation IMiDs like pomalidomide and the orally available PI ixazomib have recently entered 
clinical usage.  Pomalidomide was approved by the FDA in 2013 for use in patients who have received at 
least 2 prior therapies, including lenalidomide and a PI, and have demonstrated disease progression on or 
within 60 days of completion of the last therapy.  Accelerated approval was based on the results of a 
randomized open-label study, CC-4047-MM-002, in which 221 subjects were treated with either 
pomalidomide alone or in combination with low-dose dexamethasone (Richardson et al, 2014).  The ORR 
(including minimal response [MR], partial response [PR], and CR) was 33% in the combination regimen 
and 18% with pomalidomide monotherapy.  The CR rates were 3% and 2%, and the median PFS was 
4.2 and 2.7 months, respectively, for the 2 treatment arms.  In subjects refractory to both lenalidomide and 
bortezomib, the CR rates and median PFS for the combination and pomalidomide monotherapy arms 
were 0% and 1%, respectively, and 3.8 and 2.0 months, respectively (Richardson et al, 2014).  
In a randomized study of 722 patients with relapsed MM after 1 to 3 prior therapies, the VGPR rate was 
48% in patients treated with the orally available PI ixazomib in combination with lenalidomide and 
dexamethasone compared with 39% in subjects treated with lenalidomide and dexamethasone alone 
(Moreau et al, 2016).  Rates of serious adverse events (SAEs) were similar, whereas Grade 3 or higher 
adverse events (AEs) occurred more frequently in the patients randomized to the ixazomib arm (74% vs 
69%). 
The monoclonal antibodies daratumumab and elotuzumab, which bind CD38 and CS1/SLAMF7, 
respectively, on the surface of MM cells, have also recently been approved for use in the relapsed MM 
setting.  When it was combined with lenalidomide and dexamethasone in patients with 1 to 3 prior lines 
of therapy in the randomized Phase 3 study ELOQUENT-2, elotuzumab demonstrated a higher ORR 
(79%) vs lenalidomide and dexamethasone alone (66%) and improved PFS (19.4 vs 14.9 months; HR 
0.70, 95% confidence interval [CI] 0.57 to 0.85) (Lonial et al, 2015).  Toxicity was higher in the 
experimental arm, with higher incidence of Grade 3/4 AEs (65% vs 57%), opportunistic infections (22% 
vs 13%), and invasive secondary malignancies (9% vs 6%).   


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The efficacy of daratumumab in patients who have received at least 1 prior line of therapy was 
demonstrated in 2 randomized Phase 3 studies.  First, the POLLUX study randomized 569 subjects to 
receive lenalidomide and dexamethasone with or without daratumumab (Dimopoulos et al, 2016).  ORR 
was higher in the daratumumab-containing arm (93% vs 76%), with 76% and 25% of subjects attaining a 
VGPR or CR, respectively, compared to 44% and 12%, respectively, in the control arm.  PFS at 
12 months was also improved (83% vs 60%, respectively; HR 0.37; 95% CI 0.27 to 0.52, P < 0.001).  
Infusion reactions were observed in 47.7% of subjects in the daratumumab arm and rates of Grade 3 or 
higher neutropenia (51.9% vs 37.0%) as well as any grade of diarrhea, upper respiratory tract infection, 
and cough were higher in patients receiving daratumumab than in the control arm. 
Daratumumab also became the first FDA-approved treatment for use in patients with relapsed/refractory 
MM (RRMM) after a minimum of 3 lines of prior therapy or in patients who have documented disease 
progression following a PI and IMiD-containing regimen (ie, dual-refractory).  In 106 subjects treated in 
the open-label single-arm study SIRIUS, the ORR was 29.2%, with 9.4% and 2.8% achieving a VGPR or 
stringent CR (sCR), respectively (Lonial et al, 2016).  The median PFS was 3.7 months, and the most 
common Grade 3 or higher AEs were anemia (24%), thrombocytopenia (19%), and neutropenia (12%).   
The SIRIUS study is the first pivotal trial to enroll subjects with a minimum of 3 prior lines of treatment 
that must have included a PI and an IMiD as well as subjects who are dual-refractory to these agents.  
These are 2 groups where the unmet medical need in MM is highest.  However, because of the relative 
paucity of clinical data in this population, detailed prognostic information on these 2 subgroups of 
subjects is not yet available.  Any potential difference in outcomes in these 2 populations in KITE-585-
501 will, therefore, be examined by covariate analysis (see Section 10.2.4). 
Similar to patients with other hematologic malignancies, patients with MM typically are treated with 
novel or more potent agents with each subsequent relapse, and remissions achieved with these agents tend 
to be more shallow and shorter than the prior remission (Kumar et al, 2012).  While the extent to which 
this observation holds true in the era of novel agents, such as daratumumab, remains uncertain; this 
pattern of relapsing-remitting disease highlights the lack of curative therapy currently available to patients 
with multiply relapsed or refractory MM. 
2.1. Study Rationale 
Chimeric antigen receptor (CAR) T cells have recently demonstrated clinically meaningful results in 
CD19-expressing B-cell malignancies.  Academic and industry groups have shown durable remissions in 
a host of B-cell cancers including non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), 
and acute lymphoblastic leukemia (ALL) (Porter et al, 2011; Lee et al, 2015; Kochenderfer et al, 2017; 
Locke et al, 2017).  Furthermore, anti-B-cell maturation antigen (BCMA) CAR T-cell therapies have 
recently entered human testing (Section 2.4; NCT02954445, NCT02546167, NCT02658929, 
NCT02215967).  CAR T-cell therapy, thus, has an established clinical proof of concept in hematologic 
malignancies.  KITE-585-501 is a first-in-human study of an anti-BCMA CAR in patients with MM.  


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2.1.1. Rationale for Treatment of Subjects with Moderate Renal Impairment 
Patients with MM are at significant risk of developing acute or chronic renal failure.  Myeloma kidney is 
a frequent complication in which pathological serum light chains are deposited in the renal tubules, 
causing tubule rupture and interstitial inflammation, ultimately leading to a reduction in glomerular 
filtration rate.  Additionally, the management of MM can lead to further decreases in renal function 
predominantly via exposure to nephrotoxic agents, such as iodinated contrast, non-steroidal 
anti-inflammatory drugs, and anti-myeloma therapies, such as lenalidomide (Batts et al, 2008; Lipson et 
al, 2010).  The incidence of renal dysfunction increases with time following an initial MM diagnosis, and 
subjects who will meet eligibility criteria for this study with respect to prior treatment history commonly 
have moderate-to-severe renal failure.  In the clinical trial that led to FDA approval of daratumumab in 
subjects with RRMM who had received at least 3 prior lines of therapy, including a PI and an IMiD, or 
who had disease that was refractory to dual therapy with both a PI an and IMiD, the prior treatment 
history required in this study, only 57% of subjects had a baseline creatinine clearance of ≥ 60 mL/min; 
another 40% had a baseline creatinine clearance of 30 to < 60 mL/min.  
As discussed above, patients who have multiply-relapsed or refractory disease have few remaining 
treatment options and are in need of novel and efficacious therapies.  Additionally, patients with abnormal 
kidney function tend to have worse outcomes, representing a significant unmet need in this patient 
population (Winearls 1995; Blade et al, 1998; Knudsen et al, 2000).  However, many patients who receive 
CAR T cells, including for MM, have experienced cytokine release syndrome (CRS), which may be 
accompanied by hypotension, vascular leak, and fluid third-spacing, which may exacerbate renal 
dysfunction at least temporarily and possibly permanently.  Therefore, this study will evaluate the safety 
of KITE-585 in subjects with renal dysfunction cautiously as described in Section 3.  If KITE-585 can be 
delivered safely to subjects with moderately decreased renal function (creatinine clearance of between 
30 and 59 mL/min), a substantial additional fraction of patients with RRMM may ultimately benefit from 
this therapy.   
2.2. KITE-585 Anti-BCMA CAR T Cells 
2.2.1. BCMA Background and Tissue Expression 
BCMA, the receptor for B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), is a 
member of the tumor necrosis factor (TNF) receptor superfamily and is also known as TNF superfamily 
member 17 (TNFRSF17).  BCMA is expressed in normal human plasma cells and has limited expression 
in other tissues.  Gene and protein expression profiling has shown that BCMA is broadly expressed in 
MM cell lines and primary MM cells (Tai and Anderson 2015; Hudecek and Einsele 2016).   
In agreement with these published reports of the high prevalence of BCMA expression in MM, a Kite 
Pharma, Inc., (hereafter referred to as Kite and Kite Pharma) analysis of next-generation sequencing data 
from the Multiple Myeloma Genomics Portal (Zhan et al, 2006; Keats et al, 2007) found that BCMA 
RNA was expressed in 91 of 92 MM primary patient samples. 
Further, across at least 5 independent studies in the literature, all primary MM cell samples from 
114 unique patients tested positive for BCMA cell surface protein or RNA.  Three studies of protein 


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surface expression by flow cytometry or intracellular protein expression by immunohistochemistry, 
showed that tumor cells from 70 of 70 (100%) patients with MM were positive for BCMA protein 
expression (Novak et al, 2004; Carpenter et al, 2013; Lee et al, 2016).  Forty-four of 44 (100%) patient 
samples in 2 studies were positive for BCMA RNA expression (Moreaux et al, 2004; Bellucci et al, 
2005).  BCMA RNA was also found to be maintained in samples tested serially from diagnosis through 
subsequent relapses in 3 patients with RRMM (Lee et al, 2016).  
These analyses and published studies support that BCMA is near universally expressed in MM.  Studies 
of CAR T cells against both CD19 (Neelapu et al, 2016) and BCMA (Cohen et al, 2016) have shown that 
patients with even low levels of target antigen may experience disease remissions.  Therefore, a 
retrospective analysis of outcomes by BCMA expression levels will be performed to evaluate the 
relationship between target expression and response. 
2.2.2. Anti-BCMA CAR T-cell Product 
The active moiety for KITE-585 is autologous T cells transduced with a self-inactivating (SIN) lentiviral 
vector encoding an anti-BCMA CAR construct (Figure 2).    
Figure 2. 
KITE-585 Construct and Mechanism of Action 
 
Abbreviations:  BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; CD28, cluster of differentiation 28; CD3ζ, 
cluster of differentiation 3 ζ; LTR, long terminal repeat; 
; scFv, single-chain variable 
fragment; SIN, self-inactivating. 
 
CCI
5' LTR 
MSCV pro 
scFv 
CD28 
CD3~ 
3' SIN LTR 
CAR vector construct 
Viral vector 
Target binding domain: 
antibody derived (scfv) 
CAR-engineered 
Tull 
CAR-engineered 
T cell 
Tumor cell 
Cytolytic activity 
Cytokine release 
Proliferation 


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As shown in Figure 2 and Figure 3, the anti-BCMA CAR comprises 3 regions:  1) a human, anti-BCMA 
single-chain variable region fragment (scFv) with high specific binding to BCMA expressed on the cell 
surface; 2) 
 
 CD28; and 3) CD3ζ, the intracellular signaling component of the human T-cell 
receptor/CD3 complex.  CD3ζ provides signals that are essential for T-cell activation (Guy and Vignali 
2009), while the CD28 cytoplasmic domain provides important co-stimulatory signals that support T-cell 
survival and function (Finney et al, 1998; Boomer and Green 2010; Restifo et al, 2012). 
Figure 3. 
Anti-BCMA CAR Construct 
 
 
 
KITE-585 product is a cryopreserved, autologous, anti-BCMA CAR T-cell product that will be thawed 
and administered to patients at the bedside.  The KITE-585 manufacturing process consists of several 
distinct processing steps that occur over a period of 6 to10 days.  Refer to the KITE-585 Investigator’s 
Brochure (IB) for a detailed discussion of the KITE-585 lentiviral vector, CAR transgene, and 
manufacturing process.  
2.3. Nonclinical Experience 
2.3.1. Safety 
Details of the assay methodology and additional results and discussion of nonclinical studies are provided 
in the KITE-585 IB.  Briefly, nonclinical safety studies of KITE-585 were not performed due to the 
unavailability of suitable murine models.  Rather, the potential for off-target toxicities was addressed by 
2 in vitro specificity studies.   
The first study tested binding of the anti-BCMA CAR T cells to an array of 4,542 human plasma 
membrane proteins comprising approximately 70% of human plasma membrane proteins.  Both a primary 
screen and a confirmatory assay were performed.  Results showed that 19 gene products bound to anti-
BCMA CAR T cells in both the primary and confirmation assays.  However, 16 of the gene products also 
bound to non-transduced control T cells, suggesting binding unrelated to the anti-BCMA CAR scFv.  The 
3 remaining gene products that selectively bound to anti-BCMA CAR T cells, but not control T cells, 
were tumor necrosis factor RSF17 (TNFRSF17; another name for BCMA), Kit ligand (KITLG), and 
retinoic acid early transcript 1L (RAET1L; also known as ULBP6).  The positive results for KITLG had 
very weak fluorescence intensity.  Further, KITLG had been identified in previous studies as a CAR-
independent T-cell binding protein (data not shown).  These observations suggest that KITLG is unlikely 
to be a relevant target for anti-BCMA CAR T cells.  
CCI
CCI
CCI


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The remaining gene product that bound to anti-BCMA CAR T cells, RAET1L (also known as ULBP6), 
encodes a glycophosphatidylinositol (GPI)-anchored cell membrane protein that has a limited expression 
profile in primary human tissues (Eagle et al, 2009).  Importantly, the RAET1L receptor, NKG2D, is 
expressed on almost all T cells (Antoun et al, 2012).  Because of its weak binding in the in vitro assay and 
its known ability to bind T cells through the NKG2D receptor, RAET1L was considered an assay artifact.   
To confirm that RAETIL binding was nonspecific, co-culture cytotoxicity assays were performed using a 
Jurkat cell line known to be positive for RAET1L, but negative for BCMA.  This pattern was determined 
by flow cytometric analysis of surface BCMA and RAET1L expression.  Results showed that the anti-
BCMA CAR was not cytotoxic against Jurkat cells, while potent cytotoxic activity was seen against 
2 BCMA-expressing cell lines, confirming that RAET1L is not a binding target of anti-BCMA CAR 
T cells.  An additional confirmatory test was performed using RD-1, the monoclonal antibody from which 
the anti-BCMA scFv was derived.  In these studies, RD-1 was applied to slides containing the HEK293 
cells expressing the 19 different cell surface proteins identified in the primary screen.  Only HEK293 cells 
expressing BCMA, and not those that expressed KITLG or RAET1L, bound to RD-1, providing 
confirmation that the scFv is selective for BCMA. 
Tissue cross-reactivity of RD-1 was also assessed.  Sections from frozen tissue microarrays prepared from 
duplicate 1.5 mm cores of 36 human tissue types from 3 donors were examined by immunohistochemistry 
(IHC).  IHC staining by antibody RD-1 was not suggestive of target expression across 36 human tissues 
from all 3 donors.  Positive signals were observed in colon, placenta, and spleen, but are likely due to the 
presence of plasma cells in those tissues (Carpenter et al, 2013).  Weak, inconsistent signal was seen in 
brain cortex (1 of 5 duplicate samples), lung parenchyma (1 of 6 duplicate samples), and perineurium of a 
peripheral nerve (2 of 4 duplicate samples).  Weak RD-1 cytoplasmic staining was observed within the 
liver in 2 of 3 donors.  RD-1 staining was also observed in kidney tubule epithelium in 1 of 3 donors.   
A repeat study of RD-1 staining in whole sections of liver and kidney from 3 different donors showed no 
binding to hepatocytes or bile duct epithelium and weak, patchy, and inconsistent cytoplasmic 
immunoreactivity in kidney tubule epithelium.  Similar kidney tubule cytoplasmic staining was seen with 
an antibody included as a control that was derived from the scFv used in the CAR currently in clinical 
testing at the National Cancer Institute (NCI) (see Section 2.4).  In contrast, staining of the human MM 
cell line, MM.1s, with both RD-1 and the NCI clone, showed strong immunoreactivity on the cell 
membrane.  Although the inconsistent and weak staining seen in tubules is likely non-specific, that it is 
restricted to the cytoplasm provides further assurance that it would not be bound by a CAR, which is only 
able to bind extracellular targets.  Additionally, there have been no renal AEs reported from the ongoing 
NCI study that would suggest tubule-specific CAR T-cell-mediated toxicity.  
Additional details on the preclinical in vitro safety studies can be found in the IB. 
2.3.2. Efficacy 
A xenograft mouse model of human MM was used to evaluate anti-BCMA CAR T cells in mice.  Briefly, 
NSG mice (NOD-scid IL2Rgnull) were given intravenous injections of the human MM cell line MM.1S, 
which has high BCMA expression and contains a luciferase-expressing plasmid (pMMP-Luc-Neo), to 


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facilitate non-invasive tumor measurement.  Infusion with anti-BCMA CAR T cells caused significant 
extension of survival compared with untreated control mice.  Additionally, all mice treated with 
anti-BCMA CAR T cells had partial tumor regressions, defined as a 50% decrease in tumor burden 
relative to size before CAR T-cell infusion.  No mice had complete remissions in this study.  See the IB 
for additional detail. 
A second xenograft model of MM was also used to evaluate anti-BCMA CAR T cells in vivo.  In this 
model system, NSG mice (NOD-scid IL2Rgnull) were given subcutaneous implants of the RPMI8226 MM 
cell line.  After several days of tumor growth, mice were treated with anti-BCMA CAR T cells or 
untransduced human T cells.  The anti-BCMA CAR T-cell infusion prolonged median survival compared 
with untransduced T-cell treated mice.  Six out of 10 mice treated with anti-BCMA CAR T cells had 
complete remissions in this study, and an additional 3 out of 10 mice had a partial remission.  See the IB 
for additional detail.  
2.4. Prior Human Experience 
CAR T cells directed against BCMA have been developed and tested in human subjects with RRMM in 
several ongoing clinical trials (NCT02954445, NCT02546167, NCT02658929, NCT02215967).  An 
additional study is investigating a monoclonal antibody against BCMA conjugated to the antimitotic 
agent, monomethyl auristatin F, in subjects with MM or other BCMA-expressing malignancies 
(NCT02064387).  
Results from the first 12 subjects treated in a Phase 1 first-in-human, single center, open-label study 
(NCT02215967) were published in 2016 (Ali et al, 2016).  Following treatment with cyclophosphamide 
and fludarabine (300 mg/m2 and 30 mg/m2, respectively, each given daily for 3 days) subjects were 
treated in a 3 + 3 dose-escalation schema with increasing doses of anti-BCMA CAR T cells (0.3 x 106, 
1.0 x 107, 3.0 x 107, and 9.0 x 107 CAR T cells/kg).  
All subjects experienced at least 1 treatment-emergent adverse event (TEAE), most of which were 
expected cytopenias and laboratory abnormalities attributable to the conditioning chemotherapy regimen, 
and were generally self-limited and reversible.  With respect to anti-BCMA CAR T-cell-related AEs, 
there were several events consistent with CRS, which has been observed in clinical trials of anti-CD19 
CAR T cells.  One of 4 (25%) subjects developed significant fever, tachycardia, and hypotension within 
1 day of receiving a single, 3 x 106 anti-BCMA CAR T-cell infusion.  The AEs resolved by Day 6 after 
infusion. 
Both subjects treated with 9 x 106 cells/kg developed significant toxicity attributable to CRS.  One subject 
developed fever and tachycardia 4 hours after receiving the CAR T-cell infusion.  The subject went on to 
develop a prolonged fever lasting 7 days that reached 41°C as well as elevated C-reactive protein (CRP), 
hypotension requiring vasopressors, elevated serum creatine phosphokinase (CPK; measured 
> 20000 U/L, normal 39 to 308 U/L), and muscle weakness.  The subject was treated with tocilizumab on 
Day 3 and Day 4.  All toxicities except cytopenias resolved by Day 15. 
The second subject treated at this dose level also developed fever 4 hours after CAR T-cell infusion.  The 
subject developed elevated CRP, sustained fever, hypoxemia, and Grade 3 delirium.  Tocilizumab was 


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given at 25 hours and 5 days after infusion.  Corticosteroids were also administered for 13 days although 
the patient had known adrenal insufficiency prior to enrollment in the study.  Less than 8 weeks after 
infusion, all toxicities had resolved to Grade 1 or less except lymphopenia. 
Evidence of anti-myeloma CAR T-cell activity was observed.  Serum paraprotein, free light-chains, and 
bone marrow myeloma cell populations all reflected anti-tumor efficacy, and clinical response was 
observed, particularly at the 3 x 106 and 9 x 106 antiBCMA- CAR T cells/kg dose levels.  The ORR 
across all dosing groups was 4 of 12 (33%) and 3 of 6 (50%) in subjects who received 3 x 106 or 9 x 106 
anti-BCMA CAR T cells per kg.  
Two additional Phase 1, first-in-human trials, NCT02546167 and NCT02658929, have also recently 
reported results at international congresses.  Both therapies appear to be active, with evidence of both 
toxicity, including CRS and neurological toxicity, as well as disease control and durable responses 
(Cohen et al, 2016; Berdeja et al, 2017).  Additional details are provided in the IB. 
KITE-585 has not yet been tested in human subjects, and KITE-585-501 is a first-in-human study.  
3. STUDY DESIGN 
3.1. General Study Design 
KITE-585-501 is a Phase 1, multicenter, open-label study evaluating the safety and tolerability of 
KITE-585 in subjects with relapsed/refractory multiple myeloma (RRMM). 
Approximately 6 to 24 subjects will be enrolled in a standard 3 + 3 dose escalation scheme to evaluate the 
safety of KITE-585 regimens.  Following enrollment and treatment with cyclophosphamide and 
fludarabine conditioning chemotherapy, subjects will be enrolled into 1 of the following cohorts as 
outlined in Table 1 at a fixed dose.  This dose will be reduced by 33% for subjects weighing ≤ 53 kg.  For 
the first cohort, subjects will be enrolled one by one, with a minimum of 2 weeks between enrollment 
dates.  Safety within each cohort will be assessed for DLTs, and enrollment in each cohort will continue 
to occur sequentially until a maximum tolerated dose (MTD) is reached (see Section 9.6).    
Table 1. 
Dosing Cohorts 
Dose Level 
Total Anti-BCMA CAR T-Cell Dose† 
-1* 
 
1 
3 x 107 
2 
 
3 
 
4 
 
*If the incidence of DLTs in Cohort 1 is ≥ 2 of 6 patients treated, the sponsor may, in consultation with the safety review team, 
choose to decrease to the dose shown for Cohort -1. 
†Dose is calculated based on CAR-expressing transduced T cells. Subjects weighing less than 53 kg at enrollment will receive 
a cell dose that is reduced by 33%.  See Section 6.5.1 for additional information.  
Abbreviations:  BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor. 
CCI
CCI
CCI
CCI
•• 
•• 
•• 
•• 


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A safety review team (SRT), internal to the study sponsor and including at least one study investigator, 
will review the safety data and make recommendations on further study conduct as outlined in 
Section 9.6.  
After a dose level has been determined by the SRT to be tolerable based on the incidence of DLTs (see 
Section 9.6.1), the sponsor may, in consultation with the SRT, choose to expand enrollment in the 
following 2 expansion cohorts to further characterize the risk benefit profile.  Enrollment to each cohort 
may proceed independently of the other. 
 
Expansion Cohort 1:  Up to approximately 20 additional subjects with creatinine clearance ≥ 60 
mL/min by Cockcroft-Gault estimation 
 
Expansion Cohort 2:  Up to approximately 20 subjects with moderate renal impairment 
(creatinine clearance 30 to 59 mL/min [Grade 2 chronic kidney disease]).  The first 3 subjects in 
this expansion cohort will be enrolled with a minimum of 2 weeks between each subject.  The 
SRT will meet to review safety data after the first 6 subjects have been enrolled and have 
completed the Day 28 visit.    
The SRT will review safety data and make recommendations on further study conduct as depicted in 
Figure 4 and outlined in Section 9.6.  
All subjects enrolled in the study will follow the same study treatment schedule and procedural 
requirements.  Each subject will proceed through the following study periods (Figure 1): 
 
Screening  
 
Enrollment/Leukapheresis  
 
Bridging therapy (at the discretion of the treating investigator) 
 
Conditioning chemotherapy  
 
KITE-585 treatment  
 
Post-treatment assessment  
 
Long-term follow-up  
 
 
 
 


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Figure 4. 
Study Design 
 
 
Abbreviations:  CAR, chimeric antigen receptor; MTD, maximum tolerated dose. Cell dose is calculated based on CAR-
expressing transduced T cells.  
 
For study requirements assigned to each study period, refer to the schedule of assessments (SOAs) and 
Section 7 for details. 
A study schema is provided in the protocol synopsis. 
3.2. Participating Sites 
Approximately 5 to 15 centers located in North America will participate in this study.  During the conduct 
of the study, additional sites, regions, or countries may be added as necessary. 
3.3. Number of Subjects 
Participants in this trial will be referred to as “subjects.”  It is anticipated that approximately 
6 to 64 subjects will be enrolled into this study. 
3.4. Replacement of Subjects 
Subjects will continue to be enrolled until the specified number of subjects are attained in the DLT 
evaluable set.   
CCI
CCI
3+3 Dose Escalation 
'cy/F1u: CydophosphamidE> 300 mg/m2; Ftud3ra -ne 30 mg/mi days.-s, -4, -3. 
••~ : crea ·nine Clearancees:t:imated byCOCS/iroft-Gs.ult 
1 MTD: M aximum Tolerated Close 
''See section 6.5.1 for CAR T cell dose for subjects weighing 53 kg or less 
Up to app. 20 subjects with 
CrCI*' 
60 ml/min 
MTDt or lower 
Up to app. 20 subjects with 
CrCI*' 30 - 59 ml/min 


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3.5. Study Duration 
3.5.1. Study Duration for Individual Subjects  
The duration of the study for individual subjects will vary.  For a subject who completes the entire 
protocol from the date of informed consent through the completion of the long-term follow-up period, the 
duration of the study will take approximately 15 years to complete.    
Individual study duration will vary depending on a subject’s screening requirements, response to 
treatment, and survival.  
3.5.2. Completion of Study 
Completion of the study is defined as the time at which the last subject completes the long-term follow-up 
period, is considered lost to follow-up, withdraws consent, or dies (whichever occurs first).  
4. SUBJECT SCREENING AND ENROLLMENT 
All subjects must sign and date the Institutional Review Board/Independent Ethics Committee (IRB/IEC) 
approved consent form before initiating any study-specific procedures or activities that are not part of a 
subject’s routine care.  Refer to Section 7 and the SOA for details. 
Each subject who enters the screening period will receive a unique subject identification number before 
any study-specific procedures or activities are performed.  This number will be used to identify the 
subject throughout the study and must be used on all study documentation related to the subject. 
Furthermore, the subject identification number must remain constant throughout the entire clinical study; 
it must not be changed after enrollment or if the subject is rescreened or retreated. 
Subjects who fail to meet all eligibility criteria will be allowed to rescreen one time.  Only those 
screening assessments that led to the screen failure need to be repeated, provided that all other screening 
tests have been completed within the protocol-specified window (eg screening echocardiogram has been 
performed within 28 days before enrollment). 
5. SUBJECT ELIGIBILITY 
5.1. Inclusion Criteria 
101. Measurable myeloma as defined by the International Myeloma Working Group (IMWG) 
Consensus Criteria (Rajkumar et al, 2011), (Appendix 1): 
 
Serum and urine markers 
o Serum M-protein ≥ 0.5 g/dL (≥ 5 g/L) or 
o Urine M-protein ≥ 200 mg/24 h or 
o Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL 
(≥ 100 mg/L) provided serum FLC ratio is abnormal  


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and either: 
 
Bone marrow aspirate/biopsy demonstrates ≥ 10% clonal plasma cells or  
 
FDG-avid, biopsy-proven plasmacytoma on positron emission tomography-computed 
tomography (PET-CT) 
102. Progression of multiple myeloma as defined by IMWG Consensus Criteria (Rajkumar et al, 
2011), (Appendix 1) within 60 days after: 
 
the last dose of the last line of therapy and following treatment with at least 3 lines of 
therapy that have included a PI and an IMiD (eg, thalidomide, lenalidomide) at any 
time during the course of management or 
 
the last dose of a regimen that included both a PI and an IMiD, regardless of number of 
prior lines of therapy 
103. Age 18 years or older at the time of informed consent 
104. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 
105. Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as: 
 
Absolute neutrophil count (ANC) ≥ 1,000/µL 
 
Platelet count ≥ 75,000/µL 
 
Absolute lymphocyte count ≥ 100/µL 
 
Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min (except in 
subjects enrolled into the Expansion Cohort 2 evaluating KITE-585 in subjects with 
moderate renal impairment, in which case the creatinine clearance must be 30 to 
59 mL/min) 
 
Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5 ULN  
 
Total bilirubin ≤ 1.5 mg/dl (subjects with known Gilbert’s syndrome who have serum 
bilirubin ≤ 3.0 x ULN may be enrolled) 
 
Cardiac left ventricular ejection fraction ≥ 50% and no evidence of clinically 
significant pericardial effusion as determined by an echocardiogram (ECHO) 
 
No clinically significant electrocardiogram (ECG) findings 
 
No clinically significant pleural effusion 
 
Baseline oxygen saturation > 92% on room air 
106. 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). 
5.2. Exclusion Criteria 
201. Presence of ≥ 5% atypical or other cells suspicious for circulating plasma cells detected on 
screening complete blood count (CBC) with differential that are subsequently confirmed by 
flow cytometry to be plasma cells 
202. Non-secretory multiple myeloma 


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203. Active or prior history of central nervous system (CNS) or meningeal involvement by 
malignant plasma cells. (Subjects with calvarial disease that extends intracranially and involves 
the dura as suggested by magnetic resonance imaging [MRI] will be excluded, even if 
cerebrospinal fluid [CSF] is negative for myeloma.) 
204. Prior BCMA-targeted therapy 
205. Prior CAR therapy or other genetically modified T cells 
206. Treatment with non-immune directed systemic therapy (eg, PI, IMiD, daratumumab, 
elotuzumab) within 2 weeks or 5 half-lives, whichever is shorter, before enrollment 
207. Treatment with immune-directed systemic therapy (eg, ipilimumab, nivolumab, 
pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists) within 3 half-lives before the 
leukapheresis date 
208. Autologous stem cell transplant within 6 weeks before enrollment 
209. History of allogeneic stem cell transplantation 
210. Treatment with corticosteroid therapy at a pharmacologic dose (≥ 5 mg/day of prednisone or 
equivalent doses of other corticosteroids) and other immunosuppressive drugs within 7 days 
before the leukapheresis date 
211. Ongoing Grade ≥ 2 toxicities from prior therapies.  Subjects with peripheral neuropathy of any 
grade or clinically non-significant toxicities (eg, alopecia) of any grade may be eligible. 
212. History of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg, cervix, 
bladder, breast) unless disease-free and without anticancer therapy for at least 3 years  
213. History of severe, immediate hypersensitivity reaction attributed to aminoglycosides or any 
other agents used in this study  
214. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or 
requiring intravenous (IV) antimicrobials for management   
215. Known history of human immunodeficiency syndrome (HIV) infection 
216. Known acute or chronic active infection by hepatitis B or hepatitis C virus 
217. Active tuberculosis 
218. 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 catheters, such as a Port-a-Cath or Hickman catheter, are permitted.  
219. Significant traumatic injury within 3 weeks prior to initiation of conditioning therapy or major 
surgical procedure within 4 weeks prior to conditioning therapy 
220. History or presence of non-malignant CNS disorder, such as seizure disorder, cerebrovascular 
ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS 
involvement  
221. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York 
Heart Association Class II or greater congestive heart failure, or other clinically significant 
cardiac disease within 12 months before enrollment 
222. Current or history of clinically significant cardiac amyloid deposition  


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223. Requirement for urgent therapy due to ongoing or impending oncologic emergency (eg, tumor 
mass effect, tumor lysis syndrome); focused radiation to prevent or treat pathological fracture 
is permitted.  
224. History of autoimmune disease (eg, Crohn’s, rheumatoid arthritis, systemic lupus 
erythematosus) resulting in end organ injury or requiring systemic 
immunosuppression/systemic disease modifying agents within 2 years prior to enrollment.  
Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid 
replacement hormone and subjects with controlled Type 1 diabetes mellitus on a stable insulin 
regimen may be eligible for this study.   
225. History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic 
anticoagulation within 6 months before enrollment 
226. Treatment with a live, attenuated vaccine within 6 weeks prior to the planned start of the 
conditioning chemotherapy or anticipation of need for such a vaccine during the course of the 
study  
227. Women of childbearing potential who are pregnant or breastfeeding 
228. Subjects of either sex who are not willing to practice birth control from the time of consent 
through 6 months following KITE-585 infusion 
229. Any medical or psychiatric condition likely to interfere with assessment of safety or efficacy of 
study treatment  
230. 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. 
6. PROTOCOL TREATMENT  
If, at any time following screening and before KITE-585 infusion, there is concern for infection or other 
acute inflammatory process as suggested by the clinical findings detailed in Sections 7.3.2.1, 7.3.4.1, and 
7.3.5.1, the Kite medical monitor should be contacted, and treatment may need to be delayed until 
additional workup can be performed and/or the abnormalities return to normal.  
6.1. Treatment Terminology 
The following terms will be used to describe and define protocol treatment:  
 
Leukapheresis refers to the procedure for collection of peripheral blood mononuclear cells 
(PBMCs) used to manufacture the subject-specific KITE-585 treatment. 
 
Bridging therapy refers to the treatment used to control the subject’s disease after 
enrollment/leukapheresis and up to 7 days prior to conditioning chemotherapy. 
 
Conditioning chemotherapy refers to fludarabine and cyclophosphamide used for 
lymphodepletion prior to administration of KITE-585. 
 
The investigational product is named KITE-585.   
 
Concomitant medication refers to treatment that subject receives during the conduct of the study. 


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 
Excluded medications refers to treatment that is not to be administered, unless otherwise specified 
during the conduct of the study. 
 
Subsequent therapy refers to treatment administered after KITE-585 or standard of care (SOC) 
necessary to treat a subject’s disease. 
6.2. Leukapheresis  
Subjects will undergo leukapheresis to obtain T cells for the manufacturing of KITE-585 as described in 
Section 2.2.2 and in the KITE-585 IB.  Leukapheresed cells obtained at participating centers will be 
shipped to the Kite manufacturing facility as described in the Investigational Product Manual (IPM).   
See Section 6.7 for excluded medications prior to leukapheresis. 
Before leukapheresis commences, the criteria outlined in Section 7.3.2.1 must be met. 
After KITE-585 has been manufactured and has passed release criteria, it will be shipped to the treating 
facility and must be stored per the IPM (see Section 6.5).   
6.3. Bridging Therapy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI
I 
I 
I 
I 
I 
I 
I 
I 
I 


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conditioning chemotherapy to ensure cardiac inclusion/exclusion criteria continue to be 
met.   
 
The following therapies are not allowed for bridging therapy: 
See Section 7.3.3 for details. 
Bridging therapy should be administered per institutional guidelines.  The current product label should be 
referenced for guidance on packaging, storage, preparation, administration, including necessary dose 
reductions for organ dysfunction, and toxicity management associated with the administration of 
chemotherapy agents. 
6.4. Conditioning Chemotherapy 
All subjects with significant malignancy burden and without a contraindication such as medication 
allergy should be started on prophylaxis for tumor lysis syndrome (eg, allopurinol) as per 
institutional guidelines prior to initiation of condition chemotherapy.  Prophylaxis should be 
discontinued when the risk of tumor lysis has passed. 
Conditioning chemotherapy consisting of fludarabine and cyclophosphamide will be supplied by the 
investigative site unless otherwise noted.   
Fludarabine phosphate 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. 
Cyclophosphamide is a nitrogen mustard-derivative alkylating agent.  Following conversion to active 
metabolites in the liver, cyclophosphamide functions as an alkylating agent; the drug also possesses 
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.   
Mesna is a detoxifying agent used to inhibit the hemorrhagic cystitis induced by chemotherapy.  The 
active ingredient mesna is a synthetic sulfhydryl compound designated as sodium-2-mercaptoethane 
sulfonate with a molecular formula of C2H5NaO3S2.  Mesna should be administered to subjects at route, 
dose, and schedule commensurate with conditioning cyclophosphamide dose per institutional guidelines.  
6.4.1. Rationale for Conditioning Chemotherapy 
Increasing levels of conditioning chemotherapy correlates with clinical responses to adoptive cell therapy 
(Dudley et al, 2008).  Specifically, there appears to be a link between adequate lymphodepletion and 
CCI


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adoptively transferred T-cell expansion and function in preclinical models.  The depth and duration of the 
lymphodepletion in preclinical models correlate with anti-tumor activity of the adoptively transferred 
tumor-specific CD8+ T cells (Gattinoni et al, 2005).  Lymphodepletion may function by eradicating 
cytokine sinks for the transferred cells, eliminating T regulatory cells, or enhancing antigen presenting 
cell activation (Klebanoff et al, 2005).  Cyclophosphamide and fludarabine is a potent lymphodepleting 
regimen and has been shown to lead to an increase in serum interleukin (IL)-15 concentration, which has 
been correlated with objective responses following treatment of lymphoma with anti-CD19 CAR T cells 
(Kochenderfer et al, 2017).   
The conditioning chemotherapy dose will be cyclophosphamide (300 mg/m2) and fludarabine (30 mg/m2) 
both given for 3 concurrent days.  Cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) both 
given for 3 concurrent days has been studied and tolerated in subjects with B-cell malignancies (O'Brien 
et al, 2001).  This regimen has been evaluated in the NHL studies at Kite and has not caused undue 
toxicity in subjects with heavily pretreated and treatment-refractory NHL.  See Section 1.1 for dose 
adjustments in subjects with renal dysfunction. 
Additional regimens of conditioning chemotherapy may be explored at the recommendation of the SRT. 
6.5. Investigational Product KITE-585 
This section contains general information and is not intended to provide specific instructions.  Refer to the 
IPM for details and instruction on storage, thawing, and administration of KITE-585.   
KITE-585 is supplied cryopreserved in cryostorage bags.  The product in the bag is clear to opaque, with 
white to red including shades of white, light yellow, and orange.  The cryostorage bag(s) containing 
KITE-585 arrive cryopreserved in a liquid nitrogen dry shipper.  The bag(s) must be stored in the vapor 
phase of a liquid nitrogen, and the product must remain frozen until the subject is ready for treatment to 
assure viable 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. 
KITE-585 is a subject-specific product and the intended subject will be identified by a unique subject ID 
number.  Upon receipt, verification that the product and subject-specific labels match the subject’s 
information (eg, initials, subject ID number) is essential.  Do not infuse the product if the information on 
the subject-specific label does not match the intended subject or if the label is missing or illegible.  The 
volume of KITE-585 infused, the thaw start/stop time, and KITE-585 administration start/stop time will 
all be noted in the subject medical record.  The product must not be thawed until the subject is ready for 
the infusion.   
In case of accidental overdose, treatment should be supportive.  Corticosteroid therapy may be considered 
if any dose is associated with severe toxicity.  Refer to the current KITE-585 IB for details on the 
management of important risks associated with KITE-585. 


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If any problems related to the use of KITE-585 or to any products that support the successful delivery and 
infusion of KITE-585 (eg, cryostorage bags, subject identification labels) in this study are identified, refer 
to the instructions in the IPM for further information on reporting. 
6.5.1. Rationale for KITE-585 Dose 
In this first-in-human study, the dose escalation portion of the trial is designed to test different doses of 
KITE-585 in subjects with RRMM.  This will be conducted in a dose-escalating schema as laid out in the 
protocol synopsis, Figure 4, and further discussed in Sections 3.1 and 9.6.  
Given the absence of suitable animal toxicology models as discussed in Section 2.3, the starting dose was 
selected based on experience with anti-CD19 CAR T cells and publicly available information from other 
anti-BCMA CAR studies.  In the former, activity is observed in subjects as measured by CAR T-cell-
related toxicity (eg, CRS) and efficacy at CAR T-cell doses as low as 2 to 5 x 105 CAR T cells/kg (1.6 to 
4.0 x 107 total CAR T cells for a 80 kg subject) in a variety of malignancies, patient populations, and 
tumor burdens (Lee et al, 2015; Turtle et al, 2016; Turtle et al, 2016; Locke et al, 2017).  However, in 
most multicenter studies of anti-CD19 CAR T cells, including in all Kite-sponsored anti-CD19 CAR T-
cell studies using a CAR construct with CD28 and CD3ζ signaling domains similar to those used in 
KITE-585, cell doses of 1 x 106 or 2 x 106 per kg have been carried forward as the target dose.  These 
weight-based cell doses equate to total CAR T-cell doses ranging from 5 to 10 x 107 total CAR T cells in 
a 50 kg subject to 1 to 2 x 108 total CAR T cells in a 100 kg subject.  
In the case of anti-BCMA CAR T cells studied at the NCI, very little toxicity attributable to anti-BCMA 
CAR T cells was seen in patients treated at the 0.3 x 106 CAR T cells/kg dose level.  At the 1 x 106 CAR 
T cells/kg dose level, 2 of 3 patients treated had mild signs and symptoms of CRS including mild fever 
and sinus tachycardia.  Severe CRS and neurological events (NE) were not observed until dose level 3 (3 
x 106 CAR T cells/kg; Table 2; Ali et al, 2016).  Moreover, in another study of anti-BMCA CAR T cells, 
Grade ≥ 3 CRS was observed in 1/9 (11%) of subjects treated with dose level 3 (45 x 107 CAR T cells) 
and 1/3 (33%) of subjects treated with dose level 4 (80 x 107 CAR T cells, Table 2 [Berdeja et al, 2017]).  
The planned starting dose of KITE-585 of 3 x 107 anti-BCMA CAR T cells is, therefore, > 20-fold lower 
than the dose at which either Ali, et al., or Berdeja et al., observed ≥ 33% Grade 3 or higher CRS and, 
thus, is unlikely to cause severe toxicity.  
Table 2. 
Relationship of Cell Dose to Grade ≥ 3 CRS in Two Anti-BCMA CAR T-cell Studies 
 
Target Cell Dose 
Cell Dose in 80 kg 
Subject 
Grade ≥ 3 CRS (%) 
Study # 1 
Ali et al.  
(NCT# 02215967) 
0.3 x 106/kg 
2.4 x 107 
0/3 (0%) 
1 x 106/kg 
8 x 107 
0/3 (0%) 
3 x 106/kg 
2.4 x 108 
1/4 (25%) 
9 x 106/kg 
7.2 x 108 
2/2 (100%) 
5 x 107 
5 x 107 
0/3 (0%) 
15 x 107 
15 x 107 
0/3 (0%) 


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Study #2 
Berdeja et al. (NCT#  
02658929) 
45 x 107 
45 x 107 
1/9 (11%) 
80 x 107 
80 x 107 
1/3 (33%) 
Abbreviations:  BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; CRS, cytokine release syndrome. 
 
The dose escalation schema described in Figure 4 calls for a 
 increase between dose cohorts, similar 
to the dose escalation schema used by Ali and Berdeja (Ali et al, 2016; Berdeja et al, 2017).  As an 
additional precaution against overdosing subjects of low body weight with a relatively high flat dose of 
KITE-585, a low-dose tier and escalation schema was created using a cutoff of 150% of the KITE-585 
cell dose, normalized to body weight, which corresponds to 50% of the planned dose step-up between 
cohorts during dose escalation.  In the Kite database of subjects treated with refractory aggressive NHL in 
ZUMA-1, the median subject weight was 80 kg (Kite Pharma data on file).  Similarly, in the Phase 1 
dose-escalation study of daratumumab in RRMM, the median subject body weight was 80.5 kg (Lokhorst 
et al, 2015).  Using 80 kg as the assumed body weight of KITE-585-501 participants, a subject weighing 
53 kg would receive 150% of the cell dose per kg of body weight compared to a subject who weighs 
80 kg.  Therefore, to prevent overdose, each cell dose in the escalation schema will be reduced by 33% 
for subjects weighing less than 53 kg (see Section 3.1 for dose details).  Finally, subject weight at 
leukapheresis will be examined as a covariate of safety and efficacy outcomes. 
6.6. Concomitant Therapy  
Investigators may prescribe any concomitant medications or treatment deemed necessary to provide 
adequate supportive care, including growth factor support (eg, G-CSF) and routine anti-emetic 
prophylaxis except those medications listed in the excluded medication Section 6.7.   
For subjects who received KITE-585, all concurrent therapies, including medications, intubation, dialysis, 
oxygen, and blood products, should be recorded in the case report form (CRF) as follows: 
 
At screening (informed consent through enrollment):  ongoing concomitant medications (this 
should include all medications being taken, including prescription and over-the-counter drugs, 
dietary supplements, and homeopathic or naturopathic remedies) and concomitant medications 
associated with any SAEs (see Section 9.4 for SAE reporting requirements) 
 
Enrollment through Month 3:  All concomitant medications 
 
After Month 3 through 24 months after KITE-585 or progressive disease (PD), whichever occurs 
first: 
o All targeted concomitant medications in the category of gammaglobulin, immunosuppressive 
drugs, anti-infective drugs, and vaccinations 
o All concomitant medications associated with targeted AEs and targeted SAEs (see Sections 
9.2 and 9.4) 
 
After Month 3 through the end of study:  All concomitant medications associated with KITE-585 
related Grade 5 AEs 
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For subjects who are enrolled, but not dosed with KITE-585, concurrent therapies will only be recorded 
from the date of the informed consent through 30 days after the last study specific procedure (eg, 
leukapheresis, conditioning chemotherapy).   
For subjects who are not enrolled (eg, screen failure or who do not undergo leukapheresis), only 
concurrent therapies related to any SAE(s) will be recorded. 
Specific concomitant medication collection requirements and instructions are included in the CRF 
completion guidelines. 
6.7. Excluded Medications 
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 7 days prior to KITE-585 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 non-contrast CT scans instead.  
Corticosteroids and other immunosuppressive drugs should also be avoided for 3 months after KITE-585 
administration unless used to manage KITE-585 related toxicities.  Other medications that might interfere 
with the evaluation of KITE-585, such as non-steroidal anti-inflammatory agents, should also be avoided 
for the same period unless medically necessary.   
Treatment for MM, such as chemotherapy, immunotherapy, targeted agents, radiation, and high dose 
corticosteroid, other than defined/allowed in this protocol and other investigational agents are prohibited, 
except as needed for treatment of disease progression after KITE-585. 
If permissibility of a specific medication/treatment is in question, contact the Kite Pharma medical 
monitor.  Refer to the KITE-585 IB for additional information about excluded medications.  
6.8. Subsequent Therapy  
Subsequent therapy administered after KITE-585 necessary to treat a subject’s disease, such as non-study 
specified chemotherapy, immunotherapy, targeted agents, stem cell transplant, and radiation therapy will 
be recorded until the subject completes the long-term follow up period, is considered lost to follow up, 
withdraws consent, or dies (whichever occurs first).  
6.9. Toxicity Management  
The following potential risks of KITE-585 are based on observations made in other clinical trials with 
therapies similar to KITE-585 and in clinical trials with anti-CD19 CAR T cells conducted by Kite 
Pharma:  
 
CRS 


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 
Neurologic events 
 
Infections 
 
Cytopenias  
Details of CRS grading and management are found in Section 6.4, Tables 5 and 6 of the KITE-585 
IB, version 2.1.  As the safety experience with KITE-585 increases, the management guidance for 
CRS and other potential risks may be updated. Therefore, it is important that the most current 
version of the KITE-585 IB is consulted for guidance regarding management of KITE-585-related 
toxicities.    
7. STUDY PROCEDURES 
Research staff should refer to the SOAs (Table 4 and Table 5) for an outline of the procedures required.  
The visit schedule is calculated from KITE-585 infusion.  The KITE-585 infusion is designated as Day 0.  
An overview of study assessments/procedures is outlined below.  A description for each period of the 
study is provided in Section 7.3.   
Refer to the CRF completion guidelines for data collection requirements and documentation of study 
procedures. 
7.1. Laboratory 
The samples listed in Table 3 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. 
Table 3. 
Local and Central Laboratory Samples and Analysis 
Local Laboratory Samples and Analysis 
Central Laboratory 
Samples and Analysis 
Chemistry 
Hematology 
Other 
 
Sodium 
 
Potassium 
 
Chloride 
 
Total CO2 (bicarbonate) 
 
Creatinine 
 
Glucose 
 
Calcium total 
 
Total bilirubin 
 
ALT/GPT 
 
AST/GOT 
 
Complete blood 
count with 
differential 
(differentials 
include 
neutrophils, 
monocytes, 
lymphocytes) 
 
C-reactive protein (CRP) 
 
Urine or serum β-HCG 
pregnancy test (for women 
of childbearing potential)   
 
Serum: 
o 
Serum quantitative 
immunoglobulins 
o 
Serum free light chains 
(FLC) 
o 
Serum protein 
electrophoresis (SPEP) 
o 
Serum protein 
immunofixation 
electrophoresis (SIFE) 
 
PBMC, including 
lymphocyte subsets, 
RCL, and anti-
BCMA CAR T-cell 
levels  
 
Cytokine levels 
 
 
  
 
Tumor tissue from 
bone marrow aspirate 
and biopsy 
 
Soluble BCMA 
 
CSF 
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Local Laboratory Samples and Analysis 
Central Laboratory 
Samples and Analysis 
Chemistry 
Hematology 
Other 
Recommended: 
 
Blood urea nitrogen 
(BUN) 
 
Magnesium total 
 
Alkaline phosphatase 
 
Direct bilirubin 
 
LDH 
 
Uric acid 
 
Inorganic phosphorus 
 
Albumin 
 
Urine (based on a 24-hour 
collection): 
o 
Total protein 
o 
Urine protein 
electrophoresis (UPEP) 
o 
Urine protein 
immunofixation 
electrophoresis (UIFE) 
 
CSF 
 
Recommended, see Section 
7.3.5.5: 
o 
Ferritin  
o 
Lactate 
Abbreviations:  BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; ALT, alanine aminotransferase; GPT, 
glutamic pyruvic transaminase; AST, aspartate aminotransferase; GOT, glutamic oxaloacetic transaminase; LDH, lactate 
dehydrogenase; HCG, human chorionic gonadotropin; RCL, replication-competent lentivirus; CSF, cerebrospinal fluid; PBMC, 
peripheral blood mononuclear cell. 
 
7.2. Baseline Disease and Treatment Response Assessments 
7.2.1. Disease Staging 
Disease stage per International Staging System (ISS) will be performed at study entry (Palumbo et al, 
2015).  Serum LDH and beta-2 microglobulin will be collected. 
7.2.2. Local Serum and Urine Assessments 
The following samples will be collected at the time points indicated in the SOA and analyzed locally to 
measure disease activity.  These assessments will continue until the subject has PD, withdraws from the 
study, is lost to follow up, or dies.   
 
Serum: 
o Serum quantitative immunoglobulins 
o Serum FLC 
o Serum protein electrophoresis (SPEP) 
o Serum protein immunofixation electrophoresis (SIFE) 
 
Urine (based on a 24-hour collection): 
o Total protein 


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o Urine protein electrophoresis (UPEP) 
o Urine protein immunofixation electrophoresis (UIFE) 
7.2.3. Bone Marrow Evaluations 
Disease assessments will be evaluated locally per the IMWG Consensus Panel 1 (Rajkumar et al, 2011).  
7.2.3.1. 
Screening Assessments 
For all subjects, a screening bone marrow aspirate and biopsy will be performed within 14 days before 
enrollment and analyzed locally for: 
 
the following loci by FISH:   
o t(4;14) 
o t(14;16) 
o del17p13 
o del13q 
 
% plasma cells by flow cytometry 
 
MRD by flow cytometry or polymerase chain reaction (PCR) (if performed per SOC) 
If enrollment is delayed, then a repeat bone marrow biopsy and aspirate will be required to ensure 
baseline bone marrow is performed within 14 days before leukapheresis. 
7.2.3.2. 
On-study Assessments 
For all subjects, a bone marrow aspirate and biopsy will be performed according to the SOA until PD, 
withdrawal of consent, lost to follow-up, or death (whichever occurs first): 
 
Week 2 
 
Week 4 
 
Month 3 
 
After Month 3, per SOC 
 
If serum/urine biomarkers indicate CR, bone marrow will be collected to confirm CR per the 
IMWG criteria. 
 
If serum/urine biomarkers indicate PD, bone marrow will be collected at the time of PD and prior 
to starting subsequent anticancer therapy. 
The bone marrow samples will be analyzed locally for % plasma cells by flow per SOC. 


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7.2.3.3. 
Bone Marrow Aspirate and Biopsy Samples for Central Laboratory Analysis 
At all bone marrow evaluation time points listed in the SOA, a portion of the bone marrow aspirate and 
biopsy will be prepared per the central laboratory manual and submitted to the central laboratory for 
evaluation.  MRD and other biomarkers per Section 7.4 will be assessed centrally on these samples. 
Below is an example of the sample types that will be required: 
 
Samples from bone marrow aspirate:   
o MRD 
o Bone marrow mononuclear cells (BMMNC) 
o Bone marrow aspirate clot 
 
Samples from bone marrow biopsy prepared per your institution’s standard practice: 
o Formalin-fixed paraffin embedded block (FFPE) or 
o Core biopsy fixed in formalin or 
o Up to 20 unstained slides  
See the central laboratory manual for details regarding sample collection, processing, and shipment 
requirements. 
7.2.4. Imaging Requirements  
All subjects will have baseline images performed to establish a baseline for later comparison and/or 
confirm presence of extramedullary disease (including soft tissue plasmacytomas).   
 
Screening (all subjects) 
o MRI brain will be performed ≤ 28 days before enrollment to rule out CNS MM and establish 
a pre-treatment anatomic baseline to be used as a comparison to scans that may be obtained 
during treatment (eg, during evaluation of neurologic events).  
o PET CT of the neck, chest, abdomen, and pelvis will be performed after the last therapy 
received for MM and ≤ 14 days before enrollment.   
 
If the screening PET-CT was positive or suspicious for extramedullary disease and the 
scans are ≥ 28 days before start of conditioning chemotherapy, then the PET-CT scans 
will be repeated ≤ 28 days before start of conditioning chemotherapy.  
 
 
 
 
On-study  
o For subjects with baseline extramedullary disease, a PET-CT of the neck, chest, abdomen, 
and pelvis will be performed at the time points indicated in the SOA until PD or start of new 
anticancer therapy for MM, whichever occurs first. 
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o For subjects without baseline extramedullary disease, a PET-CT of the neck, chest, abdomen, 
and pelvis will be performed if there is suspicion of new extramedullary disease. 
7.3. Procedures by Study Period 
Investigative sites will maintain a written log of all screened subjects who were reviewed and evaluated 
for study participation.  Information collected on the screening log should include limited information, 
such as the date of screening, date the subject was enrolled, or the reason for why the subject failed 
screening. 
7.3.1. Screening  
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.   
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 informed consent form (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 re-consented with any updated version of the 
IRB/IEC approved ICF if relevant to their participation in the study. 
The screening period begins on the date the subject signs the IRB/IEC approved ICF and continues 
through enrollment, which occurs at the beginning of leukapheresis.  Subjects should sign the most 
current IRB/IEC approved ICF prior to any study-specific activity or procedure is performed.  Procedures 
that are part of SOC are not considered study-specific procedures and may be performed prior to 
obtaining consent and used to confirm eligibility provided they are performed within the screening 
windows as indicated in the SOA.   
Demographic data will be collected as per country and local regulations and guidelines.  Where 
applicable, demographic data will include sex, date of birth, race, ethnicity, and country of enrollment to 
study their possible association with subject safety and treatment effectiveness. 
After written informed consent has been obtained, subjects will be screened to confirm study eligibility 
and participation.  Only subjects who meet the eligibility criteria listed in Section 5 and who commence 
leukapheresis will be considered enrolled into 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 as outlined in the 
SOA: 


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 
Medical history  
o Relevant medical history prior to the start of AE reporting (see Section 9.2 and 9.4) will be 
collected.  Relevant medical history is defined as data on the subject’s concurrent medical 
condition dating back to the subject’s original diagnosis that would typically be shared in a 
referral letter as well as history related to the subject’s disease, treatment, and response to 
treatment.  
o For subjects who are being referred from another clinic or institution to the participating 
research center, copies from the subjects chart should be obtained. 
o All findings will be recorded in the CRFs. 
 
Physical examination including height and weight 
 
Vital signs, including blood pressure, heart rate, oxygen saturation on room air, and temperature 
 
ECOG performance status  
 
Neurological exam:  A bedside neurologic examination will be performed with any abnormalities 
of the following recorded:  level of consciousness, orientation, vision, cranial nerves and brain 
stem functions, pyramidal and extra pyramidal motor system, reflexes, muscle tone and trophic 
findings, coordination, sensory system, neuropsychological findings (eg, speech, cognition and 
emotion).  
 
ECG 
 
ECHO:  will be performed following the subject’s last chemotherapy treatment and ≤ 28 days 
prior to signing the consent may be used for confirmation of eligibility.  
 
Disease assessment: 
o Local serum and 24-hour urine (see Section 7.2.2) 
o Local and central bone marrow aspirate and biopsy (see Section 7.2.3) 
o Imaging Studies – PET-CT and brain MRI (see Section 7.2.4) 
o 
 
. 
 
MRI brain (see Section 7.2.4) 
 
Local labs  
o β-Human chorionic gonadotropin (HCG) pregnancy test (serum or urine) on all women of 
childbearing potential 
o Lumbar puncture for collection of CSF to rule out presence of plasma cells if MRI brain is 
suspicious for CNS involvement of MM; if a lumbar puncture (LP) is performed for this 
reason, then opening pressure should also be measured. 
o Chemistry panel 
o CBC with differential 
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 
SAE reporting (refer to Section 9 for safety reporting guidelines) 
 
Concomitant medications documentation (see Section 6.6) and previous cancer treatment history 
7.3.2. Enrollment/Leukapheresis  
7.3.2.1. 
Pre-leukapheresis Criteria 
Before leukapheresis commences, the following criteria must be met: 
 
In general, all eligibility criteria confirmed during screening must not be known to be violated 
prior to leukapheresis.  Additionally, the investigator must review and confirm that the last CBC 
with differential and chemistry panel drawn prior to the start of leukapheresis must meet the 
eligibility criteria detailed in Inclusion criterion 105.  If any screening assessments or procedures 
are repeated between screening and the start of leukapheresis and results are outside the eligibility 
criteria (Section 5), contact the Kite medical monitor before proceeding with leukapheresis.   
 
Subjects must have no evidence or suspicion of infection prior to leukapheresis.  Should a subject 
have an infection immediately prior to leukapheresis, cell collection must be delayed until the 
event resolves.  If leukapheresis is delayed beyond 5 days, a CBC with differential and chemistry 
panel must be repeated to confirm they meet the eligibility criteria detailed in Inclusion criterion 
105.   
 
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. 
7.3.2.2. 
Enrollment/Leukapheresis Procedures 
The following procedures/requirements will occur on the leukapheresis collection day (enrollment) as 
outlined in the SOA: 
 
Weight – this weight is used to determine the KITE-585 dose 
 
Vital signs, including blood pressure, heart rate, oxygen saturation on room air, and temperature 
 
Local labs (to be drawn prior to leukapheresis) 
o Chemistry panel 
o CBC with differential 
o CRP 
 
Central labs (to be drawn prior to leukapheresis) 
o 
 
o PBMCs   
o Cytokine levels  
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 
Leukapheresis (see Section 6.2 and 7.3.2) 
o After the pre-leukapheresis criteria are met (see Section 7.3.2.1), mononuclear cells will be 
obtained by leukapheresis (12 to 15 liter 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 manufacturing facility as described in the IPM.    
 
AE/SAE reporting (see Section 9) 
 
Concomitant medications documentation (see Section 6.6) 
7.3.3. Bridging Therapy 
Subjects may receive bridging therapy at the discretion of the treating investigator (see Section 6.3 for 
details).  
7.3.3.1. 
Bridging Therapy Administration  
 
 
7.3.3.2. 
Bridging Therapy Procedures 
The following procedures will occur after the completion of bridging therapy and prior to conditioning 
chemotherapy as outlined in the SOA. 
7.3.4. Conditioning Chemotherapy  
7.3.4.1. 
Pre-conditioning Chemotherapy Administration Criteria 
Before conditioning chemotherapy commences, the following criteria must be met.  If these criteria are 
not met, then conditioning chemotherapy must be delayed until these events resolve. 
 
No evidence or suspicion of infection 
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 
No clinically significant cardiac dysfunction 
 
Creatinine clearance above limits set in eligibility criteria (see Section 5) 
 
No acute neurological toxicity > Grade 1 (with the exception of peripheral neuropathy) 
 
 
 
. 
In addition, if any of the following are known to occur, a delay in conditioning chemotherapy may be 
required.  Contact the Kite medical monitor before conditioning chemotherapy commences for guidance. 
 
White blood cell (WBC) count of ≥ 20,000/μL within 48 hours prior to conditioning 
chemotherapy 
 
CRP is ≥ 100 mg/L  
 
Temperature is ≥ 38.0°C within 48 hours prior to conditioning chemotherapy.  Unexplained fever 
requires pan-culture, respiratory viral panel, chest CT, and any additional symptom-directed 
workup to rule out occult infection.  
 
If any screening assessments or procedures are repeated between enrollment and the start of 
conditioning chemotherapy, and results are outside the eligibility criteria (Section 5) 
7.3.4.2. 
Conditioning Chemotherapy Administration (Days -5 through -3 Before Infusion of KITE-585) 
Fludarabine and cyclophosphamide should be administered per institutional guidelines.  Refer to the 
current product label for guidance on packaging, storage, preparation, administration, and toxicity 
management associated with the administration of chemotherapy agents. 
Before conditioning chemotherapy commences, the criteria outlined in Section 7.3.4.1 must be met. 
Provided the criteria for conditioning chemotherapy are met, the 3-day conditioning regimen of 
fludarabine and cyclophosphamide will be administered in accordance with the following daily dosing 
instructions. 
 
IV hydration with 1 L of isotonic crystalloid given prior to cyclophosphamide on the day of 
infusion followed by: 
 
Cyclophosphamide 300 mg/m2 IV 
 
o An additional 1 L of isotonic crystalloid at the completion of the cyclophosphamide 
infusion  
o Add mesna per institutional guidelines  
 
Fludarabine 30 mg/m2 IV (or, in the case of subjects with moderate renal impairment, 24 mg/m2; 
see Section 7.3.4.2.1) 
  
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Subjects should be instructed to drink plenty of liquids during and for 24 hours following the 
chemotherapy (approximately 2 liters/24 hours).  In general, subjects should be kept well hydrated but 
closely monitored to prevent fluid overload.  
7.3.4.2.1. 
Dose Reduction for Renal Dysfunction 
Dose reduction of fludarabine by 20% should be performed in subjects enrolled into Expansion Cohort 2 
in accordance with standard practice and the fludarabine product label.  Therefore, the 3-day conditioning 
regimen of fludarabine and cyclophosphamide will be administered to subjects with creatinine clearance 
between 30 and 59 mL/min in accordance with the following daily dosing instructions. 
 
IV hydration with 1 L of isotonic crystalloid given prior to cyclophosphamide on the day of 
infusion followed by: 
 
Cyclophosphamide 300 mg/m2 IV 
 
o An additional 1 L of isotonic crystalloid at the completion of the cyclophosphamide 
infusion  
o Add mesna per institutional guidelines  
 
Fludarabine 24 mg/m2 IV 
  
Subjects with renal dysfunction should be adequately hydrated, but should be monitored closely for signs 
and symptoms of volume overload.  
7.3.4.3. 
Conditioning Chemotherapy Procedures 
The following procedures/requirements will occur during the conditioning chemotherapy period as 
outlined in the SOA: 
 
Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature 
 
Local labs (to be drawn prior to chemotherapy) 
o Chemistry panel 
o CBC with differential 
 
Fludarabine and cyclophosphamide chemotherapy (see Section 6.4 and 7.3.4) 
o After the pre-conditioning chemotherapy are met (see Section 7.3.4.1), subjects will receive 
conditioning chemotherapy over 3 days (Day -5 through Day -3) in an outpatient setting, 
followed by 2 days of rest (see Section 7.3.4.2), and KITE-585 on Day 0 (see Section 7.3.5).   
 
AE/SAE reporting (see Section 9) 
 
Concomitant medications documentation (see Section 6.6) 
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7.3.5. KITE-585 Treatment 
7.3.5.1. 
Pre-KITE-585 Administration Criteria 
Before KITE-585 infusion commences, the following criteria must be met.  If these criteria are not met, 
then KITE-585 infusion must be delayed until these events resolve.   
 
No evidence or suspicion of infection.  Subject must not be receiving systemic anti-microbials for 
the treatment of an active infection within 48 hours prior to KITE-585 infusion (prophylactic use 
of anti-microbials is allowed). 
 
No clinically significant cardiac dysfunction  
 
Creatinine clearance above limits set in eligibility criteria (see Section 5) 
 
No acute neurological toxicity > Grade 1 (with the exception of peripheral neuropathy) 
 
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 
KITE-585 administration.  
In addition, if any of the following are known to occur, the KITE-585 infusion may need to be delayed.  
Contact the Kite medical monitor before KITE-585 infusion commences for guidance: 
 
WBC count of ≥ 20,000/μL within 48 hours prior to KITE-585 infusion 
 
CRP is ≥ 100 mg/L 
 
Temperature is ≥ 38.0°C within 48 hours prior to KITE-585 infusion.  Unexplained fever requires 
pan-culture, respiratory viral panel, chest CT, and any additional symptom-directed workup to 
rule out occult infection. 
 
If any screening assessments or procedures are repeated between conditioning chemotherapy and 
the KITE-585 infusion and results are outside the eligibility criteria (Section 5; with the exception 
of conditioning chemotherapy-induced cytopenias) 
If the KITE-585 infusion is delayed > 2 weeks, conditioning chemotherapy must be repeated.  In all cases 
of KITE-585 infusion delays, contact the Kite medical monitor for guidance. 
7.3.5.2. 
Hospitalization for KITE-585 Administration 
All subjects will be hospitalized to receive treatment with KITE-585 followed by an observation period of 
at least 5 days.  
Due to the potential risk of CRS and neurological events following infusion of KITE-585, a 
minimum of two doses of tocilizumab should be available for immediate use within a maximum of 
two hours between the determination of the need for tocilizumab and its administration (See the 
current KITE-585 IB for additional information on the grading and management of KITE-585-
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Subjects should not be discharged from the hospital until at least 5 days have elapsed since the KITE-585 
infusion and all KITE-585-related non-hematological toxicities return to ≤ Grade 1 or baseline.  Subjects 
may be discharged with non-critical and clinically stable or improving toxicities (eg, renal insufficiency) 
even if > Grade 1, if deemed appropriate by the investigator.  Subjects should remain hospitalized for 
ongoing KITE-585-related or unexplained fever, hypotension, hypoxia, or ongoing central neurological 
toxicity > Grade 1 or if deemed necessary by the treating investigator.  If the subject is discharged before 
Day 10, the subject must return to the clinic daily through Day 10 for a history and physical examination, 
vital signs, and labs. 
Deep vein thrombosis (DVT) prophylaxis should be utilized in all subjects with reduced mobility during 
hospitalization per institutional guidelines.  Low molecular weight heparin (LMWH) is encouraged as 
long as there are no contraindications (eg, renal dysfunction, recent surgery, bleeding diathesis, platelet 
count < 50,000/µL) based on benefit/risk.  Unfractionated heparin or non-invasive mechanical 
intermittent pneumatic compression devices for DVT prophylaxis should be used in those with 
contraindications to LMWH or those who cannot receive anticoagulants due to increased bleeding risk or 
other concerns (Lyman et al, 2015). 
Given the possibility that a subject could develop AEs, including CRS or one or more neurologic events, 
after discharge from the hospital, subjects and their family members/caregivers should be educated on 
potential symptoms, such as fever, dyspnea, confusion, aphasia, dysphasia, somnolence, encephalopathy, 
ataxia, seizure, or tremor.  If subjects develop these and/or other symptoms, they should be instructed to 
immediately contact the principal investigator or to seek immediate medical attention.  
7.3.5.3. 
KITE-585 Premedication Dosing 
The following medications should be administered approximately 1 hour prior to infusion of KITE-585.  
 
Acetaminophen 650 mg PO 
 
Diphenhydramine 12.5 mg IV or 25 mg PO 
7.3.5.4. 
KITE-585 Administration (Day 0) 
Materials and instructions for the thawing, timing, and administering of KITE-585 are outlined in the 
IPM.  The IPM must be reviewed prior to administration of KITE-585.   
Central venous access, such as a port or a peripherally inserted central catheter, is required for the 
administration of KITE-585 and for the hospitalization treatment period.  Catheter care, per institutional 
guidelines, should be followed.   
Research sites should follow institutional guidelines for the infusion of cell products.  Prior to 
administration of KITE-585, the product label will be checked by 2 personnel at the research site and 
asked to complete the Kite Pharma Countersignature Form.  Sites may use their own countersignature 
form, provided that the chosen form collects at minimum the same data as required on the Kite Pharma 
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KITE-585 will be administered intravenously by gravity or IV pump set to 5 to 10 mL/min via non-
filtered tubing as follows. 
Refer to Sections 3.1 and 9.6 for dose cohort details.   
7.3.5.5. 
Other Procedures During KITE-585 Treatment Period 
The following procedures/requirements will occur during the KITE-585 treatment period as outlined in 
the SOA: 
 
Physical exam 
 
Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature will be taken: 
o Pre- and post-KITE-585 infusion 
o First morning reading for each day during hospitalization and more frequently as clinically 
indicated for subjects with fever (≥ 38.3°C) or other vital sign abnormality 
 
Neurological exam if applicable (see Sections 7.3.1) 
 
Disease assessment: 
o 
 
  
 
 
Local labs (to be drawn prior to KITE-585 infusion) 
o Chemistry panel 
o CBC with differential 
o Recommended:  Monitoring of CRP, ferritin, and LDH (only if LDH is elevated at baseline) 
levels may assist with the diagnosis and define the clinical course in regard to 
CRS/neurologic events.  It is, therefore, recommended that CRP, ferritin, and LDH (if 
elevated at baseline) be monitored daily starting at Day 0 and continuing through 
hospitalization.  In addition, lactate should be monitored as clinically indicated.    
 
Central labs (to be drawn prior to KITE-585 infusion) 
o PBMCs  
o Cytokine levels 
 
If applicable:  Lumbar puncture (including collection of opening pressure) for collection of CSF 
will be performed at the following time points: 
o Subjects with ≥ Grade 2 neurologic events and without medical contraindication  
o Subjects with symptoms of CNS malignancy, such as new onset severe headaches, neck 
stiffness, seizures, encephalopathy, cranial nerve deficits, or any focal neurologic findings on 
physical exam, will have lumbar puncture for examination of CSF.  
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o CSF samples will be analyzed locally for CNS MM (% plasma cells) and will be submitted to 
the central laboratory for additional analysis as outlined in Section 7.4. 
 
KITE-585 pre-medication (see Section 7.3.5.3) 
 
KITE-585 infusion (see Section 7.3.5) 
o After the pre-KITE-585 criteria are met (see Section 7.3.5.1), KITE-585 will be administered 
(see Section 7.3.5.4 and the IPM).  
 
AE/SAE reporting (see Section 9) 
 
Concomitant medications documentation (see Section 6.6) 
 
If the subject is discharged before Day 10, the subject must return to the clinic daily through 
Day 10 for a history and physical examination, vital signs, and labs (see Section 7.3.5.2 and the 
SOA) 
7.3.6. Post-treatment Follow-up Period  
The following procedures/requirements will occur at various time points during the post-treatment 
follow-up period (Week 2 through Month 3) as outlined in the SOA: 
 
Physical exam 
 
Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature  
 
Neurological exam if applicable (see Sections 7.3.1) 
 
Disease assessment, including serum and urine markers, bone marrow aspirate and biopsy, and, if 
applicable, imaging (see Section 7.2) 
 
Local labs 
o β-HCG pregnancy test (serum or urine) on all women of childbearing potential 
o Chemistry panel 
o CBC with differential 
o Recommended:  Monitoring of CRP, ferritin, and LDH (only if LDH is elevated at baseline) 
levels may assist with the diagnosis and define the clinical course in regards to 
CRS/neurologic events.  It is, therefore, recommended that CRP, ferritin, and LDH (if 
elevated at baseline) be monitored daily starting at Day 0 and continuing through 
hospitalization.  In addition, lactate should be monitored as clinically indicated.    
 
Central labs  
o PBMCs  
o Cytokine levels  
o 
 
) 
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o If applicable:  If, following discharge from initial hospitalization for KITE-585 infusion, the 
subject is subsequently re-admitted to the hospital with any KITE-585 related AEs, a PBMC 
and cytokine sample will be collected on the day of admission, weekly during hospitalization, 
and on the day of discharge or at the time of AE resolution. 
o If applicable, an additional cytokine sample will be collected if the subject experiences a 
Grade ≥ 3 KITE-585 related event (eg, CRS [per Lee et al, 2014 criteria]) or neurologic 
event, if not already collected on that day  
 
If applicable:  Lumbar puncture (including collection of opening pressure) for collection of CSF 
(see Section 7.3.5 for details) 
 
 
 
 
 
AE/SAE reporting (see Section 9) 
 
Concomitant medications documentation (see Section 6.6) 
At any time during the post-treatment assessment period, if a subject did not respond to treatment (ie, did 
not achieve at least a PR) or experiences disease progression following a response, the subject will 
proceed directly to the Month 3 visit and be followed for survival, subsequent therapy for MM, and 
disease outcomes in the long-term follow-up period.   
7.3.7. Long-term Follow-up Period   
The following procedures/requirements will occur during the long-term follow-up period (Month 4 
through Year 15) as outlined in the SOA: 
 
Physical exam 
 
Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature  
 
Disease assessment, including serum and urine markers, bone marrow aspirate and biopsy, and 
any applicable imaging (see Section 7.2) 
 
 
 
 
 
Survival status 
 
Local labs  
o Chemistry panel 
o CBC with differential 
 
Central labs  
o 
 
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 
 
 
 
.  
o PBMCs  
 
PBMC samples will be collected throughout the long-term follow-up (LTFU) period. 
 
Replication-competent lentivirus (RCL) testing will occur at baseline, Month 3, Month 6, 
and Month 12.  Thereafter, samples will be collected yearly and held for up to 15 years.  
If a subject tests positive for RCL at any time point within the first year, samples will 
continue to be collected and tested yearly for up 15 years or as clinically indicated.  
 
PBMC samples will also be used for continued monitoring of anti-BCMA CAR T-cell 
persistence at Months 6, 9, 12, 18, and 24. 
 
If applicable:  Lumbar puncture (including collection of opening pressure) for collection of CSF 
(see Section 7.3.5 for details) 
 
AE/SAE reporting (see Section 9) 
 
Concomitant medications documentation (see Section 6.6) 
 
Subsequent therapy for MM reporting (see Section 6.8) 
Subjects may also be contacted by telephone to confirm survival status and report targeted concomitant 
medication use.  Should a subject require lab collection, labs may be collected at the clinic or at an 
outside facility to reduce the subject burden. 
If the subject fails to return to the clinic for a scheduled protocol specific visit, sites will need to make 
2 attempts by a combination of telephone and mail to contact the subject.  Sites must document both 
attempts to contact the subject.  If a subject does not respond within 1 month after the second contact, the 
subject will be considered lost to follow-up, and no additional contact will be required. 
Subjects who received treatment with KITE-585, but who experience disease progression, will be 
followed in the LTFU period and undergo the following assessments at the time points outlined in the 
SOA: 
 
Survival status 
 
Targeted AE/SAEs (see Section 9) 
 
Targeted concomitant medications (see Section 6.6) 
Subjects who were enrolled, but did not receive treatment with KITE-585, will be followed in the LTFU 
period and undergo the following assessments at the time points outlined in the SOA: 
 
Survival status 
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 
AE/SAE reporting (see Section 9) 
7.4. Biomarkers 
Biomarker analysis will be performed on blood, bone marrow (tumor), and CSF samples to evaluate 
pharmacokinetic and pharmacodynamic markers related to safety or efficacy.  Prognostic markers specific 
for aggressive MM, related to the tumor immune environment or the safety and efficacy profile of KITE-
585, may also be evaluated.  
Analysis will include baseline and post-KITE-585 BCMA expression levels and other standard markers 
used to assess MM presence, burden, or other prognostic factors (CD38, CD138, and disease-related 
markers, such as del17p).  Remaining samples may be stored for future exploratory analysis of tumor 
specific DNA, RNA, or protein markers to better understand the safety profile of KITE-585. 
 
Levels of anti-BCMA CAR T cells in blood over time to understand the relationship between 
expansion and clinical outcome 
 
Levels of serum cytokines in blood.  The following cytokines may be included in the panel:  
pro-inflammatory and immune modulating cytokines IL-2, IL-6, IL-10, IL-15, IL-17a, TNF-α, 
interferon (IFN)-γ, CRP, and GM-CSF; immune effector molecules granzyme B and perforin; 
markers of hemophagocytic lymphohistiocytosis (HLH) (ferritin, sIL-2Rα); and chemokines IL-8, 
MIP-1α, MIP-1β, IP-10, and MCP-4.   
 
Levels of soluble BCMA will be measured to understand relationships with clinical outcome.  
 
Because KITE-585 comprises lentiviral vector transduced T cells, the presence of RCL in the 
blood of treated subjects will be monitored.   
 
Baseline leukapheresis and final KITE-585 product samples will be banked and may be analyzed 
by immunophenotyping, PCR, and/or gene expression profiling.  Remaining samples may be 
stored for future exploratory analysis of immune-related markers.  
On-study paired bone marrow aspirates and biopsies will be performed at baseline and 14 days after 
KITE-585 when we expect peak expansion and tumor infiltration with anti-BCMA CAR T cells.  
 
 
 
 
 
All mentioned samples and any other derivatives from these samples may be stored up to 15 years to 
address exploratory research or safety-related questions to the treatment or disease under study.  Each 
subject will have the right to have the sample material returned or destroyed at any time by contacting the 
investigator who, in turn, can contact the central laboratory.  The investigator should provide the sponsor 
with the study and subject number so that the sample can be located and destroyed.  
For subjects who withdraw consent, any samples that were not requested to be returned or destroyed will 
remain with the sponsor, and any data that may be generated will be entered in the study database. 
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Table 4. 
Schedule of Assessments 
Procedm·es 
Screening 
Enrollment/ 
T1·eatment Period 
Post-tnatm.ent Follow-up 
(days before 
Leukaphe.resis 
IP B,N, O 
(Calculated from Day 0) 
enrollment) 
Conditioning Chemotherapy 
Timeframe 
~28d 
14 d 
D-5 
D-4 
D-3 
D-2 D-1 
DO 
Dl - lOR 
W2 
W4 
M2 
M3 
d=da 
w=.Neek, m=month 
-ld 
±2d 
±3d 
±lw 
±lw 
X 
I 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HR, 02 sat, te1 
X 
X 
X 
X 
X 
XB 
XB,R 
X 
X 
X 
X 
ce status 
X 
X 
At time of nemolooical 
s e Section 6.9 
X 
ECHOT 
X 
Brain IJRID,I 
X 
s . s 
ss ss 
s 
Local serum and 24h urine E 
X 
X 
X 
X 
Local and central BM aspirate and 
X 
X 
X 
X 
bio s F 
PETCT 
X 
xo 
neck, chest, ab 
tional lasmac 
X 
Da 7 -14 
Local Labs 
Pregnanc test semm or urine 
X 
X 
Chemist! 
anel 
X 
X 
X 
X 
X 
X 
XR 
X 
X 
X 
X 
CBC w/differential 
X 
X 
X 
X 
X 
X 
XR 
X 
X 
X 
X 
CRP 
X 
Central Labs 
An ._ 
E-58 antibod 
X 
PBMCsK 
X 
X 
Q3DK,R 
XR 
X 
X 
X 
C okines K,L 
X 
X 
Q3D K,L,R 
XR 
X 
X 
X 
LP for collection of CSF and 
X 
At the time of 2: Grade 2 neurological symptoms A. 1 
essure A.I 
es1s 
X 
Flu am me/ 
os hamide 
X 
X 
X 
KIIB-585 it 
1011 IV M 
XM 
AE/SAE/Concomitant medication 
X 
X 
X 
XR 
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Table 5. 
Schedule of Assessment (Long-term Follow-up Pe1iod) 
Procedure 
Timeframe 
(month) 
Physical exam A 
Vitals (BP HR, 02 sat, temp) 
Disease Assessment 
Local serum and 24h urine E 
Local and central BM aspirate 
and bio s F 
PETCT 
(neck, chest, abdomen, pelvis) G 
Survival status 
serum or unne 
CBC w/differential 
Central Labs 
Anti-KITE-585 antibod J 
PBMCs 
Taroeted AE/SAEs P 
All KITE-585-related SAEs and 
Deaths re ardless of relatedness 
Targete.d concomitant medication 
Subs 
forMM 
4 
5 
6 
± l w 
±lw 
±lw 
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 
Lon2-te1·m Follow-up Pe1·iod 
Calculated from Da 0 
9 
12 
15 
18 
21 
24 
30 
36 
42 
48 
±2w 
±2w 
±2w 
±2w 
±2w 
±2w 
±lm 
±lm 
±lm 
±lm 
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 
Month 12 and at the time of suspected CR and PD per semm and/or urine biomarkers F 
For subjects with extramedullaiy disease at baseline: At time of suspected CR and suspected PD 
For subjects without extramedullaiy disease at baseline: At time extramedullaiy disease is suspected 
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 
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 
54 
±lm 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: CR, complete response; PD, progressive disease; SAE, serious adverse event; BM, bone marrow; BP, blood pressure; CBC, complete blood c.otmt; PET-CT, 
positron emission tomography-computerized tomography; HR, heal1. rate; MM, multiple myeloma; 02 sat oxygen saturation; PBMCs, peripheral blood mono1mclear cells; PET, 
positron emission tomography; SAE, serious adverse event; temp, temperature; ECOG, Eastern Cooperative Oncology Group; ECHO echocardiogram; MRI, magnetic resonance 
iniaging; CBC, complete blood cotmt; CRP, C-reactive protein; LP, hllllbar ptmc!me; CSF, cerebral pinal fluid; IV, intravenous. 
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Annually fo1· 
months 
60-180 ± 1 m 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Schedule of Assessment Footnotes: 
A Physical Exam: See footnote I. 
B Vital signs: Vital signs include blood pressure, heart rate, oxygen saturation, and temperature.  Vital signs will be taken pre- and post-KITE-585 infusion on Day 0.  First morning vital 
signs will be recorded for each day during hospitalization and more frequently as clinically indicated for subjects with fever (≥ 38.3°C) or other vital sign abnormality.   
C Neurological Exam:  All subjects will have a neurological exam at baseline and any time there are neurological symptoms (Section 6.9).  A neurologic examination will be performed with 
any abnormalities of the following recorded:  level of consciousness, orientation, vision, cranial nerves and brain stem functions, pyramidal and extra pyramidal motor system, reflexes, 
muscle tone and trophic findings, coordination, sensory system, neuropsychological findings (eg, speech, cognition and emotion).  
D Brain MRI (Section 7.2.4):  A baseline brain MRI will be performed.  On-study brain MRIs should be considered for subjects with ≥ Grade 2 neurological events (see Section 6.9). 
 E Local Serum and 24-hour Urine (Section 7.2.2):  Serum (quantitative immunoglobulins, free light chains, protein electrophoresis, protein immunofixation electrophoresis), and a 24-hour 
urine (total protein, urine protein electrophoresis, urine protein immunofixation electrophoresis) will be evaluated at the time points indicated in the SOA until the subject has PD, withdraws 
from the study, is lost to follow-up, or dies.   
F Local and Central BM aspirate and biopsy (Section 7.2.3):  A bone marrow aspirate and biopsy will be performed at the time points indicated in the SOA.  At all time points, bone 
marrow will be analyzed locally and centrally per Section 7.2.3.   
 At screening, bone marrow will be evaluated locally for high risk mutations by FISH, % plasma cells by flow cytometry, and locally/centrally for MRD.  If enrollment is delayed, then a 
repeat bone marrow biopsy and aspirate will be required to ensure baseline bone marrow is performed within 14 days before leukapheresis. 

 
  
 At Week 4 and Month 3, bone marrow will be evaluated locally for % plasma cells by flow cytometry.   
 After Month 3, a bone marrow aspirate and biopsy will be collected at the time of suspected CR and at the time of PD per serum and/or urine biomarkers and analyzed for MRD and other 
biomarkers.  At all bone marrow evaluation time points, a portion of the bone marrow aspirate and biopsy will be processed and submitted to the central laboratory per the central 
laboratory manual. 
G PET/CT neck, chest, abdomen, pelvis (Section 7.2.4):  All subjects will have a baseline PET CT after the last therapy for MM and ≤ 14 days before enrollment.  If the screening PET CT 
was positive or suspicious for extramedullary disease and the scans are ≥ 28 days before start of conditioning chemotherapy, then the PET CT scans will be repeated.  For subjects with 
extramedullary disease at baseline, on-study PET CT scans will be performed at the time of suspected CR followed by the time of suspected extramedullary PD or PD per serum and/or urine 
biomarkers.  For subjects who receive bridging therapy, a PET CT must be repeated prior to the initiation of conditioning chemotherapy.    
H 
 
 
I Lumbar puncture for collection of CSF (Sections 7.3):  CSF will be evaluated at the following times: 1) If the screening brain MRI is suspicious for CNS involvement, then an LP will be 
performed during screening, 2) Subjects with symptoms of CNS malignancy, such as new onset severe headaches, neck stiffness, seizures, encephalopathy, cranial nerve deficits, or any focal 
neurologic findings on physical exam, will have lumbar puncture for examination of cerebral spinal fluid, and 3) any time Grade ≥ 2 neurological symptoms are present (see Section 6.9).  
CSF will be analyzed locally for % plasma cells and centrally.  An opening pressure will be measured and recorded with every LP. 
J  Anti-KITE-585 antibody (Section 7.3.7):  Baseline antibody sample to be collected at enrollment prior to start of leukapheresis, at Week 4 and Month 3.  For subjects who test positive, 
additional antibody samples will be collected approximately every 3 months until Month 12 or until anti-KITE-585 antibody levels return to baseline or become negative, whichever occurs 
first. 
K PBMCs and Cytokines: Collected Q3D for the duration of hospitalization.  If, following discharge from initial hospitalization for KITE-585 infusion, the subject is subsequently re-
admitted to the hospital with any KITE-585 related adverse events, a PBMC and cytokine sample will be collected on the day of admission, weekly during hospitalization, and on the day of 
discharge.  A PBMC sample will be collected at the time of PD. 
L Cytokines:  As applicable, an additional cytokine sample will be collected if the subject experiences a ≥ Grade 3 KITE-585 related event (eg, CRS [per Lee et al, 2014 criteria] or 
neurologic event) if not already collected on that day.  
M KITE-585 Premeds (Section 7.3.5.3):  Acetaminophen and diphenhydramine will be administered approximately 1 hour prior to KITE-585 infusion. 
N KITE-585 Administration (Section 7.3.5):  Subjects will be hospitalized on Day 0 through Day 5 to received KITE-585 infusion.  See Section 7.3.5 for additional details.  
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O Additional Labs Recommended (Section 7.1):  Daily monitoring of CRP, ferritin, and LDH (only if LDH is elevated at baseline) levels is recommended daily starting at Day 0 and 
continuing through hospitalization to assist with the diagnosis and define the clinical course in regards to CRS/neurologic events.  Lactate should be monitored as clinically indicated.    
P Targeted AEs/SAEs (Section 9):  Targeted AE/SAEs are events that occur in the following systems/categories:  neurological, hematological, infections, autoimmune disorders, secondary 
malignancies.  Targeted AEs, targeted SAEs, and non-serious CRS events ≥ Grade 3 (per Lee et al, 2014 criteria) will be reported from Month 3 or initiation of another anti-cancer therapy 
(whichever occurs first) through 24 months after treatment with KITE-585 or PD, whichever occurs first.   
Q  Targeted concomitant medications:  See Section 9 for details. 
R Procedures during and after hospitalization through day 10:  Daily vital signs, chemistry, and hematology lab panels and Q3D cytokine and PBMC draws will continue through 
hospitalization regardless of day of discharge.  If subject is discharged before Day 10, the subject must return to the clinic daily through Day 10 for history and physical exam, vitals, and 
chemistry and hematology lab panels. 
S Bridging Therapy:  
 
. 
T ECHO: Repeat echocardiogram required only in study subjects who receive bridging therapy and subsequently develop evidence of new onset cardiac dysfunction including 
chest pain, shortness of breath, peripheral edema, or other signs and symptoms. 
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8. SUBJECT WITHDRAWAL 
Subjects have the right to withdraw from the study at any time and for any reason without prejudice to 
their future medical care by the physician or at the institution. 
Subjects can decline to continue to receive study required treatment and/or other protocol required 
procedures at any time during the study 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 (IP), 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 for 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; publicly 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 also be asked to 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 IP and/or other protocol-
required therapies, protocol procedures, or the study as a whole at any time prior to study completion. 
8.1. Reasons for Removal from Treatment 
Reasons for discontinuation of protocol-required IPs or procedures include any of the following: 
 
AE 
 
Subject request/non-compliance 
 
Product not available 
 
Lost to follow-up 
 
Death 
 
Decision by sponsor 


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8.2. Reasons for Removal from Study 
Reasons for removal of a subject from the study are as follows: 
 
Subject withdrawal of consent from further follow-up 
 
Investigator decision 
 
Lost to follow-up  
 
Death 
9. SAFETY REPORTING 
9.1. Adverse Events 
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.  
AEs are: 
 
Any untoward medical occurrence in a clinical trial subject.  The event does not necessarily have 
a relationship with study treatment.  
 
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, such as elective cosmetic surgery or a medical procedure 
while on study, that has not worsened during the study or involves an intervention is not 
considered an AE. 
 
Clinically significant abnormal laboratory values (eg, requires intervention, results in new or 
worsening clinical sequelae, requires therapy or adjustment of current therapy) 
o Where applicable, clinical sequelae (not the laboratory abnormality) are to be recorded as 
the AE.  
AEs that occur within the following systems/categories will be reported per Section 9.2.  These are called 
targeted AEs: 
 
Neurological  
 
Hematological 
 
Infections 
 
Autoimmune disorders 
 
Secondary malignancies 
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 
Interventions for pre-treatment conditions (such as elective cosmetic surgery) or medical 
procedures that were planned before study participation are not considered AEs.  
 
Hospitalization for study treatment infusions or precautionary measures per institutional policy 
are not considered AEs. 
 
Clinically insignificant abnormal laboratory values as determined by the investigator (eg, does 
not require intervention, does not result in new or worsening clinical sequelae, does not require 
therapy or adjustment of current therapy) 
The term “disease progression,” as assessed by biopsy 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, multiple myeloma).  
Signs and symptoms of disease progression may be recorded as AEs or SAEs and as being indicated due 
to disease progression.  Worsening of signs and symptoms of the malignancy under study should also be 
reported as AEs in the appropriate section of the CRF.  
The investigator’s clinical judgment is used to determine whether a subject is to be removed from 
treatment due to an AE.  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 
Requirements for subjects who receive treatment with KITE-585:   
 
AEs that occur from enrollment through 3 months after treatment with KITE-585 or until the 
initiation of another anti-cancer therapy, whichever occurs first, will be reported in the CRF.  
 
Thereafter, only targeted AEs (see Section 9.1 for definition of targeted AE) that occur from 
3 months after treatment with KITE-585 or initiation of another anti-cancer therapy (whichever 
occurs first) through 24 months after treatment with KITE-585 or disease progression, whichever 
occurs first, will be reported in the CRF.   
Requirements for subjects who are enrolled but do not receive KITE-585: 
 
AEs that occur from enrollment through 30 days after the last study-specific procedure (eg, 
leukapheresis, conditioning chemotherapy) will be reported in the CRF. 
Requirements for subjects who are screened, but not enrolled (ie, screen-failed):  
 
SAEs will be collected for 30 days from the last screening-related procedure (see Section 9.4). 
The investigator must provide the information listed below regarding the AEs being reported:  
 
AE diagnosis or syndrome (if not known, signs or symptoms) 


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 
Dates of onset and resolution 
 
Severity 
 
Assessment of relatedness to IP, conditioning chemotherapy, or study procedures 
 
Action taken 
Adverse event grading scale used will be the NCI Common Terminology Criteria for Adverse Events 
(CTCAE) version 4.03.  A copy of the grading scale can be downloaded from the CTEP home page 
(http://ctep.cancer.gov).  Cytokine release syndrome events will be reported using both CTCAE 4.03 and 
the modified Lee et al, 2014 criteria grading scale outlined in the Guidelines for Management of 
Important Risks section of the IB.  
In reviewing AEs, investigators must assess whether the AE is possibly related to 1) KITE-585, 2) 
conditioning chemotherapy, or 3) any protocol-required study procedure.  The relationship is indicated by 
a yes or no response and entered into the CRF.  A yes response should indicate that there is evidence to 
suggest a causal relationship between the study treatment or procedure and the AE.  Additional relevant 
data with respect to describing the AE will be collected in the CRFs. 
The investigator is expected to follow reported AEs until stabilization or resolution.  
9.3. Definition of Serious Adverse Events 
An SAE is defined as an AE that meets at least 1 of the following serious criteria: 
 
Fatal 
 
Life-threatening (places the subject at immediate risk of death) 
 
Requires in-patient hospitalization, prolongation of existing hospitalization, escalation of care 
o An AE would meet the criterion of “requires hospitalization” if the event necessitated an 
admission to a healthcare facility (eg, overnight stay).  
o Events that require an escalation of care when the subject is already hospitalized should be 
recorded as an SAE.  Examples of such events include movement from routine care in the 
hospital to the intensive care unit (ICU) or if that event resulted in a prolongation of the 
existing planned hospitalization.  
 
Results in persistent or significant disability/incapacity 
 
Congenital anomaly/birth defect 
 
Other medically important serious event 
o 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.”  


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9.4. Reporting of Serious Adverse Events and Non-serious ≥ Grade 4 CRS Events, Neurologic 
Events, and Product Infusion Reactions  
SAEs will be reported through the electronic data capture (EDC) system.  This is called eSAE reporting. 
Requirements for subjects who receive treatment with KITE-585:   
 
SAEs that occur from the date of consent through 3 months after treatment with KITE-585 or 
until the initiation of another anti-cancer therapy, whichever occurs first, will be reported to Kite 
within 24 hours using the eSAE. 
 
Thereafter, only serious targeted adverse events (see Section 9.1 for definition of targeted adverse 
event) that occur from 3 months after treatment with KITE-585 or initiation of another anti-
cancer therapy (whichever occurs first) through 24 months after treatment with KITE-585 or 
disease progression, whichever occurs first, will be reported to Kite within 24 hours using the 
eSAE. 
 
Serious adverse events, which the investigator assesses as related to KITE-585, that occurs from 
ICF through end of study will be reported to Kite within 24 hours using the eSAE. 
 
All deaths that occur from date of informed consent through end of study will be reported in the 
CRF.  
Requirements for subjects (ie, screened) who do not receive treatment with KITE-585 (ie, screen-failed, 
enrolled, but do not receive KITE-585): 
 
SAEs will be reported through 30 days after the last study-specific procedure (eg, screen 
procedure, leukapheresis, conditioning chemotherapy) in the CRF and to Kite within 24 hours 
using the SAE Report Form. 
All SAEs and non-serious ≥ Grade 4 CRS events as measured by the modified Lee criteria (Lee et 
al, 2014), product infusion reactions, and neurologic events,  must be submitted to Kite within 24 
hours of the investigator’s knowledge of the event via the eSAE system.  If the eSAE system is 
unavailable (eg, system outage), then the SAE must be submitted using the SAE Report Form and 
emailed to the SAE Reporting mailbox:  
 
Subsequently, all SAEs will be reported to the health authorities per local reporting guidelines.  
In addition to all reports of serious unexpected suspected adverse reactions, reports of deaths 
within 30 days of KITE-585 infusion, regardless of attribution, and all Grade ≥ 4 CRS, neurologic 
events, and product infusion reactions will be submitted to the FDA as expedited case reports.  
If the malignancy has a fatal outcome within 3 months of the last day of the conditioning therapy or 
KITE-585, then the event malignant neoplasm progression must be recorded as a serious adverse event 
with the outcome fatal.  
PPD


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9.5. Pregnancy and Lactation 
There is no relevant clinical experience with KITE-585 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.  This experimental therapy should not be administered to pregnant women or 
women who are breastfeeding. 
Female subjects and female partners of male subjects must use highly effective contraception for at least 
6 months after KITE-585 dosing.  Male subjects must not father a child for 6 months after the KITE-585 
dosing.  If a pregnancy occurs in a female subject enrolled into the study or a female partner of a male 
subject within 6 months after completing the KITE-585 infusion, the pregnancy must be reported to the 
key sponsor contact.  Information regarding the pregnancy and/or the outcome may be requested by the 
sponsor.  
The pregnancy should be reported to the key sponsor contact within 24 hours of the investigator’s 
knowledge of the pregnancy event.  
If a lactation case occurs while the female subject is taking protocol-required therapies, report the 
lactation case to the key sponsor contact. 
In addition to reporting a lactation case during the study, investigators should monitor for lactation cases 
that occur after the last dose of protocol-required therapies through 6 months. 
Any lactation case should be reported to the key sponsor contact within 24 hours of the investigator’s 
knowledge of the event. 
Pregnancy and lactation cases will be reported to Kite using the Pregnancy/Lactation Report Form and 
emailed to the SAE Reporting mailbox:   
 
9.6. Safety Review Team and Dose-limiting Toxicity 
The SRT will be comprised of clinical development representatives from Kite and at least one Phase 1 
study investigator.  The SRT will be specifically chartered to review safety data during the study and 
make recommendations on further study conduct based on the incidence of KITE-585 DLT and review of 
SAEs.    
9.6.1. Dose-limiting Toxicity 
Dose-limiting toxicity (DLT) is defined as the KITE-585-related events with onset within the first 28 days 
following KITE-585 infusion.  CRS will be graded according to a revised grading system (Lee et al, 
2014).  Details of CRS grading and management are found in Section 6.4, Tables 5 and 6 of the 
KITE-585 IB, version 2.1.  As the safety experience with KITE-585 increases, the management 
guidance may be updated. Therefore, it is important that the most current version of the KITE-585 
IB is consulted for guidance regarding management of KITE-585-related toxicities. AEs attributed to 
PPD


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CRS will be mapped to the overall CRS grading assessment for the determination of DLT.  Details of the 
DLT definitions, including duration of event and exceptions, are provided in Table 6. 
 
Table 6. 
Dose-limiting Toxicities 
DLT 
Exceptions 
Grade 
(CTCAE 4.03 unless otherwise 
indicated) 
Duration 
Grade 3 CRS 
(Lee et al, 2014) 
≥ 72 hours 
n/a 
Grade 4 CRS 
(Lee et al, 2014) 
Any 
n/a 
Grade 3 non-hematologic AE 
≥ 72 hours 
 
Fever 
 
Nausea 
 
Hepatic toxicity that resolves to Grade 2 or better in 
≤ 14 days 
 
Hypogammaglobulinemia 
 
Tumor lysis syndrome 
Grade 4 non-hematologic AE 
Any 
 
Fever 
 
Nausea 
 
Hepatic toxicity that resolves to Grade 3 or better in 
≤ 72 hours 
 
Hypogammaglobulinemia 
 
Tumor lysis syndrome 
 
Acute renal toxicity requiring dialysis for ≤ 7 days 
 
Intubation for airway protection for ≤ 7 days 
 
AE resolves to ≤ Grade 1 within 2 weeks and 
baseline within 4 weeks 
Grade 4 hematologic AE 
≥ 30 days 
Cytopenias attributable to ongoing or recurrent MM 
KITE-585-related Grade 5 AE  
Any 
n/a 
Abbreviations:  AE, adverse event; CRS, cytokine release syndrome; MM, multiple myeloma; n/a, not applicable; CTCAE, 
Common Terminology Criteria for Adverse Events. 
 
Subjects will be dosed in a standard 3 + 3 dose escalating fashion (see Section 3.1 for overview of dose 
cohorts).  The first 3 subjects enrolled will be dosed with a minimum of 2 weeks between each subject’s 


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infusion.  The analysis of DLTs will be based on the DLT evaluable set as defined in Section 10.5.  The 
SRT will make recommendations based on the incidence of DLTs and the overall safety profile of 
KITE-585 as outlined in Table 7. 
Table 7. 
Recommendations Based on DLTs 
# of DLTs 
Potential Recommendation 
0/3 or 1/6 
Dose determined tolerable, go to next higher dose cohort; if highest dose, then the 
highest dose will be the MTD 
1/3 
Enroll 3 more subjects at same dose level 
2/3 or 2/6 
Next lower dose cohort will be established as the MTD* 
Abbreviations:  #, number; DLT, dose-limiting toxicity; MTD, maximum tolerated dose. 
*If the incidence of DLT in the first dose-escalation cohort, dose level 1 of subjects treated the planned dose of 3 x 107 anti-
BCMA CAR T cells is ≥ 2/6, the sponsor may, in consultation with the SRT, choose to decrease the dose to 1 x 107 anti-BCMA 
CAR T cells and open another cohort of 3 to 6 subjects.  If the incidence of DLT in this cohort is ≤ 1, this dose will be established 
as the MTD. 
 
The sponsor may, in consultation with the SRT, choose to treat up to 20 additional subjects at any dose 
deemed safe by the SRT up to, and including, the MTD in Expansion Cohort 1 to further characterize 
benefit risk.  Expansion Cohort 1 will be comprised of subjects who meet all eligibility criteria specified 
for the dose escalation portion of the study.  The SRT will review the safety data after the first 10 subjects 
from Expansion Cohort 1 have been treated and have completed the Day 28 visit.  
Separately, subjects with moderate renal impairment (creatinine clearance 30 to 59 ml/min by Cockcroft-
Gault estimation) may, in consultation with the SRT, be enrolled and treated at any dose deemed safe by 
the SRT during the dose escalation phase up to, and including, the MTD established during the initial 
dose escalation in Expansion Cohort 2.  The first 3 subjects will be enrolled with a minimum of 2 weeks 
between each subject’s infusion.  The SRT will review safety data after the first 6 subjects have been 
treated and have completed the Day 28 visit.  The SRT may make study recommendations including, for 
example, treatment of additional subjects at the original dose, that the cell dose be reduced and additional 
subjects treated, or that the cohort be closed to further enrollment.  
9.6.2. Criteria to Pause Enrollment 
As part of its oversight of the study, the SRT will assess criteria to pause enrollment after 10, 20, 30, and 
50 subjects have been treated with KITE-585 (including all subjects from dose-escalation cohorts, 
Expansion Cohort 1, and Expansion Cohort 2) and have had the opportunity to be followed for 28 days.  
Enrollment will be paused if any of the following criteria is met: 
 
Any subject incidence of Grade 5 AE within 30 days of the KITE-585 infusion regardless of 
relatedness to treatment 
 
Subject incidence of ≥ 33% Grade 4 non-hematological AEs (irrespective if related to the KITE-
585 or at least possibly related) that do not decrease to Grade 2 within 7 days  


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 
Subject incidence of ≥ 33% Grade 3 KITE-585 related events of CRS, neurologic events, 
infection, or other non-hematological SAEs that do not resolve to Grade 2 or better within 
72 hours of onset and ≥ 33% Grade 4 of such events regardless of duration  
FDA will be notified within applicable safety reporting timelines if any of these pausing rules occur. 
Accrual will be resumed upon recommendation of the SRT. 
10. STATISTICAL CONSIDERATIONS 
10.1. Hypothesis 
KITE-585 at one of the dose levels planned will be considered safe as determined by the incidence of 
DLTs. 
10.2. Study Endpoints 
10.2.1. Primary 
Incidence of AEs defined as DLTs.  
10.2.2. Secondary 
 
Objective response rate (ORR):  objective response is defined as either a PR or very good PR 
(VGPR) or as a complete response (CR) or stringent CR, as determined by study investigators 
according to IMWG Consensus Panel 1 Criteria (Rajkumar et al, 2011).  Subjects who did not 
meet the criteria for objective response by the analysis cutoff date will be considered non-
responders. 
 
Progression free survival (PFS):  PFS is defined as the time from the KITE-585 infusion date to 
the date of disease progression per the IMWG Consensus Panel 1 Criteria (Rajkumar et al, 2011) 
or death from any cause.  Subjects not meeting the criteria for progression by the analysis data 
cutoff date will be censored at their last evaluable disease assessment date.  Subjects who receive 
additional anti-cancer therapy (with the exception of stem cell transplant while in KITE-585 
induced response) in the absence of documented progression will be censored at the last evaluable 
disease assessment prior to the additional therapy.  Death that occurs after additional anti-cancer 
therapy will be considered a PFS event.        
 
Duration of response (DOR):  DOR is defined for subjects who experience an objective response 
and is defined as the date of their first objective response (which is subsequently confirmed) to 
disease progression per IMWG Consensus Panel 1 Criteria (Rajkumar et al, 2011) 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.  Subjects who receive 
additional anti-cancer therapy (with the exception of stem cell transplant) in the absence of 
documented progression will be censored at the last evaluable disease assessment prior to the 
additional therapy.   


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 
Time to next treatment (TTNT): TTNT is defined as the length of time between the date of KITE-
585 infusion to the date of initiation of the next therapy that was started after documented disease 
progression.  
 
Overall survival (OS):  OS is defined as the time from KITE-585 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.  Subjects known to be alive or to have died after the data cutoff date will have 
OS time censored at the data cutoff date. 
 
Incidence of AEs and clinically significant changes in laboratory values 
10.2.3. Exploratory  
10.2.4. Covariates 
The following covariates may be used in efficacy and safety analyses: 
 
ECOG status (0 vs. 1) 
 
Prior daratumumab exposure (yes vs no) 
 
Prior autologous bone marrow transplant (yes vs no) 
 
Disease burden (≤ 50% vs ≥ 50% clonal plasma cells on bone marrow aspirate or biopsy) 
 
Disease risk stratification (≥ 1 FISH abnormalities listed in Section 7.2.3.1 vs 0 abnormalities)  
 
Dual-refractory disease (yes vs no) 
 
BCMA expression on pretreatment MM cells 
 
Subject body weight at time of leukapheresis 
10.3. Handling of Missing Data  
Missing dates will not be imputed, unless further specified in the statistical analysis plan.   
10.4. Sample Size Considerations 
Approximately 6 to 64 subjects overall will be enrolled and treated.  
 
6 to 24 subjects in the initial dose escalation portion 
 
Up to approximately 20 additional subjects with creatinine clearance ≥ 60 mL/min by Cockcroft-
Gault estimation may be treated with the MTD or a lower dose to gain additional information 
about benefit/risk (Expansion Cohort 1) 
CCI


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 
Up to approximately 20 additional subjects with moderate renal impairment (creatinine clearance 
30 to 59 mL/min [Grade 2 chronic kidney disease]) may be treated with the MTD or a lower dose 
(Expansion Cohort 2) 
10.5. Analysis Subsets   
DLT evaluable set:  The DLT evaluable set is defined for each dosing cohort in the dose escalation period 
as a subject who:   
 
Received the target dose (± 20%) and were followed for at least 28 days after the first KITE-585 
infusion; or  
 
Received a dose of KITE-585 lower than 20% below the target dose for that cohort and 
experienced a DLT during the 28-day post-first-infusion period.   
If needed, additional subjects will be enrolled to achieve enough DLT evaluable subjects at the target 
dose for each cohort to estimate the true DLT rate. 
Full analysis set (FAS):  The full analysis set is defined as all subjects treated with any dose of KITE-585.  
If not specified otherwise, this analysis set will be used for evaluation of all endpoints. 
Per protocol analysis set (PPAS):  The per protocol analysis set includes subjects who have not deviated 
from the protocol in such a manner that the assessment of efficacy endpoints may be biased.  A subject 
may be excluded from the PPAS due to insufficient exposure to study drug, important protocol deviation, 
enrollment criteria violation, or any other situation that may affect the assessment of efficacy endpoints. 
10.6. Access to Individual Subject Treatment Assignments 
This is a Phase 1, single-arm, open-label study, and subjects and investigators will be aware of treatment 
received.  Data handling procedures 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 analysis 
plan. 
10.7.  Interim Analysis 
Safety data will be reviewed by the SRT as detailed in Section 9.6 and Section 10.7.1.  Exploratory 
analysis may be performed given the study data are accumulated and reviewed. 
10.7.1. Safety Analysis 
The SRT will be chartered to review subject-level safety data at defined milestones.  During the dose 
escalation phase, the SRT will review safety data at the completion of enrollment and treatment of each 
dosing cohort (see Section 9.6) and before opening the next dose level.  During Expansion Cohort 1 and 
Cohort 2, the SRT will review safety data after 10 and 6 subjects, respectively, have been treated with 
KITE-585 and followed for 28 days.  Additional information about safety monitoring is described in the 
SRT charter.  


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10.8. Planned Method of Analysis 
Analysis to support the clinical study report (CSR) will occur after all enrolled subjects have had the 
opportunity to complete 6 months of protocol-specified visits, have died, or have withdrawn from the 
study. 
Descriptive statistics will be provided for all endpoints.  Unless otherwise stated, safety and efficacy 
analysis will be conducted on full analysis set.  Per protocol analysis set or other identified subgroups can 
be used to evaluate safety or efficacy endpoints.  Continuous measurements will be summarized using the 
following summary descriptive statistics:  number of subjects, median, minimum, and maximum.  
Frequencies and percentages will be used to summarize categorical measurements.  For time-to-event 
variables, the Kaplan-Meier method will be used for descriptive summaries. 
10.8.1. Clinical Response Rate 
The incidence of response rates, best response, and their exact 2-sided 95% confidence intervals will be 
generated. 
10.8.2. Progression-free Survival 
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for PFS time.  Estimates 
of the proportion of subjects alive and progression-free at selected time points will be provided. 
10.8.3. Overall Survival 
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for overall survival time.  
Estimates of the proportion of subjects alive at selected time points will be provided. 
10.8.4. Time to Next Treatment 
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for time to next treatment 
survival time.  Estimates of the proportion of subjects who have not required additional treatment for 
progressive MM at selected time points will be provided. 
10.8.5.  Safety Analysis 
Subject incidence rates of AEs, including all, serious, fatal, CTCAE version 4.03 Grade 3 or higher, and 
treatment-related AEs, and reported throughout the conduct of the study will be tabulated by preferred 
term and system organ class.  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 the long-term follow-up and treatment-related SAEs will be 
provided. 


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10.8.6. Long-term Data Analysis 
All subjects will be followed for survival for up to approximately 15 years after the last subject receives 
KITE-585.  No formal hypothesis testing will be performed based on data obtained after the cutoff for the 
primary analysis.  Descriptive estimates of key efficacy and safety analyses may be updated to assess the 
overall treatment profile. 
11. REGULATORY OBLIGATIONS  
This study will be conducted in accordance with the protocol and the following: 
 
Consensus ethical principles derived from international guidelines, including the Declaration of 
Helsinki 
 
Applicable International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines 
 
Applicable laws and regulations 
11.1. Independent Review Board/Independent Ethics Committee  
A copy of the protocol, ICF, and any additional subject or trial information, such as subject recruitment 
materials, must be submitted to each site’s respective IRB/IEC for approval.  After approval is obtained 
from the IRB/IEC, all documents must be provided to the key sponsor contact before subject recruitment 
can begin. 
The investigator must also receive IRB/IEC approval for all protocol and ICF changes or amendments.  
Investigators must ensure that ongoing/continuous IRB/IEC approval (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 at all material submitted to the key sponsor contact.  The 
following rules are to be applied. 
 
Subjects will be identified by a unique identification number. 
 
Date of birth or year of birth/age at time of enrollment will be reported according with local laws 
and regulations. 
For reporting of SAEs, subjects will be identified by their respective subject identification number, 
initials, and data of birth or year of birth (as per their local reporting requirements for both initials and 
date of birth). 


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Per country-specific regulations and ICH/GCP guidelines, investigators and institutions are required to 
permit authorization to the sponsor, Contract Research Organization (CRO), IRB/IEC, and regulatory 
agencies to subject’s original source documents for verification of study data.  The investigator is 
responsible for informing potential subjects that such individuals will have access to their medical 
records, which includes personal information. 
11.3. Investigator Signatory Obligations 
Each CSR will be signed by the coordinating investigator.  The coordinating investigator will be 
identified by Kite Pharma 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 
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 Pharma and the investigator reserve the right to terminate the investigator’s ability to enroll 
additional subjects or general 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, 
early termination of enrollment, or termination of study participation and provide the CRO with a copy of 
the correspondence. 
Kite Pharma reserves the unilateral right, at its sole discretion, to determine whether to manufacture CAR 
T cells and provide them to sites and subjects after the completion of the study and before treatment 
becomes commercially available. 
13. STUDY DOCUMENTATION AND ARCHIVE 
The investigator will maintain a list of qualified staff to whom study responsibilities have been delegated.  
These individuals authorized to fulfil these responsibilities 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.  Examples of such source documents may include, but are not limited to, hospital records and 
patient charts; laboratory, pharmacy, and radiology records; subject diaries; microfiches; correspondence; 
and death registries.  CRF entries may be considered as source data if the site of the original data 
collection is not available.  However, use of the CRFs as source documentation as a routine practice is not 
recommended. 


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The investigator and study staff are responsible for maintaining a comprehensive and centralized filing 
system of all subject records that are readily retrieved to be monitored and/or audited at any time by the 
key sponsor contact, regulatory authorities, and IRB/IECs.  The filing system will include at minimum: 
 
Subject content, including ICFs and subject identification lists 
 
Protocols and protocol amendments, IB, copies of pre-study documentation, and all IRB/IEC and 
sponsor communication 
 
Proof of receipt, experimental treatment flow records, and experimental product-related 
correspondence 
Original source documents supporting entries into CRFs must be maintained at the site and readily 
available upon request.  No study documents should be discarded without prior written agreement 
between Kite Pharma and the investigator.  If storage is 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. 
14. STUDY MONITORING AND DATA COLLECTION 
The key sponsor contacts, monitors, auditors, or regulatory inspectors are responsible for contacting and 
visiting the investigator for the purpose of inspecting the facilities and verifying source documents and 
records assuring that subject confidentially is respected. 
The monitor is responsible for source document verification of CRF data at regular intervals during the 
study.  Protocol adherence, accuracy, and consistency of study conduct and data collection with respect to 
local regulations will be confirmed.  Monitors will have access to subject records. 
By signing the Investigator’s 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 for 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 additional details about completing CRFs, refer to 
the CRF completion guidelines. 
15. PUBLICATION 
Authorship of publications from data generated in the Study KITE-585-501 will be determined based on 
the uniform requirements for manuscripts submitted to biomedical journals (as outlined in the 
International Committee of Medical Journal Editors December 2013), which states authorship should be 
based on: 


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 
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 re 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, collection of data, or general supervision of the research alone or in combination does not 
qualify an individual for authorship. 
Any publication, in any form, that is derived from this study must be submitted to Kite Pharma for review 
and approval.  The study contract between the institution, principal investigator, and Kite Pharma or its 
delegate will outline the requirements for publication review. 
16. COMPENSATION 
Kite Pharma 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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Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015;373(7):621-31. 
 
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APPENDIX 1 
International Myeloma Working Group (IMWG) Consensus Panel 1 Criteria 
Response 
Response Criteria 
Stringent 
complete 
response (sCR) 
 
Complete response as defined below, plus  
 
Normal FLC ratio, and 
 
Absence of clonal plasma cells (PCs) by immunohistochemistry or 
immunofluorescence1 
Complete 
response (CR)2 
 
Negative immunofixation on the serum and urine, and 
 
Disappearance of any soft tissue plasmacytomas, and 
 
< 5% PCs in bone marrow aspirates 
Very good partial 
response 
(VGPR)2 
 
Serum and urine M-protein detectable by immunofixation but not on 
electrophoresis 
Or 
 
≥ 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 hours 
Partial response 
(PR) 
 
≥ 50% reduction of serum M-protein plus reduction in 24-hour urinary M-protein 
by ≥ 90% or to < 200 mg/24 hours 
 
If the serum and urine M-protein are unmeasurable, a ≥ 50% decrease in the 
difference between involved and uninvolved FLC levels is required in place of the 
M-protein criteria 
 
If serum and urine M-protein are unmeasurable and serum-free light assay is also 
unmeasurable, ≥ 50% reduction in plasma cells is required in place of M-protein, 
provided baseline bone marrow plasma-cell percentage was ≥ 30% 
 
In addition to these criteria, if present at baseline, a ≥ 50% reduction in the size of 
soft tissue plasmacytomas is also required 
Stable disease 
(SD) 
Not meeting criteria for CR, VGPR, PR, or PD 
Progressive 
disease (PD)3 
Any one or more of the following: 
 
Increase of 25% from lowest response value in any one of the following: 
o 
Serum M-component (absolute increase must be ≥ 0.5 g/dL) 
o 
Urine M-component (absolute increase must be ≥ 200 mg/24 hours) 
o 
Only in subjects without measurable serum and urine M-protein levels:  the 
difference between involved and uninvolved FLC levels (absolute increase 
must be > 10 mg/dL) 
o 
Only in subjects without measurable serum and urine M-protein levels and 
without measurable disease by FLC levels, bone marrow PC percentage 
(absolute percentage must be ≥ 10%) 
o 
Definite development of new bone lesions or soft tissue plasmacytomas or 
definite increase in the size of existing bone lesions or soft tissue 
plasmacytomas 


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 
Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL) that can be 
attributed solely to the PC proliferative disorder 
Source: Rajkumar et al, 2011 (modified for protocol purposes) 
Abbreviations:  FLC, free light chain; PC, plasma cell. 
All response categories (CR, sCR, VGPR, PR, and PD) require 2 consecutive assessments made at any time before the institution 
of any new therapy; CR, sCR, VGPR, PR, and SD categories also require no known evidence of progressive or new bone lesions 
if radiographic studies were performed.  VGPR and CR categories require serum and urine studies regardless of whether disease 
at baseline was measurable on serum, urine, both, or neither.  Radiographic studies are not required to satisfy these response 
requirements.  Bone marrow assessments need not be confirmed.  
1 Presence/absence of clonal cells is based upon the kappa/lambda ratio.  An abnormal kappa/lambda ratio by 
immunohistochemistry or immunofluorescence requires a minimum of 100 plasma cells for analysis.  An abnormal ratio 
reflecting presence of an abnormal clone is kappa/lambda of > 4:1 or  < 1:2. 
2 Clarifications to IMWG criteria for coding CR and VGPR in subjects in whom the only measurable disease is by serum FLC 
levels:  CR in such subjects indicates a normal FLC ratio of 0.26 to 1.65 in addition to CR criteria listed above.  VGPR in such 
subjects requires a > 90% decrease in the difference between involved and uninvolved FLC levels. 
3 Clarifications to IMWG criteria for coding PD:  Bone marrow criteria for PD are to be used only in subjects without 
measurable disease by M-protein and by FLC levels; “25% increase” refers to M-protein, FLC, and bone marrow results and 
does not refer to bone lesions, soft tissue plasmacytomas, or hypercalcemia, and the “lowest response value” does not need to 
be a confirmed value.  For progressive disease, serum M-component increases of ≥ 1 gm/dL are sufficient to define relapse if 
starting M-component is ≥ 5 g/dL. 

SAP_001.pdf: 
Sponsor:
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
USA
Company Code:
KITE-585
USAN Name:
Not Applicable
Product Name:
KITE-585
Protocol:
A Phase 1 Multicenter Study of KITE-585, an Autologous Anti-BCMA
CAR T-Cell Therapy, in Subjects with Relapsed/Refractory Multiple
Myeloma
Version Number:
Version 1.0
Release Date:
2/26/2019
Replaces Previous Version(s):
Not Applicable
Date:
26 March 2019
CONFIDENTIALITY NOTICE
This document contains confidential information of Kite Pharma 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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Statistical Analysis Plan
CONFIDENTIAL
Page 2
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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
3.4.
Statistical Assumptions ..........................................................................................................................11
4.
STUDY ENDPOINTS AND COVARIATES ....................................................................................................12
4.1.
Endpoints ...............................................................................................................................................12
4.2.
Covariates...............................................................................................................................................12
5.
DEFINITIONS....................................................................................................................................................13
5.1.
General...................................................................................................................................................13
5.2.
Safety .....................................................................................................................................................13
5.3.
Efficacy..................................................................................................................................................15
6.
ANALYSIS SUBSETS.......................................................................................................................................16
6.1.
DLT evaluable set: .................................................................................................................................16
6.2.
Full Analysis Set (FAS) .........................................................................................................................16
6.3.
Safety Analyses Set................................................................................................................................16
6.4.
Per protocol analysis set (PPAS)............................................................................................................16
7.
INTERIM ANALYSIS AND EARLY STOPPING GUIDELINES...................................................................17
7.1.
Interim Analysis.....................................................................................................................................17
8.
DATA SCREENING AND ACCEPTANCE......................................................................................................18
8.1.
General Principles ..................................................................................................................................18
8.2.
Electronic Transfer and Archiving of Data ............................................................................................18
8.3.
Handling of Missing and Incomplete Data.............................................................................................18
8.3.1.
Efficacy ................................................................................................................................18
8.3.2.
Safety....................................................................................................................................18
8.4.
Detection of Bias....................................................................................................................................18
8.5.
Outliers...................................................................................................................................................18
8.6.
Distributional Characteristics.................................................................................................................19
8.7.
Validation and Configuration Management ...........................................................................................19
9.
STATISTICAL METHODS OF ANALYSIS ....................................................................................................20
9.1.
General Principles ..................................................................................................................................20
9.2.
Subject Accountability...........................................................................................................................20
9.3.
Important Protocol Deviations ...............................................................................................................20
9.4.
Demographic and Baseline Characteristics............................................................................................20
9.5.
Efficacy Analyses...................................................................................................................................21
9.5.1.
Objective Response Rate (ORR) and Best Response...........................................................22
9.5.2.
Progression Free Survival (PFS) ..........................................................................................22


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9.5.3.
Duration of Response (DOR)...............................................................................................22
9.5.4.
Overall Survival (OS)...........................................................................................................22
9.5.5.
Time to next Treatment (TTNT) ..........................................................................................22
9.5.6.
Disease burden .....................................................................................................................23
9.5.7.
Minimal residual disease (MRD) .........................................................................................23
9.6.
Safety Analyses......................................................................................................................................23
9.6.1.
Adverse Events.....................................................................................................................24
9.6.2.
Exposure to Concomitant Medications and Procedures .......................................................24
9.6.3.
Laboratory Test Results........................................................................................................25
9.6.4.
Vital Signs............................................................................................................................25
9.6.5.
25
9.6.6.
Replication Competent Lentivirus........................................................................................25
9.6.7.
Exposure to Study Treatment...............................................................................................25
9.7.
Pharmacokinetics ...................................................................................................................................26
9.8.
Pharmacodynamics ................................................................................................................................26
9.9.
Subsequent Anti-Cancer Therapy ..........................................................................................................26
9.10.
Duration Metrics ....................................................................................................................................26
10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES.............................................................................27
11.
REFERENCES ...................................................................................................................................................28
12.
APPENDICES ....................................................................................................................................................29
Appendix 1.
Conventions for Clinical Data that Require Imputation for Partial or Missing Dates ............30
Appendix 2.
Definitions related to Prolonged Cytopenias..........................................................................31
Appendix 3.
Derivation of Time to Event Endpoints and Last Date Known to Be Alive...........................32
LIST OF TABLES
Table 1.
Dosing Cohorts.........................................................................................................................8
Table 2.
Imputation Rules for Partial or Missing Start Dates...............................................................30
LIST OF FIGURES
Figure 1.
Study Schema for Study KITE-585-501.................................................................................10
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Definition
ADaM
Analysis data model
ADR
Adverse drug reaction
AE
Adverse event
ALT
Alanine Aminotransferase
AST
Aspartate aminotransferase
ASCT
Autologous stem cell transplant
CAR
Chimeric antigen receptor
CNS
Central nervous system
CRF
Case report form
CRS
Cytokine release syndrome
CTCAE
Common terminology criteria for adverse event
DMP
Data Management Plan
ECOG
Eastern Cooperative Oncology Group
FLC
Free light chain
HLGT
High-level group term
IL
Interleukin
MA
Marketing application
MM
Multiple Myeloma
MedDRA
Medical Dictionary for Regulatory Activities
NCI
National Cancer Institute
RCL
Replication-competent lentivirus
R/R
Relapsed/Refractory 
RRMM
Relapsed/Refractory Multiple Myeloma
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
SRT
Safety review team
Std Dev
Standard deviation
TEAE
Treatment-emergent adverse event


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Abbreviation
Definition
ULN
Upper limit of normal
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) provides the pre-specification and details for the statistical 
analyses to support the following study:

KITE-585-501 Amendment 2 entitled “A Phase 1 Multicenter Study of KITE-585, an 
Autologous Anti-BCMA CAR T-Cell Therapy, in Subjects with Relapsed/Refractory 
Multiple Myeloma”, dated 11 September 2017.


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2.
OBJECTIVES
The primary objective of this study is to evaluate the safety and tolerability of KITE-585 as 
measured by the incidence of dose-limiting toxicities (DLTs). The secondary objective of this 
study is to gain insight into additional features of safety, tolerability, and efficacy of KITE-585 
in subjects with intact (creatinine clearance ≥ 60 mL/min by Cockcroft-Gault estimation) and 
moderately impaired renal function (creatinine clearance 30-59 mL/min by Cockcroft-Gault), 
including depth and durability of response, minimal residual disease (MRD), survival, and 
toxicity of the regimen. 


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3.
STUDY DESIGN
3.1.
Overview
KITE-585-501 is a Phase 1, multicenter, open-label study evaluating the safety and tolerability 
of KITE-585 in subjects with relapsed/refractory multiple myeloma (RRMM).
Approximately 6 to 24 subjects will be enrolled in a standard 3 + 3 dose escalation scheme to 
evaluate the safety of KITE-585 regimens.  Following enrollment and treatment with 
cyclophosphamide and fludarabine conditioning chemotherapy, subjects will be enrolled into 
1 of the following cohorts as outlined in Table 1 at a fixed dose.  This dose will be reduced by 
33% for subjects weighing ≤53 kg.  For the first cohort, subjects will be enrolled one by one, 
with a minimum of 2 weeks between enrollment dates.  Safety within each cohort will be 
assessed for DLTs, and enrollment in each cohort will continue to occur sequentially until a 
maximum tolerated dose (MTD) is reached.
Table 1.
Dosing Cohorts
Dose Level
Total Anti-BCMA CAR T-Cell Dose†
-1*
1
3 x 107
2
3
4
*If the incidence of DLTs in Cohort 1 is ≥ 2 of 6 patients treated, the sponsor may, in consultation with the safety review team, 
choose to decrease to the dose shown for Cohort -1.
†Dose is calculated based on CAR-expressing transduced T cells. Subjects weighing less than 53 kg at enrollment will receive a 
cell dose that is reduced by 33%.  See Protocol Section 6.5.1 for additional information. 
Abbreviations:  BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor.
A safety review team (SRT), internal to the study sponsor and including at least one study 
investigator, will review the safety data and make recommendations on further study conduct. 
After a dose level has been determined by the SRT to be tolerable based on the incidence of 
DLTs, the sponsor may, in consultation with the SRT, choose to expand enrollment in the 
following 2 expansion cohorts to further characterize the risk benefit profile.  Enrollment to each 
cohort may proceed independently of the other.

Expansion Cohort 1:  Up to approximately 20 additional subjects with creatinine clearance 
≥60 mL/min by Cockcroft-Gault estimation may be treated with the MTD or a lower dose. 

Expansion Cohort 2:  Up to approximately 20 subjects with moderate renal impairment 
(creatinine clearance 30 to 59 mL/min [Grade 2 chronic kidney disease]) may be treated with 
the MTD or a lower dose.  The first 3 subjects in this expansion cohort will be enrolled with 
a minimum of 2 weeks between each subject.  The SRT will meet to review safety data after 
the first 6 subjects have been enrolled and have completed the Day 28 visit.   
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All subjects enrolled in the study will follow the same study treatment schedule and procedural 
requirements.  Each subject will proceed through the following study periods, as shown in 
Figure 1:

Screening 

Enrollment/Leukapheresis 

Bridging therapy (at the discretion of the treating investigator)

Conditioning chemotherapy 

KITE-585 treatment 

Post-treatment assessment 

Long-term follow-up


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Figure 1.
Study Schema for Study KITE-585-501
Screening
Conditioning 
Chemotherapy Period
(Day -5 to Day -3)
Fludarabine 
30 mg/m2/day, 
Cyclophosphamide 300 
mg/m2/day 
administered daily x 3 
days 
Investigational 
Product (IP) 
Treatment Period 
(Day 0)
Subject is hospitalized 
prior to treatment with 
KITE-585
KITE-585 at a target 
dose (± 20%) 
anti-BCMA CAR 
T cells to be infused 
intravenously
Post-Treatment Assessment Period 
Long-term Follow-up Period
Enrollment/Leukapheresis
Bridging Therapy 
(optional)
(
 
 
 
 
 
)
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3.2.
Hypothesis
KITE-585 at one of the planned dose levels will be considered safe as determined by the 
incidence of DLTs.
3.3.
Sample Size Consideration
Approximately 6 to 64 subjects overall will be enrolled and treated.

6 to 24 subjects in the initial dose escalation portion

Up to approximately 20 additional subjects with creatinine clearance ≥ 60 mL/min by 
Cockcroft-Gault estimation may be treated with the MTD or a lower dose to gain additional 
information about benefit/risk (Expansion Cohort 1)

Up to approximately 20 additional subjects with moderate renal impairment (creatinine 
clearance 30 to 59 mL/min [Grade 2 chronic kidney disease]) may be treated with the MTD 
or a lower dose (Expansion Cohort 2)
3.4.
Statistical Assumptions
There is no plan for formal statistical testing of any safety or efficacy endpoints; no statistical 
assumptions are made for inference.  


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4.
STUDY ENDPOINTS AND COVARIATES
4.1.
Endpoints
Primary:  Incidence of AEs defined as DLTs. 
Secondary: 

Objective response rate (ORR)

Progression free survival (PFS)

Duration of response (DOR)

Time to next treatment (TTNT)

Overall survival (OS)

Incidence of AEs and clinically significant changes in laboratory values
Exploratory
4.2.
Covariates
The following covariates may be used in efficacy and safety analyses:

Eastern Cooperative Oncology Group (ECOG) status (0 vs. 1)

Prior daratumumab exposure (yes vs no)

Prior autologous bone marrow transplant (yes vs no)

Disease burden (≤50% vs ≥50% clonal plasma cells on bone marrow aspirate or biopsy)

Disease risk stratification (≥1 FISH abnormalities vs 0 abnormalities)

Dual-refractory disease (yes vs no)

B-cell maturation antigen (BCMA) expression on pretreatment multiple myeloma (MM) cells
(%)Subject body weight at time of leukapheresis (<=53 kg vs >53 kg) 
Covariate levels that are sparse may be collapsed for purposes of statistical modeling.
Additional associative analyses of covariates with subject outcomes may be explored.
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5.
DEFINITIONS
5.1.
General
Study enrollment:  Subject is defined as enrolled as the day of leukapheresis. 
Study day 0:  Study day 0 is defined as the day the subject received the KITE-585 infusion.  The 
day prior to study day 0 will be day -1.  The day of enrollment and any days after enrollment and 
before study day -1 will be sequential and negative integer valued.  
Study day: defined as date of visit/sample/measurement – KITE-585 infusion date.
Baseline:  The baseline value is defined as the last value taken prior to conditioning 
chemotherapy.
Actual follow-up time:  Actual follow-up time among all subjects treated with KITE-585 is 
calculated from KITE-585 infusion date to as death date -1 or last date known alive, whichever is 
later.
Potential follow-up time:  Potential follow-up time is defined for all subjects treated with 
KITE-585 and is the data cutoff date - KITE-585 infusion date +1.
5.2.
Safety
Treatment-emergent adverse event (TEAE): Any adverse event with onset on or after study 
day 0.
Dose-limiting toxicities (DLT): DLT is defined as the KITE-585-related events with onset 
within the first 28 days following KITE-585 infusion. Details of the DLT definitions, including 
duration of event and exceptions, are provided in Protocol Table 6.
Adverse events of interest:  Adverse events of interest for KITE-585 treatment includes TEAE 
of cytokine release syndrome (CRS), neurologic events, infections, cytopenias, and prolonged 
cytopenia, as described below:
Neurological event: Neurological 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 
relatedness, temporal relationship, and concomitant conditions (eg, CRS).  Events are 
identified with a search list of MedDRA preferred terms (PTs).  
CRS:  CRS will be identified via collection of the syndrome on a case report form (CRF) 
specifically designed to collect CRS.  Specific symptoms of the CRS are collected on the AE 
log form and are linked to the CRS syndrome.  CRS syndrome severity is graded according 
to a modification of the grading system proposed by Lee and colleagues (Lee et al, 2014).  In 
the modified grading scale, neurologic AEs are not reported as part of the CRS syndrome; 


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rather, they are reported on the AE log form separately based on specific symptoms per 
Common Terminology Criteria for Adverse Events (CTCAE).
Cytopenias: Cytopenias (Neutropenia or Thrombocytopenia or Anemia) are identified as:
1) Neutropenia is identified using MST defined by Kite
2) Thrombocytopenia is identified using the SMQ for haematopoietic thrombocytopenia 
(narrow search)
3) Anemia (excluding aplastic anemia) is identified using the SMQ haematopoietic 
erythropenia (broad search)
Subject incidence of cytopenias will be summarized separately by the 3 blood cell lineages.
Prolonged Cytopenias (Neutropenia or Thrombocytopenia or Anemia)
Subjects with prolonged cytopenias (neutropenia or thrombocytopenia or anemia) will be 
identified with 2 methods:

Method 1: Subjects with longest consecutive period with cytopenias (neutropenia or 
thrombocytopenia or anemia) ≥ 30 days (See Appendix 2 for the definition of longest 
consecutive period with an AE of interest)

Method 2: Subjects with cytopenias (neutropenia or thrombocytopenia or anemia) present 
on or after Day 30 post KITE-585 infusion 
Prolonged cytopenias (neutropenia or thrombocytopenia or anemia) will be summarized 
separately by the 3 blood cell lineages. 
Infections:  Infections will be identified as AEs within the system organ class (SOC) of 
infections and infestations that are in MedDRA high level group terms (HLGT) that capture 
events of:
1) bacterial infection, encompassing preferred terms within the MedDRA HLGT of
a) bacterial infectious disorders 
b) chlamydial infectious disorders 
2) viral infection, encompassing preferred terms within the MedDRA HLGT of viral 
infectious disorders
3) opportunistic infections, encompassing preferred terms within the MedDRA HLGT of
a) fungal infectious disorders 
b) mycobacterial infectious disorders 


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4) Other infections, encompassing preferred terms within the MedDRA HLGT of 
infections - pathogen unspecified.
Concomitant medication: Concomitant medications are defined as the medications 
administered to subjects on or after the KITE-585 infusion.
5.3.
Efficacy
Objective Response (OR): objective response is defined as either a partial response (PR) or very 
good PR (VGPR) or as a complete response (CR) or stringent CR, as determined by study 
investigators according to IMWG Consensus Panel 1 Criteria (Rajkumar et al, 2011).  Subjects 
who did not meet the criteria for objective response by the analysis cutoff date will be considered 
non-responders. The derivation of this endpoint will only use response assessments obtained 
prior to any other anti-cancer therapy (including stem cell transplant or new anti-cancer therapy).
Best overall response (BOR): BOR is defined as the best response recorded from the day of 
KITE-585 infusion until the end of study, in descending order of precedence by sCR, CR, 
VGPR, PR, SD, PD or NE. The derivation of this endpoint will only use response assessments 
obtained prior to any other anti-cancer therapy (e.g. stem cell transplant or new anti-cancer 
therapy). 
Duration of response (DOR):  DOR is defined for subjects who experience an objective 
response and is defined as the date of their first objective response (which is subsequently 
confirmed) to disease progression per IMWG Consensus Panel 1 Criteria (Rajkumar et al, 2011)
or death due to any causeSubjects not meeting the criteria for progression or death due to PD by 
the analysis data cutoff date will be censored at their last evaluable disease assessment date.  
Subjects who receive new anti-cancer therapy (including stem cell transplant [SCT]) in the 
absence of documented progression will be censored at the last evaluable disease assessment 
prior to the new therapy or SCT.
Progression free survival (PFS):  PFS is defined as the time from the KITE-585 infusion date 
to the date of disease progression per the IMWG Consensus Panel 1 Criteria (Rajkumar et al, 
2011) or death from any cause.  Subjects not meeting the criteria for progression by the analysis 
data cutoff date will be censored at their last evaluable disease assessment date.  Subjects who 
receive new anti-cancer therapy (including SCT) in the absence of documented progression will 
be censored at the last evaluable disease assessment prior to the new therapy.
Time to next treatment (TTNT): TTNT is defined as the length of time between the date of 
KITE-585 infusion to the date of initiation of the next therapy or death due to any cause, 
whichever is earlier. Subject with no new anti-cancer therapy and alive by the time of data cutoff
will be censored at the last date known to be alive or cutoff date, whichever is earlier
Overall Survival (OS):  OS is defined as the time from KITE-585 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 cutoff date, whichever is earlier. Further details on the derivation of overall 
survival and the specific data modules that will be used to derive the last date known to be alive 
are provided in Appendix 3. 


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6.
ANALYSIS SUBSETS
6.1.
DLT evaluable set:  
The DLT evaluable set is used to evaluate the primary endpoint (DLT) and is defined for each 
dosing cohort in the dose escalation period as a subject who:  

Received the target dose (± 20%) and were followed for at least 28 days after the first KITE-
585 infusion; or 

Received a dose of KITE-585 lower than 20% below the target dose for that cohort and 
experienced a DLT during the 28-day post-first-infusion period.
6.2.
Full Analysis Set (FAS)
The full analysis set is defined as all subjects who were enrolled. The FAS will be used for 
summary of subject disposition, subject listing of deaths and other analyses as specified.
6.3.
Safety Analyses Set
The safety analyses set is defined as all subjects treated with any dose of KITE-585.  If not 
specified otherwise, this analysis set will be used for evaluation of all endpoints except for the 
primary endpoint (DLT).
6.4.
Per protocol analysis set (PPAS)
PPAS includes subjects in the safety analysis set who have not deviated from the protocol in 
such a manner that the assessment of efficacy endpoints may be biased.  A subject may be 
excluded from the PPAS due to insufficient exposure to study drug, important protocol 
deviation, enrollment criteria violation, or any other situation that may affect the assessment of
efficacy endpoints.


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7.
INTERIM ANALYSIS AND EARLY STOPPING GUIDELINES
7.1.
Interim Analysis
The SRT will be chartered to review subject-level safety data at defined milestones.  During the 
dose escalation phase, the SRT will review safety data at the completion of enrollment and 
treatment of each dosing cohort and before opening the next dose level.  During Expansion 
Cohort 1 and Cohort 2, the SRT will review safety data after 10 and 6 subjects, respectively, 
have been treated with KITE-585 and followed for 28 days.  Additional information about safety 
monitoring is described in the SRT charter. Exploratory analysis may be performed given the 
study data are accumulated and reviewed. SRT will also assess criteria to pause enrollment. For 
details, refer to protocol section 9.6.2. This is a Phase 1, dose escalation, open-label study, and 
subjects, study sponsor and investigators will be aware of treatment received.  


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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 primary analyses and the final database lock.
For interim analyses, snapshots may include data that has not passed all data cleaning procedures 
at the time the data are extracted for snapshot.
8.2.
Electronic Transfer and Archiving of Data
The Medidata Rave system will be used to collect the data in this study.  Raw data extracted 
from Medidata Rave will be archived prior to 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 (see below) 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 will be 
used.
8.3.2.
Safety
Partial adverse event start dates will be imputed. If dates are missing or incomplete for adverse 
event start dates, the algorithm defined in Appendix 1 will be used. 
8.4.
Detection of Bias
A listing of subjects with important protocol deviations will be generated. The deviations 
included in this list will be summarized. Lack of protocol compliance will be evaluated by 
summarizing the subject incidence of important protocol deviations. High rates of important 
protocol deviations may indicate bias.
8.5.
Outliers
Descriptive statistics will be used to identify potential outliers in any key variables analyzed. 
Suspected outliers will be included in all analyses unless there is sufficient scientific justification 
to exclude them.


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8.6.
Distributional Characteristics
The exact 95% confidence intervals will be generated for the response rate. The Clopper-Pearson 
method will be 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 objective response 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 Standard 
Operating Procedures. 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
Descriptive statistics will be provided for all endpoints.  Continuous measurements will be 
summarized using the following summary descriptive statistics:  number of subjects, mean, 
median, standard deviation (Std Dev), Q1, Q3, minimum, and maximum.  Frequencies and 
percentages will be used to summarize categorical measurements.  For time-to-event variables, 
the Kaplan-Meier method will be used for descriptive summaries. Unless otherwise specified, 
analyses will be done by dose level. Expansion cohort may be tabulated separately.
The goal of the primary analysis is to find the maximum tolerable dose (MTD) of KITE-585 as 
determined by subject incidence of DLT in each dose escalation cohort.  The analysis of DLTs 
will be based on the DLT evaluable set. Unless otherwise stated, safety and efficacy analysis will 
be conducted on the safety analysis set.  The per protocol analysis set or other identified 
subgroups may be used to evaluate safety or efficacy endpoints as additional analyses.
The timing of the interim and primary analyses will be based on subject accrual and disease 
assessment milestones. The primary analysis will occur after all enrolled subjects have had the 
opportunity to complete 6 months of protocol-specified visits, have died, or have withdrawn 
from the study.
9.2.
Subject Accountability
The number of subjects screened, enrolled (leukapheresed), treated with bridging therapy, treated 
with conditioning chemotherapy, and treated with KITE-585 will be summarized.  The reasons 
for discontinuing KITE-585 treatment and discontinuing study will be summarized.
Summaries of actual and potential follow-up time will be provided.
The number of subjects in each analysis set along with reasons for exclusion will be provided.
9.3.
Important Protocol Deviations
The clinical study team will define important protocol deviation categories and review all 
potential important protocol deviations prior to the database snapshot for the primary efficacy 
analysis, at a minimum. Important protocol deviations will be categorized by deviation type (eg,
entry/eligibility, use of excluded medication). The subject incidence of important protocol 
deviations will be summarized overall and by deviation category.
9.4.
Demographic and Baseline Characteristics
Summary statistics and frequencies for the following demographic and baseline characteristics 
will be tabulated:

ECOG performance status at baseline


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
Sex (male, female)

Subject body weight at time of leukapheresis and at baseline

Age at enrollment and its categories (< 65, ≥ 65)

Race:  white, Asian, other (categories may be collapsed or expanded based on accrual)

Ethnicity 

Number of prior lines of therapies

Prior daratumumab exposure (yes vs no)

Prior autologous bone marrow transplant (yes vs no)

Disease burden (≤ 50% vs ≥ 50% clonal plasma cells on bone marrow aspirate or biopsy)

Disease risk stratification (≥ 1 FISH abnormalities vs 0 abnormalities)

High cytogenetic risk (yes vs no)

Dual-refractory disease (yes vs no)

BCMA expression on pretreatment MM cells

Disease stage (I or II vs III)

Creatinine clearance (<30, <60, ≥60)
9.5.
Efficacy Analyses
Efficacy analyses will be conducted on the safety analysis set. For the primary analysis, the 
investigator’s read of disease status per IMWG Consensus Panel 1 Criteria (Rajkumar et al, 
2011) will be used (Protocol Appendix 1). The investigator will provide the determination of 
disease status: Stringent Complete Response (sCR), Complete Response (CR), Very Good 
Partial Response (VGPR), Partial Response (PR), Stable Disease (SD), Progressive Disease
(PD), Not Evaluable (NE) at each time point.
In the event any subject undergoes a stem cell transplant (SCT) or any new anti-cancer therapy 
while on study, the subject’s best response will be derived only based on disease outcomes 
assessed prior to SCT or initiation of new therapy. For subjects without documentation of disease
progression prior to initiation of new therapy (including SCT), PFS/DOR will be censored at 
their last evaluable disease assessment date prior to the initiation of new therapy (including 
SCT). Further details are discussed in Appendix 3. 


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9.5.1.
Objective Response Rate (ORR) and Best Response
The subject incidence of objective response per investigator reviewer will be calculated. The 
subject incidence of best response (sCR, CR, VGPR, PR, SD, PD, or NE) will also be calculated. 
Confidence intervals will be provided for the ORR and best response rates, calculated with the 
Clopper-Pearson method. The primary analysis of objective response and best response will 
include subjects from the safety analyses set.  
ORR and its 95% confidence interval will be generated for subgroups of the safety analyses
defined by each of the categorical variables in Section 4.2. Subgroup analyses with additional 
covariate may also be explored.
A forest plot of the ORR for each of these subgroups will be generated.  
9.5.2.
Progression Free Survival (PFS)
The number of subjects censored or having events, and the reasons for censoring and type of 
events will be summarized. Kaplan-Meier plots, estimates, and 2-sided 95% confidence intervals 
will be generated for 25%, 50%, and 75% of progression-free survival (PFS). Kaplan-Meier 
estimates and 95% confidence intervals of the proportion of subjects alive and progression-free 
at selected time points will be provided.
Subgroup analyses of the PFS rate may be generated in subgroups defined by the covariates in 
Section 4.2.
9.5.3.
Duration of Response (DOR)
The number of subjects censored or having events, the reasons for censoring, and type of events, 
will be summarized. Kaplan-Meier plots, estimates, and 2-sided 95% confidence intervals will be 
generated for 25%, 50% and 75% of DOR. Kaplan-Meier estimates and 95% confidence 
intervals of the proportion of subjects that are still in response at selected time points after first 
objective response will be provided.
Primary analysis of DOR will be conducted in the safety analyses set 
9.5.4.
Overall Survival (OS)
The analysis of OS will use the same methods as the analysis of progression-free survival.  
OS may be summarized in subgroups defined by the best response attained on study.
9.5.5.
Time to next Treatment (TTNT)
The analysis of time-to-next-treatment (TTNT) will use the same methods as the analysis of 
progression-free survival. Estimates of the proportion of subjects who have not required 
additional treatment for progressive MM at selected time points will be provided. 


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9.5.6.
Disease burden
The change in disease burden, as measured by the level of serum and urine M protein, difference 
between involved and uninvolved free light chain (FLC) levels, percentage of clonal plasma cells 
on bone marrow aspirate or biopsy and plasmacytoma diameters (only in bone and soft-tissue 
separately) from baseline to post-baseline nadir will be summarized in absolute numbers 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. Additionally, plots over time of the percent change in disease burden for each subject 
(superimposed on one graph) will be presented. Data collected after new anticancer therapy or 
SCT will not be included for the analyses.
9.5.7.
Minimal residual disease (MRD)
The subject incidence of presence of MRD will be provided at selected time points. 
9.6.
Safety Analyses
A listing of DLTs with additional information on the cohort (eg, number of subjects in each 
cohort) in the DLT evaluable analysis set will be generated.
All the other safety analyses will be conducted on the safety analyses set. The primary analysis 
of safety data will summarize all TEAEs and laboratory values. Additional summary tables will 
present all adverse events with onset time categorized by study treatment period (refer to 
definition section).  Adverse events will be summarized by SOC and PT. 
Adverse events will be coded with the Medical Dictionary for Regulatory Activities (MedDRA) 
at the time of each analysis. The version of the MedDRA may vary over time as the current 
version in use is updated. The severity of adverse events will be graded using the National 
Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 
4.03. 
Cytokine release syndrome (CRS) will be graded using a revised CRS grading scale developed 
by Lee et al (Lee et al, 2014). The incidence and severity of CRS will be reported as a syndrome 
with severity per Lee et al (Lee et al, 2014). Individual symptoms associated with CRS will be 
graded per CTCAE version 4.03.
Subjects enrolled but not dosed with KITE-585 will be followed for adverse events for 30 days 
after the last study procedure. Adverse events 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.
Safety summaries will be presented by dose and by cohort when applicable.


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9.6.1.
Adverse Events
The subject incidence of the following adverse events will be tabulated:

Overall summary of treatment emergent adverse events (eg, any, worst severity, serious, 
KTE-585 related)

All treatment emergent adverse events

All serious treatment emergent adverse events

All leukapheresis-related adverse events

All bridging therapy-related adverse events

All conditioning-chemotherapy-related adverse events

All KITE-585-related treatment emergent adverse events

All conditioning chemotherapy-related serious adverse events

All KITE-585-related serious treatment emergent adverse events

All grade 3 or higher treatment emergent adverse events

All grade 3 or higher conditioning chemotherapy-related adverse events

All grade 3 or higher KITE-585-related treatment emergent adverse events

Fatal treatment emergent adverse events

Treatment emergent adverse events of interest
Summary statistics for the onset time and duration of adverse events of interest will be provided.
Death time and reason will be listed and summarized for all the enrolled subjects.
Subgroup analyses of adverse events may be generated for the covariates listed in Section 4.2.  
9.6.2.
Exposure to Concomitant Medications and Procedures  
Concomitant medication drug basket of interest for systemic steroids, vasopressors, nonsteroidal 
immunosuppressants other than tocilizumab, and IV immunoglobulins are defined by Kite and 
are documented separately.
The subject incidence of concomitant medications will be provided and summarized. The subject 
incidence of procedures will also be tabulated.


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In addition, the subject incidence of concomitant medications and procedures used to manage 
adverse events will be tabulated.
9.6.3.
Laboratory Test Results
Laboratory results will be graded according to NCI CTCAE (version 4.03).  The incidence of 
post-infusion worst-grade laboratory toxicities for all analytes will be summarized. Additional 
summaries for the shift from baseline to the worst toxicity grade after KITE-585 infusion may 
also be generated.
9.6.4.
Vital Signs
Vital Sign data will be summarized at selected time points by descriptive statistics. Subject 
listings may also be provided.
 
9.6.6.
Replication Competent Lentivirus
The subject incidence of replication-competent lentivirus (RCL) detected in blood samples will 
be tabulated overall and by assessment time. The persistence of RCL over time will be 
summarized.
9.6.7.
Exposure to Study Treatment
Summary statistics and subject listings will be provided for the following:

Total BSA-adjusted dose of cyclophosphamide

Total BSA-adjusted dose of fludarabine

Total anti-BCMA CAR T cells of the KITE-585 infusion

Total T cells of the KITE-585 infusion

Transduction ratio

Percentages of CD4 and CD8 cells and ratio

Percentages of T-cell memory phenotypes

Interferon-gamma production in co-cultures of KITE-585 product and anti-BCMA target 
cells

Vector copy number of KITE-585 CAR product
CCI-


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Summaries may also be provided by demographics and baseline characteristics as appropriate.
9.7.
Pharmacokinetics
Analysis of biomarker and PK parameters will be provided in a separate SAP.
9.8.
Pharmacodynamics
Analysis of biomarker and pharmacodynamic parameters will be provided in separate SAP.
9.9.
Subsequent Anti-Cancer Therapy
The incidence and type (by WHO Drug coded term and categories) of subsequent anticancer 
therapy and stem cell transplant by treatment period will be summarized.
9.10.
Duration Metrics
Summary statistics will be provided for the following durations:

Days from leukapheresis to product release

Days from leukapheresis to product received at the site

Days from leukapheresis to commencement of bridging therapy

Days from bridging therapy to commencement of conditioning chemotherapy

Days from leukapheresis to commencement of conditioning chemotherapy

Days from leukapheresis to KITE-585 infusion

Days from conditioning chemotherapy to KITE-585 infusion

Duration of hospitalization for the KITE-585 infusion


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10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES
The full analyses set in this document refers to all enrolled subjects, while the full analyses set in 
the protocol has been renamed as the safety analyses set in this document.


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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.
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.
Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R, et al. Consensus 
recommendations for the uniform reporting of clinical trials: report of the International Myeloma 
Workshop Consensus Panel 1. Blood. 2011;117(18):4691-5.
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.
Definitions related to Prolonged Cytopenias
Appendix 3.
Derivation of Time to Event Endpoints and 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 following algorithm:

Adverse event start dates

Deaths (please see exceptions below)

Concomitant medication start dates

Subsequent anti-cancer therapy 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
=1st dose
yyyy
3
1
3
1
n/a
1
1
≠ 1st dose
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.
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.


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Appendix 2.
Definitions related to Prolonged Cytopenias  
1. Longest Consecutive Period with an AE of interest
Longest consecutive period with an AE of interest is calculated as the greatest number of 
consecutive days (without gaps between events) that subjects experience 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). Longest consecutive period will be used for deriving prolonged neutropenia, 
prolonged thrombocytopenia, or prolonged anemia as described in Section 5.2.


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Appendix 3.
Derivation of Time to Event Endpoints and Last Date Known to Be 
Alive
Additional detail on the derivations of Duration of Response (DOR), Progression-free Survival
(PFS), and Overall Survival (OS) is provided below.
1) Duration of Response (DOR):  DOR is defined only for subjects who experience an 
objective response and is the time from the first objective response to disease progression or
death due to disease progression, whichever comes first.  Subjects who undergo non-disease-
related death (due to reasons other than disease progression) without documented disease 
progression will be censored at the last evaluable disease assessment before the death date. 
Subjects not meeting the criteria for progression or death due to disease progression by the 
analysis data cutoff date will be censored at their last evaluable disease assessment date.  
Duration of response will be derived using disease assessments obtained on study prior to 
initiation of new anticancer therapy (including SCT). Subjects who undergo new anticancer 
therapy (including SCT) in the absence of documented disease progression will be censored 
at the last evaluable disease assessment prior to the new anticancer therapy.
Primary analysis of DOR:
Circumstance
Event / Censored
(Short Description)
Date of Event / Censoring
Disease progression prior to initiation of new 
anticancer therapy (including SCT) 
Event (Disease 
progression)
Progression date
Death due to PD without documented disease 
progression and without any new anti-cancer therapy 
(including SCT)
Event (Death due to 
PD)
Death date
Non-disease related death without disease progression 
and without any new anti-cancer therapy (including 
SCT)
Censored (Death due 
to reasons other than 
PD)
Last evaluable disease 
assessment date
Initiated new anti-cancer therapy (including SCT) 
prior to documented progression and death due to any 
cause
Censored (Initiated 
new anti-cancer 
therapy/SCT)
Last evaluable disease 
assessment date prior to initiation 
of new therapy (including SCT)
Remain in response by cut-off date without initiation 
of new anti-cancer therapy (including SCT)
Censored (Response 
ongoing)
Last evaluable disease 
assessment date
Abbreviations:  DOR, duration of response; PD, progressive disease; SCT, stem cell transplant. 
2) Progression-free Survival (PFS):  PFS is defined as the time from the KITE-585 infusion 
date to the date of disease progression or death from any cause, whichever comes first. 
Subjects alive and not meeting the criteria for progression by the analysis data cutoff date 
will be censored at their last evaluable disease assessment date. PFS will be derived using 
disease assessments obtained on study prior to initiation of new anti-cancer therapy
(including SCT). PFS for subjects who undergo any new anticancer therapy (including SCT) 
will be censored at the time of last evaluable disease assessment date prior to the new 
anticancer therapy (including SCT).


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Primary analysis of PFS:
Circumstance
Event / Censored
(Short description)
Date of Event / Censoring
Disease progression prior to initiation of new 
anticancer therapy (including SCT) 
Event (Disease 
progression)
Progression date
Death due to any cause without disease 
progression and without any new anti-cancer 
therapy (including SCT)
Event (Death due to 
any cause)
Death date
Alive without PD by cut-off date without 
initiation of new anti-cancer therapy 
(including SCT)
Censored (Alive 
without PD)
Last evaluable disease assessment date
Initiated new anti-cancer therapy (including 
SCT) prior to documented disease 
progression or death due to any cause
Censored (Initiated 
new anti-cancer 
therapy (including 
SCT))
Date of last evaluable disease assessment 
prior to initiation of new therapy (including 
SCT). 
Abbreviations:  PD, progressive disease; PFS, progression-free survival; SCT, stem cell transplant. If no disease assessment 
available before censoring date, the PFS will be censored at KITE-585 infusion date.
3) Overall Survival (OS):  OS is defined as the time from the KITE-585 infusion to the date of 
death from any cause.  Subjects who have not died by the analysis data cutoff date will be 
censored at their last date known to be alive or analysis cutoff date, whichever is earlier.
Circumstance
Event/Censored
(Short description)
Date of Event/Censoring
Death before data cutoff date for analysis
Event (Death)
Date of death
Death after data cutoff date for analysis
Censored (Alive)
Data cutoff date
Known to be alive after data cutoff date for 
analysis
Censored (Alive)
Data cutoff date
Alive up to data cutoff date and no further 
information available after data cutoff date
Censored (Alive)
Last date known to be alive 
Early termination due to Full Withdrawal of 
consent, lost to follow up prior to data cutoff 
date
Censored (Alive)
Last date known to be alive
4) Last date known to be alive
The last date known to be alive with be derived by obtaining the maximum complete date among 
the following data modules:

Start date of AE

Leukapheresis dates

Bridging therapy dates


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
Conditioning chemotherapy administration dates

KITE-585 infusion dates

Serum/Urine/FLC sample date for assessment of disease status

Bone marrow aspirate/biopsy sample date

Image sample date (PET/CT)

Optional plasmacytoma sample date

Lumbar puncture sample date for CSF

Plasmacytoma/new plasmacytoma assessment date

Disease response assessment date

Start date of new anticancer therapy/transplant date

Long term follow up subject status date where status = “alive”

End-of-treatment disposition where status is not equal to death, lost to follow up

End–of-study data where end–of-study reason is not equal to death, lost to follow up