Conditions: Non-Hodgkin's Lymphoma, Relapsed Chronic Lymphoid Leukemia in Relapse Non-Hodgkin's Lymphoma Refractory Chronic Lymphocytic Leukemia Lymphoma, Non-Hodgkin Leukemia, Lymphocytic, Chronic B-cell Chronic Lymphocytic Leukemia B-cell Non Hodgkin Lymphoma Small Lymphocytic Lymphoma
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 18
Healthy volunteers: no

Brief summary:
This is a Phase 1/2a, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of PBCAR20A in adult subjects with r/r B-cell NHL or r/r CLL/SLL.

Detailed description:
This is a multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate safety, tolerability, clinical activity, and find an appropriate dose to optimize safety and efficacy of PBCAR20A in subjects with relapsed/refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Before initiating PBCAR20A, therapy, subjects will be administered lymphodepletion chemotherapy composed of fludarabine and cyclophosphamide. At Day 0 of the Treatment Period, subjects will receive a single intravenous (IV) infusion of PBCAR20A. All subjects are monitored during the treatment period through Day 28. All subjects who receive a dose of PBCAR20A will be followed in a separate long-term follow-up (LTFU) study for 15 years after exiting this study.

Arms:
arm 1: 1 x 10\^6 chimeric antigen receptor (CAR) T cells per kg body weight.

In this study, PBCAR20A, allogeneic anti-cluster of differentiation (CD20) CAR T Cells, is used to treat patients with relapsed or refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).

Route of Administration: Intravenous infusion (IV)

Lymphodepletion Conditioning: Lymphodepletion will be conducted several days prior to PBCAR20A infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion. arm 2: 240 x 10\^6 CAR T cells (flat dose) arm 3: 480 x 10\^6 CAR T cells (flat dose)

Interventions: intervention 1: PBCAR20A intervention 2: Fludarabine intervention 3: Cyclophosphamide
Intervention descriptions: intervention 1: Single dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied. intervention 2: Fludarabine is used for lymphodepletion (30 mg/m\^2/day, Days -5 to -3). intervention 3: Cyclophosphamide is used for lymphodepletion (500 mg/m\^2/day, Days -5 to -3).

Protocol document:
Prot_000.pdf: 
Protocol PBCAR20A-01 
Precision Biosciences, Inc. 
Version 5.0 (10FEB2021) 
1 
TITLE PAGE 
Protocol title: A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment 
Study to Evaluate the Safety and Clinical Activity of PBCAR20A in Study Subjects with 
Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic 
Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) 
Protocol number: PBCAR20A-01 (version 5.0) 
Product: PBCAR20A allogeneic anti-CD20 chimeric antigen receptor (CAR) T cells 
Sponsor: Precision BioSciences, Inc.  
Legal registered address: 
302 East Pettigrew Street  
Dibrell Building, Suite A-100  
Durham, North Carolina 27701 
Regulatory agency identifying number(s): IND 19190 
Protocol date: 
10FEB2021 
Confidentiality statement 
This document is confidential information of Precision BioSciences, Inc. It may not be disclosed 
to parties not associated with the clinical investigation or used for any purpose without the prior 
written authorization of Precision BioSciences, Inc. 
NCT #NCT04030195




Protocol PBCAR20A-01 
 
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INVESTIGATOR’S AGREEMENT 
 
I have read the PBCAR20A-01 protocol and agree to conduct the study as outlined. I agree to 
maintain the confidentiality of all information received or developed in connection with this 
protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed name of investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of investigator 
 
 
 
 
 
 
 
 
Date 


Protocol PBCAR20A-01 
 
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Version 5.0 (10FEB2021) 
 
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STUDY CONTACT LIST 
Table 1: 
Key study contact information 
Role in study/purpose 
Name/title/affiliation 
Telephone number and  
e-mail address 
Serious Adverse Event Reporting 
Precision BioSciences 
Pharmacovigilance  
Email
 
Medical monitor 
IQVIA Biotech 
Phone:
E-mail
Study manager 
IQVIA Biotech 
Phone: 
E-mail:
Precision BioSciences medical 
representative 
Precision BioSciences, 
Inc. 
Mobile 
E-mail:


Protocol PBCAR20A-01 
 
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SYNOPSIS 
Name of sponsor/company: 
Precision BioSciences, Inc. 
Name of investigational product: 
PBCAR20A allogeneic anti-CD20 chimeric antigen receptor (CAR) T cells 
Name of active ingredient: 
PBCAR20A allogeneic anti-CD20 CAR T cells 
Title of study:  
A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate 
the Safety and Clinical Activity of PBCAR20A in Subjects with Relapsed/Refractory (r/r) Non-
Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic 
Lymphoma (SLL)  
Study centers: Approximately 10-15 study sites in the United States.  
Objectives:  
Primary: 
Phase 1 
To evaluate the safety and tolerability of PBCAR20A in subjects with r/r cluster of differentiation 
(CD) 20-positive (CD20+) NHL including r/r CD20+ CLL/SLL and find an appropriate dose to 
optimize safety and efficacy. 
Phase 2a 
Evaluate initial efficacy and safety of PBCAR20A in subjects with CD20+ NHL, specific to the 
population described by the inclusion/exclusion criteria 
 
Secondary: 
Phase 1 
To evaluate the clinical activity of PBCAR20A in subjects with r/r CD20+ NHL including r/r CD20+ 
CLL/SLL. 
Phase 2a 
To characterize the pharmacologic properties and evaluate the safety, tolerability, and clinical benefit 
of PBCAR20A treatment regimens in subjects with CD20+ r/r NHL and to generate hypotheses for 
studies to definitively demonstrate efficacy. 
Criteria for evaluation: 
Safety: 
• 
Identification of the maximum tolerated dose (MTD) based on the incidence of dose-limiting 
toxicities (DLTs)  
Clinical activity: 
 
• 
Objective response rate (ORR=CR+PR):  
− 
NHL: Lugano 2016 criteria  


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− 
CLL/SLL: International Workshop on Chronic Lymphocytic Leukemia 2018 
guidelines 
• Duration of Response (DOR) – defined as the duration (days) from first response to 
disease progression 
• Progression-free survival (PFS) 
− 
Defined as the duration (days) from Day 0 to disease progression or death 
• 
Incidence of AESI, SAEs, and DLTs related to the investigational product 
Methodology: 
This is a Phase 1/2a, nonrandomized, open-label, dose escalation, and dose-expansion study to evaluate 
the safety and clinical activity of PBCAR20A in adult study subjects with r/r CD20+ NHL, including 
r/r CD20+  CLL/SLL, and to identify a treatment regimen to optimize clinical efficacy while 
maintaining a favorable safety profile.  
The Phase 1 portion of the study will enroll and treat all subjects as one cohort.  
Three treatment arms are incorporated into Phase 2a to evaluate the effects of alternative dosing 
regimens in specific NHL subpopulations. Evaluation criteria will include PBCAR20A cell expansion 
and persistence as well as clinical activity and safety profile.  
All subjects will receive assigned lymphodepletion and PBCAR20A dose. Please refer to the Pharmacy 
Manual for the specific lymphodepletion regimen as it may be modified if satisfactory CAR T-cell 
expansion is not observed; lymphodepletion status will be discussed between the Sponsor Medical 
Monitor, Principal Investigators, and contract research organization Medical Monitor. 
On Day 0 of the Treatment Period, all subjects will receive an intravenous (IV) infusion of 
PBCAR20A. After the DLT evaluation has been completed, subjects may be considered for 
retreatment if there is evidence of clinically meaningful tumor response to initial dose of PBCAR20A 
followed by documented either a disease progression  or residual disease at subsequent visit; the 
criteria and procedures for retreatment are described in the protocol. 
Phase 1 (dose escalation): 
In Phase 1, up to 3 escalating dose levels will be enrolled and treated sequentially, with the possibility 
of a single de-escalation dose. Within each dose level, up to 6 subjects will be treated with PBCAR20A 
using a standard 3 + 3 design. The starting dose of PBCAR20A will be 1 × 106 CAR T cells/kg body 
weight. Subjects in subsequent dose levels will be treated with escalating doses up to a flat dose of 
480 × 106 CAR T cells. If no MTD is reached additional dose levels may be explored. 
The first treated subject in each dose level (including the dose de-escalation level, i.e., Dose -1) will be 
observed for 14 days for safety before any subsequent subject receives any study treatment to provide 
an adequate safety monitoring window. Once the first subject in each dose level has completed Day 14 
of dosing with no DLTs, any subsequent subjects can be enrolled without delays into that dose level. 
A DLT is defined as any treatment-emergent adverse event (TEAE) that meets the criteria specified. If 
a DLT is observed in ≤1 of 3 subjects at a given dose level, up to 3 additional subjects (for a total of up 
to 6 subjects) may be enrolled and treated at that dose level. When 3 additional subjects are added to 
the dose group, the dose will be increased to the next dose level if ≤1 of 6 subjects experience a DLT. 
If ≥2 of the 3 to 6 subjects in a dose group experience DLTs, the MTD has been exceeded, and up to 3 
additional subjects (for a total of 6) will be treated at the previous (lower) dose level.  


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Dose escalation may proceed once safety of the current dose level has been established, which is 
dependent upon the last subject enrolled in the current dose level completing the 28-day DLT 
evaluation period. 
The MTD in this study is defined as the highest dose at which ≤1 of 6 study subjects experiences a 
DLT. If the MTD is not exceeded, the sponsor will choose the recommended Phase 2a dose based on 
observations of clinical efficacy, safety, and/or cell kinetics.  
The investigators, medical monitor, and sponsor, designated as the Safety Review Committee (SRC), 
will monitor and convene to review safety data, including any delayed toxicities caused by 
PBCAR20A, at regular intervals to discuss any unexpected significant toxicities and to determine 
whether dose escalation is appropriate.  
After the conclusion of Phase 1, the SRC will convene to determine whether Phase 2a of the study can 
proceed. 
If DLTs are found to occur predominantly in one subtype of NHL subjects (i.e., those with indolent 
lymphoma, including follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic 
lymphoma, and marginal zone lymphoma or aggressive lymphoma, such as diffuse large B cell 
lymphoma, PMBCL, Burkitt lymphoma, and other high grade T cell lymphomas), the possibility of 
separating the cohorts for dose escalation may be explored. 
For characterization of the pharmacology, safety profile, and clinical benefit profile, up to 18 subjects 
total may be enrolled in any given dose level for which safety has been established (i.e., ≤1 of 
6 subjects experiences a DLT). These additional subjects (any subjects after subject 6) will not be 
considered for determination of the MTD and can be enrolled without delays into that dose level. 
Additionally, these subjects may receive modified lymphodepletion regimens as described in the 
Pharmacy Manual to evaluate regimens which may increase anti-tumor effect and improve 
PBCAR20A cellular kinetics. 
All subjects are monitored for DLTs and AEs during the Treatment Period through Day 28.and will 
continue to be monitored for safety after Day 28 until death, disease progression, stem cell transplant, 
withdrawal of consent, or Day 360, whichever occurs first.  
 
Phase 2a (dose expansion):  
Upon selection of the recommended Phase 2a dose (RP2D) and preferred lymphodepletion regimen, 
specific populations (defined by inclusion/ exclusion criteria for Arms A, B and C in the full protocol) 
will be enrolled to characterize clinical efficacy, safety, and pharmacology in that population. 
Long-term follow-up study: 
Study subjects who receive a dose of PBCAR20A will be followed in a separate long term follow up 
(LTFU) study after exiting this study (due to either discontinuation or completion). The LTFU study 
procedures will be described in a separate protocol. 
Number of subjects (planned): 
Phase 1 (dose escalation): Approximately 9 to 30 evaluable study subjects are planned to be enrolled. 
Evaluable study subjects for the primary variable assessment of safety and tolerability, related to the 
incidence of DLTs, are defined as those who either complete their treatment period through Day 28 or 
experience a DLT. Non-evaluable study subjects will be replaced. 


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Phase 2a (dose expansion): Approximately up to 20 subjects are planned to be enrolled in any active 
Phase 2a arm. Any arm may be discontinued if evidence of futility (e.g., unexpectedly low ORR) is 
observed. A realistic expectation for enrollment is approximately 40 subjects. 
 
Diagnosis and main criteria for inclusion: 
Study subjects are eligible to be included in the study only if all of the following criteria apply: 
Disease characteristics 
Criteria for NHL (Phase 1): 
1. Subject has r/r CD20+ B-cell NHL that is histologically confirmed by archived tumor biopsy tissue 
from the last relapse and corresponding pathology report. Alternatively, if at least 1  site is 
accessible at Screening, the subject’s diagnosis will be confirmed by pretreatment biopsy 
(excisional when possible). If a subject never had a complete response (CR) during prior lines of 
therapy, a sample from the most recent biopsy is acceptable. 
2. Measurable or detectable disease (positron emission tomography [PET]-positive) with evidence of 
disease progression after most-recent therapy according to the Lugano classification. 
3. Primary refractory disease or r/r disease after treatment with 2 prior regimens, unless per standard 
of care treatment guidance (e.g., National Comprehensive Cancer Network [NCCN]) no second 
line therapy of known benefit exists. Subjects including but not limited to those with the following 
types of lymphoma and have received the associated standard therapies are eligible:  
a. Primary mediastinal B-cell lymphoma (PMBCL)/follicular lymphoma (FL) including 
Grade 3B or transformed FL/high-grade B-cell lymphoma/diffuse large B-cell lymphoma 
(DLBCL) including Richter’s transformation. Subjects must have received rituximab or 
other anti-CD20 antibody and anthracycline-based chemotherapy. All subjects should be 
evaluated for approved anti-CD19 CAR T-cell therapy when applicable. 
b. Indolent B-cell lymphoma (Grades 1, 2, and 3A)/transformed CLL (Richter’s)/marginal 
zone lymphoma. Subjects must have received 2 prior lines of systemic therapy including 
an alkylator (e.g., bendamustine, cyclophosphamide/vincristine/ prednisone) plus an 
anti-CD20 antibody and have had documented disease progression. 
c. Subjects with r/r Burkitt’s lymphoma must have failed 1 prior therapy. 
d. MCL. Subjects must have received 2 prior lines of systemic therapy including 
chemotherapy (bendamustine/rituximab; rituximab, cyclophosphamide, doxorubicin, 
vincristine, and prednisone (R-CHOP); or Nordic-type regimen) with or without 
autologous stem cell transplant (ASCT) and a Bruton’s tyrosine kinase (BTK) inhibitor 
(e.g., ibrutinib, acalabrutinib) and have had documented disease progression. 
Criteria for CLL/SLL (Phase 1): 
4. Diagnosis of CD20+ CLL with indication for treatment based on the International Workshop on 
Chronic Lymphocytic Leukemia (iwCLL) guidelines and clinically measurable disease or CD20+ 
SLL (lymphadenopathy and/or splenomegaly and <5 × 109 CD19+ and CD5+ clonal B cells/L in 
peripheral blood at diagnosis) with measurable disease that is biopsy-proven SLL. 
5. Subjects with CLL/SLL must have previously progressed following at least 2 prior lines of 
systemic targeted therapy including a BTK inhibitor and venetoclax ± rituximab. 
 
Criteria for Phase 2a Arm A: 


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6. Diagnosis of CD20+ CLL/SLL for which subject is currently receiving, and has been receiving for 
the past 12 months, ibritunib therapy as standard of care, regardless of line of therapy, with best 
response of partial response or stable disease (no CR or CRi). Subjects must have high risk disease, 
as defined by deletion 17p or TP53 mutation. 
 
Criteria for Phase 2a Arm B: 
7. Diagnosis of CD20+ DLBCL with PET/CT indicating a partial response, but not a complete 
response, per Lugano 2016 criteria (Cheson JCO 2016), after completion of upfront 
chemoimmunotherapy (R-CHOP, per NCCN 2020 NHL Guidelines). Subjects who had refractory 
disease to (progressive disease through) upfront treatment are not eligible. 
 
Criteria for Phase 2a Arm C: 
8. Diagnosis of CD20+ high-grade B cell lymphoma after previous treatment with autologous 
CD19-targeted CAR T therapy, regardless of response. 
Criteria for all subjects (Phase 1 and 2a):  
9. Subject has CD20+ tumor. Note: If the tumor is CD20-negative by flow cytometry, it should be 
evaluated by immunohistochemistry as flow assays may result in false negatives due to 
competition with CD20-targeting treatment antibodies (e.g., rituximab). 
10. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. 
11. Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as: 
a. Estimated glomerular filtration rate >30 mL/min/1.73 m2 (calculated using the Chronic 
Kidney Disease Epidemiology Collaboration equation). A 24-hour urine collection for 
creatinine clearance may be used at the investigator’s discretion.  
b. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both 
≤3 times the upper limit of normal (ULN), unless there is suspected disease (tumor) in the 
liver. 
c. Total bilirubin <2.0 mg/dL, except in subjects with Gilbert’s syndrome, who must have 
total bilirubin ≤3 × ULN, or except those with disease (tumor) in the liver. 
d. Platelet count  ≥50,000/µL and ANC of ≥1000/ µL. Transfusions within 14 days of 
screening are not allowed, except for patients in B-ALL or NHL cohorts with high marrow 
disease burden (>70%) in which case it must be discussed with medical monitor. In the 
case of extensive bone marrow disease burden, adequate bone marrow recovery after prior 
treatment is required to be documented. 
e. Left ventricular ejection fraction (LVEF) >45% as assessed by an echocardiogram 
(ECHO) or multiple gated acquisition (MUGA) scan performed within 1 month before 
starting lymphodepleting chemotherapy. The ECHO results performed within 6 months 
before Screening and at least 28 days after the last cancer treatment may be acceptable if 
the subject has not received any treatment with cardiotoxicity risks. 
f. No evidence of pericardial effusion or pleural effusion causing clinical symptoms and 
needing immediate intervention. Any known effusion must be stable without need for 
drainage within 2 weeks of enrollment. 
g. Baseline oxygen saturation >92% on room air. 
Subject characteristics 
12. Subject must be 18 years of age or older at the time of signing the informed consent form. 
13. Any sex. 


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14. All subjects must be willing to practice birth control and refrain from donating sperms or oocytes 
from the time of enrollment in this study through 3 months after receiving the study treatment. 
15. Women of childbearing potential (WOCBP) must be tested negative for pregnancy at Screening 
because of the potentially harmful effects of the preparative chemotherapy to the fetus. The 
WOCBP are defined as any women who are not postmenopausal or who have not had a 
hysterectomy. Postmenopausal is defined as women over the age of 55 years who have not had a 
menstrual period for at least 1 year. 
16. Capable of giving signed informed consent. 
Exclusion criteria: 
Subjects are excluded from the study if any of the following criteria apply: 
17. Requirement for urgent therapy due to mass effects such as bowel obstruction, spinal cord, or 
blood vessel compression.  
18. Any history of central nervous system (CNS) disease. If active CNS involvement is suspected, 
negative imaging(CT or MRI) and negative lumbar puncture are required at Screening. 
19. Subject has had a malignancy, besides the malignancies of inclusion (B-cell NHL or CLL/SLL), 
that in the investigator’s opinion, has a high risk of relapse in the next 2 years.  
20. Recent, clinically significant fungal, bacterial, viral, protozoal, or other infection requiring 
therapeutic anti-microbial medications within 7 days of lymphodepletion. Note: subjects with 
elevated or rising C-reactive protein (CRP) must undergo infectious disease (ID) workup and 
recommendations must be discussed with the medical monitor. CRP must be trending toward the 
normal range for the laboratory. Simple urinary tract infection and uncomplicated bacterial 
pharyngitis are permitted if the subject is responding to active treatment and with medical monitor 
approval. 
21. Any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease).  
22. History of human immunodeficiency virus (HIV) infection. 
23. Active hepatitis B or hepatitis C confirmed by polymerase chain reaction (PCR). Subjects testing 
positive for inactive hepatitis B will be allowed to enroll if on prophylactic treatment.  
24. Any known uncontrolled cardiovascular disease at the time of Screening that, in the investigator’s 
opinion, is clinically significant and renders the subject ineligible. 
25. History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening.  
26. History of severe immediate hypersensitivity reaction to any of the agents used in this study.  
27. Presence of a CNS disorder that, in the opinion of the investigator, renders the subject ineligible 
for treatment. 
28. Abnormal findings during the Screening Period or any other medical condition(s) or laboratory 
findings that, in the opinion of the investigator, might jeopardize the subject’s safety.  
29. History of a genetic syndrome such as Fanconi anemia, Kostmann syndrome, 
Shwachman -Diamond syndrome, or any other known bone marrow failure syndrome.  
Prior/concomitant therapy (Phase 1 and 2a) 
30. Subjects who have received ASCT within 45 days of Screening are excluded. 
31. Subjects who have received systemic corticosteroid (greater than physiologic replacement) therapy 
for at least 7 days prior to initiating lymphodepletion chemotherapy are excluded.  
32. Subjects who have received a live vaccine within 4 weeks before Screening are excluded. Non-live 
virus vaccines are not excluded.  
33. Subjects undergoing Radiotherapy to target lesions within 4 weeks before Screening are excluded. 


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34. Subjects who have an indwelling catheter (i.e., pleural, peritoneal, pericardial as well as biliary and 
ureteral stents) are excluded. This does not apply to intravenous lines. 
Other exclusions (Phase 1 only) 
35. Subjects are excluded unless there has been documented progression of the disease after prior most 
recent systemic anti-cancer therapeutic agents and resolution of adverse events caused by their 
administration.  
 
Other exclusions (Phase 2a Arm A) 
36. Subjects are excluded specifically from Arm A if they have: 
a. CR has been achieved with Previous ibrutinib therapy. Note: progression is not required 
for enrollment if stable disease or partial response has been achieved and maintained. 
b. Ongoing grade ≥ 2 non-hematologic toxicity related to ibrutinib. 
c. High-grade transformed disease (e.g., Richter’s transformation) 
 
Other exclusions (Phase 2a Arm B) 
37. Subjects are excluded specifically from Arm B if they have a diagnosis of transformed high grade 
lymphoma (e.g., Richter’s transformation or transformed follicular lymphoma). 
 
Other exclusions (Phase 1 and 2a) 
38. Pregnant or breastfeeding women. 
39. In the investigator’s judgment, the subject is unlikely to complete all protocol required study visits 
or procedures, including follow-up visits, or is unlikely to comply with the study requirements for 
participation. 
40. Any mental condition rendering the subject unable to understand the nature, scope, and possible 
consequences of the study, and/or evidence of an uncooperative attitude. 
 
Investigational product, dosage, and mode of administration: 
PBCAR20A for IV infusion. 
Phase 1:  
Single escalating dose at 1 × 106 or 3 × 106 CAR T cells/kg body weight and flat doses of 240 × 106 or 
480 × 106 CAR T cells. A de-escalation dose (Dose -1) at 3 × 105 cells/kg body weight may be tested if 
necessary.  
Phase 2a:  
Arms in Phase 2a will use a dose at or below the MTD as determined in Phase 1. The dose will be 
determined based on PK/PD analysis, safety evaluation, and preliminary evidence of clinical activity. 
Refer to the Pharmacy Manual for the specific dosing regimen to be used in each Arm in Phase 2.  
Study duration:  
Maximum: 389 days 
• 
Screening: Days -28 to -1 


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• 
Treatment period: Days 0 to 28 
• 
Follow-up: up to Day 360 
Reference therapy, dosage and mode of administration:  
None.  
Statistical methods: 
For Phase 1, dose escalation of PBCAR20A will follow a standard 3 + 3 design with sequential groups 
of 3 study subjects treated with incrementally higher doses of PBCAR20A until a DLT is observed and 
the MTD is established.  
For Phase 2a, up to 20 subjects will be enrolled into any Arm for dose expansion and preliminary 
evaluation of efficacy at the RP2D for a total of up to 60 subjects. The data collected from subjects 
enrolled in the dose expansion will be used to confirm safety, explore potential biomarkers, and 
evaluate preliminary efficacy of PBCAR20A. Descriptive statistics will be used to describe the 
efficacy, safety, and biomarker endpoints.  


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
SIGNATURE PAGE .......................................................................................................................2 
INVESTIGATOR’S AGREEMENT ...............................................................................................3 
STUDY CONTACT LIST ...............................................................................................................4 
SYNOPSIS ......................................................................................................................................5 
TABLE OF CONTENTS ...............................................................................................................13 
LIST OF TABLES .........................................................................................................................18 
LIST OF FIGURES .......................................................................................................................19 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................20 
1. 
INTRODUCTION ......................................................................................................24 
1.1. 
Study rationale ............................................................................................................24 
1.2. 
Background .................................................................................................................24 
1.2.1. 
Drug development ......................................................................................................24 
1.2.2. 
Place in treatment – Phase 1 .......................................................................................25 
1.2.3. 
Lymphodepletion ........................................................................................................26 
1.2.3.1. 
Standard Lymphodepletion .........................................................................................27 
1.2.3.2. 
Lymphodepletion Alternative: Enhanced Lymphodepletion ......................................27 
1.2.3.3. 
Lymphodepletion Alternative: Tolerance induction ...................................................28 
1.2.3.4. 
Lymphodepletion Alternative: Sirolimus ...................................................................28 
1.2.4. 
Rationale for Phase 2a populations.............................................................................29 
1.2.4.1. 
Arm A – PBCAR20A in subjects with CLL/SLL being treated with ibrutinib 
therapy for at least 12 months .....................................................................................29 
1.2.4.2. 
Arm B – PBCAR20A in subjects with high grade DLBCL who did not 
achieve complete response after 2 cycles of front-line therapy ..................................29 
1.2.4.3. 
Arm C – PBCAR20A in subjects with high grade B cell Non-Hodgkin’s 
Lymphoma (NHL) who have previously been treated with autologous CAR 
T products and have subsequently experienced disease progression .........................30 
1.3. 
Benefit/risk assessment ...............................................................................................30 
2. 
STUDY OBJECTIVES AND PURPOSE ..................................................................32 
2.1. 
Primary objective and endpoint ..................................................................................32 
2.1.1. 
Phase 1 ........................................................................................................................32 
2.1.2. 
Phase 2a ......................................................................................................................32 


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2.2. 
Secondary objective and endpoints ............................................................................32 
2.2.1. 
Phase 1 ........................................................................................................................32 
2.2.2. 
Phase 2a ......................................................................................................................33 
2.3. 
Exploratory objectives and endpoints .........................................................................33 
3. 
STUDY DESIGN .......................................................................................................33 
3.1. 
Overall study design ...................................................................................................33 
3.1.1. 
Phase 1 (dose escalation): ...........................................................................................34 
3.1.2. 
Phase 2a (dose expansion) ..........................................................................................36 
3.1.2.1. 
Phase 2a Arm A Population: CLL/SLL being treated with ibrutinib therapy 
for at least 12 months ..................................................................................................36 
3.1.2.2. 
Phase 2a Arm B Population: DLBCL who did not achieve complete 
response after 2 cycles of front-line therapy ...............................................................36 
3.1.2.3. 
Phase 2a Arm C Population: High grade B cell Non-Hodgkin’s Lymphoma 
(NHL) who have previously been treated with autologous CAR T products 
and have subsequently experienced disease progression ............................................37 
3.1.3. 
Long-term follow-up study: ........................................................................................37 
3.2. 
Study schedule ............................................................................................................38 
3.3. 
Number of subjects .....................................................................................................42 
3.4. 
Number of Study Centers ...........................................................................................42 
3.5. 
Discussion of study design and dose justification ......................................................42 
3.6. 
Cohorts and dose escalation ........................................................................................44 
3.7. 
Retreatment criteria ....................................................................................................45 
3.8. 
Criteria for DLTs ........................................................................................................46 
3.9. 
Criteria for treatment interruption ..............................................................................47 
3.10. 
Criteria for temporarily suspending treatment ............................................................47 
3.11. 
Criteria for study termination .....................................................................................47 
4. 
SELECTION AND WITHDRAWAL OF STUDY SUBJECTS ...............................47 
4.1. 
Inclusion criteria .........................................................................................................47 
4.2. 
Exclusion criteria: .......................................................................................................50 
4.3. 
Screening ....................................................................................................................52 
4.3.1. 
Screening procedures ..................................................................................................52 
4.3.2. 
Screen failures ............................................................................................................52 
4.4. 
Study discontinuation or withdrawal ..........................................................................53 
4.4.1. 
Study participant withdrawal ......................................................................................53 


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4.4.2. 
Lost to follow-up ........................................................................................................53 
4.5. 
Study completion ........................................................................................................54 
5. 
STUDY INTERVENTION ........................................................................................54 
5.1. 
Description of study treatment ....................................................................................54 
5.1.1. 
Pre-infusion restrictions ..............................................................................................54 
5.1.2. 
Study treatments .........................................................................................................55 
5.1.3. 
Hospitalization ............................................................................................................55 
5.2. 
Concomitant medications ...........................................................................................56 
5.2.1. 
Premedication .............................................................................................................56 
5.2.2. 
Prohibited medications and substances ......................................................................56 
5.3. 
Treatment compliance ................................................................................................56 
5.4. 
Randomization and blinding .......................................................................................56 
6. 
MATERIALS AND MANAGEMENTOF INVESTIGATIONAL 
PRODUCT ..................................................................................................................56 
6.1. 
Investigational Product ...............................................................................................56 
6.2. 
Investigational product storage ...................................................................................56 
6.3. 
Investigational product handling, preparation, and administration ............................57 
6.4. 
Investigational product accountability ........................................................................57 
7. 
ASSESSMENT OF SAFETY .....................................................................................57 
7.1. 
Safety parameters ........................................................................................................57 
7.1.1. 
Vital signs ...................................................................................................................57 
7.1.2. 
Physical examination ..................................................................................................57 
7.1.3. 
Electrocardiogram .......................................................................................................58 
7.1.4. 
Laboratory assessments ..............................................................................................58 
7.1.5. 
Immunogenicity ..........................................................................................................60 
7.2. 
AEs and SAEs .............................................................................................................60 
7.2.1. 
Definition of AEs ........................................................................................................60 
7.2.1.1. 
AE ...............................................................................................................................60 
7.2.1.2. 
SAE .............................................................................................................................60 
7.2.1.3. 
Adverse events of special interest ...............................................................................61 
7.2.2. 
Assessment of intensity ..............................................................................................61 
7.2.3. 
Relationship to study treatment ..................................................................................62 
7.2.4. 
Recording AEs ............................................................................................................62 


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7.2.5. 
Reporting AEs ............................................................................................................63 
7.2.6. 
Disease-related events and/or disease-related outcomes that do not qualify as 
AEs or SAEs ...............................................................................................................63 
7.2.7. 
Pregnancy ...................................................................................................................64 
7.3. 
Management of CRS, ICANS, and GvHD .................................................................64 
7.3.1. 
CRS .............................................................................................................................65 
7.3.2. 
ICANS ........................................................................................................................66 
7.3.3. 
GvHD ..........................................................................................................................68 
8. 
ASSESSMENTS OF CLINICAL ACTIVITY ...........................................................71 
8.1. 
Assessment of response ..............................................................................................71 
8.2. 
Expansion, persistence, and phenotype of PBCAR20A .............................................74 
8.3. 
CRS biomarkers ..........................................................................................................74 
8.4. 
PET-CT scan ...............................................................................................................74 
8.5. 
BMA/bone marrow biopsy and analysis.....................................................................75 
8.6. 
Tumor biopsy ..............................................................................................................75 
9. 
STATISTICS ..............................................................................................................75 
9.1. 
General statistical methods .........................................................................................75 
9.2. 
Sample size considerations .........................................................................................76 
9.3. 
Analysis population sets .............................................................................................77 
9.4. 
Study participant description ......................................................................................77 
9.4.1. 
Disposition ..................................................................................................................77 
9.4.2. 
Demographic and Baseline characteristics .................................................................77 
9.4.3. 
Concomitant medications ...........................................................................................78 
9.4.4. 
Treatment administration/compliance ........................................................................78 
9.5. 
Safety analysis ............................................................................................................78 
9.5.1. 
AEs .............................................................................................................................78 
9.5.2. 
Laboratory tests ..........................................................................................................78 
9.5.3. 
ECGs ...........................................................................................................................79 
9.5.4. 
Vital signs and physical examination findings ...........................................................79 
9.6. 
Efficacy analysis .........................................................................................................79 
9.7. 
Interim analysis ...........................................................................................................79 
10. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................80 
10.1. 
Study monitoring ........................................................................................................80 


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10.2. 
Audits and inspections ................................................................................................80 
10.3. 
IRB ..............................................................................................................................81 
10.4. 
Data protection ............................................................................................................81 
11. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................81 
12. 
ETHICS ......................................................................................................................82 
12.1. 
Ethics review ..............................................................................................................82 
12.2. 
Ethical conduct of the study .......................................................................................82 
12.3. 
Written informed consent ...........................................................................................82 
13. 
DATA HANDLING AND RECORDKEEPING .......................................................82 
13.1. 
Inspection of records ...................................................................................................82 
13.2. 
Retention of records ....................................................................................................83 
14. 
PUBLICATION POLICY ..........................................................................................83 
15. 
REFERENCES ...........................................................................................................84 
16. 
APPENDICES ............................................................................................................88 
16.1. 
Protocol version summary of changes ........................................................................92 
16.1.1. 
Version 5.0 ..................................................................................................................92 
16.1.2. 
Version 4.0 ..................................................................................................................92 
16.1.3. 
Version 3.0 ..................................................................................................................97 
16.1.4. 
Version 2.0 ................................................................................................................100 
 
 


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LIST OF TABLES 
Table 1: 
Key study contact information ......................................................................................4 
Table 2: 
Study schedule: Phase 1 and 2a ..................................................................................38 
Table 3: 
Single escalating doses of PBCAR20A ......................................................................44 
Table 4: 
List of study treatments ..............................................................................................55 
Table 5: 
Assessment of AE intensity ........................................................................................62 
Table 6: 
Relationship assessment definitions ...........................................................................62 
Table 7: 
CRS grading and management recommendations ......................................................66 
Table 8: 
ASTCT ICANS grading and management guidelines ................................................67 
Table 9: 
GvHD grading system based on organ involvement ..................................................69 
Table 10: GvHD management recommendations .......................................................................69 
Table 11: Revised Lugano classification of response .................................................................72 
Table 12: iwCLL definition of response .....................................................................................73 
Table 13: Probability of detecting AE rates by sample size .......................................................77 
Table 14: ASTCT CRS consensus grading .................................................................................90 
Table 15: ASTCT ICANS consensus grading for adults ............................................................91 
 
 


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LIST OF FIGURES 
Figure 1: 
Study schema ..............................................................................................................36 
Figure 2: 
Dose escalation algorithm ...........................................................................................45 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
ACT 
adoptive cell therapy 
AE 
adverse event 
AESI 
adverse events of special interest 
ALL 
acute lymphocytic leukemia 
ALT 
alanine aminotransferase 
ASCT 
autologous stem cell transplant 
AST 
aspartate aminotransferase 
ASTCT 
American Society for Transplantation and Cellular Therapy 
B-ALL 
B-cell acute lymphoblastic leukemia 
BID 
Twice daily 
BMA 
bone marrow aspiration 
BSA 
body surface area 
BTK 
Bruton’s tyrosine kinase 
CAR 
chimeric antigen receptor 
CBC 
complete blood count 
CD 
cluster of differentiation 
CFR 
Code of Federal Regulations 
CGT 
Cell and Gene therapy 
CI 
confidence interval 
CLL 
chronic lymphocytic leukemia 
CNS 
central nervous system 
CR 
complete response 
CRO 
contract research organization 
CRP 
C-reactive protein 
CRS 
cytokine release syndrome 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLBCL 
diffuse large B-cell lymphoma 
DLT 
dose-limiting toxicity 
DoR 
duration of response 
DRE 
disease-related event 


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ECG 
electrocardiogram 
ECHO 
echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
FDA 
Food and Drug Administration 
FL 
follicular lymphoma 
GCP 
Good Clinical Practice 
GvHD 
graft-versus-host disease 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 
IB 
Investigator’s Brochure 
ICANS 
immune effector cell-associated neurotoxicity syndrome 
ICF 
informed consent form 
ICH 
International Council for Harmonization 
IEC 
Independent Ethics Committee 
IFN 
interferon 
IL 
interleukin 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IV 
intravenous 
iwCLL 
International Workshop on Chronic Lymphocytic Leukemia 
LD 
lymphodepletion 
LDH 
lactate dehydrogenase 
LTFU 
long-term follow-up 
LVEF 
left ventricular ejection fraction 
MCL 
mantle cell lymphoma 
MedDRA 
Medical Dictionary for Regulatory Activities 
MR 
minor response 
MRD 
minimal residual disease 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 


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MUGA 
multiple gated acquisition 
MZL 
marginal zone lymphoma 
NCI 
National Cancer Institute 
NHL 
non-Hodgkin lymphoma 
NOS 
not otherwise specified 
ORR 
objective response rate 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cell 
PC 
pentostatin + cyclophosphamide 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PMBCL 
primary mediastinal B-cell lymphoma 
PR 
partial response 
PT 
preferred term 
qPCR 
quantitative polymerase chain reaction 
QTcF 
QT interval corrected by Fredericia 
R-CHOP 
rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone 
r/r 
relapsed/refractory 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
scFv 
single-chain variable fragment 
SD 
stable disease 
SLL 
small lymphocytic lymphoma 
SoA 
Schedule of Activities 
SUSAR 
suspected unexpected serious adverse reaction 
TCR 
T-cell receptor 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
WBC 
white blood cell count 


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WOCBP 
women of childbearing potential 


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1. 
INTRODUCTION 
PBCAR20A is an allogeneic antihuman-cluster of differentiation (CD) 20 chimeric antigen 
receptor (CAR) T-cell product derived from qualified donor T cells that have been genetically 
edited to remove the expression of the endogenous T-cell receptor (TCR). Insertion and 
expression of the anti-CD20 CAR provides the ability to specifically target and bind 
CD20-positive (CD20+) cells, and the removal of the TCR significantly reduces the possibility of 
developing graft-versus-host disease (GvHD) when it is administered to human leukocyte 
antigen (HLA)-mismatched subjects. PBCAR20A is being developed as an off-the-shelf 
treatment for certain B-cell malignancies.  
1.1. 
Study rationale 
PBCAR20A is a Phase 1/2a, first-in-human study of PBCAR20A designed to evaluate the safety 
and clinical activity and optimize the treatment regimen of PBCAR20A in adult study subjects 
with relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (NHL), chronic lymphocytic 
leukemia (CLL), or small lymphocytic lymphoma (SLL). As described in the following sections, 
PBCAR20A offers potential therapeutic benefits compared with autologous CAR T-cell 
treatment for certain blood cancers.  
1.2. 
Background 
1.2.1. 
Drug development 
During the past 10 years, advances in molecular and cellular biology have led to the creation of 
genetically modified T cells in which a CAR is inserted and stably expressed in a T lymphocyte. 
CAR T cells designed to target CD19, an antigen present on B lymphocytes in all stages of 
development except for terminally differentiated plasma cells, have been used to treat subjects 
with CD19+ tumors. Autologous CAR T-cell therapies have progressed into clinical trials, with 
recent Food and Drug Administration (FDA) approvals for tisagenlecleucel (Kymriah™) to treat 
subjects with r/r B-cell acute lymphoblastic leukemia (B-ALL) up to 25 years of age (August 
2017) and adult subjects with r/r large B-cell lymphoma (May 2018). Axicabtagene ciloleucel 
(Yescarta™) has also been approved to treat r/r large B-cell lymphoma (October 2017). A 
Phase 1/2a study evaluating the safety and clinical activity of PBCAR0191, an allogeneic 
antiCD19 CAR T-cell therapy, in adults with r/r B-ALL and r/r NHL is currently ongoing 
(Investigational New Drug [IND] 18396). 
There are drawbacks to autologous CAR T-cell therapy. First, it can be difficult to obtain enough 
quality T cells from some subjects with cancer to produce a therapeutic product, particularly 
from subjects who have failed several previous lines of treatment. Second, subjects need to 
undergo apheresis and then wait several weeks while their autologous drug product is being 
manufactured. Bridging chemotherapy is often required during this waiting period, which can 
result in chemotherapy-related toxicities that can render the patient too sick to receive their CAR 
T-cell therapy. In addition, autologous CAR T-cell therapies are inherently heterogeneous. Using 
qualified donor lymphocytes as the starting material to generate CAR T cells can mitigate these 
problems.  
Approximately half of subjects with relapsed leukemia after anti-CD19 therapy lose CD19 
expression and require alternative treatments (Maloney, 2012; Sotillo et al, 2015; Gardner et al, 


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2016). CD20 is an attractive target because it is expressed in over 90% of B-cell lymphomas, 
does not internalize upon binding, and is stable on the cell surface (Press et al, 1989; Reff et al, 
1994). The CD20 antigen is another well-established target for B-cell malignancy treatments, as 
demonstrated by extensive clinical trials with rituximab, an anti-CD20 antibody. Thus, CAR 
T-cell therapy directed against CD20 provides an alternative option for subjects who relapse 
from anti-CD19 therapy.  
PBCAR20A is produced in bulk from T cells derived from qualified donors to generate hundreds 
of vials of drug product that is stored frozen and available off-the-shelf. Therefore, subjects will 
not need to undergo apheresis and bridging chemotherapy while they wait for an autologous 
CAR T-cell product to be manufactured and shipped to the treatment center for administration. 
In addition, the source of the starting material for PBCAR20A production, i.e., T cells from 
qualified donors that meet prespecified criteria, allows for better control of the CAR T-cell 
manufacturing process and production of a more homogenous and better-defined drug product. 
However, allogeneic T cells can lead to the development of GvHD when they are infused into 
HLA-mismatched recipients. In PBCAR20A, gene-editing technology is used in donor T cells to 
prevent the expression of the native TCR; thus, reducing or eliminating the likelihood of GvHD 
resulting from administration of the allogeneic CAR T-cell product. Transduction leads to 
insertion and expression of the CD20-targeting CAR transgene, thereby redirecting the 
specificity of the T cells with the goal of creating off-the-shelf CAR T-cell products that can be 
consistently manufactured and safely administered to any patient when needed. 
In this study, the allogeneic CAR T-cell product, PBCAR20A, will be administered to adult 
study subjects with r/r CD20+ NHL including r/r CD20+ CLL/SLL. 
1.2.2. 
Place in treatment – Phase 1 
Hematologic B-cell malignancies comprise a large, heterogeneous group of lymphoproliferative 
disorders that range from the slow-growing, indolent NHLs (e.g., follicular lymphoma [FL], 
SLL, and CLL) to more aggressive forms (e.g., diffuse large B-cell lymphoma [DLBCL] and 
B-ALL) (Boffetta, 2011; Hallek, 2015). B-cell disorders represent more than 85% of all NHL 
cases (Howlader et al, 2016) and 75% to 80% of all types of acute lymphocytic leukemia (ALL) 
(Chiaretti et al, 2014). The NHL incidence rates are higher among the elderly population than in 
the younger population, with diagnoses of NHL most common among subjects 65 to 74 years of 
age (Howlader et al, 2016). The most common subtype of NHL is DLBCL, which accounts for 
30% to 40% of all NHL cases (Al-Hamadani et al, 2015). FL is the second most common form 
of NHL, accounting for about 20% to 35% of all NHL cases; approximately 15% of FL cases are 
Grade 3B (Shustik et al, 2011). CLL/SLL is the third most commonly diagnosed and accounts 
for approximately 25% to 30% of leukemias in the United States; CLL is the most common type 
of leukemia in adults >19 years of age and accounts for about 35% to 40% of cases (Seigel et al, 
2019).  
Typically, front-line anthracycline-based immunochemotherapy with rituximab, 
cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or similar regimens are 
used to treat DLBCL, FL Grade 3B, and Stage III to V mantle cell lymphoma (MCL). While 
R-CHOP is expected to provide benefits to more than 50% of newly diagnosed subjects, at least 
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after achieving complete remission (Habermann et al, 2006; Sud and Friedberg, 2008; Fakhri and 
Kahl, 2017; Casulo et al, 2015).  
Management of B-cell lymphomas after failure of immunochemotherapy is challenging. While 
salvage chemotherapy followed by autologous hematopoietic cell transplant is an option, it is 
associated with signiﬁcant toxicities that would preclude many subjects with comorbidities or 
advanced age. Thus, the prognosis of r/r B-cell lymphoma as a group remains poor (Casulo et al, 
2015; Rovira et al, 2015; Van Den Neste et al, 2016; Vose, 2017). In adult subjects with r/r large 
B-cell lymphoma, axicabtagene ciloleucel (Yescarta™) showed an objective response rate (ORR) 
of 72% and a median duration of response (DoR) of 9.2 months and tisagenlecleucel 
(Kymriah™) had an ORR of 50% and the DoR was not reached, indicating that CAR T-cell 
therapy may significantly improve the prognosis for these subjects.  
CLL is the most common type of leukemia in adults; the median age of diagnosis is 70 years and 
the 5-year survival rate is 84% (Surveillance, Epidemiology, and End Results [SEER]-Medicare 
Linked Database, 2019). CLL is a biologically heterogeneous disease, and morphologic, 
immunologic, cytogenetic, biochemical, and molecular genetic characterization of leukemia 
lymphoblasts are needed to establish the diagnosis and classify the subtypes. Subjects with CLL 
have had limited success with autologous CAR T-cell therapies, likely due to the T-cell 
exhaustion associated with this malignancy (Riches et al, 2013). Thus, the administration of 
healthy donor T cells in allogeneic CAR T-cell therapy has the potential to overcome current 
challenges in CLL treatment. 
As noted above, allogeneic CAR T-cell therapy offers potential advantages compared with 
autologous CAR T-cell therapies. The activity of PBCAR20A has been investigated in 
immunodeficient mice. In a subcutaneous B-cell lymphoma model, all mice in the control group 
showed evidence of increasing tumor burden and only 1 of 5 mice survived past Day 22; at 
Day 56, 3 of the 5 mice treated with PBCAR20A survived and were tumor free. These results 
show potent in vivo clearance of CD20+ tumor cells by PBCAR20A and support its development 
as an allogeneic CAR T-cell therapy.  
Based on this context, PBCAR20A will be initially evaluated (Phase 1) for safety in subjects 
with no standard treatment options. After a recommended Phase 2 dose (RP2D) and 
lymphodepletion regimen are established, other lines of therapy in specific populations may be 
considered in Phase 2a, based on evidence of efficacy and safety observations that would inform 
risk/benefit rationale for Phase 2a Arms. 
1.2.3. 
Lymphodepletion 
Due to the allogeneic nature of PBCAR20A, it is expected that allogeneic rejection will occur at 
some point after infusion. At the time of study initiation, it is unknown what the timeframe of 
rejection will be.  
Based on observations with other PBCAR products that have been in the clinic longer than 
PBCAR20A, such as PBCAR0191, Precision Biosciences has reason to believe that alternative 
lymphodepletion regimens may be required to maximize expansion and persistence of 
PBCAR20A. As a result, alternative lymphodepletion regimens are under consideration. 
Potential regimens are based on historical clinical trial data and/or in vitro evaluations suggesting 
the selected regimens are likely to reduce rejection of allogeneic cells without reducing the 




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transfusion and adequate neutrophil counts. Prophylactic antibiotics, antivirals, and antifungals 
are encouraged per institutional standards.  
1.2.3.3. 
Lymphodepletion Alternative: Tolerance induction 
Based on the observations of clinical efforts to reduce graft versus host disease (GvHD) in 
haploidentical allogeneic stem cell transplant, a post-transplant cyclophosphamide (PTCy) 
regimen may have the potential to selectively target T cells activated against mismatched 
allogeneic antigens. Indeed, haploidentical allogeneic stem cell transplant after preparative 
chemotherapy results in clonal expansion of donor T cells against patient normal tissue antigens 
(allogeneic priming). When this is followed by high dose cyclophosphamide at a specified 
interval, those expanding T cells are selectively destroyed, which significantly reduces the 
GvHD complications in this setting (Storb et al, 1970). Following this immunologic rationale, it 
is possible that a “priming” dose of PBCAR20A may cause allogeneic activation of T cell 
populations against the allo-antigens in PBCAR20A, providing a window of opportunity to use 
high dose cyclophosphamide after a low dose of PBCAR20A to reduce allogeneic rejection. 
Following that, a full dose of PBCAR20A would be administered for full treatment effect. 
However, it is known that cyclophosphamide alone does not provide adequate cytokine support 
for CAR T expansion in autologous CAR T studies and that the addition of fludarabine can 
significantly increase CAR T expansion (Hay et al, 2017). This is also consistent with our 
observations in our PBCAR0191-01 clinical trial. Therefore, in addition to the high dose 
cyclophosphamide used in PTCy, this regimen will also include fludarabine 30mg/m2/day x 3 
days. The resulting regimen is: 
- 
PBCAR20A 30 x 106 cells (flat dose) on day -7 
- 
Cyclophosphamide 50m/kg/day x 2 days on days -5 and -4 
- 
Fludarabine 30mg/m2/day x 3 days on days -5, -4 and -3 
- 
PBCAR20A treatment dose on day 0 
1.2.3.4. 
Lymphodepletion Alternative: Sirolimus 
Because the fludarabine and cyclophosphamide regimens (both standard and enhanced) have 
effectively resulted in CAR T expansion, those regimens may be best suited to combine with an 
additional agent that could delay T cell mediated allogeneic rejection. Based on our observations, 
it is likely that an agent that could prevent T cell rejection could increase peak CAR T expansion 
and delay rejection, both of which would increase the AUC of PBCAR20A.  
Multiple agents are used in clinical practice to prevent T cell mediated allogeneic antigen 
targeting, specifically to prevent or reduce the severity of GvHD after allogeneic stem cell 
transplant. Of those agents, sirolimus is known to inhibit GvHD by interfering with the 
production of Th1 cytotoxic cytokines (Blazar et al, 1998; Arman et al, 2008) This mechanism 
prevents native T cell receptor (TCR) signaling from inducing T cell activation. However, CAR 
T cells, including PBCAR20A (and other PBCAR products), do not require native TCR 
signaling for target engagement, activation, and killing because the signaling motifs are built into 
the CAR construct. Prior reported preclinical data suggest CAR T cells can function as well or 
better in the presence of sirolimus compared with the absence of sirolimus (Oldham et al, 2018). 
Because the balance of positive effects (reducing host T cell allogeneic rejection of PBCAR20A) 


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would be difficult to assess relative to the potential negative effect (impact on PBCAR20A 
tumor-killing and expansion capability) and because the risk to the subjects is expected to be 
lower than severe lymphodepletion using chemotherapy, we seek to explore the impact of 
sirolimus in the only known relevant model for this combination, in human subjects with active 
cancer.   
Taken together, the net benefit of sirolimus may allow better CAR T efficacy as a result of minor 
impact on CAR T expansion and killing while significantly delaying CAR T rejection. The 
resulting regimen is: 
- 
Either standard or enhanced lymphodepletion regimens as described  
- 
PBCAR20A treatment dose on day 0 
- 
Sirolimus 16 mg oral loading dose day 1 
- 
Sirolimus 4 mg/day until day 60* 
* Note: 4mg/day maintenance dose may be adjusted up or down based on sirolimus serum levels, 
with a target serum concentration of 20-30 ng/dL; site staff will be reminded to stop sirolimus 
dosing immediately if evidence of infection is observed. 
1.2.4. 
Rationale for Phase 2a populations 
1.2.4.1. 
Arm A – PBCAR20A in subjects with CLL/SLL being treated with ibrutinib 
therapy for at least 12 months 
Preclinical and clinical data indicate ibrutinib may be synergistic with CAR T therapy in CLL. 
Indeed, longer prior treatment with ibrutinib seems to portend greater CAR T cell efficacy in this 
population (Fraietta et al, 2016). It has been suggested that CAR T cell “consolidation” therapy 
may be ideally timed after initial response to ibrutinib in advanced CLL (Gauthier et al, 2020; 
Kater et al, 2020). Based on published literature, the use of PBCAR20A in subjects who have 
been treated for at least 12 months with ibrutinib may provide substantial benefit by further 
reducing tumor burden. Due to the decreased tumor burden expected from ibrutinib therapy, it is 
also possible that the CAR T expansion will not need to reach a high peak, decreasing the risk of 
CRS and ICANS. Subjects will also be likely to have received less total CD20-targeting therapy 
over time, increasing the likelihood of target antigen presence at time of treatment. Together, this 
population may be an ideal opportunity to evaluate the clinical benefit of PBCAR20A.  
 
1.2.4.2. 
Arm B – PBCAR20A in subjects with high grade DLBCL who did not achieve 
complete response after 2 cycles of front-line therapy 
The clinical benefit of autologous CAR T cells has been linked, retrospectively, to lower tumor 
burden at baseline. Multiple publications have suggested that peak CAR T expansion relative to 
baseline tumor burden is closely correlated with likelihood of complete response (CR) and 
durability of response (Cappell et al, 2020; Locke et al, 2020). Recent clinical data from the 
Zuma-12 clinical trial (Neelapu, ASH 2020) suggests greater efficacy may be attainable in earlier 
lines of therapy when tumor burden is lower and there may be less tumor heterogeneity and 
potential antigen loss. Because CD20 expression can be lost or reduced over time with repeated 


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treatment with CD20 targeting agents, a deeper and more durable anti-tumor effect may be 
achieved by using a CD20 targeting CAR T in the earliest therapeutic setting in which an 
opportunity exists and no conflict with standard of care is present. In this group of patients, who 
are being treated with front line therapy (R-CHOP) and do not achieve complete response, 
overall prognosis is poor (Van Den Neste et al, 2015; Klink et al, 2020; Crump et al, 2017; 
Ekberg et al, 2017; Koh et al, 2018). Additionally, no standard of care is established in this 
setting, providing an opportunity to evaluate a novel agent that may improve outcomes for these 
subjects. By selecting subjects in whom initial chemotherapy (R-CHOP) has debulked the initial 
tumor (PR required for eligibility), and because only limited use of CD20 targeting therapy has 
been employed, PBCAR20A therapy may result in deep and meaningful clinical response with 
overall lower risk of adverse events (compared to later stage disease with bulky tumor masses) 
due to lower initial tumor burden.   
1.2.4.3. 
Arm C – PBCAR20A in subjects with high grade B cell Non-Hodgkin’s 
Lymphoma (NHL) who have previously been treated with autologous CAR T 
products and have subsequently experienced disease progression 
After treatment with commercially available autologous CAR T products, most patients with 
high grade B cell Non-Hodgkin’s lymphoma are left with no treatment options of known benefit, 
and, in most cases, repeat treatment with autologous CAR T cells is not a viable option due to 
cost or loss of CD19 expression. As of January 2021, we have enrolled 6 subjects with high 
grade lymphomas who have previously received autologous CAR T cells. Of those, most (4 of 6, 
66.6%) had been documented as being refractory to CD19 CAR T therapy as best response prior 
to enrollment in the present PBCAR20A study; the remaining subjects were 1 PR and 1 CR. Five 
of the 6 have now been evaluated for PBCAR20A response to date, with 3 of 5 (60%) achieving 
partial (2 of 5, 40%) or complete (1 of 5, 20%) response. The patient who reached complete 
response is in an ongoing complete response after 7 months on study.  Arm C will more 
prospectively explore PBCAR20A treatment effect in this population otherwise lacking 
treatment options once the RP2D and LD regimen have been defined. 
 
1.3. 
Benefit/risk assessment 
As this will be the first clinical trial of PBCAR20A, the benefit to subjects with NHL and 
CLL/SLL is not known. 
In a Phase 2a study (NCT01735604), an autologous anti-CD20 CAR T immunotherapy 
demonstrated a significant clinical benefit versus current standard of care in subjects with 
advanced B-cell lymphomas as measured by ORR, the proportion of subjects with complete 
response (CR), partial response (PR), and progression free survival, with no significant toxicities 
(Zhang et al, 2016). Axicabtagene ciloleucel (Yescarta™), an autologous anti-CD19 CAR Tcell 
immunotherapy, was shown in clinical trials to provide a significant clinical benefit versus 
current standard of care as measured by complete remission rate and DoR and has been approved 
for the treatment of adult subjects with r/r large B-cell lymphoma after ≥2 lines of systemic 
therapy, including DLBCL not otherwise specified, primary mediastinal Bcell lymphoma 
(PMBCL), high grade B-cell lymphoma, and DLBCL arising from FL. Tisagenlecleucel 
(Kymriah™), an autologous anti-CD19 CAR T immunotherapy, was shown in clinical trials to 


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provide a significant clinical benefit versus current standard of care as measured by complete 
remission rate, the duration of CR, and the proportion of subjects with a CR and minimal 
residual disease (MRD) <0.01% by flow cytometry, and has been approved for treatment of B-
ALL that is refractory or in a second or later relapse in subjects up to 25 years of age and in adult 
subjects with r/r large B-cell lymphoma after ≥2 lines of systemic therapy including DLBCL not 
otherwise specified, high grade B-cell lymphoma, and DLBCL arising from FL. Toxicities, 
including serious and life-threatening toxicities associated with development of cytokine release 
syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), were 
observed in clinical trials for both of these anti-CD19 CAR T-cell therapies. Such toxicities are 
associated with the mechanism of action of these drugs and, for most subjects, resolve over a 
period of days to weeks with appropriate supportive care or, in severe cases, with medical 
intervention.  
The potential of PBCAR0191 to cause GvHD was examined in a xenogeneic immunodeficient 
NSG mouse model. The NSG mice were sublethally irradiated on Day 1 to stimulate cell damage 
and tissue repair, which results in the activation of antigen-presenting cells and upregulation of 
major histocompatibility complex molecules on mouse tissues. On Day 2, the mice were injected 
with a control vehicle, T-cell control (mock gene‐edited, TCR+ human CD4+/CD8+ T cells or 
peripheral blood mononuclear cells [PBMC]), or gene-edited (TCR-) CAR T cells from the same 
donor. Animals that received the mock gene-edited or unmanipulated PBMC (TCR+) donor 
T cells lost weight and developed clinical symptoms consistent with GvHD. In contrast, all 
animals that received the gene‐edited (TCR-) CAR T cells behaved similarly to animals that were 
treated with the control vehicle and continued to gain weight and groom normally showing no 
behavioral signs of toxicity after recovery from radiation. The findings are supported by a 
confirmatory study using PBCAR20A and together demonstrate a lack of GvHD upon 
administration of gene edited CAR T cells. 
PBCAR20A is a second generation anti-CD20 CAR T-cell product manufactured using healthy 
donor T cells as the starting material through a process that preserves naïve and central memory 
phenotypes and comprises an approximately equal proportion of CD4+ and CD8+ T cells. 
Although one might expect the nature and severity of toxicities to be similar to those observed 
for the approved anti-CD19 CAR T-cell products, Yescarta™ and Kymriah™, the uniform 
composition and phenotype of the CAR T cells within PBCAR20A may result in improved 
clinical responses. As there are no currently approved anti-CD20 CAR T-cell therapies, 
PBCAR20A may provide benefit in subjects who have failed autologous anti-CD19 therapies 
and subjects with CLL who exhibit features of T-cell exhaustion.  
PBCAR20A has been reproducibly manufactured to the desired specifications from multiple 
healthy donors at a commercial manufacturing scale. Multiple batches of PBCAR20A have been 
evaluated for various parameters to characterize the genetic stability of the product. Importantly, 
the gene edited- CAR T-cell batches have similar profiles including consistent targeted insertion 
of the CAR transgene at the intended location within the T-cell receptor alpha constant locus 
with similar low frequency of translocations and off-target gene-editing between batches. The 
potential risks of CRS, ICANS, and GvHD will be managed and mitigated during the study 
(Section 7.3).  
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of PBCAR20A can be found in the Investigator’s Brochure (IB). 


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2. 
STUDY OBJECTIVES AND PURPOSE 
2.1. 
Primary objective and endpoint 
2.1.1. 
Phase 1 
The primary objective of Phase 1 is to evaluate the safety and tolerability of PBCAR20A in 
subjects with r/r CD20+ NHL including r/r CD20+ CLL/SLL and find an appropriate dose to 
optimize safety and efficacy. 
The primary endpoint is the identification of the maximum tolerated dose (MTD) based on the 
incidence of dose-limiting toxicities (DLTs).  
2.1.2. 
Phase 2a 
The primary objective for Phase 2a is to evaluate initial efficacy and safety of PBCAR20A in 
subjects with CD20+ NHL, specific to the population described by the inclusion/exclusion 
criteria 
The primary endpoint for each Phase 2a Arm is: 
• Phase 2a Arm A – complete response rate as measured by International Workshop on 
Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines 
• Phase 2a Arm B – complete response rate as measured by Lugano 2016 criteria 
• Phase 2a Arm C – objective response rate (ORR) as measured by Lugano 2016 
criteria, including partial and complete response rates (PR and CR rates) 
2.2. 
Secondary objective and endpoints 
2.2.1. 
Phase 1 
The secondary objective of Phase 1 is to evaluate the clinical activity and safety profile of 
PBCAR20A in study subjects with r/r CD20+ NHL including r/r CD20+ CLL/SLL.  
The secondary endpoints for Phase 1 are: 
• ORR:  
− NHL: Lugano 2016 criteria  
− CLL/SLL: International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 
2018 guidelines 
• Progression-free survival (PFS) 
− Defined as the duration (days) from Day 0 to disease progression or death 
• Incidence of AESI, SAEs, and DLTs related to the investigational product 
Additional secondary endpoints for Phase 2a only are: 
• CAR T-cell persistence: 


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a. Defined as detectable CAR T cells in the peripheral blood by qPCR and/or flow 
cytometry at a given study visit time point 
2.2.2. 
Phase 2a 
The secondary objectives of Phase 2a are to characterize the pharmacologic properties and 
evaluate the safety, tolerability, and clinical benefit of PBCAR20A treatment regimens in 
subjects with r/r CD20+ NHL, including CLL/SLL and to generate hypotheses for studies to 
definitively demonstrate efficacy. 
The secondary endpoints for Phase 2a (all arms) are:  
• Duration of Response (DoR) – defined as duration (days) from first date of response 
until disease progression or death 
• Progression-free survival (PFS) 
− Defined as the duration (days) from Day 0 to disease progression or death 
• Incidence of AESI, SAEs, and DLTs related to the investigational product 
The response criteria are detailed in Section 8.1 and Table 12, respectively.  
2.3. 
Exploratory objectives and endpoints 
The exploratory objectives of this study are to evaluate the following:  
• CAR T-cell expansion and persistence: 
− Defined as detectable CAR T cells in the peripheral blood by qPCR and/or flow 
cytometry at a given study visit time point 
• Proportion of study subjects who subsequently receive stem cell transplant  
• Expansion, trafficking, phenotype, and persistence of PBCAR20A  
• Potential development of anti-PBCAR20A immune response  
• Immune cell depletion and reconstitution after lymphodepletion and PBCAR20A 
treatment  
• Potential loss of CD20 expression on leukemia/lymphoma cells  
• Effect of anti-CD20 antibody levels on efficacy 
• Collection of blood and other biological specimens for future research analyses 
The exploratory endpoints will be described in the Statistical Analysis Plan (SAP).  
3. 
STUDY DESIGN 
3.1. 
Overall study design 
This is a Phase 1/2a, nonrandomized, open-label, dose escalation, and dose-optimization study to 
evaluate the safety and clinical activity of PBCAR20A in adults with r/r CD20+ B-cell NHL, 


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including r/r CD20+ CLL/SLL, and identify a treatment regimen to optimize clinical efficacy 
while maintaining a favorable safety profile. The Phase 1 study schematic and Schedule of 
Activities (SoA) are shown in Table 2 and Section 3.1.1, respectively. 
In this protocol amendment (Version 5.0), specific populations have been defined for potential 
enrollment in Phase 2a to evaluate the preliminary efficacy of PBCAR20A using the identified 
RP2D and selected lymphodepletion regimen as well as to further characterize safety profile and 
correlative biology.  
All subjects will receive an intravenous (IV) PBCAR20A on Day 0 of the study. 
Lymphodepletion chemotherapy will also be administered. The initial lymphodepletion 
chemotherapy regimen will be composed of fludarabine (30 mg/m2/day) and cyclophosphamide 
(500 mg/m2/day) during the Screening Period from Days -5 to -3. However, the lymphodepletion 
regimen may be modified if satisfactory CAR T-cell expansion and/or persistence is not 
observed. The lymphodepletion regimen will be assigned at the time of registration to treatment. 
Alternative lymphodepletion strategies will only be employed after safety has been established in 
each dose level. Please refer to the Pharmacy Manual for the specific regimen assigned at the 
time of registration; the lymphodepletion regimen may be discussed between the Sponsor 
Medical Monitor, Principal Investigators, and contract research organization Medical Monitor 
prior to assignment.  
For Phase 2a, the treatment regimen is expected to be uniform for all subjects enrolled into each 
arm.  
Specific criteria must be met for repeat lymphodepletion prior to repeat PBCAR20A infusion. In 
all Phase 1 Dose levels and the Phase 2a Arms, subjects may be considered for retreatment if 
there is documented clinically meaningful response to the initial treatment with PBCAR20A as 
determined by the Investigator; the criteria and procedures for retreatment are described in 
Section 3.7. 
3.1.1. 
Phase 1 (dose escalation): 
In Phase 1, 3 escalating dose groups will be enrolled and treated sequentially, with the possibility 
of a single de-escalation (see Section 3.5). Within each dose group, at least 3 and at most 6 study 
subjects will be treated with a single dose of PBCAR20A using a standard 3 + 3 design. The 
starting dose of PBCAR20A will be 1 × 106 CAR T cells/kg body weight. In the absence of 
DLTs (as described in Section 3.8), subsequent dose groups will be treated with escalating doses 
to a maximum flat dose of 480 × 106 CAR T cells. If no MTD is reached additional dose levels 
may be explored. 
The first treated subject in each dose level (including the dose de-escalation group, i.e., Dose -1) 
will be observed for 14 days for safety before any subsequent subject receives any study 
treatment to provide an adequate safety monitoring window. once the first study subject in each 
dose level has completed Day 14 after dosing with no DLTs, then subsequent subjects can be 
enrolled without delays into that dose level. 
Dose escalation may proceed once safety of the current dose level has been established, which is 
dependent upon the last study participant enrolled in the current dose level completing the 
28-day DLT evaluation period. 


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A DLT is defined as any treatment-emergent adverse event (TEAE) that meets the criteria 
specified in Section 3.8. If a DLT is observed in ≤1 of 3 study subjects at a given dose level, up 
to 3 additional study subjects (for a total of up to 6 study subjects) may be enrolled and treated at 
that dose level. When 3 additional study subjects are added to the dose group, the dose will be 
increased to the next dose level if ≤1 of 6 study subjects experiences a DLT. If ≤2 of the 3 to 6 
study subjects in a dose group experience DLTs, the MTD has been exceeded, and up to 3 
additional study subjects (for a total of 6) will be treated at the previous (lower) dose level.  
The MTD in this study is defined as the highest dose at which ≤1 of 6 study subjects experiences 
a DLT. If the MTD is not exceeded, the sponsor will choose the recommended Phase 2a dose based on 
observations of clinical efficacy, safety, and/or cell kinetics. 
The investigators, medical monitor, and sponsor, designated as the Safety Review Committee 
(SRC) will monitor and convene to review safety data, including any delayed toxicities caused 
by PBCAR20A, at regular intervals to discuss any unexpected significant toxicities and to 
determine whether dose escalation is appropriate.  
After the conclusion of Phase 1, the SRC will convene to determine whether Phase 2 can 
proceed. If DLTs are found to occur predominantly in one subtype of NHL subjects (i.e., those 
with indolent lymphoma, including follicular lymphoma, chronic lymphocytic leukemia/small 
lymphocytic lymphoma, and marginal zone lymphoma or aggressive lymphoma, such as diffuse 
large B cell lymphoma, PMBCL, Burkitt lymphoma, and other high grade T cell lymphomas), 
the possibility of separating the cohorts for dose escalation may be explored. 
Up to 18 subjects total may be enrolled in any given dose level for which safety has been 
established (i.e.,0 of 3 or ≤1 of 6 subjects experiences a DLT) for characterization of the 
pharmacology, safety profile, and clinical benefit profile. These additional 12 subjects (any 
subjects after 
 or , respectively) will not be considered for determination of the MTD 
and can be enrolled without delays into that dose level. In these additional subjects, modified 
lymphodepletion regimens may be employed, as assigned at the time of study registration and 
defined in the Pharmacy Manual, to evaluate regimens which may increase anti-tumor effect and 
improve PBCAR20A cellular kinetics. 
All study subjects are monitored for DLTs and AEs during the Treatment Period through Day 28. 
Study subjects will continue to be monitored for safety after Day 28 and will be followed until 
death, disease progression, stem cell transplant, withdrawal due to intolerable toxicity, 
withdrawal of consent, or Day 360, whichever occurs first.  


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Figure 1: 
Study schema 
 
Abbreviations: ICF=informed consent form. 
 
3.1.2. 
Phase 2a (dose expansion) 
Phase 2a Arms are intended to evaluate preliminary efficacy and further characterize safety in 
specific subject populations. As a result, the inclusion and exclusion criteria for these Arms are 
more specific than Phase 1.  
Phase 2a Arms will use a dose level at or below the MTD established in Phase 1. The dose will 
be determined based on PK/PD analysis, safety evaluation, and preliminary evidence of clinical 
activity. Refer to the Pharmacy Manual for the specific treatment regimen, including 
lymphodepletion, to be used in each Arm.  
All Phase 2a Arms will initiate simultaneously and will enroll in parallel.  
Upon selection of the recommended Phase 2a dose (RP2D) and associated lymphodepletion 
regimen, subjects will be enrolled to characterize clinical efficacy, safety, and pharmacology in 
that population. The populations are defined by the inclusion / exclusion criteria for Phase 2a. 
All subjects in any Phase 2a group are expected to meet all eligibility criteria and be treated in a 
consistent fashion within the group. 
3.1.2.1. 
Phase 2a Arm A Population: CLL/SLL being treated with ibrutinib therapy for 
at least 12 months 
Phase 2a Arm A will enroll subjects with a confirmed diagnosis of CD20+ CLL/SLL who are 
being treated with ibrutinib. Subjects must have started ibrutinib at least 12 months prior to 
treatment with PBCAR20A and must have achieved SD or a PR and be receiving maintenance 
ibrutinib. No prior CR is allowed. Subjects must also have high risk cytogenetics, defined as 
del17p or TP53 mutation. Other inclusion exclusion, in common with Phase 1, are found in 
Section 4.1 and Section 4.2. 
 
3.1.2.2. 
Phase 2a Arm B Population: DLBCL who did not achieve complete response 
after 2 cycles of front-line therapy 
 


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Phase 2a Arm B will enroll subjects with diagnosis of DLBCL who have completed treatment 
with first line chemotherapy (R-CHOP) and have reached PR but not CR. Subjects must have 
evidence of measurable or evaluable disease demonstrating a lack of CR to first line therapy. 
Subjects who have progressed on (are refractory to) first line therapy are not eligible. Other 
medical criteria in common with Phase 1 must be met, as identified in Section 4.1 and 
Section 4.2. 
3.1.2.3. 
Phase 2a Arm C Population: High grade B cell Non-Hodgkin’s Lymphoma 
(NHL) who have previously been treated with autologous CAR T products and 
have subsequently experienced disease progression 
Phase 2a Arm C will enroll subjects who have relapsed or refractory (r/r) high grade B cell 
lymphomas as defined in Section 4.1 who have been previously treated with CD19-targeted 
autologous CAR T therapy. Response to prior CAR T therapy is not required, but subjects must 
have evidence of progressive disease to be eligible. Disease must be measurable or evaluable by 
Lugano Criteria.  
 
3.1.3. 
Long-term follow-up study: 
Study subjects who receive a dose of PBCAR20A will be followed in a separate LTFU, PBCAR-
LTF, study after exiting this study (due to either discontinuation or completion). The LTFU 
study procedures will be described in a separate protocol. 


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3.2. 
Study schedule 
Table 2: 
Study schedule: Phase 1 and 2a 
 
Treatment Period 
Follow-up 
Month 
- 
1 
2 
3 
4 
5 
6 
9 
12 
Day 
-28a 
0 
1 
3 
7 
10 
14 21 28 42 60 
90 120 
150 
180 
270 
360/ 
ET 
Visit window (days) 
 
 
+1 
+1 
±1 
±1 
±2 ±2 ±2 ±5 ±5 ±5 
±5 
±5 
±5 
±7 
±7 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
X 
X 
X 
Full physical 
examination 
X 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
X 
X 
X 
Medical history 
X 
X 
 
 
 
 
 
 
 
Xb Xb 
Xb 
Xb 
Xb 
Xb 
Xb 
Xb 
Viral serologyc 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HLA haplotype 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anti-HLA antibodies 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
Brain MRI 
Xd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lumbar puncture 
(History of CNS 
involvement) 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LVEF (ECHO or 
MUGA) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Treatment Period 
Follow-up 
Month 
- 
1 
2 
3 
4 
5 
6 
9 
12 
Day 
-28a 
0 
1 
3 
7 
10 
14 21 28 42 60 
90 120 
150 
180 
270 
360/ 
ET 
Visit window (days) 
 
 
+1 
+1 
±1 
±1 
±2 ±2 ±2 ±5 ±5 ±5 
±5 
±5 
±5 
±7 
±7 
Serum pregnancy test 
(WOCBP only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical laboratory 
assessmentsf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelg 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG 
(triplicate)i 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECOG Performance 
Status 
X 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
X 
X 
X 
Fludarabine + 
cyclophosphamidej 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study treatment 
administrationk 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study participant diaryl 
 
------------------------X------------------ 
 
 
 
 
 
 
 
 
PET-CT scan (NHL 
only) 
Xm 
 
 
 
 
 
Xn 
 
X 
 
X 
X 
 
 
X 
X 
X 
Tumor/liquid biopsy 
Xo 
 
 
 
 
 
Xp 
Serum and whole blood 
samples for analysesq 
X 
Xr 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Treatment Period 
Follow-up 
Month 
- 
1 
2 
3 
4 
5 
6 
9 
12 
Day 
-28a 
0 
1 
3 
7 
10 
14 21 28 42 60 
90 120 
150 
180 
270 
360/ 
ET 
Visit window (days) 
 
 
+1 
+1 
±1 
±1 
±2 ±2 ±2 ±5 ±5 ±5 
±5 
±5 
±5 
±7 
±7 
BMA/bone marrow 
biopsy (Diagnosed w 
BM involvement)s 
X 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
X 
X 
X 
CT scan (if preferred to 
PET/CT for CLL/SLL 
only) 
X 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
X 
X 
X 
Objective response 
assessment 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
X 
X 
X 
MRD assessmentt 
X 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
X 
X 
X 
Concomitant 
medications 
X 
AE review 
X 
AESIu 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AE=adverse event; AESI=adverse event of special interest; BMA=bone marrow aspiration; CAR=chimeric antigen receptor; CLL=chronic 
lymphocytic leukemia; CNS=central nervous system; CT=computed tomography; DLBCL=diffuse large B-cell lymphoma; ECG=electrocardiogram; 
ECOG=Eastern Cooperative Oncology Group; ECHO=echocardiogram; ET=early termination; eCRF=electronic case report form; HLA=human leukocyte 
antigen; HIV=human immunodeficiency virus; IV=intravenous; LD=lymphodepletion; LVEF=left ventricular ejection fraction; MRI=magnetic resonance 
imaging; MUGA=multigated acquisition scan; NHL=non-Hodgkin lymphoma; PBMC=peripheral blood mononuclear cell; PET=positron emission 
tomography; SLL=small lymphocytic lymphoma; WOCBP=women of childbearing potential. 
a Lymphodepletion regimens will be administered as described in the Pharmacy Manual. 
b Study subjects are asked about the current status of their disease and treatment, including stem cell transplant. 
c Viral screening to include HIV antibody, hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, HLA haplotype, and anti-HLA antibodies. 
d Brain MRI is recommended for all study subjects at Baseline to assess the presence of brain disease or abnormalities. A negative MRI is required at Screening 
for NHL study subjects with a history of CNS disease. An MRI conducted as a part of the routine care within 6 weeks of initiating lymphodepletion 
chemotherapy may be used for Screening. 


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e A negative lumbar puncture is required at Screening only if the study participant has a history of CNS disease. A lumbar puncture conducted as a part of the 
routine care within 6 weeks of initiating lymphodepletion chemotherapy may be used for Screening. 
f Clinical laboratory tests for safety assessments are outlined in Section 7.1.4. Clinical laboratory tests can be performed up to 24 hours before dosing on Day 0. 
g Coagulation panel may be performed after Baseline if the investigator considers it necessary. 
h Vital signs should be measured on the day of dosing at 5 minutes (±2 minutes) before dosing, then at the end of infusion (±5 minutes), 60 minutes after the end 
of infusion (±10 minutes), and 4 hours (±15 minutes) after the end of infusion. Vital signs should also be collected as clinically indicated. 
i Additional ECGs will be collected as clinically indicated. 
j The initial lymphodepletion chemotherapy regimen will be composed of fludarabine (30 mg/m2/day IV) and cyclophosphamide (500 mg/m2/day IV) during the 
Screening Period from Days -5 to -3. However, modified lymphodepletion regimens may be used after safety is established in dose level. The lymphodepletion 
regimen will be specified at the time of registration. Please refer to the Pharmacy Manual for the lymphodepletion dosing regimen; lymphodepletion status may 
be discussed between the Sponsor Medical Monitor, Principal Investigators, and contract research organization Medical Monitor prior to registration. 
k Study subjects are evaluated for the following restrictions 2 hours (±60 minutes) prior to receiving the PBCAR20A infusion: new uncontrolled infection after 
receipt of lymphodepletion, fever, taking any corticosteroid beyond the replacement details, rapid acceleration of malignant disease, and any organ dysfunction 
since Screening. Additional details are provided in Section 5.1.1. At the investigator’s discretion, study subjects may receive premedication 1 hour (±15 
minutes) prior to receiving the PBCAR20A infusion with oral acetaminophen and oral or IV diphenhydramine according to the institutional standards. 
l Study participant diaries will be provided to study subjects on Day 0 to monitor temperature, at least daily, during the first 28 days. 
m . The PET-CT scan conducted as part of the routine care within 4 weeks of PBCAR20A administration may be used for Screening purposes. If the scan is 
performed as a part of routine care, the result will be obtained from the study participant’s physician or medical record. 
n A PET-CT scan on Day 14 is optional and will be determined by the investigator. Additional details are provided in Section 8.4. 
o Screening tumor biopsy may be omitted if a study participant has had a biopsy showing CD20+ disease within 6 months before Screening and has not received 
any anti-CD20+ therapy since then. Note: If the tumor is CD20-negative by flow cytometry, it should be evaluated by immunohistochemistry as flow assays 
may result in false negatives due to competition with CD20 targeting treatment antibodies (e.g. rituximab). 
p  Tumor biopsy may be performed to confirm imaging changes as clinically indicated. Additional biopsies may be performed pending Sponsor approval. 
q Exploratory analyses will be performed by the central laboratory. Additional analyses performed at the site that are not required by the protocol should be 
captured in the eCRF. 
r Blood samples will be collected before PBCAR20A administration on Day 0. 
s If available, the central laboratory will also test fresh BMA or bone marrow core samples for CAR T cells. 
t MRD assessment will be performed at Screening for all study subjects. Please consult the Laboratory Manual for specific sample requirements at Screening. At 
subsequent visits, MRD assessment will only be performed for study subjects who meet other standard response criteria (see Section 8.1). Please consult the 
Laboratory Manual for specific sample requirements at all subsequent visits. Note that these samples are disease-specific and may be different between 
Screening and all subsequent visits. 
u AESIs are listed in Section 7.2.1.3. 
 


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3.3. 
Number of subjects 
Phase 1 (dose escalation): Approximately 9 to 30 evaluable subjects are planned to be enrolled 
in the dose escalation phase of the study. 
Phase 2a (dose expansion): Each arm may enroll up to 20 subjects for a total of up to 60 
subjects. Futility may be determined in a rolling fashion at the sponsor’s discretion.  
3.4. 
Number of Study Centers 
Approximately 10-15 study centers in the United States. 
3.5. 
Discussion of study design and dose justification 
This is a first-in-human, Phase 1/2a study intended primarily to evaluate the safety and 
tolerability of PBCAR20A in study subjects with NHL including CLL/SLL. A single-arm, open 
label design has been chosen because of the early stage of development and the need for close 
monitoring for safety. This study is not controlled because of the serious nature of the conditions 
being studied and the lack of alternative therapies. 
Unlike small molecules and biologic drugs, optimum dosing in adoptive cell therapy (ACT) 
cannot be determined using classical pharmacokinetic (PK)/pharmacodynamic parameters based 
on body weight or body surface area (BSA). This is because cellular immunotherapies are 
“living” drugs that may expand within a patient following administration. Cellular 
immunotherapies, such as CAR T-cell products, are not metabolized in the liver or excreted by 
the kidney, and the sites and volume of distribution are not clearly understood. Therefore, dosing 
of CAR T-cell therapies based on weight or BSA is not driven by a clear understanding of PK 
parameters. Furthermore, the relationship between toxicity and therapeutic activity is not 
monotonic for ACTs. According to the FDA’s guidance, “…conventional allometric scaling 
methods for cell and gene therapy (CGT) products may be less precise than for small molecule 
drugs, and traditional PK and pharmacodynamic correlations might not be possible. Therefore, it 
may be difficult to establish an initial starting dose based on the considerations used for small-
molecule drugs. If available, previous clinical experience with the CGT product or related 
products, even if by a different route of administration or for a different condition, might help to 
justify the clinical starting dose” (FDA, 2015). 
Dose-finding trials in oncology are designed to find the MTD, the highest dose at which the 
observed toxicity rate is less than a prespecified target probability. A starting dose that is thought 
to be safe in humans is normally selected based on a combination of PK, pharmacodynamics, 
toxicity, and efficacy observations in animal models of human disease. However, in the case of 
CAR T-cell therapies, there is no relevant species other than humans that can be used to model 
drug safety and efficacy. Observations of toxicity or efficacy based on doses of human CAR 
T cells administered to immunodeficient mice bearing human tumors are useful as qualitative 
indicators of the likelihood of toxicity or efficacy in humans, but those data cannot be 
quantitatively translated (i.e., allometrically scaled) in selecting a safe starting dose in humans.  
In this study, we selected a starting dose, dose-escalation intervals, and 4 dose levels (including 
possible de-escalation) to be evaluated in Phase 1 based upon toxicity observed in 


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immunodeficient mice (tumor bearing and nontumor bearing) that were administered various 
doses of PBCAR20A, as well as on the observations of toxicity and antitumor activity in human 
clinical studies of autologous anti-CD20 CAR T-cell treatments. For example, doses as high as 
1.0 × 107 PBCAR20A CAR T cells (equivalent to 5.0 × 108 cells/kg in humans based solely on 
mg/kg conversion) were administered to immunodeficient mice bearing disseminated human 
lymphoma tumors without signs of toxicity, while doses in an order of lower magnitude still 
provided for significant antitumor efficacy. The potential for PBCAR20A to cause GvHD was 
evaluated in a xenogeneic mouse model in which doses as high as 3.0 × 107 PBCAR20A cells, 
the equivalent of 1.2 × 109 cells/kg in a human (based solely on cells/kg conversion), were 
administered without any signs of development of GvHD. Several studies involving HLA 
nonidentical stem cell transplant procedures have concluded that a threshold of approximately 
5.0 × 104 residual CD3+ donor T cells/kg can be contained within the donor graft without 
significant risk of resulting GvHD (Muller et al, 1999; Aversa et al, 1998). The proposed starting 
dose of PBCAR20A for this study is 1 × 106 CAR T cells/kg of body weight. This dose would 
contain 1.5 to 6.0 × 103 residual CD3+ T cells/kg, which is within the range considered to be a 
low risk for GvHD based on literature from unrelated donor bone marrow and stem cell 
transplants (Muller et al, 1999), and thus, should not represent a significant risk for causing 
GvHD in an HLA-mismatched host.  
The proposed starting dose and the dose-escalation intervals are also supported by observations 
of safety and efficacy in clinical trials of autologous anti-CD19 CAR T cells in adult and 
pediatric study subjects with r/r ALL and r/r NHL. Greater emphasis was given to trials of 
autologous CAR T-cell products in which the CD19-targeting moiety (FMC63 murine 
antihuman-CD19 single-chain variable fragment [scFv]) and signaling domains (4-1BB + CD3ζ) 
are more similar to the CAR construct of PBCAR0191, namely Novartis’ CTL019 
(tisagenlecleucel) and Juno Therapeutics’ JCAR017; however, dosing information for Kite 
Pharmaceuticals KTE-19 (axicabtagene ciloleucel), an autologous anti-CD19 CAR T-cell 
product in which the CAR construct consists of FMC63 scFv and CD28 and CD3ζ signaling 
domains, was also considered. For each of these CAR T-cell therapies, total doses of between 
1 × 107 and 6 ×108, with target doses of between 1 × 106 and 1 × 107 CAR T cells/kg, have been 
used in the clinic in adult subjects and resulted in acceptable levels of toxicity and a high rate of 
efficacy in terms of complete remissions. Our proposed starting dose at 1 × 106 CAR T cells/kg 
falls below this range and is expected to provide an opportunity for meaningful efficacy while 
preserving a significant margin for safety.  
The initial lymphodepletion regimen (fludarabine [30 mg/m2/day] and cyclophosphamide 
[500 mg/m2/day]) in this study is a common conditioning treatment before CAR T-cell therapy 
(Locke et al, 2017). The need to explore additional dosing and lymphodepletion regimens is 
based on findings from the currently ongoing PBCAR0191-01 study, in which PBCAR0191 has 
been well tolerated across doses ranging from 3 x 105 cells/kg to 6 x 106 cells/kg : as of 06 
November 2020, 27 subjects enrolled in the PBCAR0191-01 study across Dose Levels 1-4 have 
completed Day 28, all with no observations of GvHD and no Grade ≥3 CRS or ICANS. 
Similarly, PBCAR20A has been well tolerated in the subjects enrolled to date across doses 
ranging from 1 x 106 to 3 x 106 cells/kg, with 1 Grade 3 ICANS event was observed in a patient 
enrolled in Dose level 1 that was downgraded to Grade 2 within 24 hours. The classical 
development model for a novel therapy would be to increase the dose until either toxicity or 
maximum clinical benefit is reached; thus, the protocol was modified (Version 4.0) based on 




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Figure 2: 
Dose escalation algorithm 
 
Abbreviations: DLT=dose-limiting toxicity; MTD=maximum tolerated dose. 
*If at 480 × 106 cells (Dose 3), this would be the MTD. 
 
Phase 2a (dose optimization): 
Arms in Phase 2a will use a dose at or below the MTD as determined in Phase 1. The dose will 
be determined based on PK/PD analysis, safety evaluation, and preliminary evidence of clinical 
activity. Refer to the Pharmacy Manual for the specific dose and treatment regimens to be used 
in each Arm. Phase 2a Arms are described in Section 3.1.2. 
3.7. 
Retreatment criteria 
Retreatment refers to the specific scenario in which a subject receives all planned treatment and 
has some evidence of benefit followed by evidence of disease progression.  
All subjects will receive PBCAR20A as per Table 2. A subject may receive an additional dose of 
PBCAR20A if he/she meets retreatment criteria as determined by the investigator and agrees to 
be retreated.  
Subjects are eligible for retreatment only if the following criteria are met: 
• Subject has documented evidence of clinically meaningful tumor response to initial 
dose of PBCAR20A followed by documented either a disease progression at 
subsequent visit or has residual disease. 
Subject has biopsy-proven CD20+ tumor prior to re-treatment, unless it is deemed not safe by 
multi-disciplinary team, Subject has no evidence of GvHD and no new unresolved disease-


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related central nervous system (CNS) involvement that in the opinion of the investigator would 
impair the assessment of neurotoxicity events. 
• Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function as 
defined in Section 4.1. 
• Subject has not received another systemic treatment for NHL. 
Subjects who meet the retreatment criteria and have had a study visit within 30 days will undergo 
lymphodepletion chemotherapy and follow the SoA from the beginning. Subjects who meet the 
retreatment criteria and have discontinued the study will need to be re-enrolled into an open slot 
(Phase 1 or Phase 2a). Retreatment visits, starting from lymphodepletion visits, will be 
distinguished from initial visits in the electronic case report form (eCRF). 
Subjects eligible for retreatment may receive PBCAR20A at the highest dose level with 
established safety (see Section 3.1).  
 
3.8. 
Criteria for DLTs 
During the DLT period (28 days after dosing the last subject in a dose level), severity grades will 
be determined using the National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE) version 5.0 unless otherwise specified.  
Regardless of the investigator attribution or unless there is a clear alternative explanation, a DLT 
is defined as any of the following TEAEs:  
• CRS (per American Society for Transplantation and Cellular Therapy [ASTCT] 
consensus grading; see Section 7.3.1):  
− Any Grade 4 
− Any Grade 3 that does not resolve or reduce to Grade ≤2 within 72 hours of onset  
• GvHD: Acute GvHD Grade ≥2 regardless of the organ involved that does not resolve 
with appropriate treatment within 14 days. 
• Any Grade ≥3 neurotoxicity (per American Society for Transplantation and Cellular 
Therapy [ASTCT] ICANS criteria provided in Table 15) that does not resolve or 
reduce to Grade ≤2 within 72 hours of onset. 
• Any seizure 
• Grade 3 or 4 infusion reactions related to the study treatment that does not resolve or 
decrease to Grade ≤2 within 48 hours 
• Any Grade 4 hematologic toxicity, except lymphopenia, that does not resolve or 
decrease to Grade ≤2 within 42 days 
• Any Grade 4 non-hematologic toxicity  
• Any Grade 3 toxicity involving heart and lungs 


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• Any Grade 3 toxicity involving kidney and liver that does not resolve or reduce 
Grade ≤2 within 7 days of onset 
• Any Grade 3 toxicity to other organs that does not resolve or reduce Grade ≤2 within 
72 hours of onset  
• Any Grade 5 toxicity that was not due to underlying malignancy 
If an AE is clearly due to progressive or underlying disease and unrelated to the study treatment, 
the event would not be considered a DLT.  
3.9. 
Criteria for treatment interruption  
The infusion of PBCAR20A should be interrupted immediately if the following situation occurs:  
• Severe hypersensitivity reaction, including anaphylaxis 
The investigator will evaluate the study participant and determine whether the infusion can be 
resumed or should be permanently discontinued. If infusion is resumed, study subjects should 
receive the remainder of the dose not yet administered at one-half the rate of the initial infusion. 
If the infusion will not be completed within 2 hours from thawing, a new dose should be 
prepared for the remainder. If not already administered within 2 hours of restarting infusion, a 
minimum dose of 25 mg diphenhydramine (oral) should be administered prior to restarting 
infusion. 
3.10. 
Criteria for temporarily suspending treatment 
In addition to the staggered dosing schedule (14 days between the first 2 study subjects in each 
dose group, including the dose de-escalation group if applicable), dosing in all study subjects, 
regardless of cohort and dose group, will temporarily stop if any of the following events occur:  
• Any Grade 4 toxicity that is possibly or probably related to PBCAR20A 
• Grade ≥3 GvHD 
• Any death that is possibly or probably related to the study treatment  
Investigators and the medical monitor will conduct a comprehensive assessment of the event, the 
causal relationship to study treatment, and cumulative evidence of toxicity to determine whether 
the study can continue.  
3.11. 
Criteria for study termination 
The study can be terminated by the sponsor, Safety Review Committee, Institutional Review 
Board (IRB), or FDA at any time.  
4. 
SELECTION AND WITHDRAWAL OF STUDY SUBJECTS 
4.1. 
Inclusion criteria 
Study subjects are eligible to be included in the study only if all of the following criteria apply: 
Criteria for NHL (Phase 1): 


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1. Subject has r/r CD20+ B-cell NHL that is histologically confirmed by archived tumor 
biopsy tissue from the last relapse and corresponding pathology report. Alternatively, if at 
least 1 tumor involved site is accessible at Screening, the subject’s diagnosis will be 
confirmed by pretreatment biopsy (excisional when possible). If a subject never had a 
complete response (CR) during prior lines of therapy, a sample from the most recent 
biopsy is acceptable. 
2. Measurable or detectable disease (positron emission tomography [PET]-positive) with 
evidence of disease progression after most-recent therapy according to the Lugano 
classification. 
3. Primary refractory disease or r/r disease after treatment with 2 prior regimens, unless per 
standard of care treatment guidance (e.g., National Comprehensive Cancer Network 
[NCCN]) no second line therapy of known benefit exists. Subjects including but not 
limited to those with the following types of lymphoma and have received the associated 
standard therapies are eligible:  
• Primary mediastinal B-cell lymphoma (PMBCL)/follicular lymphoma (FL) 
including Grade 3B or transformed FL/high-grade B-cell lymphoma/diffuse large 
B-cell lymphoma (DLBCL) including Richter’s transformation. Subjects must 
have received rituximab or other anti-CD20 antibody and anthracycline-based 
chemotherapy. All subjects should be evaluated for approved anti-CD19 CAR T-
cell therapy when applicable. 
• Indolent B-cell lymphoma (Grades 1, 2, and 3A)/transformed CLL 
(Richter’s)/marginal zone lymphoma. Subjects must have received 2 prior lines of 
systemic therapy including an alkylator (e.g., bendamustine, 
cyclophosphamide/vincristine/ prednisone) plus an anti-CD20 antibody and have 
had documented disease progression. 
• Subjects with r/r Burkitt’s lymphoma must have failed 1 prior therapy. 
• MCL. Subjects must have received 2 prior lines of systemic therapy including 
chemotherapy (bendamustine/rituximab; rituximab, cyclophosphamide, 
doxorubicin, vincristine, and prednisone (R-CHOP); or Nordic-type regimen) 
with or without autologous stem cell transplant (ASCT) and a Bruton’s tyrosine 
kinase (BTK) inhibitor (e.g., ibrutinib, acalabrutinib) and have had documented 
disease progression. 
Criteria for CLL/SLL (Phase 1): 
4. Diagnosis of CD20+ CLL with indication for treatment based on the International 
Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines and clinically 
measurable disease or CD20+ SLL (lymphadenopathy and/or splenomegaly and <5 × 109 
CD19+ and CD5+ clonal B cells/L in peripheral blood at diagnosis) with measurable 
disease that is biopsy-proven SLL. 
5. Subjects with CLL/SLL must have previously progressed following at least 2 prior lines 
of systemic targeted therapy including a BTK inhibitor and venetoclax ± rituximab. 
Criteria for Phase 2a Arm A: 
6. Diagnosis of CD20+ CLL/SLL for which subject is currently receiving, and has been 
receiving for at least 12 months, ibrutinib therapy as standard of care, regardless of line 


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of therapy, with best response of partial response or stable disease (no CR or CRi). 
Subjects must have high risk disease, as defined by deletion 17p or TP53 mutation.  
Criteria for Phase 2a Arm B: 
7. Diagnosis of CD20+ DLBCL with PET/CT indicating a partial response, but not a 
complete response, per Lugano 2016 criteria (Cheson JCO 2016), after completion of 
upfront chemoimmunotherapy (R-CHOP, per NCCN 2020 NHL Guidelines). Subjects 
who had refractory disease to (progressive disease through) upfront treatment are not 
eligible. 
Criteria for Phase 2a Arm C: 
8. Diagnosis of CD20+ high-grade B cell lymphoma after previous treatment with 
autologous CD19-targeted CAR T therapy, regardless of response.  
Criteria for all subjects (Phase 1 and 2a):  
9. Subject has CD20+ tumor. Note: If the tumor is CD20-negative by flow cytometry, it 
should be evaluated by immunohistochemistry as flow assays may result in false 
negatives due to competition with CD20 targeting treatment antibodies (e.g., rituximab). 
10. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status score 
of 0 or 1. 
11. Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function 
defined as: 
• Estimated glomerular filtration rate >30 mL/min/1.73 m2 (calculated using the 
Chronic Kidney Disease Epidemiology Collaboration equation). A 24-hour urine 
collection for creatinine clearance may be used at the investigator’s discretion.  
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels 
both ≤3 times the upper limit of normal (ULN), unless there is suspected disease 
(tumor) in the liver. 
• Total bilirubin <2.0 mg/dL, except in subjects with Gilbert’s syndrome, who must 
have total bilirubin ≤3 × ULN, or except those with disease (tumor) in the liver. 
• Platelet count ≥50,000/µL and ANC of ≥1000/ µL. Transfusions within 14 days 
of screening are not allowed, except for patients in B-ALL or NHL cohorts with 
high marrow disease burden (>70%) in which case it must be discussed with 
medical monitor. In the case of extensive bone marrow disease burden, adequate 
bone marrow recovery after prior treatment is required to be documented. 
• Left ventricular ejection fraction (LVEF) >45% as assessed by an echocardiogram 
(ECHO) or multiple gated acquisition (MUGA) scan performed within 1 month 
before starting lymphodepleting chemotherapy. The ECHO results performed 
within 6 months before Screening and at least 28 days after the last cancer 
treatment may be acceptable if the subject has not received any treatment with 
cardiotoxicity risks. 
• No evidence of pericardial effusion or pleural effusion causing clinical symptoms 
and needing immediate intervention. Any known effusion must be stable without 
need for drainage within 2 weeks of enrollment. 


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• Baseline oxygen saturation >92% on room air. 
Subject characteristics 
12. Subject must be 18 years of age or older at the time of signing the informed consent form. 
13. Any sex. 
14. All subjects must be willing to practice birth control and refrain from donating sperms or 
oocytes from the time of enrollment in this study through 3 months after receiving the 
study treatment. 
15. Women of childbearing potential (WOCBP) must be tested negative for pregnancy at 
Screening because of the potentially harmful effects of the preparative chemotherapy to 
the fetus. The WOCBP are defined as any women who are not postmenopausal or who 
have not had a hysterectomy. Postmenopausal is defined as women over the age of 55 
years who have not had a menstrual period for at least 1 year. 
16. Capable of giving signed informed consent. 
4.2. 
Exclusion criteria: 
Subjects are excluded from the study if any of the following criteria apply: 
Criteria for NHL (Phase 1 and 2a): 
17. Requirement for urgent therapy due to mass effects such as bowel obstruction, spinal 
cord, or blood vessel compression.  
 
 
Criteria for NHL and CLL/SLL (Phase 1 and 2a): 
18. Any history of central nervous system (CNS) disease. If active CNS involvement is suspected, a 
negative lumbar puncture is required at Screening. 
19. Subject has had a malignancy, besides the malignancies of inclusion (B-cell NHL or 
CLL/SLL), that in the investigator’s opinion, has a high risk of relapse in the next 
2 years.  
20. Recent, clinically significant fungal, bacterial, viral, protozoal, or other infection 
requiring therapeutic anti-microbial medications within 7 days of lymphodepletion. Note: 
subjects with elevated or rising C-reactive protein (CRP) must undergo infectious disease 
(ID) workup and recommendations must be discussed with the medical monitor. CRP 
must be trending toward the normal range for the laboratory. Simple urinary tract 
infection and uncomplicated bacterial pharyngitis are permitted if the subject is 
responding to active treatment and with medical monitor approval.  
21. Any form of primary immunodeficiency (e.g., severe combined immunodeficiency 
disease).  
22. History of human immunodeficiency virus (HIV) infection. 
23. Active hepatitis B or hepatitis C confirmed by polymerase chain reaction (PCR). Subjects 
testing positive for inactive hepatitis B will be allowed to enroll if on prophylactic 
treatment.  


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24. Any known uncontrolled cardiovascular disease at the time of Screening that, in the 
investigator’s opinion, is clinically significant and renders the subject ineligible. 
25. History of hypertension crisis or hypertensive encephalopathy within 3 months prior to 
Screening.  
26. History of severe immediate hypersensitivity reaction to any of the agents used in this 
study.  
27. Presence of a CNS disorder that, in the opinion of the investigator, renders the subject 
ineligible for treatment. 
28. Abnormal findings during the Screening Period or any other medical condition(s) or 
laboratory findings that, in the opinion of the investigator, might jeopardize the subject’s 
safety.  
29. History of a genetic syndrome such as Fanconi anemia, Kostmann syndrome, 
Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome.  
Prior/concomitant therapy (Phase 1 and 2a) 
30. Subjects who have received ASCT within 45 days of Screening are excluded. 
31. Subjects who have received systemic corticosteroid (greater than physiologic 
replacement) therapy for at least 7 days prior to initiating lymphodepletion chemotherapy 
are excluded.  
32. Subjects who have received a live vaccine within 4 weeks before Screening are excluded. 
Non-live virus vaccines are not excluded.  
33. Subjects undergoing Radiotherapy to target lesions within 4 weeks before Screening are 
excluded. 
34. Subjects who have an indwelling catheter (i.e., pleural, peritoneal, pericardial as well as 
biliary and ureteral stents) are excluded. This does not apply to intravenous lines.   
Other exclusions (Phase 1 only) 
35. Subjects are excluded unless there has been documented progression of the disease after 
prior most recent systemic anti-cancer therapeutic agents and resolution of adverse events 
caused by their administration.  
 
Other exclusions (Phase 2a Arm A) 
36. Subjects are excluded specifically form Arm A if they have:  
a. Previous CR has been achieved with ibrutinib therapy. Note: progression is not 
required for enrollment if stable disease or partial response has been achieved and 
maintained.  
b. Ongoing grade ≥ 2 non-hematologic toxicity related to ibrutinib. 
c. High-grade transformed disease (e.g., Richter’s transformation) 
Other exclusions (Phase 2a Arm B) 
37. Subjects are excluded specifically from Arm B if: 


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d. Diagnosis is transformed high grade lymphoma (e.g., Richter’s transformation or 
transformed follicular lymphoma) 
Other exclusions (Phase 1 and 2a) 
38. Pregnant or breastfeeding women.  
39. In the investigator’s judgment, the subject is unlikely to complete all protocol required 
study visits or procedures, including follow-up visits, or is unlikely to comply with the 
study requirements for participation. 
40. Any mental condition rendering the subject unable to understand the nature, scope, and 
possible consequences of the study, and/or evidence of an uncooperative attitude. 
4.3. 
Screening  
4.3.1. 
Screening procedures 
After signing the ICF, potential study subjects will be screened (starting at Day -28) for 
eligibility to participate in the prior to receiving lymphodepletion chemotherapy (Day -5). The 
Screening procedures are listed in the SoA (Table 2). 
Brain MRI is required at Screening for all NHL study subjects with a history of CNS disease 
who have not had an MRI within 6 weeks of initiating lymphodepletion chemotherapy.  
Screening PET-CT scan for NHL subjects should be performed prior to initiating 
lymphodepletion treatment. The PET-CT scan conducted as a part of the routine care within 
4 weeks of PBCAR20A administration may be used for Screening purposes. If the scan is 
performed as a part of routine care, the result will be obtained from the study participant’s 
physician or medical record. 
Recent tumor biopsy results, obtained within 6 months before study entry, are acceptable to 
confirm histological diagnosis, provided the study participant has not received any anti-CD20 
therapy between the time of the biopsy and study entry.  
4.3.2. 
Screen failures 
Screen failures are defined as study subjects who consent to participate in the clinical study but 
are not subsequently enrolled or treated. A minimal set of screen failure information is required 
to be recorded at the site to ensure transparent reporting of screen failure subjects to meet the 
Consolidated Standards of Reporting Trials publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any serious adverse event (SAE). 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Rescreened study subjects should be assigned the same study participant number as 
for the initial screening. 


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4.4. 
Study discontinuation or withdrawal 
Study interventions, including lymphodepletion and PBCAR20A administration, should be 
discontinued by the investigator if the investigator believes that it is in the best interest of the 
study participant or if any of the following situations occur:  
• Disease progression; subjects should complete the 28-day safety evaluation period if 
possible 
• Death 
• Initiation of another systemic treatment for NHL, SLL, or CLL 
• Investigator’s decision 
• Study participant noncompliance/protocol violations 
• Study terminated by sponsor (see Section 3.11) 
• Study participant withdrawal (see Section 4.4.1) 
• Lost to follow-up (see Section 4.4.2) 
Upon completion, study subjects will be followed in a separate LTFU study. 
4.4.1. 
Study participant withdrawal 
A study participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
If the study participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
If a study participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the investigator must document this in the site study records. 
4.4.2. 
Lost to follow-up 
A study participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study center.  
The following actions must be taken if a study participant fails to return to the study center for a 
required study visit: 
• The site must attempt to contact the study participant to reschedule the missed visit as 
soon as possible, counsel the study participant on the importance of maintaining the 
assigned visit schedule, and ascertain whether the study participant wishes to and/or 
should continue in the study. 
• Before a study participant is deemed lost to follow-up, the investigator or designee 
must make every effort to regain contact with the study participant (where possible, 
3 telephone calls and, if necessary, a certified letter to the study participant’s last 
known mailing address or local equivalent methods). These contact attempts should 
be documented in the study participant’s medical record. 


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• Should the study participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study. 
4.5. 
Study completion 
A subject is considered to have completed the study’s primary evaluation if he/she has completed 
Day 28. Subjects experiencing disease progression prior to day 28 should continue on the study 
through Day 28 to allow for completion of study’s primary evaluation as long as another 
systemic therapy is not started. A subject is considered to have completed the entire study if the 
subject is followed according to the protocol to the Day 360 visit, disease progression, death, or 
receiving a new treatment for the diagnosed malignancy (including stem cell transplant), 
whichever occurs first.  
5. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to the 
study protocol. 
5.1. 
Description of study treatment 
In this study, treatments include the investigational product, PBCAR20A, and lymphodepletion 
chemotherapy agents, fludarabine and cyclophosphamide. 
5.1.1. 
Pre-infusion restrictions 
Before receiving the PBCAR20A infusion, each study participant will be evaluated for the 
following restrictions. If any of the restrictions are met, the infusion will not be given, and the 
investigator should discuss with the medical monitor to reschedule or suspend the study 
treatment in the study participant.  
• New uncontrolled infection after receipt of lymphodepletion chemotherapy 
• Fever (body temperature ≥38.0°C) 
• Taking any corticosteroid beyond the replacement dose (masking of fever in 
neutropenic study subjects) 
• Rapid acceleration of malignant disease 
• Any organ dysfunction since Screening 


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5.1.2. 
Study treatments 
Study treatments to be administered are outlined in Table 4. In Phase 1, the lymphodepletion 
regimen will be administered as described in the pharmacy manual. In Phase 2a, doses will be 
provided in the pharmacy manual and confirmed prior to subject starting treatment. 
Table 4: 
List of study treatments 
Study treatment 
PBCAR20A 
Fludarabine 
Cyclophosphami
de 
Sirolimus 
Dosage 
formulation 
A vial of 
cryopreserved 
solution for IV 
infusion 
Commercial 
product 
Commercial 
product 
Commercial 
product 
Route of 
administration  
IV 
IV 
IV 
tablets 
Dosing 
instruction 
Per Pharmacy 
Manual 
Per institutional 
guidelines 
Per institutional 
guidelines 
Per institutional 
guidelines 
Packaging and 
labeling 
PBCAR20A 
will be 
provided in 
cryopreserved 
vials as 
described in 
Section 6.1  
Commercial 
product 
Commercial 
product 
Commercial 
product 
Manufacturer 
Precision 
BioSciences, 
Inc. 
N/A 
N/A 
N/A 
Abbreviations: CAR=chimeric antigen receptor; IV=intravenous; N/A=not applicable. 
5.1.3. 
Hospitalization 
Study subjects with Burkitt lymphoma or high tumor burden DLBCL/Richter’s transformation 
CLL should receive prophylaxis for tumor lysis syndrome (including rasburicase, if indicated) 
and be hospitalized to undergo frequent monitoring (chemistries, lactate dehydrogenase [LDH], 
and uric acid every 6 hours for up to 96 hours post-treatment). If tumor lysis does occur, there 
should be aggressive correction of electrolytes. 
For the remaining study subjects, inpatient hospitalization is generally not required for any 
component during the study. However, the investigator may choose to hospitalize study subjects 
based on his or her clinical judgment regarding the risks of tumor lysis syndrome or other 
conditions. 


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5.2. 
Concomitant medications 
Medications used for the management of AEs may be provided by the investigator according to 
institution guidelines and will be recorded as concomitant medications in the electronic Case 
Report Form (eCRF), but these treatments are not considered study treatments. 
5.2.1. 
Premedication 
Before the administration of PBCAR20A, premedication according to institutional standards 
may be given at the investigator’s discretion. 
5.2.2. 
Prohibited medications and substances 
Study subjects must not receive corticosteroids at doses higher than 5 mg/day of prednisone or 
equivalent at any time after the CAR T-cell infusion, except when medically necessary. 
Study subjects must not receive filgrastim during the immediate pre-infusion period from 
Days -7 to 0 and post-infusion for 10 days, except when medically necessary. 
Study subjects must not receive any additional anticancer therapy, except those expressly 
intended by the protocol (e.g. ibrutinib in Arm A), without prior discussion with the medical 
monitor. 
Study subjects are prohibited from excessive use of alcohol (defined as 4 or more alcoholic 
drinks per day) and from any use of illegal drugs. 
5.3. 
Treatment compliance 
Study personnel are required to record the date, time, study intervention (including fludarabine 
and cyclophosphamide), and dose administered to each study participant in the eCRF. 
5.4. 
Randomization and blinding 
Not applicable. This is a nonrandomized, open-label study.  
6. 
MATERIALS AND MANAGEMENTOF INVESTIGATIONAL 
PRODUCT 
6.1. 
Investigational Product 
Cryopreserved PBCAR20A allogeneic T cells will be supplied in 6 mL vials and stored in the 
vapor phase of liquid nitrogen.  
6.2. 
Investigational product storage 
PBCAR20A vials will be stored in the vapor phase of liquid nitrogen (temperature not to exceed 
130°C). The manufactured drug product will be stored centrally (Fisher BioServices) and 
delivered to study centers. Individually overwrapped vials will be stored in a box in racks in the 
manufacturer-supplied dry shipper package, which can be held for up to 21 days prior to dosing; 
sites that are able to store the drug product in liquid nitrogen will not be limited by this duration. 


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The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatment received and any discrepancies are reported and 
resolved prior to study treatment administration. 
6.3. 
Investigational product handling, preparation, and administration 
Personal protective gear should be worn when opening the shipper and boxes to remove the 
vials. Thawing instructions are specified in the Pharmacy Manual. 
Only study subjects enrolled in the study may receive study intervention and only authorized 
study staff may supply or administer study intervention. All study intervention must be stored in 
a secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the investigator and authorized study 
staff. 
Detailed instructions for the preparation and handling of PBCAR20A and information for the 
final disposition of unused study interventions are provided in the Pharmacy Manual for 
PBCAR20A. The study is not randomized or controlled. 
6.4. 
Investigational product accountability 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for the study treatment accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records). 
7. 
ASSESSMENT OF SAFETY 
7.1. 
Safety parameters 
Planned time points for all safety assessments are provided in the Table 2. Institutions should 
follow institutional guidelines for monitoring CAR T-cell infusion-related side effects. Study 
participant diaries will be provided to subjects to monitor temperature, at least daily, during the 
first 28 days. 
7.1.1. 
Vital signs 
Temperature, pulse rate, respiratory rate, and blood pressure will be assessed at the time points 
listed in Table 2. 
7.1.2. 
Physical examination 
A complete physical examination will include, at a minimum, assessments of the cardiovascular, 
respiratory, gastrointestinal, and neurological systems. Height and weight will also be measured 
and recorded. 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 


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7.1.3. 
Electrocardiogram 
Single 12-lead electrocardiograms (ECGs) will be obtained at time points listed in Table 2 using 
an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, QTc, 
and QT corrected by Fredericia (QTcF) intervals.  
The ECGs are required to be done in triplicate; 3 individual ECG tracings should be obtained as 
closely as possible in succession, but no more than 2 minutes apart. The full set of triplicates 
should be completed in less than 4 minutes. 
7.1.4. 
Laboratory assessments 
Clinical laboratory tests can be performed up to 24 hours before dosing on Day 0. The tests listed 
below will be performed by local laboratories.  
Hematology: 
• Hemoglobin  
• Hematocrit 
• Red blood cell count and indices: 
− Mean corpuscular volume 
− Mean corpuscular hemoglobin 
• White blood cell count (WBC) with differential: 
− Neutrophils 
− Lymphocytes 
− Monocytes 
− Eosinophils 
− Basophils 
• Platelets  
Biochemistry:  
• Serum cytokines (when part of standard study site practice; additional biomarkers 
will be tested for exploratory purposes) 
• Sodium 
• Potassium 
• Calcium 
• Chloride 
• Glucose  
• Total protein 
• Creatinine  


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• Blood urea nitrogen 
• Total and direct bilirubin 
• AST/serum glutamic-oxaloacetic transaminase 
• ALT/serum glutamic-pyruvic transaminase 
• Alkaline phosphatase 
• LDH 
• C-reactive protein (CRP) 
• Ferritin 
Urinalysis:  
• Specific gravity 
• pH, glucose, protein, blood, ketones by dipstick 
• Microscopic examination (if blood or protein is abnormal) 
Recommended coagulation panel (coagulation panel may be performed after Baseline if 
investigator considers it necessary): 
• Prothrombin time 
• Activated partial thromboplastin time 
• D dimer 
• Fibrinogen 
Other Screening tests:  
• Serum or urine pregnancy test 
• Serology:  
− HIV (antibody)  
− Hepatitis B surface antigen  
− Hepatitis B core (antibody)  
− Hepatitis C virus ([HCV]; antibody, then HCV ribonucleic acid by PCR if 
antibody is positive)  
− HLA haplotype 
− Anti-HLA antibodies 
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes that meet the definition of AEs in the eCRF. The laboratory reports 
must be filed with the source documents. Clinically significant abnormal laboratory findings are 
those that are not associated with the underlying disease, unless judged by the investigator to be 
more severe than expected for the study participant's condition. 


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All laboratory tests with values considered clinically significantly abnormal during participation 
in the study should be repeated weekly until the values return to normal/Baseline or are no longer 
considered clinically significant by the investigator or medical monitor. 
If clinically significant abnormal values do not return to normal/Baseline within a period of time 
judged reasonable by the investigator, the etiology should be determined, and the sponsor should 
be notified. 
If laboratory values from non-protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in study participant management or are considered 
clinically significant by the investigator (e.g., SAE or AE or dose modification), then the results 
must be recorded in the eCRF. 
7.1.5. 
Immunogenicity 
Blood samples will be collected from all study subjects according to Table 2 and analyzed at the 
local laboratory. These samples may be tested for immune reactivity against PBCAR20A when 
PBCAR20A is not detectable at early time points after administration. Blood samples may also 
be tested by local laboratories for donor-specific HLA antibodies.  
Blood samples should also be collected at the final visit and shipped to the central laboratory for 
study subjects who have discontinued study treatment or withdrawn from the study.  
7.2. 
AEs and SAEs 
7.2.1. 
Definition of AEs 
7.2.1.1. 
AE 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation study 
participant administered a pharmaceutical product, which does not necessarily have to have a 
causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporally associated with 
the use of a medicinal product, whether or not considered related to the medicinal product. 
All AEs will be collected from the initiation of lymphodepletion chemotherapy until death, 
disease progression, subsequent systemic therapy, withdrawal due to intolerable toxicity, 
withdrawal of consent, or Day 360, whichever occurs first and be recorded in the eCRF, 
regardless of whether or not they are related to the study treatment. All AEs collected through 
Day 28 will be used for assessment of DLTs; any AEs occurring after Day 28 will be considered 
in dose-escalation decisions and monitoring procedures as appropriate. 
All AEs, including SAEs, that occur after signing the ICF and before administration of any 
protocol-specified treatment will be recorded as Medical History in the appropriate eCRF. 
7.2.1.2. 
SAE 
An SAE is an AE occurring during the study and at any dose of the investigational product, 
comparator, or placebo that fulfills at least 1 of the following: 
• Results in death 


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• Is immediately life-threatening 
• Requires in-patient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
• Results in a congenital abnormality or birth defect 
• Is an important medical event that may jeopardize the study participant or may 
require medical intervention to prevent one of the outcomes listed above 
All SAEs that occur during the AE review period as noted above must be recorded in the eCRF, 
whether or not they are related to the study treatment. 
7.2.1.3. 
Adverse events of special interest 
The following adverse events of special interest (AESIs) are AEs that are of particular concern in 
CAR T-cell therapy: 
• CRS  
• ICANS (note: in the event of encephalitis, notify sponsor within 24 hours) 
• GvHD 
Because AESIs may theoretically occur after Day 28, AESIs will be assessed separately from 
AEs. Study subjects will be assessed for AESI from the administration of PBCAR20A through 
Day 360. Any occurrence of an AESI will be monitored closely until stabilization or resolution.  
See Section 7.2.5 for additional details regarding reporting AESIs.  
7.2.2. 
Assessment of intensity 
The investigator will assess the intensity of each AE reported during the study based on the NCI 
CTCAE version 5.0 (NCI CTCAE, 2018). If an AE is not addressed in NCI CTCAE, intensity 
will be assessed according to the standards presented in Table 5. It is important to note that an 
AE of severe intensity may not necessarily be considered serious (refer to SAE criteria in 
Section 7.2.1.2). 
The intensity of AEs and SAEs related to CRS and ICANS will be assessed based on the ASTCT 
grading and management recommendations (see Table 7 and Table 8, respectively). 


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Table 5: 
Assessment of AE intensity 
Intensity grade 
Intensity assessment standard 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
Grade 2 
Moderate; minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate instrumental ADL.a 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL.b 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE. 
Abbreviations: ADL=activities of daily living; AE=adverse event; CTCAE=Common Terminology Criteria for 
Adverse Events. 
a Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc. 
b Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
Source: NCI CTCAE, version 5.0 (NCI CTCAE, 2018). 
7.2.3. 
Relationship to study treatment 
An investigator must make the determination of relationship to the investigational product for 
each AE (“related” or “not related”) according to the definitions and guidance provided in 
Table 6. The investigator should decide whether, in his or her medical judgment, there is a 
reasonable possibility that the event may have been caused by the study treatment. If no valid 
reason exists for suggesting a relationship, then the AE should be classified as “not related.” If 
there is any valid reason, even if undetermined, for suspecting a possible cause-and-effect 
relationship between the investigational product and the occurrence of the AE, then the AE 
should be considered “related.” 
Table 6: 
Relationship assessment definitions 
Relationship assessment 
Definition/guidance 
Not related 
 
Event or laboratory test abnormality, with a time to drug intake that 
makes a relationship unlikely; is more likely explained by disease or 
other drugs. 
Related 
Event or laboratory test abnormality with reasonable time relationship 
to treatment administration that makes a relationship likely. 
Unlikely to be attributed to disease or other medications.  
7.2.4. 
Recording AEs 
AEs spontaneously reported by the subject and/or in response to an open question from the study 
staff or revealed by observation will be recorded during the study at the study center. Abnormal 
values that constitute an AE or lead to discontinuation of the administration of the study 
treatment must be reported and recorded as an AE. The AE term should be reported in standard 


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medical terminology when possible. For each AE, the investigator will evaluate and report the 
onset (date and time), resolution (date and time), intensity, causality, action taken, outcome, and 
whether it caused the study participant to discontinue the study. 
It is important to distinguish between serious and severe AEs. Severity is a measure of intensity 
whereas seriousness is defined by the criteria presented in Section 7.2.2. An AE of severe 
intensity may or may not be considered serious.  
7.2.5. 
Reporting AEs 
The sponsor is responsible for notifying both the local regulatory authority and other regulatory 
agencies about the safety of a study intervention under clinical investigation. The sponsor will 
comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB, and investigators. 
The IND safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary. 
An investigator who receives a safety report describing an SAE or other specific safety 
information (e.g., summary or listing of SAEs) from the sponsor will review and file it along 
with the IB and notify the IRB, if appropriate, according to local requirements. 
Expedited reporting to the FDA will be conducted for the following types of AEs: 
• SUSAR 
• Serious adverse reaction 
• Death regardless of attribution if it occurs within 30 days of the infusion of the study 
treatment 
• Grade ≥4 PBCAR20A-related infusion reactions  
• Any ICANS or CRS event that reaches the definition of DLT (see Section 3.8) 
7.2.6. 
Disease-related events and/or disease-related outcomes that do not qualify as 
AEs or SAEs 
Disease-related events (DREs) that are common in the study population, i.e., study subjects with 
r/r NHL or r/r CLL/SLL, can be serious and life-threatening (shown below). However, because 
these events are typically associated with the disease under study and with prior treatment, they 
may not be reported as individual case safety reports even though the event may be listed in the 
study reference safety information. These events will be recorded in the corresponding eCRF 
page in the study participant’s eCRF during the study.  
DREs and prior treatment-related events:  
• Progression of the underlying disease. 
• Cytopenias related to bone marrow involvement due to the underlying disease, 
including thrombocytopenia, anemia, neutropenia, lymphopenia. 


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• Infections associated with disease-related immunodeficiencies and due to extensive 
prior chemotherapy of the underlying disease. These include fever and bacterial, 
fungal, and viral infections. These infections may develop at various sites, but most 
typically develop in blood (bacteremia, fungemia), lungs (pneumonia), urinary tract 
(urinary tract infection, pyelonephritis), and skin and soft tissues. These infections 
may be caused by opportunistic pathogens, e.g., aspergillosis, pneumocystis, herpes 
simplex, and herpes zoster infections.  
• Bleeding related to thrombocytopenia or a bleeding diathesis including bleeding in 
the CNS, lungs, or other sites. 
NOTE: However, the event must be recorded as an SAE and not a DRE if investigator 
considers that there is a reasonable possibility that the event was related to the study 
treatment based on greater intensity, frequency, or duration than expected for the individual 
study participant. 
Such an event will then be assessed for expedited reporting and reported within regulatory 
timelines if it meets the IND Safety Reporting criteria per 21 Code of Federal Regulations (CFR) 
312.32.  
DREs will be assessed at least monthly to determine if there is a greater incidence of any DRE 
than would be expected from historical rates in study subjects with r/r NHL, r/r CLL, and 
r/r SLL. If such an imbalance is identified, the case series will be reported as an IND Safety 
Report per 312 CFR 312.32. 
7.2.7. 
Pregnancy 
Details of all pregnancies in female study subjects and, if indicated, female partners of male 
study subjects will be collected throughout the study (through Day 360). 
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of learning 
of the pregnancy and should follow the procedures outlined in Appendix 1. 
Pregnancy in itself is not regarded as an AE; however, complications of pregnancy or certain 
pregnancy outcomes may constitute an AE. Contraceptive failure attributed to the investigational 
product may be an AE. 
The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth, or 
congenital abnormality) must be followed up and documented even if the study participant was 
discontinued from the study. 
All reports of congenital abnormalities/birth defects will be considered SAEs. Spontaneous 
miscarriages should also be reported and handled as SAEs. Elective abortions without 
complications should not be handled as AEs. 
7.3. 
Management of CRS, ICANS, and GvHD 
Once discharged from the study center or hospital, study subjects will be advised to maintain 
ready access to a caregiver and health care facilities (recommend access to treating hospital 
within 30 minutes of driving) through Day 28 in the event of a medical emergency.  


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Educational material will be provided to each study participant/caregiver to monitor for possible 
signs of CRS, ICANS, and GvHD at home, along with instructions to contact the study center or 
local hospital as needed. 
7.3.1. 
CRS 
CRS is identified based on clinical presentation. Investigators will evaluate and treat other causes 
of fever, hypoxia, and hypotension. Key manifestations include high fever, lower than normal 
blood pressure, difficulty breathing, and may be associated with hepatic, renal, and cardiac 
dysfunction, and coagulopathy. Risk factors for severe CRS are high pre-infusion tumor burden 
(>50% blasts in bone marrow), uncontrolled or accelerating tumor burden following 
lymphodepleting chemotherapy, active infections, and/or inflammatory processes. Infusion of 
PBCAR20A should be delayed if the study participant has unresolved serious adverse reactions 
from preceding chemotherapy or worsening tumor burden. CRS is associated with significantly 
elevated cytokines including interleukin (IL)-10, IL-6, and interferon (IFN)-ɣ. In subjects with 
CRS, IL-6 levels are elevated during maximal T-cell proliferation. Targeting IL-6 by using IL-6 
inhibitor tocilizumab showed rapid reversal of CRS in subjects treated with CAR T cells and 
blinatumomab (Teachey et al, 2013). Tocilizumab (Actemra®) IV injection has been approved 
for the treatment of CAR T cell-induced severe or life-threatening CRS in subjects 2 years of age 
or older.  
In this study, study subjects will be closely monitored for CRS and managed according to 
severity defined by the ASTCT consensus grading (Lee et al, 2019). The CRS grading and 
management recommendations are outlined in Table 7; complete ASTCT CRS consensus 
grading is provided in Table 14. Treatment with tocilizumab, or a combination of tocilizumab 
and corticosteroids if indicated, will be provided if CRS is suspected. Study subjects who 
experience Grade 2 or higher CRS (e.g., hypotension that is not responsive to fluids, or hypoxia 
requiring supplemental oxygenation) should be monitored with continuous cardiac telemetry and 
pulse oximetry. For study subjects experiencing severe CRS, consider performing an ECHO to 
assess cardiac function. For severe or life-threatening CRS, consider intensive care supportive 
therapy. 


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Table 7: 
CRS grading and management recommendations 
ASTCT CRS Grade 
Management 
Grade 1 
Fever with temperature ≥38°C but no 
hypotension or hypoxia 
• 
Antipyretics and IV hydration 
• 
Diagnostic work-up to rule out infection 
• 
Consider growth factors and antibiotics if 
neutropenic to address neutropenic fever 
Grade 2 
Fever (≥38°C) with hypotension not requiring 
vasopressors and/or hypoxia requiring 
low-flow nasal cannula 
• 
Supportive care as in Grade 1 
• 
IV fluid boluses and/or supplemental oxygen 
• 
Tocilizumaba ± dexamethasone or its equivalent 
of methylprednisolone 
Grade 3 
Fever (≥38°C) with hypotension requiring a 
vasopressor with or without vasopressin, 
and/or hypoxia requiring high-flow nasal 
cannula, facemask, nonrebreather mask, or 
Venturi mask 
• 
Supportive care as in Grade 1 
• 
Consider monitoring in intensive care unit 
• 
Vasopressor support and/or supplemental oxygen 
• 
Tocilizumaba + dexamethasone 1 to 20 mg IV 
every 6 hours or its equivalent of 
methylprednisolone 
Grade 4 
Fever (≥38°C) with hypotension requiring 
multiple vasopressors (excluding vasopressin) 
and hypoxia requiring positive pressure (e.g., 
CPAP, BiPAP, intubation, mechanical 
ventilation) 
• 
Supportive care as in Grade 1 
• 
Monitoring in intensive care unit 
• 
Vasopressor support and/or supplemental oxygen 
via positive pressure ventilation 
• 
Tocilizumaba + methylprednisolone 1000 mg/day 
Abbreviations: ASTCT=American Society for Transplantation and Cellular Therapy; BiPAP=bilevel positive 
airway pressure; CPAP=continuous positive airway pressure; CRS=cytokine release syndrome; IV=intravenous. 
a Tocilizumab 8 mg/kg IV over 60 min or per institutional standards. If no clinical improvement in signs/symptoms 
of CRS after first dose, up to 3 additional doses may be administered with at least 8 hours between consecutive 
doses. 
7.3.2. 
ICANS 
ICANS, which can be fatal or life-threatening, has been observed following administration of 
anti-CD20 CAR T therapies. In the majority of cases, ICANS occurs within the first 8 weeks 
following CAR T-cell infusion and can be concurrent with CRS. The most common symptoms 
include headache, encephalopathy, tremor, dizziness, delirium, aphasia, insomnia, and anxiety. 
Study subjects should be monitored for signs and symptoms of ICANS for 4 weeks after 
administration of PBCAR20A infusion and treated promptly if indicated; ASTCT ICANS 
grading and management guidelines are outlined in Table 8 (Lee et al, 2019). Complete ASTCT 
ICANS consensus grading is provided in Table 15. Other causes of neurologic symptoms should 
be ruled out. Study subjects with Grade ≥2 ICANS should be monitored with continuous cardiac 
telemetry and pulse oximetry. Intensive care support should be provided for study subjects with 
severe or life-threatening ICANS, and best care should be provided according to the 
investigator’s experience. Investigators should consider non-sedating, anti-seizure medicines 
(e.g., levetiracetam) for seizure prophylaxis for Grade ≥2 ICANS.  


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Table 8: 
ASTCT ICANS grading and management guidelines 
ASTCT ICANS 
grade  
Defining features of grade 
Management 
Grade 1 
• 
ICE score 7 to 9 and/or depressed 
level of consciousness but awakens 
spontaneously  
• 
No seizures, motor weakness, or 
raised ICP/cerebral edema 
• 
Aspiration precautions and IV 
hydration 
• 
Seizure prophylaxis with 
levetiracetam 
• 
EEG  
• 
Imaging of brain 
• 
Consider tocilizumab if there is 
concurrent CRS 
Grade 2 
• 
ICE score 3 to 6 and/or depressed 
level of consciousness but awakens 
to voice 
• 
No seizures, motor weakness, or 
raised ICP/cerebral edema 
• 
Supportive care as in Grade 1 
• 
Consider dexamethasone or its 
equivalent of methylprednisolone 
Grade 3 
• 
ICE score 0 to 2 and/or depressed 
level of consciousness but awakens 
to tactile stimulus 
• 
Any clinical seizure focal or 
generalized that resolves rapidly; or 
nonconvulsive seizures on EEG that 
resolve with intervention  
• 
No motor weakness 
• 
Focal/local edema on neuroimaging 
 
 
• 
Supportive care as in Grade 1 
• 
Dexamethasone 10 to 20 mg IV 
every 6 hours or its equivalent of 
methylprednisolone 
• 
Control seizures with 
benzodiazepines (for short-term 
control) and levetiracetam 
± phenobarbital and/or lacosamide 
• 
Dexamethasone 10 to 20 mg IV 
every 6 hours or its equivalent of 
methylprednisolone 
• 
High-dose methylprednisolone 1000 
mg/day 


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ASTCT ICANS 
grade  
Defining features of grade 
Management 
Grade 4 
• 
ICE score 0 and study participant is 
unarousable or requires vigorous or 
repetitive tactile stimuli to arouse or 
stupor or coma  
• 
Life-threatening prolonged seizure 
(>5 minutes); or repetitive clinical 
or electrical seizures without return 
to Baseline in between  
• 
Deep focal motor weakness such as 
hemiparesis or paraparesis  
• 
Diffuse cerebral edema on 
neuroimaging; decerebrate or 
decorticate posturing; or cranial 
nerve VI palsy; or papilledema; or 
Cushing's triad 
 
• 
Supportive care as in Grade 1 
• 
High-dose methylprednisolone 1000 
mg/day  
• 
Control seizures with 
benzodiazepines (for short-term 
control) and levetiracetam 
± phenobarbital and/or lacosamide 
• 
Imaging of spine 
• 
Lower ICP by hyperventilation, 
hyperosmolar therapy with 
mannitol/hypertonic saline, and/or 
neurosurgery consultation for 
ventriculoperitoneal shunt 
Abbreviations: ASTCT=American Society for Transplantation and Cellular Therapy; CRS=cytokine release 
syndrome; EEG=electroencephalogram; ICANS=immune effector cell-mediated neurotoxicity syndrome; 
ICE=immune effector cell-associated encephalopathy; ICP=intracranial pressure; IV=intravenous. 
7.3.3. 
GvHD 
Study subjects who develop GvHD will be assigned a single grade based on organ involvement 
and severity according to Jacobsohn and Vogelsang (2007) (Table 9). Whenever possible, the 
clinical diagnosis of a GvHD should be confirmed by biopsy of an affected end organ, and other 
complications affecting the skin, liver, and gastrointestinal tract should be ruled out by 
appropriate testing.  


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Table 9: 
GvHD grading system based on organ involvement 
Grade 
 
 
 
I 
Stages 1 to 2 skin, none in liver and gut 
II 
Stage 3 skin or Stage 1 liver or Stage 1 gut 
III 
Stages 2 to 3 liver or Stages 2 to 4 gut  
IV 
Stage 4 skin or Stage 4 liver 
Stage 
Skin 
Liver (bilirubin) 
Gut (stool output/day) 
0 
No GvHD rash 
<2 mg/dL 
<500 mL/day or persistent 
nausea 
1 
Maculopapular rash <25% 
BSA 
2 to 3 mg/dL 
500 to 999 mL/day 
2 
Maculopapular rash 25% to 
50% BSA 
3.1 to 6 mg/dL 
1000 to 1500 mL/day 
3 
Maculopapular rash >50% 
BSA 
6.1 to 15 mg/dL 
Adult: >1500 mL/day 
4 
Generalized erythroderma 
plus bullous formation 
>15 mg/dL 
Severe abdominal pain with 
or without ileus 
Abbreviations: BSA=body surface area GvHD=graft-versus-host disease. 
Treatment for GvHD should follow the established institutional guidelines or the consensus by 
National Institutes of Health (Carpenter et al, 2015) (Table 10). Decisions to begin treatment 
depend not only on the severity of GvHD manifestations but also on the rate of progression. 
Rapidly progressing GvHD manifestations require prompt treatment (Martin et al, 2012). 
 
Table 10: 
GvHD management recommendations 
Organ system 
Prevention 
Treatment 
Skin and 
appendages 
Photoprotection – sun avoidance and 
physical sunblockers (e.g., protective 
clothing, UVA, and UVB sunscreens). 
Avoidance of photosensitizing agents 
(e.g., voriconazole). 
Surveillance for malignancy.  
For intact skin – topical emollients 
including urea-containing products, 
corticosteroids, antipruritic agents, and 
others (e.g., PUVA or narrow band 
UVB, calcineurin inhibitors). 
For erosions/ulcerations – 
microbiologic cultures, topical 
antimicrobials, protective films or 
other dressings, debridement, 
hyperbaric oxygen, wound care 
specialist consultation. 
Mouth and oral 
cavity 
Maintain good oral/dental hygiene. 
Routine dental cleaning and radiographs. 
Surveillance for infection and malignancy. 
Topical high and ultra-high potency 
corticosteroids and topical calcineurin 
inhibitors. Topical analgesics. Therapy 
for oral dryness (e.g., salivary 


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Organ system 
Prevention 
Treatment 
Nutritional counseling, if needed. 
stimulants, sialogogues) and for 
prevention of related complications 
(i.e., dental decay). 
Eyes 
Photoprotection. Surveillance for 
infection, cataract formation, and 
increased intraocular pressure. 
Artificial tears, ocular ointments, 
topical corticosteroids or cyclosporine, 
punctal occlusion, humidified 
environment, occlusive eye wear, 
moisture chamber eyeglasses, 
cevimeline, pilocarpine, gas-permeable 
scleral contact lens, autologous serum, 
microbiologic cultures, topical 
antimicrobials, doxycycline. 
Vulva and 
vagina 
Surveillance for estrogen deficiency, 
infection (herpes simplex virus, human 
papilloma virus, yeast, bacteria), and 
malignancy.  
Water-based or silicone lubricants, 
topical estrogens, topical 
corticosteroids or calcineurin 
inhibitors, dilators or vibrators, surgery 
for extensive synechiae or obliteration, 
early gynecology consultation. Avoid 
glycerin, paraben, fragrance, and other 
additive products.  
Gastrointestinal 
tract and liver 
Surveillance for infection (viral, bacterial, 
fungal, parasites).  
Rule out other potential etiologies. 
Dietary modification, enzyme 
supplementation for pancreatic 
insufficiency, bile salt resins, 
gastroesophageal reflux management, 
esophageal dilatation, ursodeoxycholic 
acid, topical glucocorticoids, limitation 
of ethanol/intake, avoidance of 
hepatotoxins. 
Lungs 
Surveillance for infection (Pneumocystis 
jirovecii, viral, fungal, bacterial). 
Rule out other potential etiologies 
(e.g., infection, gastroesophageal 
reflux). Inhaled corticosteroids, 
bronchodilators, supplementary 
oxygen, pulmonary rehabilitation. 
Consideration of lung transplantation 
in appropriate candidates. 
Hematopoietic 
Surveillance for infection 
(cytomegalovirus, parvovirus). 
Rule out other potential etiologies 
(e.g., drug toxicity, infection). 
Hematopoietic growth factors, 
immunoglobulin for immune 
cytopenias.  
Neurologic 
Calcineurin drug level monitoring. Seizure 
prophylaxis as indicated, including blood 
pressure control, electrolyte replacement, 
anticonvulsants. Electromyography 
monitoring and staging in symptomatic 
Occupational and physical therapy to 
prevent falls and improve function, 
treatment of neuropathic syndromes 
with tricyclic antidepressants, SSRI, or 
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Organ system 
Prevention 
Treatment 
study subjects taking medications known 
to cause neuropathy. Close monitoring of 
distal extremities for wounds in insensate 
study subjects. 
Orthotics and assistive devices (canes 
and walkers). Bracing, splinting or 
surgical release for entrapment 
neuropathies. 
Immunologic 
and 
infectious 
diseases 
Immunizations and prophylaxis against 
Pneumocystis jirovecii, varicella zoster 
virus, and encapsulated bacteria based on 
CDC guidelines. Consider 
immunoglobulin replacement based on 
levels and recurrent infections. 
Surveillance for infection (viral, bacterial, 
fungal, atypical). 
Organism-specific antimicrobial 
agents. Empiric parenteral broad-
spectrum antibacterial coverage for 
fever. 
Musculoskeletal Surveillance for decreased range of 
motion, bone densitometry, calcium levels 
and 25-OH vitamin D. Physical therapy, 
calcium, vitamin D, and bisphosphonates. 
Flexion-extension X-rays to look for 
instability. 
Physical therapy, bisphosphonates for 
osteopenia, and osteoporosis. Spinal 
orthosis for instability and/or 
intractable pain. Walking program, 
resistance training, core strengthening. 
Abbreviations: CDC=Centers for Disease Control; GvHD=graft-versus-host disease; PUVA=psoralen and 
ultraviolet A; SSRI=selective serotonin reuptake inhibitor; UVA=ultraviolet A; UVB=ultraviolet B. 
 
8. 
ASSESSMENTS OF CLINICAL ACTIVITY 
8.1. 
Assessment of response 
Blood samples will be drawn from study subjects at time points indicated in Table 2 to measure 
complete blood count (CBC), WBC with differentials, and CAR T cells. The criteria for response 
are outlined below. 
MRD assessment will be performed at Screening for all study subjects. The MRD assessment 
method and status for study subjects with a CR will be determined as clinically indicated using 
flow cytometry, qPCR, Next Generation Sequencing, or by local institutional standard. 
Acceptable samples for MRD assessment include BMA or PBMCs for study subjects with CLL, 
plasma for study subjects with DLBCL, and PBMCs for study subjects with NHL (including 
SLL). Further details for sample preparation and shipping are specified in the Laboratory 
Manual. 
NHL 
The response criteria for local and central assessments of study subjects with NHL are based on 
the revised Lugano classification (Cheson et al, 2016), which incorporates PET-CT (Table 11). 


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The PET-CT scan or CT scan for study subjects without PET-avid tumors will be performed for 
NHL study subjects at time points specified in the study schedules, Section 3.2.  
The ORR is the rate of CR + PR. 
Table 11: 
Revised Lugano classification of response 
Response and site 
PET-CT-based response 
Complete 
Complete metabolic response. 
 
Lymph nodes and 
extralymphatic sites 
Score 1, 2, or 3 with or without a residual mass on 5PS. 
It is recognized that in Waldeyer’s ring or extranodal sites with high 
physiologic uptake or with activation within spleen or marrow (e.g., with 
chemotherapy or myeloid colony-stimulating factors), uptake may be greater 
than normal mediastinum and/or liver. In this circumstance, complete 
metabolic response may be inferred if uptake at sites of initial involvement is 
no greater than surrounding normal tissue even if the tissue has high 
physiologic uptake. 
New lesions 
None. 
Bone marrow 
No evidence of FDG-avid disease in marrow. 
Partial 
Partial metabolic response. 
Lymph nodes and 
extralymphatic sites 
Score 4 or 5 with reduced uptake compared with Baseline and residual 
mass(es) of any size. 
At interim, these findings suggest responding disease. 
At end of treatment, these findings indicate residual disease. 
New lesions 
None. 
Bone marrow 
Residual uptake higher than uptake in normal marrow but reduced compared 
with Baseline (diffuse uptake compatible with reactive changes from 
chemotherapy allowed). If there are persistent focal changes in the marrow in 
the context of a nodal response, consideration should be given to further 
evaluation with MRI or biopsy or an interval scan.  
No response or 
stable disease 
No metabolic response. 
Target nodes/nodal 
masses, extranodal 
lesions 
Score 4 or 5 with no significant change in FDG uptake from Baseline at 
interim or end of treatment. 
New lesions 
None. 
Bone marrow 
No change from Baseline. 
Progressive disease 
Progressive metabolic disease. 
Individual target 
nodes/nodal masses 
Score 4 or 5 with an increase in intensity of uptake from Baseline and/or new 
foci compatible with lymphoma. 
Extranodal lesions 
New FDG-avid foci consistent with lymphoma at interim or end-of-treatment 
assessment. 


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Response and site 
PET-CT-based response 
Nonmeasured lesions 
None. 
New lesions 
New FDG-avid foci consistent with lymphoma rather than another etiology 
(e.g., infection, inflammation). If uncertain regarding etiology of new lesions, 
biopsy or interval scan may be considered. 
Bone marrow 
New or recurrent FDG-avid foci. 
Abbreviations: 5PS=5-point scale; CT=computed tomography; FDG=fluorodeoxyglucose; MRI=magnetic 
resonance imaging; PET=positron emission tomography. 
Note: PET 5-point scale: 1, no uptake above background; 2, uptake ≤ mediastinum; 3, uptake > mediastinum but 
≤ liver; 4, uptake moderately > liver; 5, uptake markedly higher than liver and/or new lesions; X, new areas of 
uptake unlikely to be related to lymphoma. 
 
CLL/SLL 
The response criteria for local and central assessments of subjects with CLL/SLL are based on 
the iwCLL 2018 guidelines as outlined in Table 12.  
Table 12: 
iwCLL definition of response 
Group 
Parameter 
CR 
PR 
PD 
SD 
A 
Lymph nodes 
None ≥1.5 cm 
Decrease ≥50% 
from Baselinea 
Increase ≥50% 
from Baseline or 
from response 
Change of -49% to 
+49% 
Liver and/or 
spleen sizeb 
Spleen size 
<13 cm; liver size 
normal 
Decrease ≥50% 
from Baseline 
Increase ≥50% 
from Baseline or 
from response 
Change of -49% to 
+49 
Constitutional 
symptoms 
None 
Any 
Any 
Any 
Circulating 
lymphocyte 
count 
Normal 
Decrease ≥50% 
from Baseline 
Increase ≥50% 
from Baseline 
Change of -49% to 
+49 
B 
Platelet count 
≥100 × 109/L 
≥100 × 109/L or 
increase ≥50% 
over Baseline 
Decrease of ≥50% 
from Baseline 
secondary to CLL 
Change of -49% to 
+49 
Hemoglobin 
≥11.0 g/dL 
(untransfused and 
without 
erythropoietin) 
≥11.0 g/dL or 
increase ≥50% 
over Baseline 
Decrease of 
≥2 g/dL from 
Baseline 
secondary to CLL 
Increase 
<11.0 g/dL or 
<50% over 
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Marrow 
Normocellular, no 
CLL cells, no 
B-lymphoid 
nodules 
Presence of CLL 
cells, or of 
B-lymphoid 
nodules, or not 
done 
Increase of CLL 
cells by ≥50% on 
successive 
biopsies 
No change in 
marrow infiltrate 
Abbreviations: CLL=chronic lymphocytic leukemia; CR=complete response; CT=computed tomography; 
iwCLL=International Workshop on Chronic Lymphocytic Leukemia; PD=progressive disease; PR=partial response; 
SD=stable disease; SLL=small lymphocytic lymphoma 
a Sum of the products of 6 or fewer lymph nodes as evaluated by CT scans and physical examination. 
b Spleen size is considered normal if <13 cm as evaluated by imaging and manual palpation. 
8.2. 
Expansion, persistence, and phenotype of PBCAR20A 
For exploratory purposes and to understand basic PK and pharmacodynamic properties, 
including persistence, PBCAR20A cells will be measured in whole blood, tumor tissue and bone 
marrow specimens using quantitative polymerase chain reaction (qPCR) and flow cytometry by 
the central laboratory, if available.  
The phenotype of PBCAR20A cells in blood, tumor tissue and bone marrow samples will be 
evaluated by flow cytometry evaluating the expression of markers of T-cell maturation such as 
CD45RO and CD45RA, CCR7 or CD62L, CD25, and HLA-DR. 
Instructions for blood sample collection and tumor tissue or bone marrow samples (when 
available) and shipping to the central laboratory will be provided in the Laboratory Manual.  
8.3. 
CRS biomarkers 
Thirty cytokines and other potential markers for CAR toxicities, including IFN-γ, IL-6, and CRP 
(through Day 28) in blood samples will be quantified using a multiplex 
electrochemiluminescence assay (Cytokine Panel 1, Chemokine Panel 1, and Proinflammatory 
Panel 1 from Meso Scale Discovery) enzyme-linked immunosorbent assay at the time points 
noted in the study schedules, Section 3.2. 
Most exploratory analyses are performed by the central laboratory and a select few will be 
performed at local laboratories; instructions for collecting and shipping whole blood samples for 
exploratory testing are described in the Laboratory Manual. 
8.4. 
PET-CT scan 
PET-CT scan should be performed at least 7 days prior to study treatments. If the scan is 
performed as a part of routine care, the result will be obtained from the subject’s physician or 
medical record. 
A PET-CT scan on Day 14 is optional and will be determined by the investigator. Whenever 
possible, the CT scan performed as part of the PET-CT scan should be of diagnostic quality 
(performed with contrast and with slice thickness ≤5 mm). If the CT scan performed in the 
PET-CT scan is not of diagnostic quality, a diagnostic quality CT scan is required to be 
performed at the same time as the PET-CT scan. 


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8.5. 
BMA/bone marrow biopsy and analysis 
Bone marrow aspiration (BMA) and/or biopsy (unless clinically contra-indicated, or against 
institutional guidelines) should be performed during the Screening Period before 
lymphodepletion to determine if cytopenias are related to leukemic infiltration of the marrow in 
study subjects with CLL/SLL.  
On Day 28, BMA and biopsy (unless clinically contra-indicated) should be performed to 
measure the tumor burden and to assess the presence of PBCAR20A cells in bone marrow in all 
CLL/SLL study subjects according to the timepoints indicated in the study schedule in 
Section 3.2. A marrow biopsy is mandatory to confirm a CR in CLL/SLL subjects (see 
Section 3.2). During study visits at 1, 2, 3, 6, 9, and 12 months or at the time of disease relapse, 
BMA and biopsy (unless clinically contra-indicated) will be performed in all subjects with 
previous evidence of bone marrow disease and if it is clinically indicated.  
The BMAs/biopsies will be analyzed using smears and flow cytometry by the local laboratories. 
If BMA/biopsy samples are available and sent to the central laboratory, they will be tested for 
the presence of PBCAR20A. 
In addition, the bone marrow aspirates collected at each time point will be analyzed by the 
central laboratory for MRD in study subjects with CLL/SLL with a CR (see Section 8.1).  
8.6. 
Tumor biopsy 
Core needle biopsies (ideally 4 will be obtained) may be performed in study subjects with mass 
lesions at any time at least 14 days post-treatment and/or as clinically indicated. For lymph 
nodes, an excisional biopsy is preferred.  
A tumor biopsy may be performed to confirm imaging changes as clinically indicated. 
Additional biopsies may be performed pending Sponsor approval. Any tumor tissue that remains 
following a biopsy may be sent to the central laboratory. Please consult the Laboratory Manual 
for specific sample requirements and shipping information. 
9. 
STATISTICS 
9.1. 
General statistical methods 
This is a Phase 1/2a, multicenter, nonrandomized, single-dose, open-label study that will employ 
the 3 + 3 dose-escalation (Phase 1) design and subsequent dose expansion (Phase 2a). 
Results of statistical analyses, descriptive statistics will be presented by PBCAR20A Phase 1 
Dose or by Phase 2 Arm. In addition, descriptive statistics will be calculated for subjects across 
all PBCAR20A Phase 1 dose levels. Supporting listings will be sorted by Phase, Subject ID and 
Dose/Arm. 
Statistical analysis for all safety and efficacy parameters will be primarily descriptive in nature. 
Categorical variables will be summarized by frequency distributions (number and percentages of 
study subjects). Continuous variables will be summarized by mean, standard deviation, median, 
minimum, maximum, and time-to-event variables will be summarized using Kaplan-Meier 
methods and figures for the estimated median time. No formal statistical hypothesis testing is 


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planned; however, if exploratory analyses are conducted and confidence intervals (CIs) are 
provided for estimates, the 95% CIs are consistent with a 2-sided 5% significance level. All 
analyses, summaries, and listings will be performed using SAS® (Cary, North Carolina) 
software (version 9.4 or higher). 
A detailed methodology for summary and statistical analysis of the data collected in this study 
will be documented in an SAP that will be finalized prior to database lock. The SAP may modify 
the data analysis plans outlined in the protocol; any modifications will be clearly documented in 
the SAP. Any major modifications of the study design or study endpoints and/or its analysis will 
also be reflected in a protocol amendment. 
9.2. 
Sample size considerations 
Phase 1 (dose escalation): 
Subjects will be enrolled in dose groups with 3 to 6 subjects for each dose. Dose escalation of 
PBCAR20A will follow a standard 3 + 3 design with sequential groups of 3 subjects treated with 
incrementally higher doses of PBCAR20A until a DLT is observed and the MTD is established 
(see Section 3.1). Per the standard oncology 3 + 3 Phase 1 dose-escalation design, the total 
number of subjects to be enrolled cannot be precisely determined because the sample size is 
dependent upon the observed safety profile, which will determine the number of subjects per 
dose group and the number of dose escalations required to achieve the MTD.  
For Phase 1, 4 dose levels may be tested. It is anticipated that approximately 9-30 study subjects 
will be required to reach the MTD.  
Phase 2a (dose expansion):  
Enrollment in Phase 2a will begin once the MTD has been determined in Phase 1. A sample of 
20 subjects per Arm will evaluate clinical benefit and further characterize safety and  
pharmacologic properties in specific populations of subjects and allow for the estimation of an 
ORR within 22% using a 95% CI. 
A total of up to 60 subjects will be enrolled for Phase 2a dose optimization. The data collected 
from subjects enrolled in the dose expansion will be used to confirm safety, explore potential 
biomarkers, and evaluate potential signals of activity of PBCAR20A. 
Under Simon’s two stage the minimax design calculation in nQuery, assuming the minimum 
meaningful clinical response rate is defined as 40% versus maximum ineffective rate of 15%, a 
sample size of 19 is required to test a null hypothesis of H₀: π ≤ 0.15 versus an alternative 
hypothesis of H₁: π ≥ 0.4 with a one-sided significance level of 0.05 and 81.32% power, where π 
is the true proportion of response.  
If the number of responses is less than or equal to 1 out of 9 subjects in the first stage then the 
Arm will be stopped. If the Arm proceeds to the second stage, 19 subjects in total will be needed 
for evaluation. If 5 or less responses are observed, then that dose is rejected. 
For safety, the probabilities of observing at least 1 AE given the true event rate are shown in 
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Table 13: 
Probability of detecting AE rates by sample size  
True event rate 
Probability of observing ≥1 event in 20 subjects 
1% 
18.2% 
5% 
64.2% 
10% 
87.8% 
15% 
96.1% 
20% 
98.8% 
25% 
99.7% 
Abbreviations: AE=adverse event. 
9.3. 
Analysis population sets 
For purposes of planned analysis, the following analysis populations are defined: 
• Intent-to-Treat analysis population includes all subjects who are eligible for 
treatment based on inclusion and exclusion criteria and enrolled into the study. 
• Safety analysis population includes all subjects who receive study treatment. This 
population will be used to summarize the demographic and baseline characteristics 
and safety data. 
• Response Evaluable analysis population includes all subjects who received study 
treatment PBCAR20A and have at least 1 post-Baseline efficacy assessment. Subjects 
who discontinue due to disease progression, have a transplant, die, or 
treatment-related toxicity prior to having a disease assessment will be included in the 
Response Evaluable population. 
9.4. 
Study participant description  
9.4.1. 
Disposition 
A detailed description of subject disposition will be provided. It will include the number of 
subjects who were enrolled, screen failures, completion/earlier termination status and reasons for 
termination; first screening date, dose starting and ending dates per dose, number of subjects in 
Safety and Response Evaluable Populations by Dose and by Arm for each phase.   
More details will be provided in the SAP.  
 
9.4.2. 
Demographic and Baseline characteristics 
Demographic characteristics including age, gender, race, and ethnicity will be presented in the 
form of tabular descriptive statistics. Other Baseline characteristics including, but not limited to, 
weight, height, body mass index, initial stage of disease, prior therapies, and ECOG Performance 
Status will be presented similarly. 


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9.4.3. 
Concomitant medications 
The number and proportion of study subjects using different concomitant medications will be 
tabulated and summarized by the World Health Organization Drug Anatomical Therapeutic 
Chemical and preferred term (PT).  
9.4.4. 
Treatment administration/compliance 
Study treatment administrations (include both LD and PBCAR20A) will be listed for each 
subject with drug name, dosing day, dose and number of cells for PBCARCD20A with 
compliance information, and summarized by Dose, and by Arm for each phase. 
9.5. 
Safety analysis 
All subjects who receive at least one dose study treatment (any dose of LD regimen or 
PBCAR20A) will be included in the summaries and listings of safety data. All analyses will be 
descriptive.  
9.5.1. 
AEs 
The AEs will be classified using the Medical Dictionary for Regulatory Activities (MedDRA) 
classification system version 20.0 or higher. The severity of the toxicities will be graded 
according to the NCI CTCAE version 5.0. 
In all summaries, emphasis will be placed on TEAEs, namely those with initial onset or those 
that worsen in severity after the first dose of PBCAR20A. The AEs will be summarized by the 
frequency of study subjects experiencing TEAEs corresponding to body systems and the 
MedDRA PT and by worst NCI CTCAE (version 5.0) grade. Summaries will also be provided of 
treatment-related TEAEs, namely those judged by the investigator to be related or likely related 
to PBCAR20A.  
The SAEs, AEs Grade ≥3, and AEs resulting in discontinuation of PBCAR20A treatment, 
withdrawal from the study, and deaths occurring during the study will be tabulated. 
All DLTs in Phase 1 will be summarized and listed by PBCAR20A dose.  
All AESIs, as defined in Section 7.2.1.3, and infections will be assessed and analyzed separately 
from AEs from the administration of PBCAR20A to end of study participation.  
9.5.2. 
Laboratory tests 
Laboratory data will be summarized for the observed values at each scheduled assessment, 
together with the corresponding changes from Baseline (the value obtained prior to dosing on 
Day 1) using descriptive statistics.  
For those analytes with CTCAE version 5.0 severity criteria, abnormal laboratory values will be 
summarized by shift tables displaying numerical values and percentages classified by Baseline 
grade (i.e., grade prior to dosing on Day 1) and maximum grade on treatment. All laboratory data 
will be presented in listings. 


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9.5.3. 
ECGs 
The ECG parameters (PR interval, QRS duration, QT, QTc, and QTcF) will be summarized 
descriptively by Dose or by Arm and overall. 
9.5.4. 
Vital signs and physical examination findings 
Vital signs data will be summarized using descriptive statistics by the observed valued at each 
scheduled assessment and the corresponding changes from Baseline. 
Physical examination findings will be presented in data listings.  
9.6. 
Efficacy analysis 
Since the primary objective of this study is to determine the safety and tolerability of 
PBCAR20A, an appropriate dose to optimize safety and efficacy, and to optimize the treatment 
regimen, an estimation approach will be applied to efficacy data analyses. ORR to treatment with 
PBCAR20A through Day 360 will be noted using the Lugano criteria for NHL and iwCLL for 
CLL/SLL (Section 8.1). The ORR is defined as the proportion of study subjects meeting the 
definition of response (PR+CR for both Phase 1 and 2a Arm C NHLs and PR+CR for Phase 1 
CLL/SLL subtype). The ORR will be summarized by number and percentage of subjects meeting 
the definition of ORR along with the corresponding exact 95% CIs for all Phase 1 dose level and 
for Phase 2a Arm B and C, where CR with corresponding exact 95% CI will be presented for 
Phase 2a Arm A. 
DoR, defined as the duration (days) from initial response to disease relapse or progression or 
death; PFS, defined as the duration (days) from Day 0 to disease relapse, progression, or death 
will be descriptively analyzed using Kaplan-Meier methods. Exploratory efficacy analyses 
include changes from Baseline in CBC counts, CAR T cells, cytokines, and CRP levels, and the 
number of subjects who have received allogeneic stem cell transplant. Exploratory efficacy 
endpoints and detailed analyses will be included in the SAP.  
9.7. 
Interim analysis 
A formal interim analysis is planned for the Phase 1 data when the last subject completed the 
study.  
Dose escalation investigator calls consisting of the investigators, the medical monitor, and 
sponsor representative(s) will provide safety oversight during the study. The group will review 
safety data at regular intervals to discuss any unexpected significant toxicities and to determine 
whether dose escalation is appropriate. 
.  


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10. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
10.1. 
Study monitoring 
Before a study center can enter a study participant into the study, a representative of the sponsor 
will visit the study center to: 
• Determine the adequacy of the facilities. 
• Discuss with the investigator(s) and other personnel their responsibilities regarding 
protocol adherence, and the responsibilities of the sponsor or its representatives. This will 
be documented in a Clinical Study Agreement between the sponsor and the investigator. 
During the study, a medical monitor from the sponsor or representative will have regular 
contacts with the investigational site, for the following: 
• Provide information and support to the investigator(s). 
• Confirm that facilities remain acceptable. 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the eCRFs, and that investigational product accountability checks 
are being performed. 
• Perform source data verification. This includes a comparison of the data in the eCRFs 
with the study participant’s medical records at the hospital or practice, and other records 
relevant to the study. This will require direct access to all original records for each study 
participant (e.g., clinic charts). 
• Record and report any protocol deviations not previously sent to the sponsor. 
• Confirm AEs and SAEs have been properly documented in the eCRFs and confirm any 
SAEs have been forwarded to the sponsor and those SAEs that met criteria for reporting 
have been forwarded to the IRB. 
The medical monitor will be available between visits if the investigator(s) or other staff needs 
information or advice. 
10.2. 
Audits and inspections 
Authorized representatives of the sponsor, a regulatory authority, an Independent Ethics 
Committee (IEC) or an IRB may visit the site to perform audits or inspections, including source 
data verification. The purpose of an audit or inspection is to systematically and independently 
examine all study-related activities and documents to determine whether these activities were 
conducted, and data were recorded, analyzed, and accurately reported according to the protocol, 
Good Clinical Practice (GCP) guidelines of the ICH, and any applicable regulatory requirements. 
The investigator should contact the sponsor immediately if contacted by a regulatory agency 
about an inspection. 


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10.3. 
IRB 
The Principal Investigator must obtain IRB approval for the investigation. Initial IRB approval 
and all materials approved by the IRB for this study, including the ICF and recruitment 
materials, must be maintained by the investigator and made available for inspection. 
10.4. 
Data protection 
Study subjects will be assigned a unique identifier by the sponsor. Any study participant records 
or datasets that are transferred to the sponsor will contain the identifier only; study participant 
names or any information that would make the study participant identifiable will not be 
transferred.  
The study participant must be informed that his/her personal study-related data will be used by 
the sponsor in accordance with local data protection laws. The level of disclosure must also be 
explained to the study participant.  
The study participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB members, and by inspectors from regulatory authorities. 
11. 
QUALITY CONTROL AND QUALITY ASSURANCE 
All study participant data relating to the study will be recorded in the eCRF unless transmitted to 
the sponsor or designee electronically (e.g., laboratory data). The investigator is responsible for 
verifying that data entries are accurate and correct by signing the eCRF.  
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.  
The investigator must permit study-related monitoring, audits, IRB review, and regulatory 
agency inspections and provide direct access to source data documents.  
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data.  
Medical monitors will perform ongoing source data verification to confirm that data entered in 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of study subjects are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.  


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12. 
ETHICS 
12.1. 
Ethics review 
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB or IEC as appropriate. The investigator must submit 
written approval to the sponsor before he or she can enroll any study participant into the study. 
The Principal Investigator is responsible for informing the IRB or IEC of any amendments to the 
protocol in accordance with local requirements. In addition, the IRB or IEC must approve all 
advertising used to recruit study subjects for the study. The protocol must be re-approved by the 
IRB or IEC upon receipt of amendments and annually, as local regulations require. 
The Principal Investigator is also responsible for providing the IRB with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product. The sponsor will provide this information to the Principal Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or IEC according to local regulations and guidelines. 
12.2. 
Ethical conduct of the study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH GCP, applicable regulatory requirements, 
and the sponsor’s policies. 
12.3. 
Written informed consent 
The Principal Investigator(s) at each center will ensure that the study participant is given full and 
adequate oral and written information about the nature, purpose, and possible risk and benefit of 
the study. Study subjects must also be notified that they are free to discontinue from the study at 
any time. The study participant should be given the opportunity to ask questions and allowed 
time to consider the information provided. 
The study participant’s signed and dated ICF must be obtained before conducting any study 
procedures. 
The Principal Investigator(s) must maintain the original, signed ICF. A copy of the signed ICF 
must be given to the study participant. 
13. 
DATA HANDLING AND RECORDKEEPING 
13.1. 
Inspection of records 
The sponsor will be allowed to conduct site visits to the study centers for the purpose of 
monitoring any aspect of the study. The investigator agrees to allow the medical monitor to 
inspect the drug storage area, study treatment stocks, drug accountability records, study 
participant charts and study source documents, and other records relative to study conduct. 


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13.2. 
Retention of records 
The Principal Investigator must maintain all documentation relating to the study for a period of 
2 years after the last marketing application approval, or if not approved, 2 years following the 
discontinuance of the test article for investigation. If it becomes necessary for the sponsor or the 
regulatory authority to review any documentation relating to the study, the investigator must 
permit access to such records. 
14. 
PUBLICATION POLICY 
This study is registered on the US National Institute of Health’s web site www.clinicaltrials.gov.  


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15. 
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Food and Drug Administration. Guidance for Industry. Considerations for the design of 
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Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, et al. A new equation 
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Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, et al. Phase 1 results of 
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patients with diffuse large B cell lymphoma not reaching complete response or relapsing after 
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Seigel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7-34. 
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Storb R, Buckner CD, Dillingham LA, Thomas ED. Cyclophosphamide Regimens in Rhesus 
Monkeys with and without Marrow Infusion. Cancer Res. 1970;30:2195-203. 
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chimeric antigen receptor-modified T cells in patients with relapsed or refractory B-cell 
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16. 
APPENDICES 
Appendix 1. Contraceptive guidance and collection of pregnancy information 
Definitions 
Woman of childbearing potential (WOCBP) 
A WOCBP is defined as any woman who is not postmenopausal or who has not had a 
hysterectomy. Postmenopausal is defined as being over the age of 55 and not having had a 
menstrual period for at least 1 year. 
Contraception guidance 
Male study subjects 
Male study subjects with female partners of childbearing potential are eligible to participate if 
they agree to ONE of the following during the study treatment period (Day 0 through Day 90):  
• Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent 
• Agree to use a male condom plus partner use of a highly effective contraceptive 
method when having penile-vaginal intercourse with a WOCBP who is not currently 
pregnant. 
In addition, male study subjects must refrain from donating sperm for the duration of the study. 
Male study subjects with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile penetration 
during the study treatment period. 
Female study subjects 
Female study subjects of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception. 
Highly effective contraceptive method  
At least 1 of the methods below should be used in combination with male condoms:  
• Combined (estrogen- and progesterone-containing) hormonal contraception 
associated with inhibition of ovulation, delivered orally, intravaginally, or 
transdermally.  
• Progestogen-only hormonal contraception associated with inhibition of ovulation, 
delivered orally, via injection, or implanted.  
• An intrauterine device.  
• An intrauterine hormone-releasing system.  
Pregnancy testing 
The WOCBP should only be included after a negative pregnancy test at screening.  
Pregnancy test will be performed whenever a menstrual cycle is missed or when pregnancy is 
otherwise suspected.  


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Collection of pregnancy information 
Male study subjects with partners who become pregnant  
The investigator will attempt to collect pregnancy information on any male study participant’s 
female partner who becomes pregnant while the male study participant is in this study. This 
applies only to male study subjects who receive PBCAR20A. 
After obtaining the necessary signed ICF from the pregnant female partner directly, the 
investigator will record pregnancy information on the appropriate form and submit it to the 
sponsor within 24 hours of learning of the partner’s pregnancy. The female partner will also be 
followed to determine the outcome of the pregnancy. Information on the status of the mother and 
child will be forwarded to the sponsor. Generally, the follow-up will be no longer than 6 to 
8 weeks following the estimated delivery date. Any termination of the pregnancy will be 
reported regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure.  
Female study subjects who become pregnant  
The investigator will collect pregnancy information on any female study participant who 
becomes pregnant while participating in this study. Information will be recorded on the 
appropriate form and submitted to the sponsor within 24 hours of learning of a study participant's 
pregnancy. The study participant will be followed to determine the outcome of the pregnancy. 
The investigator will collect follow-up information on the study participant and the neonate and 
the information will be forwarded to the sponsor. Generally, follow-up will not be required for 
longer than 6 to 8 weeks beyond the estimated delivery date. Any termination of pregnancy will 
be reported, regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous abortion is 
always considered to be an SAE and will be reported as such. Any poststudy pregnancy-related 
SAE considered reasonably related to the study intervention by the investigator will be reported 
to the sponsor as described in Section 7.2.5. While the investigator is not obligated to actively 
seek this information in former study subjects, he or she may learn of an SAE through 
spontaneous reporting.  
Any female study participant who becomes pregnant after receiving PBCAR20A will be 
followed through after giving birth or after the pregnancy is terminated. 
 


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Appendix 2. ASTCT consensus grading 
Table 14: 
ASTCT CRS consensus grading 
CRS parameter 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Fevera 
Temperature ≥38°C 
Temperature ≥38°C 
Temperature ≥38°C 
Temperature ≥38°C 
 
 
With 
Hypotension 
None 
Not requiring vasopressors Requiring a vasopressor 
with or without 
vasopressin 
Requiring multiple 
vasopressors (excluding 
vasopressin) 
 
 
And/Orb 
Hypoxia 
None 
Requiring low-flow nasal 
cannulac or blow-by 
oxygen delivery 
Requiring high-flow nasal 
cannulac, facemask, 
nonrebreather mask, or 
Venturi mask 
Requiring positive 
pressure (e.g., CPAP, 
BiPAP, intubations, 
mechanical ventilation) 
Abbreviations: ASTCT=American Society for Transplantation and Cellular Therapy; BiPAP=bilevel positive airway pressure; CPAP=continuous positive airway 
pressure; CRS=cytokine release syndrome. 
a Fever is defined as temperature ≥38°C not attributable to any other cause. In study subjects with CRS who then receive antipyretic or anticytokine therapy, 
such as tocilizumab or steroids, fever is no longer required to grade subsequent CRS severity. In this case, CRS grading is driven by hypotension and/or 
hypoxia. 
b CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. For example, a patient with a temperature of 
39.5°C, hypotension requiring 1 vasopressor, and hypoxia requiring low-flow nasal cannula is classified as Grade 3 CRS. 
c Low-flow nasal cannula is defined as oxygen delivered at ≤6 L/min. Low flow also includes blow-by oxygen delivery, sometimes used in pediatrics. High-flow 
nasal cannula is defined as oxygen delivered at >6 L/min. 
Source: Lee et al, 2019. 


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Table 15: 
ASTCT ICANS consensus grading for adults 
 
Neurotoxicity domain 
 
ICE scorea 
Depressed level of 
consciousnessb 
Seizure 
Motor findingsc 
Elevated ICP/cerebral 
edema 
Grade 1 
7 to 9 
Awakens spontaneously 
N/A 
N/A 
N/A 
Grade 2 
3 to 6 
Awakens to voice 
N/A 
N/A 
N/A 
Grade 3 
0 to 2 
Awakens only to tactile 
stimulus 
Any clinical seizure 
focus or generalized 
that resolves rapidly or 
nonconvulsive seizures 
on EEG that resolve 
with intervention 
N/A 
Focal/local edema on 
neuroimagingd 
Grade 4 
0 (study participant is 
unarousable and unable 
to perform ICE) 
Study participant is 
unarousable or requires 
vigorous or repetitive 
tactile stimuli to arouse. 
Stupor or coma 
Life-threatening 
prolonged seizure 
(>5 min); or repetitive 
clinical or electrical 
seizures without return 
to Baseline in between 
Deep focal motor 
weakness such as 
hemiparesis or 
paraparesis 
Diffuse cerebral edema 
on neuroimaging; 
decerebrate or 
decorticate posturing; or 
cranial nerve VI palsy; 
or papilledema; or 
Cushing’s triad 
Abbreviations: ASTCT=American Society for Transplantation and Cellular Therapy; CTCAE=Common Terminology Criteria for Adverse Events; 
EEG=electroencephalogram; ICANS=immune effector cell-mediated neurotoxicity syndrome; ICE=immune effector cell-associated encephalopathy; 
ICP=intracranial pressure; N/A=not applicable. 
a A study participant with an ICE score of 0 may be classified as Grade 3 ICANS if awake with global aphasia, but a study participant with an ICE score of 0 
may be classified as Grade 4 ICANS if unarousable. 
b Depressed level of consciousness should be attributable to no other cause (e.g., no sedating medication). 
c Tremors and myoclonus associated with IEC therapies may be graded according to CTCAE v5.0, but they do not influence ICANS grading. 
d Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is excluded from ICANS grading. It may be graded 
according to CTCAE v5.0. 
Note: ICANS grade is determined by the most severe event (ICE score, level of consciousness, seizure, motor findings, raised ICP/cerebral edema) not 
attributable to any other cause. For example, a study participant with an ICE score of 3 who has a generalized seizure is classified as Grade 3 ICANS. 
Source: Lee et al, 2019. 


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16.1. 
Protocol version summary of changes 
16.1.1. 
Version 5.0 
The following substantive changes were made from version 4.0 (dated 09 Sep 2020) to 
version 5.0 (dated 09 Feb 2021). Administrative and editorial changes were also made for 
correction and/or consistency throughout the document. 
Global changes: 
• Phase 2a arms A, B, and C were added along with rationale for associated 
lymphodepletion and PBCAR20A treatment regimens 
• Primary and secondary objectives and endpoints for Phase 2a arms were added 
• Inclusion/exclusion criteria were updated for clarity and to reflect specific cohorts to be 
enrolled in each Phase 2a arm 
• Enrollment for Phase 2a was increased to up to 20 subjects in each arm 
• Dose Level 2 was changed to 240 × 106 cells 
• Criteria for retreatment were clarified 
16.1.2. 
Version 4.0 
The following substantive changes were made from version 3.0 (dated 13 Jan 2020) to 
version 4.0 (dated 09 Sep 2020). Administrative and editorial changes were also made for 
correction and/or consistency throughout the document. 
Global changes: 
• In Phase 1 of the study, the NHL and CLL/SLL cohorts have been combined for safety 
evaluation. In Phase 2a, the study will enroll two separate cohorts (one for NHL and one 
for CLL/SLL). 
• Clarification that subjects in Phase 2a will be dosed at or below the MTD determined in 
Phase 1. 
• The number of subjects and study centers has been adjusted to account for protocol 
changes. 
• Phase 1 Dose Level 3 has been changed to a flat dose of 480 x 106 cells with a maximum 
dose of 4.8 x 108 cells. 
• Updates have been made to the inclusion/exclusion criteria, including removal of the 
exclusion criterion for subjects with active hemolytic anemia. 
• Overall survival (OS) has been removed as a secondary endpoint. 
• Retreatment criteria have been added for subjects who exhibit some evidence of 
therapeutic benefit following one dose of PBCAR20A. 
• A timeframe has been specified for the DLT of Grade ≥3 neurotoxicity (per American 
Society for Transplantation and Cellular Therapy [ASTCT] ICANS such that if there is 


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resolution or reduction to Grade ≤2 within 72 hours of onset, it is no longer considered a 
DLT. 
• Staggering between the first and second subject in a dose level has been reduced from 28 
to 14 days. 
• Clarification that BMA or bone marrow core biopsy will be collected.  
• The Synopsis has been updated where relevant to reflect all changes. 
 


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Section 
Original text 
Revised text 
Rational
e 
Table 1; 
Key study 
contact 
informatio
n 
Precision BioSciences medical 
representative was originally 
Precision BioSciences medical 
representative has been updated to 
Update/ 
clarificati
on 
3.1, 
Overall 
study 
design 
This is a Phase 1/2a, 
nonrandomized, open-label, 
parallel assignment, single-dose, 
dose-escalation, and dose-
expansion study to evaluate the 
safety and clinical activity of 
PBCAR20A in adults with r/r 
CD20+ B-cell NHL (Cohort A) or 
r/r CD20+ CLL/SLL (Cohort B). 
This is a Phase 1/2a, nonrandomized, 
open-label, parallel assignment, single-
dose, dose-escalation, and dose-
expansion study to evaluate the safety 
and clinical activity of PBCAR20A in 
adults with r/r CD20+ B-cell NHL 
including r/r CD20+ CLL/SLL. 
Starting with protocol version 4.0, as all 
subjects enrolled to date have been 
NHL subjects, the Phase 1 portion of 
the study will continue to enroll and 
treat all subjects as one cohort. The 
Phase 2 portion of the study will enroll 
two separate cohorts, 1 for NHL 
subjects and 1 for CLL/SLL subjects. 
 
Phase 1 
disease 
cohorts 
have 
been 
combined 
for safety 
evaluatio
n. 
3.1, 
Overall 
study 
design 
New text added to clarify dosing 
cohorts and number of intended 
subjects. 
If DLTs are found to occur 
predominantly in one subtype of NHL 
subjects (i.e., those with indolent 
lymphoma, including follicular 
lymphoma, chronic lymphocytic 
leukemia/small lymphocytic lymphoma, 
and marginal zone lymphoma or 
aggressive lymphoma, such as diffuse 
large B cell lymphoma, PMBCL, 
Burkitt lymphoma, and other high grade 
T cell lymphomas), the possibility of 
separating the cohorts for dose 
escalation may be explored. 
For characterization of the 
pharmacology, safety profile, and 
clinical benefit profile, up to 18 subjects 
total may be enrolled in any given dose 
level for which safety has been 
established (i.e., ≤1 of 6 subjects 
experiences a DLT). These additional 
12 subjects (any subjects after subject 
6) will not be considered for 
determination of the MTD and can be 
Clarificat
ion 


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Section 
Original text 
Revised text 
Rational
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enrolled without delays into that dose 
level. 
3.3, 
Number 
of study 
subjects 
Part 1 (dose escalation):  
Approximately 12 to 18 evaluable 
study participants are planned to 
be enrolled in each of the 2 disease 
cohorts for a total of 24 to 36 
study participants. 
 
Part 1 (dose escalation):  
Approximately 9 to 30 evaluable 
subjects are planned to be enrolled in 
Phase 1 of the study. 
 
Update/ 
clarificati
on 
3.4, 
Number 
of study 
centers 
Approximately 4 study centers for 
Phase 1 and approximately 
8 additional centers for Phase 2a in 
the United States. 
 
Approximately 10-15 study centers in 
the United States. 
 
Update/ 
clarificati
on 
3.6, 
cohorts 
and dose 
escalation 
Dose 
level 
Number 
of CAR T 
cells/kg 
Max 
cells/dose 
Dose 
-1 
3 × 105 
3 × 107 
Dose 
1 
(starti
ng) 
1 × 106 
1 × 108 
Dose 
2 
3 × 106 
3 × 108 
Dose 
3 
6 × 106 
6 × 108 
Dose 
level 
Number of 
CAR T  
Max 
cells/dose 
Dose -
1 
3 × 105 
cells/kg 
3 × 107 
Dose 1 
(startin
g) 
1 × 106 
cells/kg 
1 × 108 
Dose 2 
3 × 106 
cells/kg 
3 × 108 
Dose 3 
480 × 106 
cells 
4.8 × 108 
 
Added 
flat dose 
for Dose 
Level 3 
and 
adjusted 
maximu
m 
cells/dose
. 


Protocol PBCAR20A-01 
 
Precision Biosciences, Inc. 
Version 5.0 (10FEB2021) 
 
96 
Section 
Original text 
Revised text 
Rational
e 
3.7, 
Retreatme
nt criteria 
New section added.  
Retreatment refers to the specific 
scenario in which a subject receives all 
planned treatment and has some 
evidence of benefit followed by 
evidence of disease progression.  
All subjects will receive PBCAR20A as 
per the Schedule of Activities (SoA; 
Table 2). A subject may receive an 
additional dose of PBCAR20A if he/she 
meets retreatment criteria as determined 
by the investigator and agrees to be 
retreated.  
Subjects are eligible for retreatment 
only if the following criteria are met: 
• 
Subject has documented evidence 
of tumor response to initial dose of 
PBCAR20A followed by documented 
disease progression at subsequent visit. 
• 
Subject has biopsy-proven CD20+ 
tumor at progression. 
• 
Subject has no evidence of GvHD 
and no new disease-related central 
nervous system (CNS) involvement. 
• 
Subject has adequate bone marrow, 
renal, hepatic, pulmonary, and cardiac 
function as defined in Section 4.1. 
• 
Subject has not received another 
systemic treatment for NHL. 
Subjects who meet the retreatment 
criteria and have had a study visit 
within 30 days will undergo 
lymphodepletion chemotherapy and 
follow the SoA from the beginning. 
Subjects who meet the retreatment 
criteria and have discontinued the study 
will need to be re-enrolled into an open 
slot (Phase 1 or Phase 2a). Retreatment 
visits, starting from lymphodepletion 
visits, will be distinguished from initial 
visits in the electronic case report form 
(eCRF). 
Subjects eligible for retreatment may 
receive PBCAR20A at the highest dose 
level with established safety (see 
Section 3.1). 
New 
addition 
to this 
protocol 
to allow a 
second 
dose of 
PBCAR2
0A in 
subjects 
who 
demonstr
ate some 
evidence 
of 
efficacy. 


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Version 5.0 (10FEB2021) 
 
97 
Section 
Original text 
Revised text 
Rational
e 
3.8, 
Criteria 
for DLTs  
• 
Any Grade ≥3 neurotoxicity 
(per American Society for 
Transplantation and Cellular 
Therapy [ASTCT] ICANS criteria 
provided in Table 15). 
• 
Any Grade ≥3 neurotoxicity (per 
American Society for Transplantation 
and Cellular Therapy [ASTCT] ICANS 
criteria provided in Table 15) that does 
not resolve or reduce to Grade ≤2 
within 72 hours of onset. 
To ensure 
MTD is 
adequatel
y 
evaluated
. 
3.10, 
Criteria 
for 
temporaril
y 
suspendin
g 
treatment 
In addition to the staggered dosing 
schedule (28 days between the 
first 2 study participants and 
14 days between the second and 
third study participant in each dose 
group, including the dose de-
escalation group if applicable). 
In addition to the staggered dosing 
schedule (14 days between the first 2 
study subjects in each dose group, 
including the dose de-escalation group 
if applicable). 
Based on 
data 
collected 
in 
PBCAR0
191-01; 
14 day 
safety 
evaluatio
n period 
is 
adequate. 
4.1 and 
4.2, 
Inclusion 
and 
Exclusion 
Criteria 
Several updates have been made to 
the I/E criteria across NHL and 
CLL/SLL. The most notable 
changes are captured below:  
 
Refer to track changes version of the 
protocol for a full comparison of 
changes made to the I/E criteria.  
Clarificat
ions 
4.5, Study 
completio
n 
A study participant is considered 
to have completed the entire study 
if the study participant is followed 
according to the protocol to the 
Day 360 visit, disease progression, 
death, or receiving a new 
treatment for MM (including stem 
cell transplant), whichever occurs 
first. 
Subjects experiencing disease 
progression prior to day 28 should 
continue on the study through Day 28 to 
allow for completion of study’s primary 
evaluation as long as another systemic 
therapy is not started. A subject is 
considered to have completed the entire 
study if the subject is followed 
according to the protocol to the Day 
360 visit, disease progression, death, or 
receiving a new treatment for the 
diagnosed malignancy (including stem 
cell transplant), whichever occurs first. 
To ensure 
subject 
monitorin
g and 
collection 
of data. 
 
16.1.3. 
Version 3.0 
The following substantive changes were made from version 2.0 (dated 04 Oct 2019) to 
version 3.0 (dated 13 Jan 2020). Administrative and editorial changes were also made for 
correction and/or consistency throughout the document. 


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Version 5.0 (10FEB2021) 
 
98 
Global changes: 
• The dose levels were increased and a maximum number of cells (based on 100 kg 
subject) for each dose level was added. 
• The Screening window was increased from 21 days to 28 days. Windows for 
Screening MRIs and lumbar punctures were added. 
• Duration of response was removed as an endpoint. 
• Additional secondary endpoints were added: 
− Progression-free survival 
− Overall survival 
− Incidence of AEs, SAEs, and DLTs related to the investigational product 
• The dose escalation procedure was clarified. 
• A window of -5 days was added to lymphodepletion chemotherapy. 
• AEs and concomitant medications will be collected through Day 360 
 
Section 
Original text 
Revised text 
Rationale 
Table 2, 
schedule of 
activities 
 
A row for MRD assessment was 
added with the corresponding 
footnote:  
MRD assessment will be 
performed at Screening for all 
subjects. Please consult the 
Laboratory Manual for specific 
sample requirements at Screening. 
At subsequent visits, MRD 
assessment will only be performed 
for subjects who meet other 
standard response criteria (see 
Section 8.1). Please consult the 
Laboratory Manual for specific 
sample requirements at all 
subsequent visits. Note that these 
samples are disease-specific and 
may be different between 
Screening and all subsequent 
visits. 
Clarification 
of 
procedures. 


Protocol PBCAR20A-01 
 
Precision Biosciences, Inc. 
Version 5.0 (10FEB2021) 
 
99 
 
Section 
Original text 
Revised text 
Rationale 
3.6, cohorts and 
dose escalation 
Dose 
level 
Number of CAR 
T cells/kg 
Dose -1 
3 × 104 
Dose 1 
(starting) 
3 × 105 
Dose 2 
1 × 106 
Dose 3 
3 × 106 
 
Dose 
level 
Number 
of CAR 
T 
cells/kg 
Max 
cells/dose 
Dose -1 
3 × 105 
3 × 107 
Dose 1 
(starting) 
1 × 106 
1 × 108 
Dose 2 
3 × 106 
3 × 108 
Dose 3 
6 × 106 
6 × 108 
Increased 
dose level to 
improve 
efficacy. 
4.1, inclusion 
criteria 
Estimated glomerular filtration 
rate >60 mL/min/1.73 m2 
Estimated glomerular filtration 
rate >30 mL/min/1.73 m2 
Clarification. 
4.2, exclusion 
criteria 
Criteria for NHL: 
Active central nervous system 
(CNS) disease. A negative 
computed tomography 
(CT)/magnetic resonance 
imaging (MRI) is required at 
Screening if the study 
participant has a history of 
CNS lymphoma. 
 
Criteria for CLL/SLL: 
Active CNS disease. A 
negative lumbar puncture is 
required at Screening if the 
study participant has a history 
of CNS disease. 
Criteria for NHL: 
Any history of central nervous 
system (CNS) disease. If active 
CNS involvement is suspected, a 
negative computed tomography 
(CT)/magnetic resonance imaging 
(MRI) is required at Screening. 
 
Criteria for CLL/SLL: 
Any history of CNS disease. If 
active CNS involvement is 
suspected, a negative lumbar 
puncture is required at Screening. 
Clarification. 
7.1.5, 
immunogenicity 
Blood samples will be 
collected from all study 
participants according to Table 
2 and shipped to the central 
laboratory, where they are 
archived as PBMCs and serum. 
Blood samples will be collected 
from all study participants 
according to Table 2 and analyzed 
by the local laboratory. 
Clarification 
of 
procedures. 
7.2.1.1 AE 
All AEs will be collected from 
the initiation of 
lymphodepletion 
chemotherapy through Day 28 
and be recorded in the eCRF, 
regardless of whether or not 
All AEs will be collected from the 
initiation of lymphodepletion 
chemotherapy until death, disease 
progression, subsequent systemic 
therapy, withdrawal due to 
intolerable toxicity, withdrawal of 
consent, or Day 360, whichever 
occurs first and be recorded in the 
Clarification 
of 
procedures. 
 


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Version 5.0 (10FEB2021) 
 
100 
 
Section 
Original text 
Revised text 
Rationale 
they are related to the study 
treatment.  
eCRF, regardless of whether or 
not they are related to the study 
treatment. All AEs collected 
through Day 28 will be used for 
assessment of DLTs; any AEs 
occurring after Day 28 will be 
considered in dose-escalation 
decisions and monitoring 
procedures as appropriate. 
 
16.1.4. 
Version 2.0 
The following substantive changes were made from version 1.0 (dated 30 Jul 2019) to version 
2.0 (dated 04 Oct 2019). Administrative and editorial changes were also made for correction 
and/or consistency throughout the document.  
Global changes 
• “Data Safety Monitoring Board” was changed to “Safety Review Committee” for 
Phase 1 
• The dose escalation algorithm and DLT definition were clarified 
 
 


Protocol PBCAR20A-01 
 
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Version 5.0 (10FEB2021) 
 
101 
Section 
Original text 
Revised text 
Rationale 
2.3, 
exploratory 
objectives 
and 
endpoints 
 
Removed RECIL assessment from 
exploratory objectives. 
Clarification
. 
3.1, overall 
study design 
The first treated study participant 
in each dose group (including the 
dose de-escalation group, i.e., 
Dose 1) will be observed for 14 
days for safety before any 
subsequent study participant 
receives any study treatment to 
provide an adequate safety 
monitoring window. Once the 
first study participant in each 
cohort has completed Day 14 of 
dosing with no DLTs, the second 
and third study participants can 
be enrolled simultaneously at the 
same dose. 
 
 
The first treated study participant in 
each dose group (including the dose 
de-escalation group, i.e., Dose 1) 
will be observed for 28 days for 
safety before any subsequent study 
participant receives any study 
treatment to provide an adequate 
safety monitoring window. There 
will be a staggered interval of 14 
days between the second and third 
study participants. If no DLTs are 
observed, then subsequent study 
participants at that dose level can be 
treated without a formal stagger 
delay. Cohorts A and B will proceed 
with dose escalation separately. 
 
The following paragraph was added: 
During Part 2, a Data and Safety 
Monitoring Board (DSMB) will 
meet regularly to review safety and 
efficacy data during Part 2 of the 
study. A DSMB charter will be 
established before Part 2 of the 
study commences. 
Modified 
staggered 
dosing 
intervals and 
clarification 
of 
procedures.  
3.2, Table 2 
schedule of 
activities 
 
Tumor/liquid biopsy (NHL only) is 
optional from Day 14 to Day 360.  
 
Footnote m was modified: 
m. Screening tumor biopsy may be 
omitted if a study participant has 
had a biopsy showing CD20+ 
disease within 6 months before 
Screening and has not received any 
anti-CD20+ therapy since then. 
Note: If the tumor is CD20-negative 
by flow cytometry, it should be 
evaluated by immunohistochemistry 
as flow assays may result in false 
negatives due to competition with 
Clarification 
of 
procedures. 


Protocol PBCAR20A-01 
 
Precision Biosciences, Inc. 
Version 5.0 (10FEB2021) 
 
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Section 
Original text 
Revised text 
Rationale 
CD20 targeting treatment antibodies 
(e.g. rituximab). 
 
Footnote n was added: 
Tumor biopsy may be performed to 
confirm imaging changes as 
clinically indicated. Additional 
biopsies may be performed pending 
Sponsor approval. 
3.7, criteria 
for DLTs 
• CRS (per American Society 
for Transplantation and 
Cellular Therapy [ASTCT] 
consensus grading; see 
Section 7.3.1): Grade ≥3 
that does not resolve or 
reduce below Grade 3 
within 7 days.  
• Grade ≥3 toxicity of vital 
organs (heart, lung, liver, 
and kidney) associated with 
CRS that does not decrease 
to Grade ≤2 within 7 days or 
is not clinically manageable. 
• Any Grade 4 neurotoxicity 
(per American Society for 
Transplantation and Cellular 
Therapy [ASTCT] ICANS 
criteria provided in Table 
16), regardless of duration, 
or Grade 3 neurotoxicity 
that shows no evidence of 
improvement for >72 hours 
after onset or that extends 
beyond 7 days. Evidence of 
improvement at 72 hours 
includes at least 1 of the 
following:  
− Increase in ICE score 
from worst score 
− Improvement in 
depressed level of 
consciousness to Grade 
• CRS (per American Society for 
Transplantation and Cellular 
Therapy [ASTCT] consensus 
grading; see Section 7.3.1):  
− Any Grade 4 
− Any Grade 3 that does not 
resolve or reduce to Grade 
≤2 within 72 hours of 
onset  
• Any Grade ≥3 neurotoxicity 
(per American Society for 
Transplantation and Cellular 
Therapy [ASTCT] ICANS 
criteria provided in Table 15) 
• Any seizure 
• Grade 3 or 4 infusion reactions 
related to the study treatment 
that does not resolve or 
decrease to Grade ≤2 within 48 
hours 
• Any Grade 4 hematologic 
toxicity, except lymphopenia, 
that does not resolve or 
decrease to Grade ≤2 within 42 
days 
− Any Grade 4 non-
hematologic toxicity  
− Any Grade 3 toxicity 
involving heart and lungs 
− Any Grade 3 toxicity 
involving kidney and liver 
Clarification 
of DLTs. 


Protocol PBCAR20A-01 
 
Precision Biosciences, Inc. 
Version 5.0 (10FEB2021) 
 
103 
Section 
Original text 
Revised text 
Rationale 
1 or 2 level, if 
previously Grade 3 
− No evidence of 
ongoing seizure events 
if seizure events were 
recorded 
− Improvements of motor 
weakness if any 
previously identified 
− Resolution of elevated 
intracranial pressure or 
cerebral edema if any 
observed 
• Any Grade 3 neurotoxicity 
lasting >3 consecutive days 
despite medical 
management, except for 
intermittent Grade 3 
headache or isolated motor 
deficits, such as aphonia, 
that do not significantly 
affect activities of daily 
living. 
• Any Grade 4 hematologic 
toxicity, except 
lymphopenia, that does not 
resolve or decrease to Grade 
≤2 within 42 days. 
• Any non-CRS related TEAE 
Grade ≥3 to vital organs 
(heart, lung, liver, and 
kidney) that does not 
decrease to Grade ≤2 within 
4 days and is clinically 
meaningful. 
• Any Grade 5 CRS or any 
Grade 5 toxicity that was not 
due to underlying 
malignancy. 
that does not resolve or 
reduce Grade ≤2 within 7 
days of onset 
− Any Grade 3 toxicity to 
other organs that does not 
resolve or reduce Grade 
≤2 within 72 hours of 
onset  
• Any Grade 5 toxicity that was 
not due to underlying 
malignancy 


Protocol PBCAR20A-01 
 
Precision Biosciences, Inc. 
Version 5.0 (10FEB2021) 
 
104 
Section 
Original text 
Revised text 
Rationale 
• Other Grade 3 or 4 
toxicities, unless there is a 
clear alternative explanation. 
3.8, criteria 
for 
treatment 
interruption 
Previously Section 4.4.2. 
No changes to text. 
Clarification
. 
3.9, criteria 
for 
temporarily 
suspending 
treatment 
In addition to the 14-day 
staggered dosing schedule 
between the first 2 study 
participants in each dose group 
(including the dose de-escalation 
group if applicable), dosing in all 
study participants, regardless of 
cohort and dose group, will 
temporarily stop if any of the 
following events occur:  
• Grade 4 toxicities related to 
CRS 
• Grade ≥3 GvHD 
• Any death that is possibly or 
probably related to the study 
treatment  
In addition to the staggered dosing 
schedule (28 days between the first 
2 study participants and 14 days 
between the second and third study 
participant in each dose group, 
including the dose de-escalation 
group if applicable), dosing in all 
study participants, regardless of 
cohort and dose group, will 
temporarily stop if any of the 
following events occur:  
• Any Grade 4 toxicity that is 
possibly or probably related to 
the study treatment 
• Grade ≥3 GvHD 
• Any death that is possibly or 
probably related to the study 
treatment 
Clarification 
of 
procedures. 
4.1, 
inclusion 
criteria 
5. Study participants with 
CLL/SLL must have previously 
failed/tolerant to at least 2 prior 
lines of systemic targeted therapy 
of known benefit. 
 
 
 
 
 
 
 
 
 
7. Total bilirubin <2.0 mg/dL, 
except in study participants with 
5. Study participants with CLL/SLL 
must have previously failed/tolerant 
to at least 2 prior lines of systemic 
targeted therapy including a Bruton 
tyrosine kinase inhibitor and 
venetoclax ± rituximab. 
 
6. Study participant has CD20+ 
tumor. Note: If the tumor is CD20-
negative by flow cytometry, it 
should be evaluated by 
immunohistochemistry as flow 
assays may result in false negatives 
due to competition with CD20 
targeting treatment antibodies 
(e.g., rituximab). 
 
Clarification
. 


Protocol PBCAR20A-01 
 
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Version 5.0 (10FEB2021) 
 
105 
Section 
Original text 
Revised text 
Rationale 
Gilbert’s syndrome, who must 
have total bilirubin ≤5 × ULN. 
8. Total bilirubin <2.0 mg/dL, 
except in study participants with 
Gilbert’s syndrome, who must 
have total bilirubin ≤3 × ULN 
4.2, 
exclusion 
criteria 
29. Study participant must not 
have received systemic 
corticosteroid therapy for at least 
1 day prior to initiating 
lymphodepletion chemotherapy. 
Titration may be managed by the 
investigator. 
30. Study participant must not have 
received systemic corticosteroid 
therapy for at least 7 days prior to 
initiating lymphodepletion 
chemotherapy. Titration may be 
managed by the investigator. 
Clarification
. 
4.4, study 
discontinuat
ion or 
withdrawal 
 
“Study participant 
noncompliance/protocol violation,” 
“study terminated by sponsor,” 
“study participant withdrawal,” and 
“lost to follow-up” were added to 
the reasons for study 
discontinuation or withdrawal. 
Clarification 
of 
procedures. 
5.1.3, 
hospitalizati
on 
 
The following was added:  
Study participants with Burkitt 
lymphoma or high tumor burden 
DLBCL/Richter’s transformation 
CLL should receive prophylaxis for 
tumor lysis syndrome (including 
rasburicase, if indicated) and be 
hospitalized to undergo frequent 
monitoring (chemistries, LDH, and 
uric acid every 6 hours for up to 96 
hours post-treatment). If tumor lysis 
does occur, there should be 
aggressive correction of 
electrolytes. 
Clarification 
of 
procedures. 
7.3.1, Table 
8, CRS 
grading and 
management 
recommend
ations 
 
Footnote was added: 
a. Tocilizumab 8 mg/kg IV over 60 
min or per institutional standards. If 
no clinical improvement in 
signs/symptoms of CRS after first 
dose, up to 3 additional doses may 
be administered with at least 8 hours 
between consecutive doses. 
Clarification 
of 
procedures. 


Protocol PBCAR20A-01 
 
Precision Biosciences, Inc. 
Version 5.0 (10FEB2021) 
 
106 
Section 
Original text 
Revised text 
Rationale 
8.1, 
assessment 
of response 
 
The following text was moved from 
Section 8.5 and Section 8.6 and 
applies to all study participants. 
The MRD assessment method and 
status for study participants with a 
CR will be determined as clinically 
indicated using flow cytometry, 
qPCR, Next Generation 
Sequencing, or by local institutional 
standard. 
Clarification
. 
8.6, tumor 
biopsy for 
NHL study 
participants 
Core needle biopsies (minimum 
of 4 should be obtained) will be 
performed in study participants 
with NHL at time points in Table 
2 or as clinically indicated. For 
lymph nodes, an excisional 
biopsy is preferred. A core 
biopsy at Day 14 is optional for 
restaging and analysis of T-cell 
infiltration, which will be 
performed in selected study 
participants based on the 
investigator’s judgment and 
discussion with the study 
participant. 
 
Core needle biopsies (ideally 4 will 
be obtained) may be performed in 
study participants with mass lesions 
at any time at least 14 days post-
treatment and/or as clinically 
indicated. For lymph nodes, an 
excisional biopsy is preferred.  
 
A tumor biopsy may be performed 
to confirm imaging changes as 
clinically indicated. Additional 
biopsies may be performed pending 
Sponsor approval.  
Clarification 
of 
procedures. 
 

SAP_001.pdf: 
Precision BioSciences, Inc.
Page 1 of 27 
Title: Statistical Analysis Plan (SAP) for “A Phase 1/2a, Open-label, Dose-escalation, 
Dose-expansion, Parallel Assignment Study to Evaluate the Safety and Clinical Activity of 
PBCAR20A in Study Subjects with Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma 
(NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma 
(SLL)” 
Protocol number: PBCAR20A-01 v5.0 10FEB2021 
Product: PBCAR20A 
Sponsor: Precision BioSciences, Inc.  
Effective date: March 29, 2022 
Confidentiality statement 
This document is confidential information of Precision BioSciences, Inc. It may not be disclosed 
to parties not associated with the clinical investigation or used for any purpose without the prior 
written authorization of Precision BioSciences, Inc. 
Description: 
The purpose of this SAP is to describe the planned analyses and outputs to be 
included in the Clinical Study Report for Protocol PBCAR20A-01 (version 5.0), 
dated 10 February 2021. 
This SAP is intended to describe the efficacy, safety analyses required for the study. 
This SAP will be provided to the study team members to convey the content of 
statistical package. 
NCT #NCT04030195


 
 
 
 
 
 
 
Precision BioSciences, Inc.
 
 
 
 
 
 
Page 2 of 27 
 
SAP Authors and Signatures 
 
Author’s Name and Functional Area: 
Function  
Name/title 
Lead Author 
 Precision BioSciences, Inc. 
Contributing Author 
 Precision BioSciences, Inc.  
Contributing Author 
 Precision BioSciences, Inc. 
 
 
 
 
 
 
 
I give my approval for the attached SAP entitled “A Phase 1/2a, Open-label, Dose-escalation, 
Dose-expansion, Parallel Assignment Study to Evaluate the Safety and Clinical Activity of 
PBCAR20A in Study Subjects with Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma 
(NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma 
(SLL)” dated March 29, 2022. 
 
SAP Approval Signatures  
Roles 
Name/title 
Signature 
Date 
Lead Author 
 
, PBI 
 
 
Statistical Reviewer 
, 
PBI 
 
 
Clinical Trial 
Manager 
 
, PBI 
 
 
Medical Director 
 
, PBI 
 
 
Lead Programmer 
 
, PharStat, Inc 
 
 
 
 
 
 


 
 
 
 
 
 
 
Precision BioSciences, Inc.
 
 
 
 
 
 
Page 3 of 27 
 
Table of Contents 
1 
SUMMARY OF KEY PROTOCOL INFORMATION 
7 
1.1 
Change to the Protocol Defined Statistical Analysis Plan 
7 
1.2 
Study Objectives and Endpoints 
7 
1.3 
General Study Design 
8 
1.4 
Statistical Hypotheses 
10 
2 
SAMPLE SIZE 
10 
3 
PLANNED ANALYSES 
10 
3.1 
Interim Analyses and Data Monitoring 
10 
3.2 
Final analysis 
11 
4 
ANALYSIS POPULATIONS 
11 
4.1 
Protocol Deviations 
12 
5 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING CONVENTIONS 12 
5.1 
Data Quality Assurance 
13 
5.2 
Study Assessments Windows 
13 
5.3 
Study Treatment Display Descriptors 
13 
5.4 
Handling of Missing Data 
13 
5.5 
Multiple Comparisons 
14 
5.6 
Covariates and Subgroups Analysis 
14 
5.7 
Data Derivations and Transformations 
14 
5.8 
Reporting Process and Standards 
15 
6 
STUDY POPULATION 
15 
6.1 
Subject Disposition 
15 
6.2 
Demographic and Baseline Variables 
15 
7 
EFFICACY ANALYSES 
16 
7.1 
Efficacy Analysis 
16 
7.1.1 
Objective Response Rate (ORR) 
16 
7.1.2 
Progression-Free Survival (PFS) 
16 
8 
SAFETY ANALYSES 
16 
8.1 
Extent of Exposure 
17 
8.2 
Adverse Events 
17 
8.2.1 
Adverse Event Summaries 
17 
8.2.2 
Adverse Events of Special Interest (AESI) 
18 
9 
REPORTING CONVENTIONS 
18 
10 
QUALITY ASSURANCE OF STATISTICAL PROGRAMMING 
18 
11 
LISTING OF TABLES, LISTINGS AND FIGURES 
20 
12 
APPENDICES 
24 
12.1 
Appendix A: Schedule of Activities 
24 
 


 
 
 
 
 
 
 
Precision BioSciences, Inc.
 
 
 
 
 
 
Page 4 of 27 
 
List of Abbreviations 
 
Abbreviation 
Definition 
AE 
adverse event 
AESI 
adverse events of special interest 
ALL 
acute lymphoblastic leukemia 
ASTCT 
American Society for Transplantation and Cellular Therapy 
B-ALL 
B-cell acute lymphoblastic leukemia 
BMA 
bone marrow aspiration 
BMI 
body mass index 
BOR 
best overall response 
CAR 
chimeric antigen receptor 
CBC 
complete blood count 
CI 
confidence interval 
CLL 
Chronic lymphocytic leukemia 
CNS 
Central nervous system 
CS 
clinically significant 
CR 
complete response 
CRi 
complete response with incomplete recovery of counts 
CRP 
C-reactive protein 
CRS 
cytokine release syndrome 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
dose-limiting toxicity 
DoR 
duration of response 
ECG 
electrocardiogram 
ECHO 
echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
FDA 
Food and Drug Administration 
GvHD 
graft-versus-host disease 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 
ICANS 
immune effector cell-mediated neurotoxicity syndrome 


 
 
 
 
 
 
 
Precision BioSciences, Inc.
 
 
 
 
 
 
Page 5 of 27 
 
ICF 
Informed consent form 
ICH 
International Council for harmonization 
ITT 
Intent-to-Treat 
IV 
intravenous 
kg 
kilogram 
KM 
Kaplan-Meier 
LTFU 
long-term follow-up 
LVEF 
Left ventricular ejection fraction 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
MRD 
minimal residual disease 
MRI 
Magnetic Resonance Imaging 
MTD 
maximum tolerated dose 
MUGA 
Multiple gated acquisition scan 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NCS 
Not clinically significant 
NHL 
non-Hodgkin lymphoma 
ORR 
objective response rate 
OS 
overall survival 
PD 
progressive disease 
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PR 
partial response 
PT 
Preferred Term 
QC 
quality control 
qPCR 
quantitative polymerase chain reaction 
RE 
Response Evaluable 
RNA 
ribonucleic acid 
r/r 
relapsed/refractory 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan  


 
 
 
 
 
 
 
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SD 
stable disease 
SLL 
Small lymphocytic leukemia 
SoA 
Schedule of Activities 
SOC 
System Organ Class 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
WHO 
World Health Organization 
 
 


 
 
 
 
 
 
 
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1 SUMMARY OF KEY PROTOCOL INFORMATION 
1.1 Change to the Protocol Defined Statistical Analysis Plan  
Any changes from the originally planned statistical analysis specified in the protocol are 
outlined in Table 1. 
Table 1: Change to protocol defined analysis plan 
Protocol 
Statistical Analysis Plan 
Rationale for Changes 
PBCAR20A-01 
v4.0 09SEP2020 
Cohort A(NHL) and Cohort B 
(CLL/SLL) will be combined for all 
analyses.   
Protocol V4 has combined 
the two cohorts into one 
cohort, and dose level 3 has 
been changed to a flat dose 
of 480x10^6 cells. 
PBCAR20A-01 
v5.0 10FEB2021 
Subject enrollment will be 
discontinued after the completion of 
Phase 1. The study will not progress to 
Phase 2a. All subsequent sections in 
the SAP apply to only Phase 1.  
 
Actual dose level given in the study 
will be used for summary tables  
This study includes only 
Phase 1 due to the project 
not moving forward. 
 
Dose level 2: 240x10^6 cells 
were not given as dose level 
2 dosing has been completed 
based on protocol V4.  
 
1.2 Study Objectives and Endpoints 
The primary, secondary, and exploratory objectives and corresponding endpoints for Phase 1 
are listed in Table 2. Due to early study termination, only a synopsis will be generated, and 
exploratory endpoints will not be included.  
Table 2: Study objectives and endpoints 
Objective 
Endpoints 
Primary Objective 
Primary Endpoints 
Evaluate the safety and tolerability of 
PBCAR20A in subjects with r/r CD20+ NHL 
including r/rCD20+ CLL/SLL and find an 
appropriate dose to optimize safety and 
efficacy 
The identification of the maximum tolerated 
dose (MTD) based on the incidence of dose-
limiting toxicities (DLTs) 
Secondary Objectives 
Secondary Endpoints 
Evaluate the clinical activity and safety 
profile of PBCAR20A in study subjects 
with r/r CD20+ NHL including r/r CD20+ 
CLL/SLL 
Objective response rate (ORR) 
• NHL: Lugano 2016 criteria 
• CLL/SLL: International Workshop 
on Chronic Lymphocytic Leukemia 
(iwCLL) 2018 guidelines 
 
Progression-free survival (PFS) 
• Defined as the duration (days) from 
Day 0 to disease progression or 
death 
 
Incidence of AESI, SAEs, and DLTs related 


 
 
 
 
 
 
 
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to the investigational product 
 
1.3 General Study Design 
This study is a nonrandomized, open-label, dose escalation Phase 1 study. Essential 
components of the study design and key features are summarized in Table 3. 
Table 3: Overview of study design and key features 
Design Features 
Three escalating dose groups will be enrolled and treated 
sequentially, with the possibility of a single de-escalation. 
• Within each dose group, at least 3 and at most 6 study 
subjects will be treated with a single dose of 
PBCAR20A using a standard 3 + 3 design. 
• The starting dose of PBCAR20A will be 1×106 CAR T 
cells/kg body weight. 
• In the absence of DLTs, subsequent dose groups will be 
treated with escalating doses to a maximum flat dose of 
480×106 CAR T cells. 
• If a DLT is observed in 1 of 3 study subjects at a given 
dose level, 3 additional study subjects (for a total of up 
to 6 study subjects) will be enrolled and treated at that 
dose level. 
• When 3 additional study subjects are added to the dose 
group, the dose will be increased to the next dose level if 
≤1 of 6 study subjects experiences a DLT. 
• If ≥2 of the 3 to 6 study subjects in a dose group 
experience DLTs then the MTD has been exceeded. The 
dose level will then be lowered to the previous dose and 
up to 3 additional study subjects (for a total of 6) will be 
treated at the previous (lower) dose level. 
• See the flow chart of the dose escalation algorithm in 
Figure 1. 
 
Dosing Schedule 
• Lymphodepletion (LD) chemotherapy will be 
administered during the Screening Period from Days -5 
to -3. 
• All subjects will receive an intravenous (IV) 
PBCAR20A on Day 0 of the study. 
• The first treated subject in each dose level (including the 
dose de-escalation group, i.e., Dose -1) will be observed 
for 14 days for safety before any subsequent subject 
receives any study treatment to provide an adequate 
safety monitoring window. 
• Once the first study subject in each dose level has 
completed Day 14 after dosing with no DLTs, then 
subsequent subjects can be enrolled without delays into 
that dose level. 
• See Figure 2 for the study design schematic. 


 
 
 
 
 
 
 
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Treatment assignment 
No randomization scheme or treatment arm assignment applies. 
Three PBCARCD20A doses are planned: 
Dose 1: 1x10^6 cells/kg, Protocol V3 
Dose 2: 3x10^6 cells/kg, Protocol V3 
Dose 3: 480x10^6 cells, Protocol V4 
 
All subjects will receive fludarabine 30 mg/m2/day and 
cyclophosphamide 500 mg/m2/day from Day -5 to Day -3. 
Blinding 
Blinding of study subjects or study staff does not apply. 
Interim /Analysis 
• No formal interim analyses are planned. 
• A Safety Monitoring Committee will review safety data 
at regular intervals and to determine whether dose 
escalation is appropriate 
 
Figure 1: Dose escalation algorithm 
 


 
 
 
 
 
 
 
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Figure 2: Study schema 
 
Abbreviations: ICF=informed consent form. 
1.4 Statistical Hypotheses 
Statistical analysis for all safety and efficacy parameters will be descriptive in nature. 
Categorical variables will be summarized by frequency distributions (number and 
percentages of study subjects). Continuous variables will be summarized by mean, standard 
deviation, median, minimum, and maximum, and time-to-event variables will be summarized 
using Kaplan-Meier methods and figures for the estimated median time. 
No formal statistical hypothesis testing is planned; however, if exploratory analyses are 
conducted and confidence intervals (CIs) are provided for estimates, the 95% CIs are 
consistent with a 2-sided 5% significance level. All analyses, summaries, and listings will be 
performed using SAS® (Cary, North Carolina) software (version 9.4 or higher). 
2 SAMPLE SIZE 
Subjects will be enrolled in dose groups with 3 to 6 subjects for each dose. Dose escalation of 
PBCAR20A will follow a standard 3 + 3 design with sequential groups of 3 subjects treated 
with incrementally higher doses of PBCAR20A until a DLT is observed and the MTD is 
established. Per the standard oncology 3 + 3 Phase 1 dose-escalation design, the total number 
of subjects to be enrolled cannot be precisely determined because the sample size is 
dependent upon the observed safety profile, which will determine the number of subjects per 
dose group and the number of dose escalations required to achieve the MTD. For this Phase 1 
study, 4 dose levels (including possible de-escalation) may be tested. It is anticipated that 
approximately 9-30 study subjects will be required to reach the MTD. 
3 PLANNED ANALYSES 
3.1 Interim Analyses and Data Monitoring 
No formal interim analyses are planned. 
Dose escalation investigator calls consisting of the investigators, the medical monitor, and 
sponsor representative(s) will meet regularly to review safety and efficacy data and to 
provide safety oversight during the study. The group will review safety data at regular 
intervals to discuss any unexpected significant toxicities and to determine whether dose 


 
 
 
 
 
 
 
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escalation is appropriate. 
3.2 Final analysis 
The final planned primary analyses will be performed after the completion of the following 
sequential steps: 
1. All subjects have completed a 28 Day Safety observation period of the study as 
defined in the protocol. 
2. All required database cleaning activities have been completed, and the final database 
release and database freeze have been declared by Data Management. 
4 ANALYSIS POPULATIONS 
The analysis populations along with their inclusion criteria are defined in Table 4.  
Following protocol amendment V4, enrolment for CLL/SLL and NHL cohorts have been 
combined, therefore, these two cohorts will be combined in the tables/figures and will be 
identified in the data listings if needed. 
Table 4: Analysis populations 
Population 
Definition / Criteria 
Analyses 
Evaluated 
All Screened 
• All subjects who sign the informed consent 
form (ICF) and participate the screening 
assessments. 
• Note: screening failures, screened but 
never enrolled are included in this 
population. 
• Study 
population 
display 
• Screening 
failures 
display 
Intent-To-Treat 
(ITT) / Enrolled 
• Includes all subjects who are eligible for 
treatment based on inclusion and exclusion 
criteria and enrolled into the study. 
• Subjects will only appear once in the ITT 
population, even if they are retreated with 
PBCAR20A. 
• Study 
population 
• Safety 
displays (vital 
sign, ECG, 
labs, etc.) 
Safety 
• Includes all subjects who receive study 
treatment, starting with Lymphodepletion. 
• This population will be used to summarize 
the demographic and baseline 
characteristics and safety data. 
• Subjects will only appear once in the 
Safety population, even if they are retreated 
with PBCAR20A. 
• TEAE-related 
safety 
displays 
• Demographic 
and baseline 
characteristics 
Response 
Evaluable (RE) 
• Includes all subjects who received study 
treatment PBCAR20A and have at least 1 
post-Baseline efficacy assessment. 
• Efficacy 
displays 


 
 
 
 
 
 
 
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Population 
Definition / Criteria 
Analyses 
Evaluated 
• Subjects who discontinue due to disease 
progression, have a transplant, die, or have 
a treatment-related toxicity prior to having 
a disease assessment will be included in the 
Response Evaluable population. 
• Subjects who are retreated will be included 
in the Response Evaluable population for 
each treatment of PBCAR20A 
 
Enrolled (ITT) and Safety population consists of the same subjects for this study. ‘Safety’ 
population will be used tables and listings. 
4.1 Protocol Deviations 
Protocol deviations (including deviations related to study inclusion/exclusion criteria, 
conduct of the trial, patient management or patient assessment) will be summarized or listed. 
A separate summary and listing of all inclusion/exclusion criteria deviations will also be 
provided, if any. This summary will be based on data as recorded on the inclusion/exclusion 
page of the eCRF. 
Major protocol deviations will be summarized for the Safety Population. A listing of all 
protocol deviations will be provided.  
Protocol deviations will be tracked by the study team throughout the conduct of the study in 
accordance with the Protocol Deviation Management Plan. Data will be reviewed prior to 
freezing the database to ensure all important deviations are captured and categorized on the 
protocol deviations dataset. This dataset will be the basis for the summaries or listings of 
protocol deviations. If there are many protocol deviations, a summary will be produced. If 
there are only a few protocol deviations, a listing will be produced. 
5 CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
Statistical analyses will be primarily descriptive in nature. Unless otherwise specified, 
continuous variables will be summarized by presenting the number of non-missing 
observations, mean, standard deviation, median, minimum, and maximum. Categorical 
variables will be summarized by presenting the number of subjects and percentage for each 
category.  
Time-to-event variables will be summarized using Kaplan-Meier (KM) methods and figures 
for the estimated median time. No formal statistical hypothesis testing is planned; however, if 
exploratory analyses are conducted and confidence intervals (CIs) are provided for estimates, 
the 95% CIs are consistent with a 2-sided 5% significance level. 
Results of statistical analyses, descriptive statistics, and supporting listings will be presented 
by PBCAR20A dose levels. 


 
 
 
 
 
 
 
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All tabulations will be based on pooled data across centers. 
Analyses will be performed using SAS for Windows statistical software, version 9.4 or 
higher (SAS, Cary, NC), except where other software may be deemed more appropriate.  
Pharstat will perform all efficacy and safety statistical analyses described in this SAP. 
5.1 Data Quality Assurance 
Once all the source verification is complete, all queries are resolved, and the database has 
been updated accordingly, the database will be locked and made available to Pharstat for final 
analysis.  
PBI’s biostatisticians will review the data when: 
1. Final analysis: All subjects complete Day 360 visit or discontinue from the study. 
2. Ad-hoc analyses: Based on planned publications and presentations, ad-hoc analyses 
will be requested. Source verification and query resolution will be an ongoing 
process. Targeted data quality checks will be performed by Data Management when 
ad-hoc analyses are requested. 
5.2 Study Assessments Windows 
Data will be summarized by nominal study visit recorded in the database. 
See Table 9 in Section 12.1 (Appendix A) for the timing of all relevant assessments. 
5.3 Study Treatment Display Descriptors 
The treatment descriptions to be used for the displays are listed in Table 5. 
 
Table 5: Treatment descriptions for displays 
Footnote Description 
Table Header 
Order 
1 × 106 cells/kg 
DL1 
1 
3 × 106 cells/kg 
DL2 
2 
480 × 106 cells 
DL3 
3 
 
5.4 Handling of Missing Data 
Except for the time-to-event endpoints (described below), partial first diagnosis date and 
partial end dates of concomitant medications will be listed as they are recorded, all other 
“Unknown” or “not done” data will be treated as missing; unless otherwise specified, no 
method for imputation is planned. 
Missing data on the PFS endpoint will have events coded as right censored per Table 6 based 
on the FDA’s Guidance for Industry document Clinical Trial Endpoints for the Approval of 
Non-small Cell Lung Cancer Drugs and Biologics (April 2015) [1]; Table C1. 
Table 6: Censoring methods for PFS 


 
 
 
 
 
 
 
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Situation 
Date of Progression or Censoring 
Outcome 
Progression documented between 
scheduled visits 
Earliest date of radiological 
assessment documenting 
progression  
PFS event 
No progression  
Date of last radiological assessment 
of measured lesions 
Censored 
Treatment discontinuation for 
undocumented progression 
Date of discontinuation 
PFS event 
Treatment discontinuation for 
toxicity or other reason 
Date of discontinuation 
PFS event 
New anticancer treatment started  
Date of start of new anticancer 
treatment 
PFS event 
Death before first progressive 
disease (PD) assessment 
Date of death 
PFS event 
Death between adequate 
assessment visits 
Date of death 
PFS event 
Death or progression after more 
than 1 missed visit 
Date of first missed visit 
PFS event 
 
5.5 Multiple Comparisons 
There are no multiple comparisons. 
5.6  Covariates and Subgroups Analysis 
Given this is a dose escalation study, no covariates or subgroups analysis will be done.  
5.7 Data Derivations and Transformations 
The following derivations will be used in this study: 
Study day:  
• =Date of assessment – Day 0 date (first PBCAR20A administration) + 1 for 
assessments done after date of first PBCAR20A administration. 
• =Date of assessment – Day 0 date (first PBCAR20A administration) for assessments 
done before date of first PBCAR20A administration. 
 
Weight: Baseline weight extracted from screening visit. 
Duration:  
• Duration on study (days) (or Time to Next Treatment) = end of study date – screening 
date + 1 
• Time to AEs onset = AE onset date – Day0 date + 1 


 
 
 
 
 
 
 
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• Duration of AE = AE end date -AE start date + 1 
• Follow-up time = Last contact/assessment date – Day 0 date +1 
 
5.8 Reporting Process and Standards 
Table 7 
Software 
SAS version 9.4 will be used 
Datasets 
SDTM: Not applicable 
ADAM: Not applicable 
RAW: Medidata will be used to create analysis datasets 
Location 
Programs will be located at Box\ClinFinalData\PBCAR20A\PBCAR20A-
01\Program 
Datasets will be located at Box\ClinFinalData\PBCAR20A\PBCAR20A-
01\Data\RAW 
Outputs will be located at Box\ClinFinalData\PBCAR20A\PBCAR20A-
01\Output 
QC 
QC programs and output will be located at 
\Box\ClinFinalData\PBCAR20A\PBCAR20A-01\QC 
Precision 
Calculated values will be presented at no more than 3 significant digits 
Unscheduled 
visits 
Unscheduled visits will not be included in summary tables. 
Unscheduled visits will be included in figures. 
All unscheduled visits will be only included in figures and listings. 
Descriptive 
Summary 
Categorical Data: N, n, frequency, % 
Continuous Data: N, n, mean, median, standard deviation (SD), min, max. 
 
6 STUDY POPULATION 
6.1 Subject Disposition 
A summary table (frequency counts and percentages) of all subjects in the All Screened 
population be provided including study completion status and reasons for early termination. 
Subject disposition will be tabulated by dose level and overall. First screening (first subject 
first visit) and last contact/assessment date as well as first and last PBCAR20A injection 
dates for each dose will be presented in the table.  
Screen failures with reasons (inclusion/exclusion criteria numbers recorded in the eCRF) as 
well as early discontinuations with reasons will be listed for all subjects.  
A by-subject listing for screened population will be created. It will include Screen failure 
subjects with reasons (inclusion/exclusion criteria numbers recorded in the eCRF) and 
subjects who started LD but did not dose with their reasons for discontinuation and time on 
study. 
6.2 Demographic and Baseline Variables 
Descriptive statistics will be used to summarize the demographic characteristics (including age 
(≥65 years vs. <65 years), gender, race, ethnicity, height, weight, and body mass index (BMI) 
at Screening) for the Safety population.  


 
 
 
 
 
 
 
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Descriptive statistics will be used to summarize the baseline characteristics for subjects in the 
Safety population with the data collected at Screening or Day 0 pre-dose only. Baseline data 
will include disease type, disease stage, prior autologous stem cell transplant, prior line 
therapy, refractory subgroup, and baseline Eastern Cooperative Oncology Group (ECOG) 
performance status. 
7 EFFICACY ANALYSES 
All efficacy analyses described below will be carried out on the RE population. Unless 
otherwise specified, data will be summarized by dose level and overall. 
7.1  Efficacy Analysis 
Efficacy analyses on ORR and PFS will be performed. 
7.1.1 Objective Response Rate (ORR) 
The ORR is defined as the proportion of study subjects as responder, including partial 
response (PR) and complete response (CR) rates (i.e., the ORR is the rate of CR + PR). The 
response to treatment with PBCAR20A through Day 360 will be evaluated using the Lugano 
criteria for NHL and iwCLL for CLL/SLL (see Protocol Section 8.1). 
Since the primary objective of this study is to determine the safety and tolerability of 
PBCAR20A, to identify an appropriate dose to optimize safety and efficacy, and to optimize 
the treatment regimen, an estimation approach will be applied to efficacy data analyses. The 
ORR will be summarized by number and percentage of subjects for all dose levels and along 
with the corresponding exact 95% CIs (Exact binomial CI: Clopper-Pearson method). 
7.1.2 Progression-Free Survival (PFS) 
PFS is defined as the interval between the date of first PBCAR20A administration and the 
date of disease relapse, progression, or death, whichever occurs (i.e., the number of days from 
Day 0 to disease relapse, progression, or death). Details on censoring method can be found in 
Section 5.4, Table 6. 
PFS (days) = Date of disease relapse or progression or death or last assessment (or 
retreatment date) − Date of first PBCAR20A administration + 1 
A PFS summary by dose will also be provided. 
Individual PFS will be plotted with swimmer plot and grouped by dose level and indicated as 
responder, non-responder, starting new SCT treatment or death. 
For subjects who meet the retreatment criteria and have had a study visit within 30 days, their 
PFS will be calculated from each PBCAR20A infusion. 
8 SAFETY ANALYSES 
All subjects in the Safety population will be included in the summaries and listings of safety 
data. No formal hypothesis testing will be performed to compare differences between dose 
groups. The safety data will be summarized for the overall AEs and specially AESI. Any 
clinically significant events related to laboratory tests, electrocardiograms (ECGs), and vital 
signs will be captured as AEs. All summaries will be descriptive. 


 
 
 
 
 
 
 
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8.1 Extent of Exposure 
Study treatment administrations (including both LD and PBCAR20A) will be listed for each 
subject with drug name, dose, total cells infused (in 10^6 cells), and total lymphodepletion 
administered. Subject compliance with treatment will also be noted in this listing. 
8.2 Adverse Events 
An adverse event (AE) is defined as any untoward medical occurrence in a subject or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily 
have to have a causal relationship with this treatment. 
All AEs will be collected until death, disease progression, stem cell transplant, withdrawal 
due to intolerable toxicity, withdrawal of consent, or Day 360, whichever occurs first, and 
recorded on the eCRF, regardless of whether they are related to the study treatment. All AEs 
collected through Day 28 will be used for assessment of DLTs; any AEs occurring after Day 
28 will be considered in dose-escalation decisions and monitoring procedures as appropriate. 
AEs, including SAEs, that occur after signing of informed consent and before administration 
of any protocol-specified medication will be recorded as Medical History on the appropriate 
eCRF. 
The AEs will be classified using the Medical Dictionary for Regulatory Activities (MedDRA) 
classification system version 22.1. The severity of the toxicities will be graded according to 
the NCI CTCAE version 5.0. 
8.2.1 Adverse Event Summaries  
A treatment-emergent adverse event (TEAE) is an AE with initial onset or that worsens in 
severity after the first dose of PBCAR20A. 
Non-TEAE is defined as an AE that occurred prior to the PBCAR20A injection, but after the 
initiation of lymphodepletion, and they will be summarized separately from TEAEs by 
system organ class (SOC) and prefer term (PT) based on ITT (Enrolled) population. 
The following summaries will be tabulated: 
i. 
The number and percentage of subjects experiencing a TEAE, 
ii. 
The number and percentage of subjects experiencing a SAE, 
iii. 
The number and percentage of subjects experiencing an AESI, 
iv. 
The number and percentage of subjects experiencing a fatal AE. 
Additionally, the following information will be provided: 
v. 
The number and percentage of subjects experiencing a serious adverse event related to 
each of the study medications (PBCAR20A, Lymphodepletion (Cyclophosphamide & 
Fludarabine)) by max toxicity grade, 
vi. 
Listing of all TESAEs, 
vii. 
Listing of all subjects who died on study. 
All TEAEs will be listed. The listing will contain the following information: dose level, PT, 
PT grade, whether the event was an SAE, DLT, or AESI, symptom grade, relationship to 
study medications (PBCAR20A, Cyclophosphamide, Fludarabine), whether the adverse event 
attributed to the disease, study day at onset, duration of the adverse event in days, treatment 
given to treat the adverse event, and the outcome. Listings will be sorted by subject and AE 


 
 
 
 
 
 
 
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onsite date. 
8.2.2 Adverse Events of Special Interest (AESI) 
The following AESI are AEs are of particular concern in CAR T cell therapy: 
• CRS 
• ICANS 
• GvHD 
Subjects will be assessed for AESI from the administration of PBCAR20A through Day 360.  
The following will be presented by dose and overall: 
i. 
Summary of onset and duration of All AESIs,  
ii. 
The number and percentage of subjects with symptoms from each type of AESI (CRS, 
ICANS, GvHD) by dose and by max grade (ASTCT grade or GvHD grade), 
iii. 
Summary of AESIs and symptoms by max toxicity grade and dose,  
iv. 
The number and percentage of AESIs and Infections by max toxicity grade and dose, 
v. 
Summary of medications given for AESIs, 
Listing of all Cytokine Release Syndrome, ICANS, and GvHD will also be provided. All 
occurrences of these AESIs will be listed for each subject. The listing will contain the 
following information: dose level, AE PT, PT grade, associated symptoms of the AESI, 
associated symptoms grade, AE onset days on study, duration of the AESI in days, treatment 
given to treat the adverse event, and the outcome. Listings will be sorted by subject and AE 
onset date. 
The median time (range) to onset of an AESI from the first dose of PBCAR20A and the 
median duration (range) of an AESI: 
Duration of AESI (days) = Date of Resolution – Date of Onset + 1. 
Time to AESI onset(days) = Date of AE onset – Day 0 Date + 1. 
 
For an AESI that is ongoing at the time of the analysis, the date of data cutoff will be used to 
calculate the duration. 
9 REPORTING CONVENTIONS 
The mean, standard deviation, and any other statistics other than quantiles, will be 
reported to one decimal place greater than the original data. Quantiles, such as median, 
minimum, and maximum, will use the same number of decimal places as the original 
data. 
10 QUALITY ASSURANCE OF STATISTICAL PROGRAMMING 
Analyses will be performed using SAS for Windows statistical software, version 9.4 or 
higher (SAS, Cary, NC), except where other software may be deemed more appropriate.  
To provide high quality code that is understandable and allows reproduction of the analysis, 
the following points will be followed: 


 
 
 
 
 
 
 
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• The population to be used in a table or figure will be explicitly set at the start of a 
block of code that computes the output, ideally by looking up the population from the 
table of tables. 
• Any outputs will have the 
o date and time included, 
o the name of the code file that produced the analysis, 
o programmer initials or user IDs. 
• At the start of any code file there will be a set of comments that give 
o the author, 
o the date and time of writing, 
o references to inputs and outputs, 
o reference to any parent code file that runs the child code file. 
All coding and output should adhere to one of three levels of quality control (QC), as outlined 
below: 
• Level 1: the QC programmer/statistician will conduct a manual review of the data and 
compare the output to the raw listing. 
• Level 2: the QC programmer/statistician will review the program, output, and log to 
ensure that these files are error-free. 
• Level 3: a second review programmer/statistician will independently reproduce the 
analyses and output. 
Most listings are classified as QC level 1, most summaries are classified as QC level 2, and 
all summaries and analyses involving primary endpoints and AESI are classified as QC level 
3 (see Section 11 for QC level classifications for specific listings and tables). 
 
 


 
 
 
 
 
 
 
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11 LISTING OF TABLES, LISTINGS AND FIGURES 
This section is to give precise details for each table, listing or figure to be produced. 
Mock tables, listings and figures should be provided. Including the title, number, analysis 
population, etc. 
Tables: # of decimal digits, formatting (e.g., confidence in brackets, in parentheses, in 
separate columns). 
Figures: labels for all axes, legends, plotting symbols. 
These detailed specifications can have minor revisions during the production phase without 
needing to revise the SAP, this may include changing the table numbers if a reordering or 
deletion is appropriate, providing that the specifications in the main body of the SAP sections 
4 to 8 are met. 
Suggestions for ordering or organizing TLFs: 
e.g., Tables E for efficacy and S for safety and nothing for patient disposition. 
Disposition is Table of Figure 1.xxx 
Efficacy is Table or Figure 2.xxx 
Safety is Table or Figure 3.xxx 
The following numbering will be applied for SAP generated displays: 
Table 8: Numbering for SAP generated displays 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.xxx 
1.1 to 1.xxx 
Efficacy 
2.1 to 2.xxx 
2.1 to 2.xxx 
Safety 
3.1 to 3.xxx 
3.1 to 3.xxx 
Section 
Listings 
ICH Listings 
1 to xx 
Other Listings 
xx+1 to yy 
 


 
 
 
 
 
 
 
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Table 10: Study population tables and listings 
No. 
Population 
Example 
Shell 
Title 
Programming Notes 
Quality 
Control 
Deliverable 
[Priority] 
  Subject Disposition 
 1.1 
All 
Screened 
SD1 
Summary of Subject Disposition 
Retreated subject will be included 
under actual dose level received 
3  
FP [1] 
1 
All 
Screened 
L-SD1 
Listing of Screen Failures 
 
 1 
FP [1] 
  Protocol Deviation 
 1.2 
Safety 
PD1 
Summary/Listing of Major Protocol 
Deviations  
  
If no major deviations, then put a 
blank table as ‘As no data to 
present. If few, only listing needed 
1  
FP [1] 
  Demographic and Baseline Characteristics 
 1.3 
Safety 
DMBC1 
Summary of Demographics and Baseline 
Characteristics 
Retreated subject will not be 
included in the summary 
3 
FP [1] 
 
 
 
 
 
 
 
 
 
Table 11: Efficacy tables, figures and listings 
No. 
Population 
Example 
Shell 
Title 
Programming Notes 
Quality 
Control 
Deliverable 
[Priority] 
  Response 
 2.1 
RE 
ORR1 
Summary of Objective Response Rate by Initial 
Treatment 
Responder=CR+PR, no 
retreatment data 
3  
FP [1] 
 2 
RE 
L-ORR1 
Listing of Objective Response Data 
Include retreatment data 
3  
FP [1] 
2.1 
RE 
F-SW 
Swimmer plot for Progression Free Survival 
For retreatment subject, combine 
the initial data with retreatment 
1 
FP [1] 


 
 
 
 
 
 
 
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data 
  
Table 12: Safety tables and listings 
No. 
Population 
Example 
Shell 
Title 
Programming Notes 
Quality 
Control 
Deliverable 
[Priority] 
  Extent of Exposure 
3.1 
Safety 
L-TA1 
Listing of Planned and Actual Treatment 
Administered 
Including dose level, lot number, 
date and time, drug name, 
compliance, and total quantity 
administered  
1  
FP [1] 
All AEs 
 3.2 
Safety 
AEAll1 
Summary of Overall Adverse Events by 
Treatment 
Combine the initial and retreatment 
periods safety data, this will be the 
summary for each individual 
2  
FP [1] 
3 
Safety 
L-AE1 
Listing of All Treatment Emergent Adverse 
Events 
 
2 
FP [1] 
  AEs of Special Interest 
3.3 
Safety 
AEAll2 
Summary of Onset and Duration for all AESIs 
Onset and duration are related to 
max grade of each type of AE 
3 
FP [1] 
 3.4 
Safety 
AESI2 
Summary of AESIs and Symptoms by Dose and 
Max Toxicity Grade 
AE and CRS data should be 
combined to identify the CRS 
events and symptoms 
 3 
FP [1] 
 3.5 
Safety 
AESI1 
Summary of AEs of Special Interest and 
Infections by Max Toxicity Grade and Dose 
Infection will combine all infection 
Aes, and max grade 
3 
FP [1] 
3.6 
Safety 
CM1 
Summary of Concomitant Medications Given 
for AESI 
Select the Toxi, Dex and other 
medications for fever,  
1 
FP [1] 
4 
Safety 
L-
AEAll1 
Listing of All Cytokine Release Syndrome, 
ICANS, GvHD 
 
1 
FP [1] 


 
 
 
 
 
 
 
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  SAEs 
3.7 
Safety 
SAE1 
Summary of All PBCARCD20A-related Serious 
Adverse Event By Max Toxicity Grade  
 
1 
FP [1] 
3.8 
Safety 
SAE1 
Summary of All Lymphodepletion-related 
Serious Adverse Event By Max Toxicity Grade 
 
1 
FP [1] 
 5 
Safety 
L-SAE1 
Listing of All TESAEs  
  
 1 
FP [1] 
 6 
Safety 
L-SAE1  Listing of All Deaths 
  
 1 
FP [1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
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12 APPENDICES 
12.1 Appendix A: Schedule of Activities 
 
Table 9: Study schedule 
 
Treatment Period 
Follow-up 
Month 
- 
1 
2 
3 
4 
5 
6 
9 
12 
Day 
-28a 
0 
1 
3 
7 
10 
14 
21 
28 
42 
60 
90 
120 
150 
180 
270 
360/ 
ET 
Visit window (days) 
 
 
+1 
+1 
±1 
±1 
±2 
±2 
±2 
±5 
±5 
±5 
±5 
±5 
±5 
±7 
±7 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
X 
X 
X 
Full physical examination 
X 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
X 
X 
X 
Medical history 
X 
X 
 
 
 
 
 
 
 
Xb 
Xb 
Xb 
Xb 
Xb 
Xb 
Xb 
Xb 
Viral serologyc 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HLA haplotype 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anti-HLA antibodies 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
Brain MRI 
Xd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lumbar puncture (History of 
CNS involvement) 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
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Treatment Period 
Follow-up 
Month 
- 
1 
2 
3 
4 
5 
6 
9 
12 
Day 
-28a 
0 
1 
3 
7 
10 
14 
21 
28 
42 
60 
90 
120 
150 
180 
270 
360/ 
ET 
Visit window (days) 
 
 
+1 
+1 
±1 
±1 
±2 
±2 
±2 
±5 
±5 
±5 
±5 
±5 
±5 
±7 
±7 
LVEF (ECHO or MUGA) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test 
(WOCBP only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical laboratory 
assessmentsf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelg 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (triplicate)i 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECOG Performance 
Status 
X 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
X 
X 
X 
Fludarabine + 
cyclophosphamidej 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study treatment 
administrationk 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study participant diaryl 
 
------------------------X------------------ 
 
 
 
 
 
 
 
 
PET-CT scan (NHL only) 
Xm 
 
 
 
 
 
Xn 
 
X 
 
X 
X 
 
 
X 
X 
X 
Tumor/liquid biopsy 
Xo 
 
 
 
 
 
Xp 
Serum and whole blood 
samples for analysesq 
X 
Xr 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


 
 
 
 
 
 
 
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Page 26 of 27 
 
 
Treatment Period 
Follow-up 
Month 
- 
1 
2 
3 
4 
5 
6 
9 
12 
Day 
-28a 
0 
1 
3 
7 
10 
14 
21 
28 
42 
60 
90 
120 
150 
180 
270 
360/ 
ET 
Visit window (days) 
 
 
+1 
+1 
±1 
±1 
±2 
±2 
±2 
±5 
±5 
±5 
±5 
±5 
±5 
±7 
±7 
BMA/bone marrow 
biopsy (Diagnosed w BM 
involvement)s 
X 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
X 
X 
X 
CT scan (if preferred to 
PET/CT for CLL/SLL 
only) 
X 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
X 
X 
X 
Objective response 
assessment 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
X 
X 
X 
MRD assessmentt 
X 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
X 
X 
X 
Concomitant medications 
X 
AE review 
X 
AESIu 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AE=adverse event; AESI=adverse event of special interest; BMA=bone marrow aspiration; CAR=chimeric antigen receptor; CLL=chronic lymphocytic 
leukemia; CNS=central nervous system; CT=computed tomography; DLBCL=diffuse large B-cell lymphoma; ECG=electrocardiogram; ECOG=Eastern Cooperative 
Oncology Group; ECHO=echocardiogram; ET=early termination; eCRF=electronic case report form; HLA=human leukocyte antigen; HIV=human immunodeficiency 
virus; IV=intravenous; LD=lymphodepletion; LVEF=left ventricular ejection fraction; MRI=magnetic resonance imaging; MUGA=multigated acquisition scan; NHL=non-
Hodgkin lymphoma; PBMC=peripheral blood mononuclear cell; PET=positron emission tomography; SLL=small lymphocytic lymphoma; WOCBP=women of 
childbearing potential. 
a Lymphodepletion regimens will be administered as described in the Pharmacy Manual. 
b Study subjects are asked about the current status of their disease and treatment, including stem cell transplant. 
c Viral screening to include HIV antibody, hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, HLA haplotype, and anti-HLA antibodies. 


 
 
 
 
 
 
 
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Page 27 of 27 
 
d Brain MRI is recommended for all study subjects at Baseline to assess the presence of brain disease or abnormalities. A negative MRI is required at Screening for NHL 
study subjects with a history of CNS disease. An MRI conducted as a part of the routine care within 6 weeks of initiating lymphodepletion chemotherapy may be used for 
Screening. 
e A negative lumbar puncture is required at Screening only if the study participant has a history of CNS disease. A lumbar puncture conducted as a part of the routine care 
within 6 weeks of initiating lymphodepletion chemotherapy may be used for Screening. 
f Clinical laboratory tests for safety assessments are outlined in Protocol Section 7.1.4. Clinical laboratory tests can be performed up to 24 hours before dosing on Day 0. 
g Coagulation panel may be performed after Baseline if the investigator considers it necessary. 
h Vital signs should be measured on the day of dosing at 5 minutes (±2 minutes) before dosing, then at the end of infusion (±5 minutes), 60 minutes after the end of infusion 
(±10 minutes), and 4 hours (±15 minutes) after the end of infusion. Vital signs should also be collected as clinically indicated. 
i Additional ECGs will be collected as clinically indicated. 
j The initial lymphodepletion chemotherapy regimen will be composed of fludarabine (30 mg/m2/day IV) and cyclophosphamide (500 mg/m2/day IV) during the Screening 
Period from Days -5 to -3. However, modified lymphodepletion regimens may be used after safety is established in dose level. The lymphodepletion regimen will be 
specified at the time of registration. Please refer to the Pharmacy Manual for the lymphodepletion dosing regimen; lymphodepletion status may be discussed between the 
Sponsor Medical Monitor, Principal Investigators, and contract research organization Medical Monitor prior to registration. 
k Study subjects are evaluated for the following restrictions 2 hours (±60 minutes) prior to receiving the PBCAR20A infusion: new uncontrolled infection after receipt of 
lymphodepletion, fever, taking any corticosteroid beyond the replacement details, rapid acceleration of malignant disease, and any organ dysfunction since Screening. 
Additional details are provided in Protocol Section 5.1.1. At the investigator’s discretion, study subjects may receive premedication 1 hour (±15 minutes) prior to receiving 
the PBCAR20A infusion with oral acetaminophen and oral or IV diphenhydramine according to the institutional standards. 
l Study participant diaries will be provided to study subjects on Day 0 to monitor temperature, at least daily, during the first 28 days. 
m . The PET-CT scan conducted as part of the routine care within 4 weeks of PBCAR20A administration may be used for Screening purposes. If the scan is performed as a 
part of routine care, the result will be obtained from the study participant’s physician or medical record. 
n A PET-CT scan on Day 14 is optional and will be determined by the investigator. Additional details are provided in Protocol Section 8.4. 
o Screening tumor biopsy may be omitted if a study participant has had a biopsy showing CD20+ disease within 6 months before Screening and has not received any anti-
CD20+ therapy since then. Note: If the tumor is CD20-negative by flow cytometry, it should be evaluated by immunohistochemistry as flow assays may result in false 
negatives due to competition with CD20 targeting treatment antibodies (e.g. rituximab). 
p  Tumor biopsy may be performed to confirm imaging changes as clinically indicated. Additional biopsies may be performed pending Sponsor approval. 
q Exploratory analyses will be performed by the central laboratory. Additional analyses performed at the site that are not required by the protocol should be captured in the 
eCRF. 
r Blood samples will be collected before PBCAR20A administration on Day 0. 
s If available, the central laboratory will also test fresh BMA or bone marrow core samples for CAR T cells. 
t MRD assessment will be performed at Screening for all study subjects. Please consult the Laboratory Manual for specific sample requirements at Screening. At subsequent 
visits, MRD assessment will only be performed for study subjects who meet other standard response criteria (see Protocol Section 8.1). Please consult the Laboratory Manual 
for specific sample requirements at all subsequent visits. Note that these samples are disease-specific and may be different between Screening and all subsequent visits. 
u AESIs are listed in Protocol Section 7.2.1.3.