A Phase 1 Study of Autologous Activated T-cells Targeting the B7-H3 Antigen in Subjects With Recurrent Epithelial Ovarian Cancer
Phase: PHASE1
Conditions: Epithelial Ovarian Cancer
Sponsor: UNC Lineberger Comprehensive Cancer Center

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CLINICAL RESEARCH PROTOCOL 
DRUG: 
CAR.B7-H3 T cells 
STUDY NUMBER(S): 
LCCC 1818-ATL 
PROTOCOL(S) TITLE: 
A Phase 1 Study of Autologous Activated T-cells 
Targeting the B7-H3 Antigen in Subjects with 
Recurrent Epithelial Ovarian Cancer  
IND NUMBER: 
19641 
SPONSOR: 
Lineberger Comprehensive Cancer Center 
ORIGINAL PROTOCOL DATE: 
05 January 2020 
VERSION NUMBER: 
Version 4.0 
VERSION DATE: 
April 12, 2023 

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SUMMARY OF CHANGES 
 
Protocol Amendment #3 
 
LCCC1818-ATL: A Phase 1 Study of Autologous Activated T-cells Targeting the B7-H3 Antigen 
in Subjects with Recurrent Epithelial Ovarian Cancer  
AMENDMENT INCORPORATES: 
X    Editorial, administrative changes 
X     Scientific changes (IRB approval) 
X    Therapy changes (IRB approval) 
X   Eligibility Changes (IRB approval) 
 
AMENDMENT RATIONALE AND SUMMARY: The purpose of this amendment is to amend 
and consolidate inclusion and exclusion criteria, update the lymphodepletion dose of fludarabine 
to 30 mg/m2 for consistency with other similar protocols, and reduce restrictions for the number of 
prior lines of therapy to improve recruitment. Other changes include 1) updating links to 
institutional guidelines for CRS and CNS toxicity management, 2) updating storage time for 
biospecimens, 3) HTLV was removed from the list of prohibited infections in the eligibility 
criteria, 4) allowing local follow up appointments to occur after 3 months, and 5) updating the 
Principal Investigator. 
 
Administrative/Editorial Changes: 
Throughout 
Editorial and formatting changes 
Section 9.2 
The last sentence in Section 9.2 was removed 
APPENDIX I – Names 
of Study Personnel 
Principal Investigator updated to Dr. Van Le 
 
Scientific Changes: 
 
Time & Events Table 
• Footnote 1 of the T&E table was corrected to indicate 
that tocilizumab must be onsite prior to cell infusion. 
• Footnotes 2 and 3 of the T&E table were amended to 
clarify that long term follow up visits occurring after 
the 3 month visit can occur locally. 
• Footnote 4 of the T&E table amended to allow for 
ECHO to occur up to 90 days prior to procurement with 
the caveat that if a cardiac toxic therapy occurs after the 
ECHO it will need to be repeated prior to procurement. 
• Footnote 7 amended to remove HTLV testing. 
 

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Section 7.2.5 
Removed HTLV testing 
Section 
Biobank 
Repository7.4 
Biospecimen storage time was updated 
 
 
Therapy Changes: 
 
Sections 1.4.2, 4.1.4, 4.2, 8.2, 8.2.2.5, 
and Figure 1 
 
The lymphodepletion dose of fludarabine was 
increased from 25 to 30 mg/m2 
 
APPENDIX III – CRS Grading 
Criteria and Management Guidelines 
and APPENDIX IV – Management 
of Neurotoxicity/Immune Effector 
Cell-Associated 
Neurotoxicity 
Syndrome (ICANS) from CAR-T 
Therapy 
Hyperlinks to management guidelines were updated 
for both CRS and ICANS  
 
 
Eligibility Changes: 
 
Section 5.1 
Inclusion and exclusion criteria have been combined 
Criterion 5.1.1 
Amended to include reference to a legally authorized 
representative 
Criterion 0 
Criterion relating to prior lines of therapy was removed 
Criteria Error! Reference 
source not found. - 5.1.22 
These criteria were previously exclusion criteria and were 
amended to make them part of the eligibility for cell 
procurement. 
Criterion 5.1.22 
Amended to remove HTLV 
Criterion 5.1.23 
Criterion added to clarify that intolerance to fludarabine is 
not permitted. 
Criterion 5.1.25.5 
Added (pulse oximetry) to organ function requirements 
Section 5.2 
Section was reorganized for clarity and some criteria were 
added for consistency with the cell procurement eligibility 
(5.2.3 – 5.2.9; 5.2.10.1-5.2.10.3. 5.2.12-5.2.19; 5.2.21-
5.2.23). 
 
Section 5.2.11 
Organ function prior to lymphodepletion adjusted. 
 
 
 
 
THE ATTACHED VERSION DATED APRIL 12, 2023, INCORPORATES THE ABOVE REVISIONS 

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SUMMARY OF CHANGES 
 
Protocol Amendment #2 
 
LCCC1818-ATL: A Phase 1 Study of Autologous Activated T-cells Targeting the B7-H3 Antigen 
in Subjects with Recurrent Epithelial Ovarian Cancer  
AMENDMENT INCORPORATES: 
X  Editorial, administrative changes 
X  Scientific changes (IRB approval) 
     Therapy changes (IRB approval) 
 X  Eligibility Changes (IRB approval) 
Rationale for amendment: The primary purpose of this amendment is to clarify the stopping 
rules of the study. Modifications are made to ensure toxicities governing the stopping rules of the 
study are those toxicities associated with CAR-T cell treatment. Progression was clarified as 
progressive disease identified post the initial 6 week scan.  Progression biopsy was updated to be 
completed at the discretion of the investigator.  If imaging at the initial 6-week follow-up indicate 
full or partial response and the patient progresses afterward, a progression biopsy will be both 
clinically and scientifically important.   If imaging at 6-week follow up indicate disease 
progression, the treating investigator may chose not to have a progression biopsy, as it may not be 
clinically significant and to reduce risk burden on patients who underwent a prior biopsy during 
catheter removal. The rational for this is that the study utilizes RNA based CAR-T product, which 
does not persist and expand as DNA based CAR-T products. RNA product is diluted during 
cellular division and it is unlikely to find RNA-expressing cells post infusion. Progressive disease 
after the initial 6-week scan most likely present true progression for these patients.   Repeat 
imaging at 8-12 weeks in the case of progressive disease has been removed. The ability to perform 
a blood draw for procurement has been added; however, leukapheresis remains an option to obtain 
a sufficient amount of cells for product generation. The use of Bard ports is removed and instead 
further description of Aspira is added. The CRS and ICANS grading and guidelines are updated. 
Eligibility was updated to exclude subjects with untreated or symptomatic brain metastases. The 
data capture system was updated from OnCore to Advarra. The medical monitor was updated. 
Editorial, Administrative Changes 
Section 13 
The data capture system was updated from OnCore to Advarra. 

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Section 
4.2 
Time 
and 
Events Table 
Removed the W0 D2 Column.  
Section 7.1.6 
A duplicated sentence was removed. 
Section 18.1, 
Appendix I 
The medical monitor was updated from Jonathan Serody, M.D. to Natalie 
Grover, M.D. 
Scientific changes: 
Summary, 
Schema, 
footnote #1; 
Section 
4.1.2; 
Section 4.2, 
footnote #17 
The procurement procedures have been updated to allow for a peripheral blood 
draw. However, leukapheresis is still allowed if needed.  
Section 4.1.3 
The use of Bard ports is removed and instead language for Aspira use is added. 
Section 
4.2 
Time 
and 
Events Table 
Footnote #2, second sentence was updated to indicate the visit being described 
was for day 3 not day 2. 
Section 
4.2 
Time 
and 
Events Table 
and Section 
7.1.6 
Footnote 8 of the Time and Events table is updated to remove the repeat imaging 
at 8-12 weeks in the case of progressive disease. Section 7.1.6 repeats this edit 
and further clarifies that the subject will be removed from the study. 
Section 4.2, 
footnote 
15 
and Section 
7.3.3 
The time of specimen collection was changed from last cellular product 
administration to the time of intraperitoneal catheter removal. Further, the 
biopsy at the time of disease progression may occur at the discretion of the 
treating investigator. This progression biopsy is further clarified as progression 
after the initial 6-week scan. 
Section 11.2 
The section is updated to specify that sequential boundaries will be used to 
monitor Grade ≥ 4 non-hematologic toxicity at least possibly related to CAR-T 
cells. 
Appendix III 
Updated CRS Grading Criteria and Management Guidelines with edits and 
updated hyperlink 

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Appendix IV 
Updated Management of Neurotoxicity/Immune Effector Cell-Associated 
Neurotoxicity Syndrome (ICANS) from CAR-T Therapy with updated 
information and hyperlink. 
Eligibility Changes 
Section 5.1  
Criterion #11 updated to clarify the timing of the biopsy from cell infusion to 
intraperitoneal catheter removal and to further clarify the timing of the biopsy 
relative to disease progression with the addition of  “if not at their first scan.” 
Section 5.2  
Added criterion #4 to exclude subjects with brain metastases. However, a 
subject with prior brain metastasis may be considered if they have completed 
their treatment for brain metastasis at least 4 weeks prior to being screened for 
eligibility, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic 
 
 
THE ATTACHED VERSION DATED SEPTEMBER 27, 2021 INCORPORATES THE 
ABOVE REVISIONS 
 
 

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CAR T-Cells Targeting B7-H3 Antigen in Recurrent Epithelial Ovarian Cancer 
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SUMMARY OF CHANGES 
 
Protocol Amendment #1 
 
LCCC1818-ATL: A Phase 1 Study of Autologous Activated T-cells Targeting the B7-H3 Antigen 
in Subjects with Recurrent Epithelial Ovarian Cancer  
AMENDMENT INCORPORATES: 
X  Editorial, administrative changes 
X  Scientific changes (IRB approval) 
     Therapy changes (IRB approval) 
X   Eligibility Changes (IRB approval) 
Rationale for amendment: The primary purpose of this amendment is to amend the sample 
collection timepoints for blood and ascites fluid. This study is using mRNA for the CAR-T product  
and the expression is transient. If we do not see CAR expression, this may be due to lack of 
expansion or that the CAR is no longer expressed on the cell. The additional PK timepoint at day 
3 of each infusion is necessary to evaluate if they were able to expand considering the transient 
nature of the CAR expression. 
Editorial, administrative changes: 
 
Mechanical edits made throughout. 
Scientific changes: 
Section 
4.2 
Time 
and 
Events Table 
and 
Footnotes 
The Time and Events Table was updated to include correlative blood and ascites 
fluid collections at day 3 after cell infusion. Footnotes 9 and 16 were updated to 
reflect this change. 
 
Section 
4.2 
Time 
and 
Events Table 
Correlative blood sample collection on W0D2 was removed 
Section 7.3.4 
The section was updated to include the new timepoint (day 3 after cell infusion) 
for ascites collection. 

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THE ATTACHED VERSION DATED February 17, 2021 INCORPORATES THE ABOVE 
REVISIONS 
 
 

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LCCC 1818-ATL 
A Phase 1 Study of Autologous Activated T-cells Targeting the B7-H3 Antigen in Subjects 
with Recurrent Epithelial Ovarian Cancer 
 
CONFIDENTIALITY AND INVESTIGATOR STATEMENT 
The information contained in this protocol and all other information relevant to CAR.B7-H3 T 
cells are the confidential and proprietary information of Lineberger Comprehensive Cancer Center, 
and except as may be required by federal, state or local laws or regulation, may not be disclosed 
to others without prior written permission of Lineberger Comprehensive Cancer Center. 
I have read the protocol, including all appendices, and I agree that it contains all of the necessary 
information for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein, in accordance with the regulations stated in the Federal Code of Regulations for 
Good Clinical Practices and International Conference on Harmonization guidelines, and will make 
a reasonable effort to complete the study within the time designated. 
I will provide all study personnel under my supervision copies of the protocol and any 
amendments, and access to all information provided by Lineberger Comprehensive Cancer Center 
or specified designees. I will discuss the material with them to ensure that they are fully informed 
about CAR.B7-H3 T cells and the study. 
 
 
 
 
 
 
Principal Investigator Name (printed) 
Signature 
______________________________ 
___________________________ 
Date 
_______________ 

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Study Summary 
Title:  
A Phase 1 Study of Autologous Activated T-cells Targeting the B7-H3 
Antigen in Subjects with Recurrent Epithelial Ovarian Cancer 
Rationale:  
There is a critical need to identify new treatment options for recurrent 
ovarian cancer. Preclinical observations support B7-H3 as a viable target of 
CAR-T therapy. Based on these observations, we will conduct a phase 1 
study of CAR.B7-H3 T cells in subjects with recurrent epithelial ovarian 
cancer to determine the safety and tolerability of this treatment modality and 
identify a recommended phase 2 dose for further study. 
Target 
Population: 
Women with relapsed or refractory platinum resistant epithelial ovarian 
cancer after up to 4 lines of prior therapy 
Number of 
Subjects: 
21 
Primary 
Objective:  
To determine the safety and tolerability of autologous CAR.B7-H3 T cell 
product administered intraperitoneally after lymphodepletion with 
cyclophosphamide and fludarabine to subjects with relapsed or refractory 
platinum-resistant epithelial ovarian cancer. 
Secondary 
Objectives: 
To determine the disease control rate (DCR) mediated by autologous 
CAR.B7-H3 T cell product administered to subjects with relapsed or 
refractory platinum-resistant epithelial ovarian cancer. 
To determine the progression free survival (PFS) after lymphodepletion with 
cyclophosphamide and fludarabine and administration of the CAR.B7-H3 T 
cell product in subjects with relapsed or refractory platinum-resistant 
epithelial ovarian cancer. 
To determine the overall survival (OS) in adult subjects with relapsed or 
refractory 
platinum-resistant 
epithelial 
ovarian 
cancer 
following 
lymphodepletion with cyclophosphamide and fludarabine and infusion with 
autologous CAR.B7-H3 T cells. 
Study 
Design: 
This is single center, open-label phase 1 dose escalation trial that uses 
modified 3+3 design to identify a recommended phase 2 dose (RP2D) of 
CAR.B7-H3 T cell product. An expansion cohort will enroll additional 
subjects at the RP2D for a total enrollment of up to 21 subjects on the 
protocol. 
Primary 
Endpoint:  
Toxicity will be classified and graded according to the National Cancer 
Institute’s Common Terminology Criteria for Adverse Events (CTCAE), 
version 5.0, CRS Grading Criteria (APPENDIX III – CRS Grading Criteria 

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and Management Guidelines) and ICANS Grading Criteria (APPENDIX 
IV – Management of Neurotoxicity/Immune Effector Cell-Associated 
Neurotoxicity Syndrome (ICANS) from CAR-T Therapy). 
Secondary 
Endpoints: 
Disease control rate will be defined as the percentage of subjects with 
[complete response (CR) + partial response (PR) + stable disease] at 6 
months per RECIST 1.1 (APPENDIX II – Tumor Measurement Based on 
RECIST 1.1) criteria.  
PFS will be measured from the time of lymphodepletion prior to infusion 
with CAR.B7-H3 to progression (as defined per RECIST 1.1 (APPENDIX 
II – Tumor Measurement Based on RECIST 1.1) or death. 
OS will be measured from the date of lymphodepletion prior to CAR.B7-
H3 T cell product administration to the date of death. 
 
 
 
 

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TABLE OF CONTENTS 
SUMMARY OF CHANGES .............................................................................................2 
SUMMARY OF CHANGES .............................................................................................4 
SUMMARY OF CHANGES .............................................................................................7 
CONFIDENTIALITY AND INVESTIGATOR STATEMENT ...................................9 
STUDY SUMMARY ........................................................................................................10 
TABLE OF CONTENTS ................................................................................................14 
TABLE OF FIGURES .....................................................................................................23 
TABLE OF TABLES .......................................................................................................23 
LIST OF ABBREVIATIONS .........................................................................................24 
1 
INTRODUCTION AND RATIONALE .................................................................29 
1.1 
Background ..........................................................................................................29 
1.2 
Current Standard of Care ...................................................................................29 
1.3 
Investigational Treatment: B7-H3 CAR-T Therapy for Ovarian 
Cancer ...................................................................................................................30 
1.3.1 
Clinical Experience with B7-H3 Monoclonal Antibodies ...........................30 
1.3.2 
Experience with Regional CAR-T Cell Product Administration ..............31 
1.3.3 
Toxicities Associated with CAR-T Cells ......................................................33 
1.4 
Rationale for LCCC 1818-ATL Study ...............................................................34 
1.4.1 
CAR.B7-H3 T cell Dose Rationale ................................................................34 
1.4.2 
Rationale for Lymphodepleting Chemotherapy .........................................35 
1.5 
Correlative Studies...............................................................................................36 
2 
STUDY OBJECTIVES ............................................................................................37 
2.1 
Primary .................................................................................................................37 
2.1.1 
To determine the safety and tolerability of autologous CAR.B7-H3 
T cell product administered intraperitoneally after 
lymphodepletion with cyclophosphamide and fludarabine to 
subjects with relapsed or refractory platinum-resistant epithelial 
ovarian cance. .................................................................................................37 
2.2 
Secondary..............................................................................................................37 
2.2.1 
To determine the disease control rate (DCR) mediated by 
autologous CAR.B7-H3 T cell product administered to subjects 
with relapsed or refractory platinum-resistant epithelial ovarian 
cancer. .............................................................................................................37 
2.2.2 
To determine the progression free survival (PFS) after 
lymphodepletion with cyclophosphamide and fludarabine and 
administration of the CAR.B7-H3 T cell product in subjects with 
relapsed or refractory platinum-resistant epithelial ovarian 
cancer. .............................................................................................................37 
2.2.3 
To determine the overall survival (OS) in adult subjects with 
relapsed or refractory platinum-resistant epithelial ovarian cancer 
following lymphodepletion with cyclophosphamide and 
fludarabine and infusion with autologous CAR.B7-H3 T cells..................37 

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2.3 
Exploratory ...........................................................................................................37 
2.3.1 
To measure if CAR.B7-H3 T cells administered intraperitoneally 
enter the blood stream and persist. ..............................................................37 
2.3.2 
To measure and compare cytokines and immunophenotypes in the 
peripheral blood after CAR.B7-H3 T cell administration. ........................37 
2.3.3 
To evaluate changes in the tumor microenvironment before and 
after treatment with CAR.B7-H3 T cells. ....................................................37 
2.3.4 
To measure changes in B7.H3 expression before and after 
treatment with CAR.B7-H3 T cells. .............................................................37 
2.3.5 
To study immunogenomics and evaluate changes in the expression 
of genes and/or proteins that may be relevant to toxicity and 
durability of response to therapy in the ascites fluid before and 
after treatment. ..............................................................................................37 
3 
STUDY ENDPOINTS ..............................................................................................38 
3.1 
Primary .................................................................................................................38 
3.1.1 
Toxicity will be classified and graded according to the National 
Cancer Institute’s Common Terminology Criteria for Adverse 
Events (CTCAE), version 5.0, CRS Grading Criteria (APPENDIX 
III – CRS Grading Criteria and Management Guidelines) and 
ICANS Grading Criteria (APPENDIX IV – Management of 
Neurotoxicity/Immune Effector Cell-Associated Neurotoxicity 
Syndrome (ICANS) from CAR-T Therapy). ...............................................38 
3.2 
Secondary..............................................................................................................38 
3.2.1 
Disease control rate will be defined as the percentage of subjects 
with [complete response (CR) + partial response (PR) + stable 
disease] at 6 months per RECIST 1.1 (APPENDIX II – Tumor 
Measurement Based on RECIST 1.1) criteria. ............................................38 
3.2.2 
PFS will be measured from the time of lymphodepletion prior to 
infusion with CAR.B7-H3 to progression (as defined per RECIST 
1.1 (APPENDIX II – Tumor Measurement Based on RECIST 1.1) 
or death. ..........................................................................................................38 
3.2.3 
OS will be measured from the date of lymphodepletion prior to 
CAR.B7-H3 T cell product administration to the date of death................38 
3.3 
Exploratory ...........................................................................................................38 
3.3.1 
CAR.B7-H3 T cells entering the blood stream will be measured by 
flow cytometry in samples of peripheral blood. ..........................................38 
3.3.2 
Cytokines and immunophenotypes will be analyzed from the 
peripheral blood at specified timepoints after administration of 
CAR.B7-H3. Cytokines will be measured by ELISA and 
immunophenotypes will be measured by flow cytometry, T-cell 
receptor sequencing and molecular gene expression profiling. .................38 
3.3.3 
Changes in tumor mutation and/or gene expression will be 
evaluated in the tumor samples obtained in subjects before 
treatment, after the 3rd CAR.B7-H3 infusion and at the time of 
progression. Tumor response and microenvironment changes will 

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be analyzed utilizing DNA sequencing, RNA sequencing, and flow 
cytometry to compare variations in gene expression, presence of 
neoantigens and driver mutations, immune cellular factors 
present, and T-cell repertoires. .....................................................................39 
3.3.4 
B7-H3 expression will be measured via IHC on tumor samples 
before treatment, after the 3rd infusion and at the time of 
progression......................................................................................................39 
3.3.5 
Changes in the gene expression of CAR T cells will be evaluated in 
the ascites fluid samples (where available) from subjects before 
treatment, after each infusion and at the time of progression. 
Tumor response and microenvironment changes will be analyzed 
utilizing DNA sequencing, RNA sequencing, and flow cytometry to 
compare variations in gene expression, presence of neoantigens 
and driver mutations, immune cellular factors present, and T-cell 
repertoires. ......................................................................................................39 
4 
STUDY PLAN ...........................................................................................................40 
4.1 
Study Treatment ..................................................................................................40 
4.1.1 
Dose Escalation Rules ....................................................................................40 
4.1.2 
Cell Procurement ...........................................................................................41 
4.1.3 
Intraperitoneal Catheter Placement ............................................................41 
4.1.4 
Lymphodepleting Chemotherapy .................................................................41 
4.1.5 
Premedication for Intraperitoneal Cellular Product 
Administration ...............................................................................................41 
4.1.6 
CAR.B7-H3 Cell Administration ..................................................................41 
4.1.7 
Definition of Dose Limiting Toxicity ............................................................42 
4.1.8 
Definition of Recommended Phase 2 Dose (RP2D) .....................................43 
4.1.9 
Potential Toxicities of the Cellular Product Administration .....................43 
4.1.10 
Clinical Monitoring ........................................................................................43 
4.1.11 
Dose Delays .....................................................................................................43 
4.1.12 
Supportive Care .............................................................................................44 
4.1.13 
Concomitant Medications/Treatments.........................................................44 
4.2 
Time & Events Table ...........................................................................................45 
5 
STUDY POPULATION ...........................................................................................49 
5.1 
Inclusion Criteria Prior to Cell Procurement ...................................................49 
5.1.1 
Written informed consent and HIPAA authorization for release of 
personal health information.  Subjects or their Legally Authorized 
Representative must sign a consent to undergo cell procurement. 
Subject will be given a copy of the informed consent form........................49 
5.1.2 
Age ≥ 18 years at the time of consent. ..........................................................49 
5.1.3 
Subject has adequate performance status as defined by ECOG 
score of ≤ 2 (see APPENDIX VI – ECOG Performance Status 
[73])..................................................................................................................49 
5.1.4 
Subjects must have histologically or cytologically confirmed 
epithelial ovarian, peritoneal or fallopian tube cancer and must 

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have a histological diagnosis of a high-grade serious histology 
based on local histopathological findings. ....................................................49 
5.1.5 
Subjects must have recurrent platinum-resistant or platinum-
refractory disease defined as: .......................................................................49 
5.1.6 
Subjects must have evaluable disease – defined as: ....................................49 
5.1.7 
Subjects must be able to have an intraperitoneal port placed either 
by vascular interventional radiology or surgically in the operating 
room. (Note: The intraperitoneal port will not be placed until the 
subject is determined to be otherwise eligible to receive the 
CAR.B7-H3 infusion and until the subject is determined to be 
otherwise eligible to receive lymphodepletion)............................................50 
5.1.8 
Female subjects of childbearing potential must be willing to 
abstain from heterosexual activity or to use 2 forms of highly 
effective methods of contraception from the time of informed 
consent until 180 days after study treatment discontinuation. The 
two contraception methods can be comprised of two barrier 
methods, or a barrier method plus a hormonal method or an 
intrauterine device that meets < 1% failure rate for protection 
from pregnancy in the product label. ...........................................................50 
5.1.9 
Subject is willing and able to comply with study procedures based 
on the judgement of the investigator or protocol designee. .......................50 
5.1.10 
Subject is willing to undergo a biopsy prior to treatment, at the 
time of intraperitoneal catheter removal, and at the time of disease 
progression (if not at their first scan), and the tumor site is 
determined to be safe by the treating investigator for biopsy 
collection. ........................................................................................................50 
5.1.11 
Subjects must not be pregnant or lactating (Note: Breast milk 
cannot be stored for future use while the mother is being treated 
on study). .........................................................................................................50 
5.1.12 
Subjects must not be deemed unlikely to be a candidate for 
successful intraperitoneal catheter placement by radiographic 
assessment. ......................................................................................................50 
5.1.13 
Subject must not have intraparenchymal lung metastases (note 
that pleural effusions are not exclusionary and that subjects with 
intraparenchymal liver disease and subjects with retroperitoneal 
disease are allowed on the study). .................................................................50 
5.1.14 
Subject must not have brain metastases. A subject with prior 
brain metastasis may be considered if they have completed their 
treatment for brain metastasis at least 4 weeks prior to being 
screened for eligibility, have been off of corticosteroids for ≥ 2 
weeks, and are asymptomatic. ......................................................................50 
5.1.15 
Subject must not have current signs and/or symptoms of bowel 
obstruction or signs and/or symptoms of a bowel obstruction 
within 3 months prior to starting treatment................................................50 

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5.1.16 
Subject must not have a history of intra-abdominal abscess within 
the past 3 months. ..........................................................................................50 
5.1.17 
Subject must not have a history of gastrointestinal perforation. ..............50 
5.1.18 
Subject must not have a history of symptomatic diverticular 
disease, confirmed by CT or colonoscopy. ...................................................51 
5.1.19 
Subjects must not be dependent on intravenous hydration or total 
parenteral nutrition. ......................................................................................51 
5.1.20 
Subject must not have a known additional malignancy that is 
active and/or progressive requiring treatment; exceptions include 
basal cell or squamous cell skin cancer, in situ cervical or bladder 
cancer, or other cancer for which the subject has been disease-free 
for at least five years. .....................................................................................51 
5.1.21 
Subject must not be currently using systemic corticosteroids at 
doses ≥10 mg prednisone daily or its equivalent; those receiving 
<10 mg daily may be enrolled at discretion of investigator. Inhaled 
steroids are allowed. Physiologic replacement hydrocortisone at 
doses 6-12 mg/m²/day is allowed. Equivalently dosed alternative 
steroids are allowed at discretion of investigator, though not to 
exceed 10 mg prednisone per day .................................................................51 
5.1.22 
Subject must not have an active infection with HIV, HTLV, HBV, 
HCV (tests can be pending at the time of cell procurement; only 
those samples confirming lack of active infection will be used to 
generate transduced cells). Note: To meet eligibility subjects are 
required to be negative for HIV antibody or HIV viral load, 
negative for HTLV1 and 2 antibody or PCR negative for HTLV1 
and 2, negative for Hepatitis B surface antigen, negative for HCV 
antibody or HCV viral load. .........................................................................51 
5.1.23 
Subjects must not have a history of intolerance to fludarabine. 
Subjects with an intolerance to bendamustine may be allowed to 
enroll at the discretion of the clinical investigator if he/she thinks 
that the subject is a candidate for lymphodepletion with 
cyclophosphamide and fludarabine..............................................................51 
5.1.24 
Subject has life expectancy ≥ 3 months. .......................................................51 
5.1.25 
Subject has evidence of adequate organ function as defined by: ..............51 
5.1.26 
Subjects must have active disease by imaging assessment within 90 
days prior to procurement. ...........................................................................51 
5.1.27 
Female subjects of childbearing potential must have a negative 
serum pregnancy test within 72 hours prior to cell procurement. 
Note: Females are considered of childbearing potential unless they 
are surgically sterile (have undergone a hysterectomy, bilateral 
tubal ligation, or bilateral oophorectomy) or they are naturally 
postmenopausal for at least 12 consecutive months. 
Documentation of postmenopausal status must be provided. ....................52 
5.2 
Eligibility Criteria Prior to Lymphodepletion ..................................................52 

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5.2.1 
Written informed consent explained to, understood by and signed 
by the subject prior to lymphodepletion; subject given a copy of 
informed consent form. .................................................................................52 
5.2.2 
Subject has an intraperitoneal catheter/port in place. (Note: The 
intraperitoneal port will not be placed until the subject is 
determined to be otherwise eligible to receive lymphodepletion 
prior to the CAR.B7-H3 infusion). ...............................................................52 
5.2.3 
Subject had no major surgery within 28 days prior to 
lymphodepletion. ............................................................................................52 
5.2.4 
Subject has not received any investigational agents or any tumor 
vaccines within 21 days prior to lymphodepletion. .....................................52 
5.2.5 
Subjects must have stopped systemic chemotherapy or radiation 
therapy for at least 21 days prior to lymphodepletion. ..............................52 
5.2.6 
Subject must have stopped bevacizumab for at least 6 weeks prior 
to lymphodepletion.........................................................................................52 
5.2.7 
Subject must have stopped hormonal therapy (tamoxifen, 
letrozole, etc.) for at least 21 days prior to lymphodepletion. ....................52 
5.2.8 
Subject is not receiving a prohibited medication at the time of 
starting lymphodepletion up through 72 hours after the last dose 
of cyclophosphamide listed in Section 8.2.1.7. .............................................52 
5.2.9 
Current use of systemic corticosteroids at doses ≥10 mg 
prednisone daily or its equivalent; those receiving <10 mg daily 
may be enrolled at discretion of investigator. Inhaled steroids are 
allowed. Physiologic replacement hydrocortisone at doses 6-12 
mg/m²/day is allowed. Equivalently dosed alternative steroids are 
allowed at discretion of investigator, though not to exceed 10 mg 
prednisone per day. ........................................................................................52 
5.2.10 
Imaging results from within 10 days prior to lymphodepletion. 
Imaging must occur at least 3 weeks after most recent therapy 
(used as baseline measure for documentation of progression before 
the lymphodepletion) to document measurable or assessable 
disease. Imaging does not need to be repeated if it is within 10 days 
prior to lymphodepletion. Subjects must have evaluable disease 
defined as: .......................................................................................................52 
5.2.11 
Subject must demonstrate adequate organ function prior to 
lymphodepletion as defined below. All tests must be obtained 
within 48 hours prior to lymphodepletion: ..................................................53 
5.2.12 
Subject does not have intraparenchymal lung metastases (Note: 
Pleural effusions are not exclusionary and that subjects with 
intraparenchymal liver disease and subjects with retroperitoneal 
disease are allowed on the study.) .................................................................53 
5.2.13 
Subject does not have a known brain metastasis. A subject with 
prior brain metastasis may be considered if they have completed 
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lymphodepletion, have been off corticosteroids for ≥ 2 weeks, and 
are asymptomatic. ..........................................................................................53 
 
Subject must have available autologous transduced activated T 
cells product that meets the Certificate of Analysis acceptance. ...............53 
5.2.14 
53 
5.2.15 
Subject does not have current signs and/or symptoms of bowel 
obstruction or signs and/or symptoms of a bowel obstruction 
within 3 months prior to lymphodepletion. .................................................53 
5.2.16 
Subject does not have a history of intra-abdominal abscess within 
3 months of lymphodepletion. .......................................................................54 
5.2.17 
Subject does not have a history of gastrointestinal perforation ................54 
5.2.18 
Subject does not have a history of symptomatic diverticular 
disease, confirmed by CT or colonoscopy ....................................................54 
5.2.19 
Subject is not dependent on intravenous hydration or total 
parenteral nutrition. ......................................................................................54 
5.2.20 
Negative serum pregnancy test within 72 hours prior to 
lymphodepleting therapy for female participants of childbearing 
potential. Note: Females are considered of childbearing potential 
unless they are surgically sterile (have undergone a hysterectomy, 
bilateral tubal ligation, or bilateral oophorectomy) or they are 
naturally postmenopausal for at least 12 consecutive months. ..................54 
5.2.21 
Subject is not lactating (Note: Breast milk cannot be stored for 
future use while the mother is being treated on study). .............................54 
5.2.22 
Subject does not have rapidly progressive disease, per treating 
oncologist’s discretion. ...................................................................................54 
5.2.23 
Subject is a good candidate for CAR.B7-H3 T cell therapy, per 
treating oncologist’s discretion. ....................................................................54 
5.3 
Eligibility Criteria Prior to Cellular Product Administration After 
Lymphodepletion .................................................................................................54 
5.3.1 
Subject has no evidence of uncontrolled infection or sepsis. .....................54 
5.3.2 
Negative serum pregnancy within 7 days of the initial cellular 
product administration. If the pre-lymphodepletion pregnancy test 
is within the 7 day window, then the pregnancy test does not need 
to be repeated. ................................................................................................54 
5.3.3 
Evidence of adequate organ function as defined by: ..................................54 
5.3.4 
Subject has no clinical indication of rapidly progressing disease in 
the opinion of the clinical investigator. ........................................................54 
5.3.5 
Subject is a good candidate for treatment with CAR.B7-H3 cell 
product per the clinical investigator’s discretion. .......................................54 
5.4 
Single Subject Exceptions ...................................................................................55 
6 
STUDY CONDUCT..................................................................................................56 
6.1 
Duration of Therapy ............................................................................................56 
6.2 
Duration of Follow-Up .........................................................................................56 
6.3 
Removal of Subjects from Protocol Therapy ....................................................56 
6.4 
Off-Study Criteria ................................................................................................57 

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6.5 
Subject Withdrawal .............................................................................................57 
6.6 
Subjects Lost to Follow-Up .................................................................................57 
7 
DESCRIPTION OF STUDY PROCEDURES .......................................................59 
7.1 
Clinical Assessments ............................................................................................59 
7.1.1 
Demographics .................................................................................................59 
7.1.2 
Medical History ..............................................................................................59 
7.1.3 
Physical Examination ....................................................................................59 
7.1.4 
Performance Status ........................................................................................59 
7.1.5 
Assessment of Safety ......................................................................................60 
7.1.6 
Assessment of Efficacy ...................................................................................60 
7.2 
Laboratory Assessments ......................................................................................60 
7.2.1 
Hematology .....................................................................................................60 
7.2.2 
Serum Chemistries .........................................................................................60 
7.2.3 
Cancer Antigen-125 Level .............................................................................61 
7.2.4 
Serum Cortisol Level .....................................................................................61 
7.2.5 
Virus Testing ..................................................................................................61 
7.2.6 
HAMA Testing ...............................................................................................61 
7.2.7 
Pregnancy Testing ..........................................................................................61 
7.3 
Correlative Studies...............................................................................................61 
7.3.1 
Function and Persistence Studies .................................................................62 
7.3.2 
Sample Collection Requirement if CRS or Severe Toxicity Occurs .........62 
7.3.3 
Fresh Tissue Studies ......................................................................................63 
7.3.4 
Ascites Fluid Analysis ....................................................................................63 
7.4 
Biobank Repository .............................................................................................63 
7.5 
Protocol Deviations ..............................................................................................65 
8 
STUDY DRUG MANAGEMENT ...........................................................................66 
8.1 
CAR.B7-H3 Cell Product ....................................................................................66 
8.1.1 
Construction of the mRNA ...........................................................................66 
8.1.2 
Generation of Genetically Modified T-cells .................................................66 
8.1.3 
Source Material ..............................................................................................66 
8.1.4 
Cell Activation and ex vivo Expansion.........................................................66 
8.1.5 
RNA Electroporation of T cells ....................................................................67 
8.1.6 
Cryopreservation of T cells ...........................................................................67 
8.1.7 
Testing .............................................................................................................67 
8.1.8 
Potential Toxicities .........................................................................................67 
8.2 
Lymphodepleting Chemotherapy .......................................................................69 
8.2.1 
Cyclophosphamide .........................................................................................69 
8.2.2 
Fludarabine ....................................................................................................71 
9 
ADVERSE EVENTS ................................................................................................74 
9.1 
Definitions .............................................................................................................74 
9.1.1 
Adverse Event (AE) .......................................................................................74 
9.1.2 
Suspected Adverse Reaction (SAR) ..............................................................74 
9.1.3 
Unexpected AE or SAR .................................................................................75 
9.2 
Documentation of Non-Serious Adverse Events or SARs ................................75 
10 SERIOUS ADVERSE EVENT ................................................................................76 

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10.1 
Definition of Serious Adverse Event ..................................................................76 
10.2 
Documentation of SAEs or Serious SARs ..........................................................76 
10.2.1 
Timing .............................................................................................................76 
10.2.2 
Documentation and Notification ...................................................................77 
10.3 
Adverse Event Reporting ....................................................................................77 
10.3.1 
IRB Reporting Requirements .......................................................................77 
10.3.2 
FDA Expedited Reporting Requirements for Studies Conducted 
Under an IND .................................................................................................77 
10.3.3 
Institutional Biosafety Committee (IBC) Reporting Requirements ..........79 
11 STATISTICS .............................................................................................................80 
11.1 
Study Design .........................................................................................................80 
11.2 
Stopping Rules ......................................................................................................80 
11.3 
Sample Size, Accrual and Duration of Accrual.................................................80 
11.4 
Data Analysis Plans..............................................................................................81 
12 STUDY MANAGEMENT........................................................................................82 
12.1 
Required Documentation ....................................................................................82 
12.2 
Institutional Review Board (IRB) Approval and Consent ...............................82 
12.3 
Institutional Biosafety Committee Approval.....................................................83 
12.4 
Registration Procedures ......................................................................................83 
12.5 
Adherence to Protocol .........................................................................................83 
12.6 
Emergency Modifications ....................................................................................83 
12.7 
Study Files and Record Retention ......................................................................83 
12.8 
Source Documentation.........................................................................................84 
12.9 
Data and Safety Monitoring Plan .......................................................................84 
13 AUDITING AND MONITORING ..........................................................................86 
14 AMENDMENTS .......................................................................................................87 
15 STUDY DISCONTINUATION ...............................................................................88 
16 CONFIDENTIALITY ..............................................................................................89 
17 REFERENCES .........................................................................................................90 
18 APPENDICES ...........................................................................................................95 
18.1 
APPENDIX I – Names of Study Personnel........................................................95 
18.2 
APPENDIX II – Tumor Measurement Based on RECIST 1.1 ........................96 
18.2.1 
Baseline Documentation of Target and Non-Target Lesions .....................96 
18.2.2 
Evaluation of Target Lesions using RECIST 1.1 Criteria .........................97 
18.2.3 
Evaluation of Non-Target Lesions using RECIST 1.1 Criteria .................97 
18.2.4 
Evaluation of Best Overall Response using RECIST 1.1 Criteria ............98 
18.3 
APPENDIX III – CRS Grading Criteria and Management Guidelines .........99 
18.4 
APPENDIX IV – Management of Neurotoxicity/Immune Effector 
Cell-Associated Neurotoxicity Syndrome (ICANS) from CAR-T 
Therapy ...............................................................................................................102 
18.5 
APPENDIX V – Treatment Algorithm for Macrophage Activation 
Syndrome ............................................................................................................105 
18.6 
APPENDIX VI – ECOG Performance Status [75] .........................................107 

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TABLE OF FIGURES 
Figure 1 Study Schema for Dosing with Prior Lymphodepletion ...............................12 
Figure 2 Dosing Schema ..................................................................................................13 
Figure 3 The effects of BY-H3.CAR-28ζ-Ts and B7-H3.CAR-BBζ-Ts on the growth 
of OC cell lines SW626, SK-0V-3 and CaoV-3 ......................................32 
Figure 4 The effect of CAR.B7-H3 on tumor growth in vivo .......................................32 
Figure 5 Schematic Representation of the Construct ...................................................66 
 
TABLE OF TABLES 
Table 1 Dose Escalation Rules (3+3) ..............................................................................40 
Table 2 Dose levels of CAR.B7-H3 T cells to be tested during dose escalation ..........42 
Table 3 Stopping Boundaries ..........................................................................................80 
Table 4 Best Overall Response........................................................................................98 
Table 5 Signs and Symptoms of CRS .............................................................................99 
Table 6 CRS Grading ....................................................................................................100 
Table 7 ICE 102 
Table 8 ICANS Grading ................................................................................................103 
 
 

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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
ANC 
Absolute Neutrophil Count 
AST 
Aspartate Aminotransferase 
ATL 
Autologous T Lymphocyte – Chimeric Antigen Receptor 
β-HCG 
Beta-Human Chorionic Gonadotropin 
BUN 
Blood Urea Nitrogen 
CAP 
College of American Pathologists 
CAR-T 
Chimeric Antigen Receptor T Cell 
CBCD 
Complete Blood Count with Differential 
cfDNA 
Circulating Free Deoxyribonucleic Acid 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Comprehensive Metabolic Panel 
CNS 
Central Nervous System 
CoA 
Certificate of Analysis 
CPO 
Clinical Protocol Office 
CR 
Complete Response 
CRS 
Cytokine Release Syndrome 
CT 
Computer Tomography 
DCR 
Disease Control Rate 
DL 
Dose Level 

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DLT 
Dose Limiting Toxicity 
DNA 
Deoxyribonucleic Acid 
DSMB 
Data Safety Monitoring Board 
DSMC 
Data Safety Monitoring Committee 
ECHO 
Echocardiography 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EFS 
Event-Free Survival 
ELISPOT 
Enzyme-Linked ImmunoSpot 
FDA 
Food and Drug Administration  
GCP 
Good Clinical Practice 
GeMCRIS 
Genetic Modification Clinical Research Information System 
GM-CSF 
Granulocyte-Macrophage Colony-Stimulating Factor 
GMP 
Good Manufacturing Practices 
HAMA 
Human Anti-Mouse Antibodies 
HBs-Ag 
Hepatitis B surface Antigen 
HBc 
Hepatitis B Core Antigen 
HBV 
Hepatitis B Virus 
HBC 
Hepatitis C Virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HIPEC 
Hyperthermic Intraperitoneal Chemotherapy 
HIV 
Human Immunodeficiency Virus 
HLH 
Hemophagocytic Lymphohistiocytosis 
HTLV 
Human T-Lymphotropic Virus 

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IB 
Investigator’s Brochure 
IBC 
Institutional Biosafety Committee 
ICANS 
Immune effector cell-associated neurotoxicity syndrome 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IDS 
Investigational Drug Service 
IEC 
Independent Ethics Committee 
IFN 
Interferon 
Ig 
Immunoglobulin 
IHC 
Immunohistochemistry 
IL 
Interleukin 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IV 
Intravenous 
kg 
Kilogram 
L 
Liters 
LCCC 
Lineberger Comprehensive Cancer Center 
LDH 
Lactate Dehydrogenase 
LVEF 
Left Ventricular Ejection Fraction 
mAb 
Monoclonal Antibody 
MAS 
Macrophage Activation Syndrome 
mg 
Milligram 
min 
Minute 
MRI 
Magnetic Resonance Imaging 

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MTD 
Maximum Tolerated Dose 
NCI-CTCAE 
National Cancer Institute – Common Terminology Criteria for Adverse 
Events 
NIH 
National Institute of Health 
NK 
Natural killer 
OC 
Ovarian Cancer 
OHRE 
Office of Human Research Ethics 
ORR 
Objective Response Rate 
OS 
Overall Survival 
OSP 
NIH Office of Science Policy 
PARP 
Poly ADP Ribose Polymerase 
PBMC 
Peripheral Blood Mononuclear Cells 
PCR 
Polymerase Chain Reaction 
PD 
Progressive Disease 
PET 
Positron Emission Tomography 
PFS 
Progression Free Survival 
PI 
Principal Investigator 
PR 
Partial Response 
PRC 
Protocol Review Committee 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
qPCR 
Quantitative Polymerase Chain Reaction 
RAC 
NIH Recombinant DNA Advisory Committee 
RECIST 
Response Evaluation Criteria in Solid Tumors 

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RFS 
Relapse-Free Survival 
RNA 
Ribonucleic Acid 
RP2D 
Recommended Phase 2 Dose 
SAE 
Serious Adverse Event 
SAR 
Suspected Adverse Reaction 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TCD 
Tolerable Cell Dose 
TLS 
Tumor Lysis Syndrome 
ULN 
Upper Limit of Normal 
UNC 
University of North Carolina 
USP 
United States Pharmacopeia 
 

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1 INTRODUCTION AND RATIONALE 
1.1 
Background 
There were approximately 22,240 new cases of and 14,070 deaths from ovarian cancer in 
the United States in 2018. The majority of women (approximately 80%) are diagnosed with 
stage III or IV disease at the time of presentation [1, 2]. For most of them, standard therapy 
involves a combination of chemotherapy and surgery. Most women undergo cytoreductive 
surgery followed by chemotherapy, which can be intravenous, intraperitoneal or a 
combination of both [3-6]. However, some women undergo neoadjuvant chemotherapy 
followed by surgery. These therapies result in response rates of 70-80%, depending on if 
the patient is optimally (< 1 cm residual disease) or suboptimally (> 1 cm residual disease) 
cytoreduced [6, 7]. Despite these excellent response rates, the majority of patients will have 
a disease recurrence. At disease recurrence prognosis depends on when recurrence 
occurred in relation to the last cycle of a platinum-based regimen. Women who are 
platinum-sensitive (> 12 months after completion of prior platinum before recurrence) have 
a 50 – 65% response rate to subsequent platinum therapy. However, these women 
ultimately develop platinum-resistant disease. For women who are either platinum-
resistant (recurrence < 6 months) or potentially platinum-sensitive (recurrence 6 – 12 
months) after completion of initial chemotherapy, there are treatment options available, but 
most are not curative [8]. Therefore, there is a critical need to identify new treatment 
options for women with recurrent ovarian cancer. 
1.2 
Current Standard of Care 
National Comprehensive Cancer Network (NCCN) guidelines outline a variety of second- 
and third-line agents that are available for the treatment of recurrent epithelial ovarian 
cancer. While these have traditionally involved other chemotherapeutic agents 
(gemcitabine, liposomal doxorubicin, topotecan, etc.) more recently other agents such as 
bevacizumab and poly ADP ribose polymerase (PARP) inhibitors have been approved. In 
women with platinum-resistant disease, response rates range from 10-25% and duration of 
response is generally less than 6 months with the most usual chemotherapeutic agents [8-
14]. Treatment in the setting of relapsed disease is typically not curative and is given with 
the intent of prolonging life or palliation of symptoms. Bevacizumab in combination with 
chemotherapy has been shown to improve progression free survival by 4 months 
(AURELIA trial) and as a single agent, response rates range from 13-16% [15]. PARP 
inhibitors have recently been approved for use as both maintenance agents after first line 
therapy and for treatment of recurrent ovarian cancer [7, 16-21]. Some of the medications 
are reserved for women who have either a germline or a somatic mutation in BRCA, 
however, niraparib has been recently approved for women who do not harbor a mutation 
in either their germline or in their tumor and are platinum-sensitive after their first 
recurrence [19].  
There are currently several trials evaluating novel combinations of approved or 
investigational agents, new immunotherapy trials, and targeted agents. Vaccine trials 

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including dendritic cell vaccines, vaccines directed at antigens enriched in tumor cells and 
patient-specific autologous tumor cell vaccines. Despite all of these agents and strategies, 
many women will have limited treatment options after 2 – 3 regimens for the treatment of 
their recurrent epithelial ovarian cancer. 
1.3 
Investigational Treatment: B7-H3 CAR-T Therapy for Ovarian Cancer 
Chimeric antigen receptor T (CAR-T) cells are immune cells that are isolated from patients 
and then genetically modified in order to make them able to identify and eliminate cancer 
cells based on the proteins that are expressed on the tumor cell surface. Impressive clinical 
responses have been reported in B-cell malignancies using CAR-T cells specific for the 
CD-19 antigen [22-24]. However, adapting this strategy to solid tumors has been more 
difficult because tumor-associated antigens which are expressed on the tumor surface are 
also often shared with normal tissues. These are also often characterized by both inter- and 
intratumor heterogeneity and are often not expressed across tumor types [25-27]. 
B7-H3 is a type I transmembrane protein that belongs to the B7 and CD28 families [28, 
29]. B7-H3 protein is not overly expressed in normal tissue, such as breast, prostate, liver, 
and colon [30, 31], but it is aberrantly expressed in 60% to 93% of tumor cells in several 
cancer types including melanoma, leukemia, breast, prostate and ovarian cancer [31-35]. 
In addition, B7-H3 is found overexpressed by the tumor-associated vasculature and stroma 
fibroblasts [31, 32]. Overexpression of B7-H3 on tumor cells frequently correlates with 
fewer tumor-infiltrating lymphocytes, faster cancer progression, and poor clinical outcome 
in several malignancies, such as prostate cancer, ovarian cancer, lung cancer and clear cell 
renal carcinoma [32-42]. 
1.3.1 
Clinical Experience with B7-H3 Monoclonal Antibodies 
B7-H3-specifc monoclonal antibodies (mAbs) showed antitumor activity against B7-
H3+ tumor cells in preclinical xenograft mouse models, and phase 1 clinical trials are 
currently ongoing to test safety and antitumor activity (NCT01099644, NCT01502917, 
NCT02381314 and NCT02982941) [31, 43-46]. Preliminary phase 1 data with the B7-
H3-specific MGA271 (enoblituzumab) antibody did not show toxicity (STIC 2015). 
This study was a dose escalation study of MGA271 in patients with a variety of tumors; 
for cycle 1 the patients received weekly dosing for 4 weeks and then off for 4 weeks. 
After cycle 2, they were dosed weekly for three weeks followed by one week off prior 
to repeating the cycle. In this patient cohort, the antibody was considered safe in that 
no treatment related discontinuations or severe immune-mediated toxicity was 
observed. Of the 116 patients, only 5 (4%) had any grade 3 – 4 adverse events and only 
1 (1%) had a grade 3-4 infusion-related reaction/cytokine release syndrome [36]. At 
the time of presentation, 88 patients had evaluable disease and the interim results 
supported continued evaluation of MGA271 as monotherapy and in combination with 
checkpoint inhibitors. 

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1.3.2 
Experience with Regional CAR-T Cell Product Administration  
Ovarian cancer is characterized with metastatic spread in the peritoneal cavity. While 
extra-peritoneal recurrences can occur (retroperitoneal nodes, chest, brain, etc.), the 
majority of women will recur with peritoneal based disease and will succumb to the 
effects of complications related to this, which can include progressive bowel 
obstruction. Intraperitoneal therapy has been a hallmark of ovarian cancer treatment for 
decades and new advances continue supporting this strategy. In 2006, the NCI released 
a clinical announcement in support of the benefits of intraperitoneal chemotherapy in 
women with optimally debulked ovarian cancer [47]. Despite the survival advantage 
reported from these regimens [48], there has been slow adoption of this treatment 
strategy in part due to catheter-related complication, treatment toxicity and increased 
number of visits for patients. The most recent iteration of this strategy has involved 
intraperitoneal chemotherapy during surgery delivered under hyperthermic conditions 
(HIPEC-hyperthermic intraperitoneal chemotherapy). The strategy behind this 
treatment includes that the hyperthermia increases the penetration of chemotherapy at 
the peritoneal level, that it increases the sensitivity of the cancer to the 
chemotherapeutic agents, and that it induces apoptosis, inhibits angiogenesis, and has 
additional effects [49]. A recent randomized phase III trial of HIPEC in patients 
undergoing interval cytoreduction after neoadjuvant chemotherapy was recently 
published. In this study, the addition of HIPEC led to a hazard ratio for recurrence or 
death of 0.66 (95% CI, 0.50 to 0.87, p=0.003). Additionally, the percentage of patients 
who had grade 3 – 4 toxicity was no different between the two treatment arms (25% v 
27%, p=0.76).  Both after initial cytoreductive surgery in the absence of neoadjuvant 
chemotherapy and in the setting of interval cytoreductive surgery, intraperitoneal 
therapy appears to improve outcomes for women with advanced ovarian cancer. This 
has also been shown in colorectal cancer in which patients who underwent 
cytoreductive surgery and HIPEC had an improved overall survival as compared to 
those who underwent intravenous chemotherapy [50, 51]. Therefore, it is reasonable to 
explore intraperitoneal therapy in the recurrent setting. 
Our group (Dotti et al.) investigated the antitumor effects of CAR.B7-H3 T cells in 
ovarian cancer models. Three human OC cell lines (SW626, SK-OV-3 and CaoV-3) 
which showed B7-H3 expression were co-cultured with CAR.CD19 T cells, B7-
H3.CAR-28ζ-Ts or B7-H3.CAR-BBζ-Ts at T cell to tumor cell ratio of 1:5. As shown 
in Figure 3, both B7-H3.CAR-28ζ-Ts and B7-H3.CAR-BBζ-Ts effectively controlled 
[52]the growth of OC cell lines and led to released cytokines (IFN-γ and IL-2) in the 
culture supernatants. 

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(A and B) Representative bioluminescence images (A) and bioluminescence kinetics (B) of Fflu-SK-
OV-3 tumor growth upon IP inoculation into NSG mice (5x105 cells/mouse) and treatment 14 days later 
with IP inoculation of CD19.CAR-Ts, B7-H3.CAR-28ζ-Ts and B7-H3.CAR-BBζ-Ts (5x106 
cells/mouse). Error bars denote SD, ***p<0.0001, Chi-square test. (C) Kaplan-Meier survival curve of 
mice developing OC (5 mice/group), **p=0.0091, Chi-square test. 
Katz et al, published similar findings in a colorectal cancer model leading to the 
conclusion that this data supported the development of IP CAR-T therapy in patients 
with peritoneal malignancies [52]. 
1.3.3 
Toxicities Associated with CAR-T Cells 
The four most common toxicities seen with CAR T cells are cross reactivity, cytokine 
release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome 
(ICANS) and macrophage activation syndrome [53, 54].  
Cross reactivity is due to the expression of the targeted antigen in normal tissues in 
addition to tumor cells [55]. Depending on the normal tissues targeted, side effects can 
be manageable, such as the B cell aplasia observed in patients treated with CD19-
specific CAR-T cells, or lethal if organs such as heart, lung or liver are affected [53, 
56-59]. However, this on-target off-tumor toxicity, can be a major obstacle to the use 
of CAR-T cells engineered for the treatment of solid malignancies such as ovarian 
cancer [60]. As a result, in this study mRNA-engineered T cells will be used evaluate 
the safety of CAR-T cells targeting antigens on solid tumors in a more controlled and 
transient manner as previously performed by Beatty et. Al. to demonstrate initial safety 
of CAR-T cells targeting mesothelin in patients with mesothelin-expressing solid 
tumors [60]. RNA based CAR-T cells will not persist long term as the RNA is diluted 
during cellular division and thus it is unlikely to find RNA-expressing cells more than 
10 days after treatment, thereby mitigating the on-target, off tumor toxicities. 
CRS symptoms can vary from mild flu-like symptoms to more severe toxicities such 
as vascular leak, hypotension, coagulopathy, pulmonary edema and multi-organ failure 
[56-59]. CRS-associated toxicities, when severe, require intensive medical 
management including vasoactive agents for hemodynamic support, mechanical 
ventilation, anti-epileptics, and antipyretics [53]. Cytokine elevations are detectable in 
most subjects; however, the degree of elevation does not correlate with the severity of 
CRS or response to therapy. The management of CRS to date involves supportive care 
measures and targeted therapy with tocilizumab (monoclonal antibody that blocks the 
IL-6 receptor) administered with or without corticosteroid therapy to suppress the 
immune response. Currently, the use of tocilizumab appears to be effective in most 
patients with limited inherent toxicity. As a result, with the initial approval of 
KymriahTM, the first FDA approved CAR-T cell product, tocilizumab was approved 
for the treatment of severe or life-threatening CAR-T cell inducted CRS in adult and 
pediatric subjects [61]. In some cases, concomitant administration of corticosteroids 
with tocilizumab may be required to alleviate symptoms related to CRS [62]. 

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Neurological toxicities such as progressive confusion, aphasia, word finding difficulty, 
obtunded states with airway compromise and encephalopathy have been described in 
subjects experiencing ICANS [54, 63]. ICANS can occur on its own or concurrently 
with or after CRS.  
Although rare, hemophagocytic lymphohistiocytosis (HLH) / macrophage activation 
syndrome, and sepsis have also been described as CAR-T-cell-related safety concerns 
[64]. Macrophage activation syndrome is characterized by pancytopenia, liver 
insufficiency, coagulopathy and neurological symptoms and is thought to be mediated 
by uncontrolled proliferation and activation of T cells leading to macrophage activation 
and differentiation and cytokine production with hemophagocytosis. 
Clinical experience with these toxicities has evolved and continues to grow. A recent 
review by Lee et al. provides guidance for the management of CAR-T-cell-related 
toxicities [54]. In contrast to the delayed onset of autoimmune toxicities associated with 
immune checkpoint inhibitor therapies, toxicities intimately associated with CAR-T-
cell therapy tend to be acute, less diverse, and more predictable. Importantly, intensive 
monitoring and prompt management of toxicities is essential to minimize the morbidity 
and mortality associated with CAR-T cell therapy. 
1.4 
Rationale for LCCC 1818-ATL Study 
The preclinical observations summarized in Section 1.3 support B7-H3 as a viable target 
of CAR-T therapy for ovarian cancer. Based on these observations, we will conduct a phase 
1 study of CAR.B7-H3 T cell product in subjects with recurrent epithelial ovarian cancer. 
Escalating doses of CAR.B7-H3 T cells ranging from 7.5 × 107 cells/infusion to 2 × 108 
transduced cells/infusion will be evaluated in up to 12 subjects to determine the safety and 
tolerability of this treatment modality and identify a recommended phase 2 dose for further 
study based on 3+3 dose finding rules. After dose-finding is completed, an expansion 
cohort will enroll up to 12 subjects at the estimated RP2D to further assess the safety and 
efficacy of CAR.B7-H3 T cells. Additionally, disease control rates (DCR), and progression 
will be determined based on imaging data and RECIST 1.1 criteria. The trial will also 
evaluate cytokine profiles and the expansion and persistence of CAR.B7-H3 T cells in 
peripheral blood samples after infusion. We anticipate the maximum expansion of 
CAR.B7-H3 T cells to occur within 7 days following cellular product administration. 
1.4.1 
CAR.B7-H3 T cell Dose Rationale 
Other phase I trials in women with ovarian cancer have had starting doses of 3×105/kg 
(MUC-16ecto) and 3×107/m2 (Mov19-BBZ) (NCT03585764) [65]. However, for this 
trial, mRNA electroporated CAR-T cells are being used; due to the transient expression 
of the CAR as compared to stable insertion of the CAR in T cells in other products, the 
overall effect of our product is completely dependent on the dose of CAR-T cells since 
there is no expansion of these cells in vivo. Therefore, dosing based on Beatty et. Al. 
will be used [60]. The Beatty et. Al. phase I trial evaluated mRNA-engineered T cells 
that targeted mesothelin and patients received 3 intravenous infusions or in the case of 

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patient 2 received 8 intravenous infusions and 2 intratumoral injections, with doses 
starting at 3×108 cells. In the Beatty et. Al. trial, there were no adverse events with 
weekly dosing at this dose level. Therefore, for this trial the starting dose will be 
7.5×107 cells/infusion for 3 weekly infusions with a dose escalation to 2×108 
cells/infusion for 3 weekly infusions with lymphodepletion.    
It is understood that cross reactivity due To the expression of the target antigen in 
normal tissue in addition to the tumor tissue may result in toxicity and can be a major 
obstacle to the use of CAR-T cells engineered for the treatment of solid malignancies 
such as ovarian cancer [65]. As a result, in this study mRNA-engineered T cells will be 
used to evaluate the safety of CAR-T cells targeting antigens on solid tumors in a more 
controlled and transient manner as previously performed by Beatty et. Al. to 
demonstrate initial safety of CAR-T cells targeting mesothelin in patients with 
mesothelin-expressing solid tumors [65]. RNA based CAR-T cells will not persist long 
term as the RNA is diluted during cellular division and thus it is unlikely to find 
persistent RNA-expressing cells. Beatty et. Al. showed that maximal levels of 
transgene introduced in T cells by mRNA were detected within 2 hours of infusion 
when mRNA-based CAR-T cells were infused directly intravenously [65]. Due to the 
biodegradable nature of the transgene, the levels then progressively decreased on 
successive days [65]. This will mitigate the on-target, off-tumor toxicities. It is 
anticipated that maximal detection of CAR.B7-H3 cells to occur within 7 days 
following cellular product administration, which is the rationale for the weekly doses.  
With regards to our two dosing strategies, dose level will increase by 2.6-fold for each 
of the three weekly infusions. In other CAR-T trials, the proposed dose increases 
between cohorts was 3 fold: 3×105 cells/kg; 1×106 cells/kg; 3×106 cells/kg; 1×107 
cells/kg [60]. Therefore, this dose escalation is consistent with those used in other 
CAR-T cell trials. While these were not mRNA-engineered trials, this dose increase is 
consistent and due to the transient nature of the product, this dosing strategy should 
have less off-tumor on-target toxicity and be safer for the patients. 
1.4.2 
Rationale for Lymphodepleting Chemotherapy 
Lymphodepleting chemotherapy has been shown to improve the persistence of 
modified T cells and has been associated with improved progression free survival.  
Brentjens et al. studied the safety and persistence of chimeric antigen receptor T cells 
with antibody against CD19 and found improved clinical benefit in subjects who 
received prior conditioning chemotherapy and had low tumor burden or minimal 
residual disease [22]. In addition, subjects that were treated with modified T cells 
without prior cyclophosphamide had very low frequency of T cells detected in the 
peripheral blood. In contrast, subjects who received cyclophosphamide conditioning 
had T cells more readily detected over time in the blood and bone marrow.  
Lymphodepleting chemotherapy also reduces the number of the host’s suppressive 
cells, such as regulatory T cells, allowing the genetically modified T cells to expand 

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and eradicate tumor cells [66]. The conditioning regimen may also stimulate the 
production of cytokines such as IL-7 or IL-15, which may also favor expansion of the 
infused cells [23, 67]. Grupp et al. showed improved T-cell counts and proliferation in 
subjects who received CAR-T cells on day 2 after conditioning chemotherapy 
compared to day 90, supporting the theory that T cell infusion should occur early after 
conditioning [68]. 
In this phase 1 dose-finding trial, subjects will receive a lymphodepleting 
chemotherapy consisting of cyclophosphamide 300 mg/m2/day and fludarabine 30 
mg/m2/day IV for 3 consecutive days administered 2 – 14 days prior to initial cellular 
product administration. Cyclophosphamide and fludarabine were chosen given 
documented cyclophosphamide activity in patients with recurrent epithelial ovarian 
cancer [69, 70] and the benefits of fludarabine for lymphodepletion prior to CAR T cell 
infusion [66]. 
1.5 
Correlative Studies 
We will perform function and persistence studies, which will include functional assays, 
such as in vitro reactivation of PBMCs and immunophenotyping using flow cytometry. 
CAR.B7-H3 T cells entering the blood stream will be measured by flow cytometry. Pre- 
and post-treatment tumor samples and ascites fluid (when available) samples will be 
obtained and analyzed to evaluate changes after CAR.B7-H3 T cell product administration. 
Changes in tumor mutation and/or gene expression will be evaluated in the tumor samples 
or ascites obtained before and after treatment. Gene expression will be measured using 
either single cell or bulk RNA-sequencing, Nanostring or qPCR.  Mutational analysis will 
be performed using whole genome or whole exome sequencing.  T cell repertoire analysis 
will be evaluated using next generation sequencing of T cell receptor Vβ and/or paired 
sequencing for Vαβ. 
 

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2 STUDY OBJECTIVES 
2.1 
Primary 
2.1.1 
To determine the safety and tolerability of autologous CAR.B7-H3 T cell product 
administered intraperitoneally after lymphodepletion with cyclophosphamide and 
fludarabine to subjects with relapsed or refractory platinum-resistant epithelial 
ovarian cancer. 
2.2 
Secondary 
2.2.1 
To determine the disease control rate (DCR) mediated by autologous CAR.B7-H3 T 
cell product administered to subjects with relapsed or refractory platinum-resistant 
epithelial ovarian cancer. 
2.2.2 
To determine the progression free survival (PFS) after lymphodepletion with 
cyclophosphamide and fludarabine and administration of the CAR.B7-H3 T cell 
product in subjects with relapsed or refractory platinum-resistant epithelial ovarian 
cancer.  
2.2.3 
To determine the overall survival (OS) in adult subjects with relapsed or refractory 
platinum-resistant epithelial ovarian cancer following lymphodepletion with 
cyclophosphamide and fludarabine and infusion with autologous CAR.B7-H3 T 
cells. 
2.3 
Exploratory 
 

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3 STUDY ENDPOINTS  
3.1 
Primary 
3.1.1 
Toxicity will be classified and graded according to the National Cancer Institute’s 
Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, CRS 
Grading Criteria (APPENDIX III – CRS Grading Criteria and Management 
Guidelines) and ICANS Grading Criteria (APPENDIX IV – Management of 
Neurotoxicity/Immune Effector Cell-Associated Neurotoxicity Syndrome 
(ICANS) from CAR-T Therapy).  
(Note: The safety evaluation period for DLT assessment will encompass toxicities 
related to the cell therapy that are experienced starting on the day of initial CAR.B7-
H3 T cell product administration up through 4 weeks after the final (third) CAR.B7-
H3 T cell product administration. See Sections 4.1.7 and Section 4.1.8 of the protocol 
for definitions of DLTs and RP2D, respectively. General safety monitoring will begin 
at the time of procurement). 
3.2 
Secondary 
3.2.1 
Disease control rate will be defined as the percentage of subjects with [complete 
response (CR) + partial response (PR) + stable disease] at 6 months per RECIST 1.1 
(APPENDIX II – Tumor Measurement Based on RECIST 1.1) criteria.  
3.2.2 
PFS will be measured from the time of lymphodepletion prior to infusion with 
CAR.B7-H3 to progression (as defined per RECIST 1.1 (APPENDIX II – Tumor 
Measurement Based on RECIST 1.1) or death.  
3.2.3 
OS will be measured from the date of lymphodepletion prior to CAR.B7-H3 T cell 
product administration to the date of death. 
3.3 
Exploratory 

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4 STUDY PLAN 
This single center, open-label phase 1 study will determine the safety and tolerability of 
escalating doses of autologous activated T lymphocytes expressing the chimeric antigen 
receptor specific for B7-H3 in recurrent epithelial ovarian cancer. During dose finding, up to 
12 subjects will receive infusions of the cellular product expressing the CAR.B7-H3. 
4.1 
Study Treatment 
4.1.1 
Dose Escalation Rules 
Dose escalation will be performed as described below considering the dose limiting 
toxicities listed in section 4.1.7. Two doses will be explored with prior 
lymphodepletion. The starting dose will be 7.5 × 107 cells/infusion (Dose Level (DL) 
1). If there are no dose limiting toxicities (DLTs) within 4 weeks of the third cellular 
product administration in these 3 subjects, then the next cohort will evaluate 2 × 108 
cells/infusion (DL2). The maximum tolerated cell dose is defined as a dose with the 
probability of DLT of 20%. The estimated maximum tolerated cell dose after the 3+3 
design is the higher dose with observed DLT rate less than 33%.  If enough cells for 3 
infusions are not generated, then a subject may be treated at a previously cleared dose 
level on which they would have enough cells to receive all three infusions. Their DLT 
data will be incorporated in the dose escalation/de-escalation algorithm and will be 
used to estimate the maximum tolerated cell dose. A dose level may be expanded to 4-
9 subjects to obtain more data at that dose. If more than 3 subjects are enrolled at a dose 
and ≥0.33 of the total number of subjects on a dose level experiences a DLT, the study 
would not escalate to the next highest dose level and the MTD would be exceeded. 
Recommended phase 2 tolerable cell dose (RP2D) will be decided based on the 
maximum tolerated cell dose and additional factors. 
If dose level 1 is not tolerated, subjects may be enrolled on dose level -1 at a dose of 
3.75 x 106 cells/infusion. After dose escalation is completed, an expansion cohort will 
enroll up to 12 subjects to further assess the safety and efficacy of CAR.B7-H3 T cells. 
Subjects enrolled in the expansion cohort will continue to be monitored for safety using 
the stopping rules included in Section 11.2. 
Table 1 Dose Escalation Rules (3+3) 
Number of Subjects with DLT 
Action 
0 out of 3 subjects 
Escalate to next dose level 
1 out of 3 subjects 
Accrue 3 additional evaluable subjects at current 
dose level 
1 out of 6 subjects 
Escalate to the next dose level 
2 or more subjects in a dosing cohort 
D-escalate to the next lower dose level 

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The first three subjects evaluated on each dose level must complete a 4-week evaluation 
period after the initial infusion before additional subjects are dosed in that cohort. Prior 
to escalating or de-escalating to the next dose level, all subjects in the prior cohort must 
have cleared the DLT evaluation window. 
The doses of cells to be explored are provided in Section 4.1.6. 
See Section 4.1.7 for definitions of DLT and Section 4.1.8 for the definition of the 
RP2D. 
4.1.2 
Cell Procurement 
Peripheral blood, up to 300 mL (in up to 3 collections) will be obtained from subjects 
for cell procurement. In subjects with inadequate lymphocyte count in the peripheral 
blood, a leukapheresis may  be performed to isolate sufficient T cells. The parameters 
for apheresis will be up to 2 blood volumes. 
4.1.3 
Intraperitoneal Catheter Placement 
The intraperitoneal catheter will be placed in patients who are determined to be 
otherwise eligible for lymphodepletion. 
Aspira Drainage system (Meritmedical) will be placed either in the operating room at 
the time of laparoscopically directed biopsies or, if the patient has ascites, by vascular 
radiology. This device is cleared by the FDA.  
4.1.4 
Lymphodepleting Chemotherapy 
Subjects will require lymphodepletion and will receive a lymphodepleting 
chemotherapy regimen with cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 
administered IV x 3 days per institutional standard prior to initial cellular product 
administration. Prophylaxis (e.g., mesna, hydration, antiemetics, etc.) needed prior to 
cyclophosphamide chemotherapy will be provided per institutional guidelines. 
4.1.5 
Premedication for Intraperitoneal Cellular Product Administration 
Subjects may be pre-medicated with diphenhydramine up to 1 mg/kg IV (max 50 mg) 
and acetaminophen 10 mg/kg PO (max 650 mg) prior to each cellular product 
administration. We will pre-medicate subjects who have a history of reactions to blood 
products. Corticosteroids should be avoided given their detrimental effect on the 
survival of the infused T cells. Anti-emetics in appropriate dosage for each subject will 
be prescribed as necessary. 
4.1.6 
CAR.B7-H3 Cell Administration 
Prior to CAR.B7-H3 administration, in the absence of ascites, 100-200 mL of saline 
will be infused into subjected intraperitoneally via an IP port/catheter. CAR.B7-H3 T 

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cell product will be administered by a licensed healthcare individual intraperitoneally 
over 5-10 minutes via an intraperitoneal port/catheter. The volume of infusion will 
depend upon the concentration of the cells when frozen and the size of the subject. The 
expected volume will be up to 50 mL. After the cellular product administration 
intraperitoneal catheter should be flushed with normal saline solution (up to 2x the 
volume of the CAR.B7-H3 infusion). The subject will then be rolled per institutional 
intraperitoneal chemotherapy protocols to distribute the intraperitoneally infused 
product. 
Subjects will receive three weekly CAR.B7-H3 T cell product infusions at the same 
dose. The cell dose levels that will be evaluated are outlined below. The starting dose 
will be 7.5 × 107 cells/infusion of transduced cells. If this dose is not tolerated, then a 
lower dose (DL -1) of 3.75 × 106 cells/infusion will be explored. If there is an 
insufficient number of cells manufactured to treat a subject with 3 infusions of 
CAR.B7-H3 T cells on their assigned dose level, then the subject may be treated on a 
lower dose level. Subjects will only be treated on dose levels for which enough cells 
have been manufactured to complete all three infusions. 
Table 2 Dose levels of CAR.B7-H3 T cells to be tested during dose escalation 
Dose Level 
Dose (number of cells/infusion) 
-1 
3.75 × 106 
1 
7.5 × 107 
2 
2 × 108 
4.1.7 
Definition of Dose Limiting Toxicity 
An event will be considered a DLT per NCI CTCAE criteria, version 5.0, CRS grading 
criteria (APPENDIX III – CRS Grading Criteria and Management Guidelines) or 
ICANS grading criteria (APPENDIX IV – Management of Neurotoxicity/Immune 
Effector Cell-Associated Neurotoxicity Syndrome (ICANS) from CAR-T Therapy) if 
it occurs within the DLT reporting period (i.e., evaluation period following the initial 
cellular product administration and continuing until 4 weeks after the final cellular 
product administration) as specified below: 
o Any treatment-emergent Grade ≥ 3 CRS event that does not decrease to Grade 
≤ 2 within 7 days;  
o Any treatment-emergent NCI-CTCAE Grade 5 event; 
o Any treatment-emergent autoimmune toxicity Grade ≥ 3; 
o NCI-CTCAE Grade ≥ 3 allergic reactions related to the cellular product; 

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o NCI-CTCAE Grades ≥ 3 organ toxicity (cardiac, dermatologic, gastrointestinal, 
hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing or due 
to the underlying malignancy and occurring within 4 weeks of the final cell 
infusion; 
o Any Grade ≥4 febrile neutropenia or bleeding.  
DLTs are defined as at least possibly related to CAR.B7-H3 T cell product. If an 
apparent DLT is clearly due to underlying epithelial ovarian cancer and is unrelated to 
the cell infusion, then the investigator will specify that the event is not a DLT. 
4.1.8 
Definition of Recommended Phase 2 Dose (RP2D) 
The maximum tolerated cell dose is the higher dose among the two studied with 
observed DLT rate less than 33%. Recommended phase 2 tolerable cell dose (RP2D) 
will be decided based on the maximum tolerated cell dose, DLTs observed in the dose-
finding portion of the study and additional factors including the ability to manufacture 
the appropriate quantity of cells and the number of subjects who are removed early 
from treatment and do not proceed with receiving all 3 infusions. 
4.1.9 
Potential Toxicities of the Cellular Product Administration 
Potential toxicities may be categorized as those related to infusion of T cells; cross-
reactivity with normal tissues; cytokine release syndrome (CRS), Immune Effector 
Cell-Associated Neurotoxicity Syndrome (ICANS), and macrophage activation 
syndrome (also refer to Section 8.1.8). 
4.1.10 
Clinical Monitoring 
Monitoring will be undertaken according to institutional standards for administration 
of blood products. Subjects will be monitored for at least 4 hours after each cellular 
product administration. 
Fever will mandate initial hospitalization for subjects discharged after this observation 
period. Any evidence of ICANS will also mandate hospitalization for all subjects. All 
phase 1 subjects must reside in local housing (as designated by the Cellular 
Therapeutics Program Local Housing SOP). Subjects with medical indications for 
inpatient care or those whose physicians assess that outpatient care will pose an undue 
risk will remain inpatient for their treatment until indications for inpatient care have 
resolved. Subjects will be monitored as outlined in the Time & Events Table. 
4.1.11 
Dose Delays 
For subjects who receive lymphodepleting chemotherapy, the initial administration of 
CAR.B7-H3 T cell product may be delayed per Principal Investigator’s discretion if a 
subject has unresolved serious adverse reactions (including pulmonary reactions, 

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cardiac reactions, or hypotension) from preceding chemotherapies, active uncontrolled 
infection, or worsening tumor burden following lymphodepleting chemotherapy. This 
may extend the time between lymphodepletion in those subjects and cellular product 
administration beyond the 14 days outlined within the protocol.   
The44econdd and/or third infusion will be delayed for any treatment emergent non-
hematological >grade 2 adverse events determined to be related to the CAR.B7-H3 T 
cell product. The CAR.B7-H3 T cell administrations may resume when the treatment 
emergent Aes resolve to baseline. If a subject has treatment delayed >4 weeks, then the 
subject will be permanently discontinued from treatment. 
4.1.12 
Supportive Care 
Subjects will receive supportive care for acute or chronic toxicity, including blood 
components or antibiotics, and other intervention as appropriate.   
4.1.12.1 
Cytokine Release Syndrome  
Please refer to APPENDIX III – CRS Grading Criteria and Management Guidelines 
for the CRS treatment algorithm.  
4.1.12.2 
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) 
Please refer to APPENDIX IV – Management of Neurotoxicity/Immune Effector 
Cell-Associated Neurotoxicity Syndrome (ICANS) from CAR-T Therapy for the 
ICANS treatment algorithm. 
4.1.12.3 
Macrophage Activation Syndrome  
Please refer to APPENDIX V – Treatment Algorithm for Macrophage Activation 
Syndrome for the treatment algorithm for macrophage activation syndrome.   
4.1.13 
Concomitant Medications/Treatments 
Ideally, subjects should not receive other antineoplastic agents for at least 4 weeks after 
their final CAR-T cell infusion (for purposes of efficacy evaluation); however, subjects 
with progressive disease may receive other therapy if needed at the discretion of their 
attending physician. If subjects receive other therapy for progressive disease, they will 
come off study

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4.2 
Time & Events Table 
Study Assessments 
Screening1 
 
 
 
 
 
 
Study Treatment Follow-Up2 
Follow-
Up2, 3 
Pre-
procure-
ment 
CELL PROCUREMENT    ||    BRIDGING THERAPY17 
Pre-
lymp
h 
LYMPHODEPLETION13 
W0
D0 
W0 
D3 
W1
D0 
W1 
D3 
W2
D0 
W2 
D3 
W3
D0 
W4
D0 
W6
D0 
M3 
M6 
M9 
M12 
 
Medical history  
× 
× 
× 
 
× 
 
× 
 
× 
× 
× 
× 
× 
× 
× 
× 
Physical exam 
× 
× 
× 
 
× 
 
× 
 
× 
× 
× 
× 
× 
× 
× 
× 
Performance status 
× 
× 
× 
 
× 
 
× 
 
× 
 
 
× 
× 
× 
× 
 
Eligibility 
× 
× 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
Echocardiography4 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test5 
× 
× 
×5 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology6 
× 
×6 
×6 
 
× 
 
× 
 
 
× 
× 
× 
× 
× 
× 
 
Virus testing7 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IP catheter placement 
 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistries6 
× 
×6 
×6 
 
× 
 
× 
 
 
× 
× 
× 
× 
× 
× 
 
Serum cortisol 
 
× 
 
 
 
 
 
 
 
 
× 
× 
× 
× 
× 
 
CA 125 
× 
× 
× 
 
 
 
 
 
 
 
× 
× 
× 
× 
× 
×3 
Tumor imaging8 
×8 
×8 
 
 
 
 
 
 
 
 
× 
× 
× 
× 
× 
×8 
Correlative Blood Sample9 
 
×9 
×9 
x 
× 
x 
× 
x 
× 
× 
× 
 
 
 
 
 
HAMA testing10 
 
× 
 
 
 
 
 
 
 
 
× 
 
 
 
 
 
Toxicity assessment11 
× 
× 
× 
 
× 
 
× 
 
× 
× 
× 
 
 
 
 
 
Certificate of analysis12 
 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infusion of CAR.B7-H314 
 
 
× 
 
× 
 
× 
 
 
 
 
 
 
 
 
 
Tissue biopsy15 
 
 
× 
 
 
 
 
× 
 
 
At the Time of Progression 
Ascites collection16 
 
 
× 
× 
x 
× 
x 
× 
x 
 
At the Time of Progression 

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Footnotes to Time &Events Table 
1. Screening includes tests to confirm eligibility for procurement, lymphodepletion and cell treatment. The 
presence of two doses of tocilizumab onsite must be confirmed prior to each cell infusion. Some pre-
infusion screening tests may not be performed until the day of infusion. A window of 7 days will apply 
to all procurement labs unless specified below.  
2. A window of ±3 days will apply to all study visits for the first 4 weeks unless otherwise noted below. A 
window of ±1 day will apply to the Week 0 Day 3 visit. A window of +7 days will apply to the 6 week 
visit. A window of ±10 days will apply to the every 3 months study visits, and a window of ±30 days 
will apply to visits separated by ≥ 6 months. Yearly follow-up visits during long-term follow-up until 
disease progression or for a total of 5 years. Follow-up visits on month 3 and beyond can be conducted 
locally (i.e., local health care provider, local treating oncologist, etc.).  The study team would continue 
to contact the subjects at the long-term follow-up time points and request they visit their local healthcare 
provider to complete the follow-up test and assessments, where applicable. The study team would collect 
clinical information, tests and assessments results, other clinical observations from the subject’s medical 
record and their local health care provider. 
3. Performed every 3 months (±14 day window) starting at month 3 until disease progression or for up to 
2 years post initial infusion and then will be performed every 6 months (±30 day window) thereafter for 
up to 5 years post initial infusion. Follow-up visits on month 3 and beyond can be conducted locally (i.e., 
local health care provider, local treating oncologist, etc.).  
4. Echocardiography to measure left ventricular ejection fraction (LVEF). A window of 90 days prior to 
procurement will be allowed for the ECHO. If a subject undergoes cardiac toxic therapy after 
echocardiography, it must be repeated prior to procurement. 
5. Serum pregnancy testing will be done in female subjects of childbearing potential within 72 hours prior 
to procurement. It should be repeated within 72 hours prior to lymphodepletion. Serum pregnancy test 
will be done within 7 days of initial cell infusion (does not need to be repeated if pre-lymphodepletion 
pregnancy test is within this window). 
6. Hematology and serum chemistries (CMP) must be collected within 72 hours of lymphodepletion and 
24 hours of the initial cellular product administration.  
7. HIV, HBV, HCV testing required for confirmation that no active infection exists at the time of 
procurement. Results of this testing can be pending at the time of cell procurement; only those samples 
with a confirmed absence of active infection will be used to generate the cellular product. A window of 
30 days will apply to virus testing. 
8. Tumor imaging for disease assessment will be performed at baseline (within 90 days before 
procurement) and within 10 days prior to lymphodepletion. Imaging prior to lymphodepletion must 
occur at least 3 weeks after the subject’s most recent therapy to document measurable or assessable 
disease. Imaging will then occur at 6 weeks ±7-days following the initial infusion of CAR.B7-H3. 
Imaging will be performed every 3 months (±14 day window) at treating investigator’s discretion starting 
at month 3 until disease progression for up to 2 years post initial infusion and then will be performed 
every 6 months (±30 day window) thereafter for up to 5 years post initial infusion. The choice of imaging 
will depend on what studies have been most informative in following the subject’s disease (i.e., PET, 
CT scans, MRI, nuclear imaging). If imaging studies are performed at other times after treatment on this 
study, the data will be collected, and information gained will be used for this study. The tests performed 
at baseline for assessment of disease should be performed consistently throughout the study. Follow-up 

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visits on month 3 and beyond can be conducted locally (i.e., local health care provider, local treating 
oncologist, etc.). 
9. The analyses will be used to monitor function and persistence in peripheral blood and will include 
functional assays such as in vitro reactivation of PBMCs in subjects for whom the appropriate reagents 
are available and for immunophenotyping. Cytokines will also be measured. Blood samples will be 
collected pre-lymphodepletion and also collected on the day of initial cell infusion at pre-dose 
(approximately 19 mL of blood), 1 hour (±15 minutes) post infusion, between 3 – 4 hours post infusion 
and day 3 of each weekly infusion (approximately 16 mL of blood) to monitor function, persistence and 
cytokine levels. See Section 7.3 and the Laboratory Manual for the amount of blood collected/type of 
tube used for all of the correlative studies. 
10. Serum from blood drawn for functional studies prior to lymphodepletion and week 6 will be stored for 
measurement of human anti-mouse antibodies (HAMA). These studies will be performed in the event of 
a suspected immunologic reaction. See Section 7.2.6 for additional details. 
11. Data on all adverse experiences/toxicities regardless of seriousness must be collected for documentation 
purposes only for 4 weeks after the final cellular product administration per NCI-CTCAE criteria, 
version 5.0, CRS Grading Criteria (APPENDIX III – CRS Grading Criteria and Management 
Guidelines) and ICANS Grading Criteria (APPENDIX IV – Management of Neurotoxicity/Immune 
Effector Cell-Associated Neurotoxicity Syndrome (ICANS) from CAR-T Therapy) from CAR-T 
Therapy). Adverse event data collection will cease in subjects that receive therapy for relapse of their 
primary malignancy. Data on disease status will continue to be collected as appropriate.  
a. During dose finding the DLT safety assessment period = 4 weeks after the final (third) cellular product 
administration 
b. If CRS signs and symptoms occur, a serum sample (~1 mL) for IL-6 analysis and approximately 20 mL 
of blood should be collected before instituting treatment for CRS. See Section 7.3.2 for additional details.  
Sample collection can be repeated daily until signs and symptoms of CRS resolve. 
c. Serum (~1 mL) and approximately 20 mL of blood should also be collected for serious toxicities related 
to cell infusion that develop that require hospitalization. See Section 7.3.2 for additional details.  
d. A blood sample (~20 mL) may be collected if any subject develops an AE or event of clinical 
significance that is thought to be at least possibly related to the CAR T cells. 
12. Certificate of Analysis generated at completion of required studies for production/QA of cells. The CofA 
must be available prior to lymphodepletion. 
13. Subjects will receive lymphodepleting chemotherapy consisting of cyclophosphamide of 300 mg/m2/day 
administered IV and fludarabine 30 mg/m2/day administered IV over 3 consecutive days. 
14. CAR.B7-H3 T cells will be administered 2 – 14 days after lymphodepletion. Additional dose delays 
beyond 14 days may be allowed as detailed in Section 4.1.11. Research personnel will keep track of any 
subjects who undergo procurement but do not undergo treatment with cellular product, and the reason 
for withholding treatment. 
15. CT-guided, ultrasound-guided or operative research biopsy at the time of intraperitoneal catheter 
placement. CT-guided or ultrasound-guided research biopsy at the time of intraperitoneal catheter 
removal. A biopsy at the time of disease progression may be performed at the investigator’s discretion 

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for subjects who have initial response at their week 6 imaging. Subjects with progression at their week 
6 tumor imaging will not require a biopsy.  
16. Collection of ascites fluid at the time of intraperitoneal catheter placement, at the time of each cellular 
product administration and at day 3 of each weekly infusion (if ascites fluid is present). 
17.  Peripheral blood, up to 300 mL (in up to 3 collections) will be obtained from subjects for cell 
procurement. In subjects with inadequate lymphocyte count in the peripheral blood, a leukapheresis may 
be performed to isolate sufficient T cells. The parameters for apheresis will be up to 2 blood volumes.   

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5 STUDY POPULATION 
During the period after cell procurement and during CAR-T cell production, subjects are 
allowed to receive additional standard of care therapy e.g., chemotherapy or radiation therapy 
to stabilize their disease if the treating physician feels it is in the subject’s best interests. 
5.1 
Inclusion Criteria Prior to Cell Procurement 
5.1.1 
Written informed consent and HIPAA authorization for release of personal health 
information.  Subjects or their Legally Authorized Representative must sign a consent 
to undergo cell procurement. Subject will be given a copy of the informed consent 
form. 
5.1.2 
Age ≥ 18 years at the time of consent. 
5.1.3 
Subject has adequate performance status as defined by ECOG score of ≤ 2 (see 
APPENDIX VI – ECOG Performance Status [75]). 
5.1.4 
Subjects must have histologically or cytologically confirmed epithelial ovarian, 
peritoneal or fallopian tube cancer and must have a histological diagnosis of a high-
grade serous histology based on local histopathological findings. 
5.1.5 
Subjects must have recurrent platinum-resistant or platinum-refractory disease 
defined as: 
5.1.5.1 
Disease that has progressed by imaging while receiving platinum OR  
5.1.5.2 
Disease that has recurred within 6 months of the last receipt of platinum-
based chemotherapy. Rising CA-125 only is not considered as platinum-
resistant or refractory disease. 
5.1.5.3 
Having received at least 2 prior regimens. 
5.1.5.4 
Have failed prior therapy with a PARP inhibitor if the subject has a 
germline or somatic BRCA mutation. 
5.1.6 
Subjects must have evaluable disease – defined as: 
5.1.6.1 
Measurable disease per RECIST 1.1 (see APPENDIX II – Tumor 
Measurement Based on RECIST 1.1) OR 
5.1.6.2 
Non-measurable disease (defined as solid and/or cystic abnormalities on 
radiographic imaging that do not meet RECIST 1.1 definitions for target 
lesions) OR 

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5.1.6.3 
Ascites and/or pleural effusion that has been pathologically demonstrated 
to be disease-related in the setting of a CA-125 > 2 × ULN. 
 
5.1.7 
Subjects must be able to have an intraperitoneal port placed either by vascular 
interventional radiology or surgically in the operating room. (Note: The intraperitoneal 
port will not be placed until the subject is determined to be otherwise eligible to receive 
the CAR.B7-H3 infusion and until the subject is determined to be otherwise eligible to 
receive lymphodepletion). 
5.1.8 
Female subjects of childbearing potential must be willing to abstain from heterosexual 
activity or to use 2 forms of highly effective methods of contraception from the time of 
informed consent until 180 days after study treatment discontinuation. The two 
contraception methods can be comprised of two barrier methods, or a barrier method 
plus a hormonal method or an intrauterine device that meets < 1% failure rate for 
protection from pregnancy in the product label. 
5.1.9 
Subject is willing and able to comply with study procedures based on the judgement 
of the investigator. 
5.1.10 
Subject is willing to undergo a biopsy prior to treatment, at the time of intraperitoneal 
catheter removal, and at the time of disease progression (if not at their first scan), and 
the tumor site is determined to be safe by the treating investigator for biopsy 
collection. 
5.1.11 
Subjects must not be pregnant or lactating (Note: Breast milk cannot be stored for 
future use while the mother is being treated on study). 
5.1.12 
Subjects must not be deemed unlikely to be a candidate for successful intraperitoneal 
catheter placement by radiographic assessment. 
5.1.13 
Subject must not have intraparenchymal lung metastases (note that pleural effusions 
are not exclusionary and that subjects with intraparenchymal liver disease and 
subjects with retroperitoneal disease are allowed on the study). 
5.1.14 
Subject must not have brain metastases. A subject with prior brain metastasis may be 
considered if they have completed their treatment for brain metastasis at least 4 weeks 
prior to being screened for eligibility, have been off of corticosteroids for ≥ 2 weeks, 
and are asymptomatic. 
5.1.15 
Subject must not have current signs and/or symptoms of bowel obstruction or signs 
and/or symptoms of a bowel obstruction within 3 months prior to starting treatment. 
5.1.16 
Subject must not have a history of intra-abdominal abscess within the past 3 months. 
5.1.17 
Subject must not have a history of gastrointestinal perforation. 

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5.1.18 
Subject must not have a history of symptomatic diverticular disease, confirmed by CT 
or colonoscopy. 
5.1.19 
Subjects must not be dependent on intravenous hydration or total parenteral nutrition. 
5.1.20 
Subject must not have a known additional malignancy that is active and/or 
progressive requiring treatment; exceptions include basal cell or squamous cell skin 
cancer, in situ cervical or bladder cancer, or other cancer for which the subject has 
been disease-free for at least five years. 
5.1.21 
Subject must not be currently using systemic corticosteroids at doses ≥10 mg 
prednisone daily or its equivalent; those receiving <10 mg daily may be enrolled at 
discretion of investigator. Inhaled steroids are allowed. Physiologic replacement 
hydrocortisone at doses 6-12 mg/m²/day is allowed. Equivalently dosed alternative 
steroids are allowed at discretion of investigator, though not to exceed 10 mg 
prednisone per day. 
5.1.22 
Subject must not have an active infection with HIV, HBV, HCV (tests can be pending 
at the time of cell procurement; only those samples confirming lack of active 
infection will be used to generate transduced cells). Note: To meet eligibility subjects 
are required to be negative for HIV antibody or HIV viral load, negative for Hepatitis 
B surface antigen, negative for HCV antibody or HCV viral load. 
5.1.23 
Subjects must not have a history of intolerance to fludarabine. . 
5.1.24 
Subject has life expectancy ≥ 3 months. 
5.1.25 
Subject has evidence of adequate organ function as defined by: 
5.1.25.1 
Total bilirubin ≤ 1.5 × ULN, unless attributed to Gilbert’s Syndrome 
5.1.25.2 
AST / ALT ≤ 3 × ULN (Note: if intrahepatic liver metastases are present, 
AST and ALT must be ≤ 5 × ULN) 
5.1.25.3 
Creatinine ≤ 2 × ULN 
5.1.25.4 
Left ventricular ejection fraction (LVEF) ≥ 40%, as measured by ECHO, 
with no additional evidence of decompensated heart failure. 
5.1.25.5 
Pulse oximetry ≥ 90% on room air 
5.1.26 
Subjects must have active disease by imaging assessment within 90 days prior to 
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5.1.27 
Female subjects of childbearing potential must have a negative serum pregnancy test 
within 72 hours prior to cell procurement. Note: Females are considered of childbearing 
potential unless they are surgically sterile (have undergone a hysterectomy, bilateral 
tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at 
least 12 consecutive months. Documentation of postmenopausal status must be 
provided. 
5.2 
Eligibility Criteria Prior to Lymphodepletion 
5.2.1 
Written informed consent explained to, understood by and signed by the subject prior 
to lymphodepletion; subject given a copy of informed consent form. 
5.2.2 
Subject has an intraperitoneal catheter/port in place. (Note: The intraperitoneal port 
will not be placed until the subject is determined to be otherwise eligible to receive 
lymphodepletion prior to the CAR.B7-H3 infusion). 
5.2.3 
Subject had no major surgery within 28 days prior to lymphodepletion. 
5.2.4 
Subject has not received any investigational agents or any tumor vaccines within 21 
days prior to lymphodepletion.  
5.2.5 
Subjects must have stopped systemic chemotherapy or radiation therapy for at least 
21 days prior to lymphodepletion. 
5.2.6 
Subject must have stopped bevacizumab for at least 6 weeks prior to 
lymphodepletion. 
5.2.7 
Subject must have stopped hormonal therapy (tamoxifen, letrozole, etc.) for at least 
21 days prior to lymphodepletion. 
5.2.8 
Subject is not receiving a prohibited medication at the time of starting lymphodepletion 
up through 72 hours after the last dose of cyclophosphamide listed in Section 8.2.1.7. 
5.2.9 
No current use of systemic corticosteroids at doses ≥10 mg prednisone daily or its 
equivalent; those receiving <10 mg daily may be enrolled at discretion of investigator. 
Inhaled steroids are allowed. Physiologic replacement hydrocortisone at doses 6-12 
mg/m²/day is allowed. Equivalently dosed alternative steroids are allowed at discretion 
of investigator, though not to exceed 10 mg prednisone per day. 
5.2.10 
Imaging results from within 10 days prior to lymphodepletion. Imaging must occur at 
least 3 weeks after most recent therapy (used as baseline measure for documentation of 
progression before the lymphodepletion) to document measurable or assessable 
disease. Imaging does not need to be repeated if it is within 10 days prior to 
lymphodepletion. Subjects must have evaluable disease defined as: 

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5.2.10.1 
Measurable disease per RECIST 1.1 (see APPENDIX II – Tumor 
Measurement Based on RECIST 1.1) OR 
5.2.10.2 
Non-measurable disease (defined as solid and/or cystic abnormalities on 
radiographic imaging that do not meet RECIST 1.1 definitions for target 
lesions) OR 
5.2.10.3 
Ascites and/or pleural effusion that has been pathologically demonstrated 
to be disease-related in the setting of a CA-125 > 2 × ULN. 
5.2.11 
Subject must demonstrate adequate organ function prior to lymphodepletion as 
defined below. All tests must be obtained within 48 hours prior to lymphodepletion: 
5.2.11.1 
Hemoglobin ≥ 8 g/dL 
5.2.11.2 
Absolute neutrophil count ≥ 1.0 × 109/L 
5.2.11.3 
Platelet count ≥ 100 × 109/L 
5.2.11.4 
Total bilirubin ≤ 1.5 × ULN, unless attributed to Gilbert’s Syndrome 
5.2.11.5 
AST / ALT ≤ 3 × ULN (Note: if intrahepatic liver metastases are present, 
AST and ALT must be ≤ 5 × ULN) 
5.2.11.6 
Creatinine ≤ 2 × ULN 
5.2.12 
Subject does not have intraparenchymal lung metastases (Note: Pleural effusions are 
not exclusionary and that subjects with intraparenchymal liver disease and subjects 
with retroperitoneal disease are allowed on the study.) 
5.2.13 
Subject does not have a known brain metastasis. A subject with prior brain metastasis 
may be considered if they have completed their treatment for brain metastasis at least 
4 weeks prior to lymphodepletion, have been off corticosteroids for ≥ 2 weeks, and 
are asymptomatic.  
5.2.14 
Subject must have available autologous transduced activated T cells product that 
meets the Certificate of Analysis acceptance. 
5.2.15 
Subject does not have current signs and/or symptoms of bowel obstruction or signs 
and/or symptoms of a bowel obstruction within the last 3 months prior to 
lymphodepletion. 

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5.2.16 
Subject does not have a history of intra-abdominal abscess within 3 months of 
lymphodepletion. 
5.2.17 
Subject does not have a history of gastrointestinal perforation. 
5.2.18 
Subject does not have a history of symptomatic diverticular disease, confirmed by CT 
or colonoscopy. 
5.2.19 
Subject is not dependent on intravenous hydration or total parenteral nutrition. 
5.2.20 
Negative serum pregnancy test within 72 hours prior to lymphodepleting therapy for 
female participants of childbearing potential. Note: Females are considered of 
childbearing potential unless they are surgically sterile (have undergone a 
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally 
postmenopausal for at least 12 consecutive months. 
5.2.21 
Subject is not lactating (Note: Breast milk cannot be stored for future use while the 
mother is being treated on study). 
5.2.22 
Subject does not have rapidly progressive disease, per treating oncologist’s discretion. 
5.2.23 
Subject is a good candidate for CAR.B7-H3 T cell therapy, per treating oncologist’s 
discretion. 
5.3 
Eligibility Criteria Prior to Cellular Product Administration After Lymphodepletion 
5.3.1 
Subject has no evidence of uncontrolled infection or sepsis. 
5.3.2 
Negative serum pregnancy within 7 days of the initial cellular product administration. 
If the pre-lymphodepletion pregnancy test is within the 7 day window, then the 
pregnancy test does not need to be repeated. 
5.3.3 
Evidence of adequate organ function as defined by: 
5.3.3.1 
Total bilirubin ≤ 2 × ULN, unless attributed to Gilbert’s syndrome 
5.3.3.2 
AST / ALT ≤ 5 × ULN, unless attributed to intrahepatic liver metastases 
5.3.3.3 
Creatinine ≤ 3 × ULN 
5.3.4 
Subject has no clinical indication of rapidly progressing disease in the opinion of the 
clinical investigator. 
5.3.5 
Subject is a good candidate for treatment with CAR.B7-H3 cell product per the 
clinical investigator’s discretion. 

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5.4 
Single Subject Exceptions 
Eligibility single subject exceptions are not permitted for Lineberger Comprehensive 
Cancer Center Investigator Initiated Trials under any circumstances. Other types of single 
subject exceptions may be allowed if proper regulatory review has been completed in 
accordance with Lineberger Comprehensive Cancer Center’s Single Subject Exceptions 
Policy. 

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6 STUDY CONDUCT 
6.1 
Duration of Therapy 
Therapy in the LCCC1818-ATL study involves three sequential intraperitoneal 
administrations of CAR.B7-H3 T cell product. Study treatment will be administered unless 
the subject meets criteria delineated in Section 6.3 including:  
• Subject decides to withdraw from study treatment, 
• The second and/or third infusion is delayed due to treatment emergent non-
hematological >grade 2 adverse events determined to be related to the CAR.B7-H3 
T cell product that do not resolve to baseline for >4 weeks or 
• General or specific changes in the subject’s condition render the subject 
unacceptable for further treatment in the judgment of the investigator. 
6.2 
Duration of Follow-Up 
Subjects will be followed for up to 5 years or until death, whichever occurs first. Subjects 
removed from the study for unacceptable adverse events will be followed until resolution 
or stabilization of the adverse event. Subjects who experience unequivocal disease 
progression after a cellular product administration will come off study. 
6.3 
Removal of Subjects from Protocol Therapy 
Subjects will be removed from protocol therapy and the Principal Investigator notified 
when any of the criteria listed below apply.  
• Subject experiences a DLT 
• Progressive disease is noted during disease re-evaluation 
• Subject develops Grade 4 non-hematologic toxicity after cell treatment 
• Subject experiences Grade 3 – 4 allergic reaction to investigative agents 
• The second and/or third infusion is delayed due to treatment emergent non-
hematological >grade 2 adverse events determined to be related to the CAR.B7-H3 
T cell product that do not resolve to baseline for >4 weeks 
• Positive pregnancy test 
• Subject decides to withdraw from therapy 
• Physician decision 

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The reason for discontinuation of protocol therapy will be documented on the eCRF. In the 
case where a subject decides to prematurely discontinue protocol therapy (“refuses 
treatment”), the subject should be asked if she or he may still be contacted for further 
scheduled study assessments. The outcome of that discussion should be documented in 
both the medical records and in the eCRF. 
6.4 
Off-Study Criteria 
Subjects will be removed from the study if they meet any of the below criteria: 
• After completion of 5 years of follow-up OR the subject has been determined to 
have progressive disease (whichever is earliest)  
• Death 
• Lost to follow up  
• Withdrawal of consent for any further data submission 
6.5 
Subject Withdrawal 
If a subject decides to withdraw from the study (and not just from protocol therapy) an 
effort should be made to complete and report study assessments as thoroughly as possible.  
At the time of withdrawal, the investigator should attempt to establish as completely as 
possible the reason for the study withdrawal. 
• The subject should be asked if they are willing to allow for the abstraction of 
relevant information from their medical record in order to meet the long term follow 
up (e.g., survival) objectives outlined in the protocol.  
• A complete final evaluation at the time of the subject’s study withdrawal should be 
obtained with an explanation of why the subject is withdrawing from the study. 
• If the subject is noncompliant and does not return for an end of study follow up 
assessment, this should be documented in the eCRF.  
• If the reason for removal of a subject from the study is an adverse event, the 
principal specific event will be recorded on the eCRF.  
Excessive subject withdrawals from protocol therapy or from the study can render the study 
un-interpretable; therefore, unnecessary withdrawal of subjects should be avoided. 
6.6 
Subjects Lost to Follow-Up 
Subject will be considered lost to follow-up if he or she fails to return for three scheduled 
visits and is unable to be contacted by the study site staff.  

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The following actions must be taken if a subject fails to return to the clinic for a required 
study visit: 
• The site will attempt to contact the subject and reschedule the missed visit and 
counsel the subject on the importance of maintaining the assigned visit schedule 
and ascertain if the participant wishes to and/or should continue in the study. 
• Before a subject is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the subject (where possible, three telephone calls 
and, if necessary, a certified letter to the participant’s last known mailing address 
or local equivalent methods). These contact attempts should be documented in the 
subject’s medical record or study file.  
• Should the subject continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 

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7 DESCRIPTION OF STUDY PROCEDURES 
7.1 
Clinical Assessments 
Clinical assessments will be performed as outlined in the Time & Events Table. 
Procurement happens after pre-procurement screening and prior to lymphodepletion and 
initial cellular product administration. Any therapy received after procurement and prior to 
cellular product administration must be documented. Additionally, research personnel 
must keep track of any subjects who undergo procurement but do not undergo treatment 
with cellular products, and the reason for withholding treatment. 
7.1.1 
Demographics 
Demographic information (date of birth, gender, race, ethnicity) will be recorded at the 
pre-procurement screening visit. 
7.1.2 
Medical History 
Relevant medical history, including history of current disease, other pertinent history, 
and information regarding underlying diseases will be recorded at procurement, pre-
lymphodepletion (if applicable) and pre-infusion screening visits and a focused medical 
history on symptoms/toxicity will be performed thereafter. BRCA mutation status 
should be captured, if known. In the event that a subject experiences an SAE or AE on 
study that leads to hospitalization, the number of days that the subjects spends in the 
hospital should be captured. 
7.1.3 
Physical Examination 
A complete physical examination including height (at initial screening only), weight, 
vital signs and performance status.  
Baseline information collected prior to procurement or cellular product administration 
will be compared to changes that occur during study treatment. New abnormal physical 
exam findings must be documented and will be followed by a physician or other 
qualified staff at the next scheduled visit. 
Vital signs (temperature, heart rate, respiratory rate, pulse oximetry, and blood 
pressure) will be performed by either the investigator or other qualified staff (MD, NP, 
RN, or PA). 
7.1.4 
Performance Status 
Performance status will be assessed by the ECOG scale provided in APPENDIX IV – 
Management of Neurotoxicity/Immune Effector Cell-Associated Neurotoxicity 
Syndrome (ICANS) from CAR-T Therapy. 

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7.1.5 
Assessment of Safety 
All subjects consented for the study will be included in the safety analysis. The safety 
analysis will be divided into the following categories: events occurring between cell 
procurement and lymphodepletion, events occurring between lymphodepletion and 
CAR.B7-H3 product administration, and events occurring after CAR.B7-H3 cell 
product administration. Each subject will be assessed periodically for the development 
of any toxicity according to the Time & Events Table. Toxicity will be assessed 
according to the NCI CTCAE, version 5.0, CRS Grading Criteria provided in 
APPENDIX III – CRS Grading Criteria and Management Guidelines and 
Neurotoxicity/ICANS Grading Criteria provided in APPENDIX IV – Management of 
Neurotoxicity/Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) 
from CAR-T Therapy. 
7.1.6 
Assessment of Efficacy 
All subjects who receive three intraperitoneal infusions of CAR.B7-H3 T cell product 
will be included in the efficacy analysis. To assess disease response, imaging will be 
performed within 10 days of lymphodepletion and at 6 weeks (±7-day window) 
following the initial intraperitoneal administration of CAR.B7-H3 T cell product. If 
imaging is consistent with progressive disease, the subject will come off of study. 
Imaging will be performed every 3 months (±14 day window) starting at month 3 until 
disease progression for up 2 years post initial infusion and then will be performed every 
6 months (±30 day window) thereafter for up to 5 years post initial infusion. The 
Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 criteria will be 
used for measurement of tumor response (see APPENDIX II – Tumor Measurement 
Based on RECIST 1.1). If imaging studies are performed at other times after treatment 
on this study, the data will be collected, and information gained will be used for this 
study. The choice of imaging will depend on what studies have been most informative 
in following the subject’s disease (i.e., CT scans, MRI, PET scans). The tests performed 
at baseline for assessment of disease should be performed consistently throughout the 
study. Additionally, CA 125 tumor marker level will be measured according to the 
Time & Events Table. 
7.2 
Laboratory Assessments 
7.2.1 
Hematology 
Blood will be obtained during the study as outlined in the Time & Events Table and 
sent to the clinical site hematology laboratory for assessment of complete blood count 
with white blood cell differential. 
7.2.2 
Serum Chemistries 
Blood will be obtained during the study as outlined in the Time & Events Table and 
sent to the clinical site chemistry laboratory for determination of a comprehensive 

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metabolic panel (sodium, potassium, chloride, CO2, BUN, creatinine, glucose, 
calcium, albumin, total protein, total bilirubin, AST, ALT, alkaline phosphatase). 
7.2.3 
Cancer Antigen-125 Level 
CA-125 will be assessed as outlined in the Time & Events Table. 
7.2.4 
Serum Cortisol Level 
Serum cortisol will be assessed as outlined in the Time & Events Table. 
7.2.5 
Virus Testing 
HIV, HBV, HCV testing required for confirmation that no active infection exists; 
results can be pending at the time of cell procurement; only those samples confirming 
lack of active infection will be used to generate transduced cells. 
7.2.6 
HAMA Testing 
Serum from blood drawn for functional studies at baseline and at week 6 will be stored 
for measurement of human anti-mouse antibodies (HAMA). These studies will be 
performed in the event of a suspected immunologic reaction. 
7.2.7 
Pregnancy Testing 
A serum pregnancy test will be obtained from female subjects who are of childbearing 
potential as outlined in the Time & Events Table. 
o Serum pregnancy test done within 72 hours prior to procurement 
o Serum pregnancy test done within 72 hours prior to lymphodepletion 
o Serum pregnancy test done within 7 days prior to cellular product 
administration (does not need to be repeated if the pre-lymphodepletion 
pregnancy is within window) 
7.3 
Correlative Studies 
The following investigations will be used to monitor function and persistence in peripheral 
blood and safety of transduced T cells at time points indicated in the Time and Events 
Tables. Please consult the study Laboratory Manual for details on correlative blood sample 
collection. If a subject’s hemoglobin is less than 8.0 g/dL at any of the evaluation times, 
the amount of blood drawn for the evaluation will be reduced and may be obtained over 
more than one venipuncture, if necessary.  

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Cytokines: Our standard array for cytokine determination includes multiple cytokines 
(UNC Immune Monitoring Core) which among others include: IL-2, IFNγ, TNFα, IL-6, 
IL-10, IL-13, IL-1Rα, IL-8, IL-12, IL-15, and GM-CSF. 
7.3.1 
Function and Persistence Studies 
Immunophenotyping for the presence of the CAR construct will also be conducted 
when applicable.  Additionally, we will use surface immunophenotyping and/or 
intracellular cytokine by flow cytometry to evaluate both CAR-expressing and other T 
cells post-infusion. Blood sampling for characterizing the pharmacokinetics of the 
CAR.B7-H3 T cell product will follow the correlative blood sample collections defined 
in the Time & Events Table. As this is an RNA based product and CAR T cells will be 
infused intraperitoneally, we anticipate the maximum detection of CAR.B7-H3 T cells 
in the peripheral blood to occur within the first 4 hours upon administration if CAR-T 
cells enter the bloodstream from the peritoneal space. Beatty et. al. showed that 
maximal levels of transgene introduced in T-cells by mRNA were detected within 2 
hours of infusion when mRNA-based were infused directly intravenously [60]. Due to 
the biodegradable nature of the transgene the levels then progressively decreased on 
successive days. Quantitative RT-polymerase chain reaction (RT-PCR) will be used to 
quantify the persistence of the CAR.B7-H3 T cells. mRNA will be extracted from total 
PBMC and reverse transcribed. CAR expression will then be quantified by real time 
PCR using primers and probes spanning a specific sequence of the CAR transgene. 
Function and persistence studies may also include functional assays such as in vitro 
reactivation of PBMCs in subjects for whom the appropriate reagents are available. 
7.3.2 
Sample Collection Requirement if CRS or Severe Toxicity Occurs 
A serum sample (~1 mL) for IL-6 analysis and approximately 20 mL of blood should 
be collected in any subject who develops signs and symptoms of CRS regardless of 
whether their symptoms meet severity requirements for DLT. This sample should be 
collected before treatments are administered to alleviate CRS symptoms. Subsequent 
samples may be collected at the discretion of the investigator (e.g., a single sample 
collection may be obtained each day until the event resolves) and will depend on the 
condition of the subject.  
In addition, a serum sample (~1 mL) for IL-6 analysis and approximately 20 mL of 
blood should be collected in any subject who develops a SAE (i.e., requiring 
hospitalization) related to the cell infusion. Subsequent samples may be collected at the 
discretion of the investigator. 
An additional blood sample of ~20 mL may be collected if any subject develops an AE 
or event of clinical significance that is thought to be at least possibly related to the CAR 
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7.3.3 
Fresh Tissue Studies 
Subjects with measurable disease per RECIST 1.1 criteria will have their tissue 
specimens collected prior to or at the time of intraperitoneal catheter installation via 
CT-guided, ultrasound-guided or operative biopsy; at the time of intraperitoneal 
catheter removal via CT-guided or ultrasound-guided biopsy. Subjects who have initial 
response at their week 6 imaging may have a biopsy performed at the time of 
progression (if not at their first scan). This will be at the investigator’s discretion. 
Biopsy material will be used to analyze molecular signature of the tumor before and 
after treatment and at the time of progression, to study immunogenomics.  This will be 
performed using either single cell or bulk RNA-sequencing, NanoString analysis or 
quantitative PCR.  Tumor mutation analysis will be performed by whole genome or 
whole exome analysis. 
B7H3 expression will be measured by performing staining on fixed samples using 
methodologies that have been previously published for glioblastoma in Neham et. al. 
[71].  
7.3.4 
Ascites Fluid Analysis 
If present, ascites fluid will be collected by large volume paracentesis at the time of 
intraperitoneal catheter installation; at the time of each cellular product administration; 
and at day 3 after each weekly infusion; and at the time of progression. Ascites fluid 
will be used to isolate cells by Ficoll-Paque processing, which will then be sub-divided 
and 1 fraction will be cryopreserved and the other will be pelleted to be used fresh. 
Cells will be used to analyze molecular signature of the tumor before and after 
treatment, to study immunogenomics.  This will be performed using either single cell 
or bulk RNA-sequencing, NanoString analysis or quantitative PCR.  Tumor mutation 
analysis will be performed by whole genome or whole exome analysis. 
7.4 
Biobank Repository 
Subjects participating in this trial may consent to allow researchers to store their biological 
specimens.  Participants in this trial will also be required to sign a separate HIPAA 
authorization form to allow investigators to review their medical records.    
CAR.B7-H3 T cells will be stored at the GMP facility according to standard procedures. 
Other specimens collected during this study as described in Sections 7.3.3 and 7.3.4 of this 
protocol will be stored at the University of North Carolina at Chapel Hill in the 
immunotherapy laboratory in locked liquid nitrogen tanks with controlled access. The 
samples will be labeled with the study ID number and date and time of sample collection.  
The purpose of this repository or biobank is to store samples for immediate or future 
analyses to answer study-related questions, not to increase general knowledge outside the 
parameters of the study. These goals will be accomplished using several different kinds of 
specimens collected during the study as described in section 7.3.  

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These specimens include: 
• Tissue samples from biopsies or ascites 
• Unused CAR.B7-H3 T cells 
• Unused additional material collected during procurement (peripheral blood 
mononuclear cells) 
• Leftover tissue obtained for any standard of care procedure that may provide 
additional information about CAR.B7-H3 T cell therapy  
For example, analyses will be performed to assist in determining if the CAR.B7-H3 T cells 
are associated with the tumor and if the CAR.B7-H3 T cells are present. 
Information about the subject’s disease will be linked to the specimens stored in the 
repository database. Immunotherapy laboratory-associated research staff, LCCC 
Bioinformatics staff who support the database and the LCCC Data Warehouse, and 
researchers with IRB-approval for access to personal health information for each subject 
in this study will be able to link specimens to relevant medical information. Some results 
from laboratory analyses that occurred during the subject’s participation in the clinical 
study may also be included. This information may be important for understanding how the 
subject’s cancer developed and responded to treatment. 
Storage Time: 
• CAR.B7-H3 T cells and material from procurement are to be stored for up to 15 
years for subject treatment and safety purposes. If storage of the CAR-T cells and/or 
extra material from procurement is no longer deemed necessary as determined by 
the Principal Investigator with appropriate consult, as needed (e.g., attending 
physician, treating physicians, etc.), the CAR-T cells and/or the extra material from 
procurement may be released for archiving or destruction earlier than 15 years. At 
the time of release determination by the Principal Investigator, if the subject did not 
consent for their specimens to be used for further research or quality 
assurance/quality control (QA/QC) activities, the specimens will be destroyed at 5 
years. The subject may withdraw their consent at any time to prevent the use of 
their specimens for further research or QA/QC activities. Withdrawing of consent 
will result in the destruction of the samples at 5 years or at the time consent is 
withdrawn if this occurs after the initial 5 years in storage. 
• Archived samples will be stored in the GMP lab (the ACT facility) and will be 
designated in the inventory system for use in laboratory research and/or QA/QC 
activities.  Samples will be de-identified when they are used for laboratory research 
or QA/QC activities. Total storage time (initial storage and archiving) may be up 
to 15 years, and then the samples will be destroyed. 

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• Tissue obtained from tumor biopsies or ascites, or any leftover tissue obtained 
through standard of care procedure that may provide additional information about 
CAR.B7-H3 T cell therapy will be stored for up to 15 years. 
7.5 
Protocol Deviations 
A protocol deviation is any unplanned variance from an IRB approved protocol that: 
• Is generally noted or recognized after it occurs; 
• Has no substantive effect on the risks to research participants; 
• Has no substantive effect on the scientific integrity of the research plan or the value 
of the data collected; 
• Did not result from willful or knowing misconduct on the part of the investigator(s). 
An unplanned protocol variance is considered a violation if the variance meets any of the 
following criteria:  
• Has harmed or increased the risk of harm to one or more research participants; 
• Has damaged the scientific integrity of the data collected for the study; 
• Results from willful or knowing misconduct on the part of the investigator(s); 
• Demonstrates serious or continuing noncompliance with federal regulations, State 
laws, or University policies.  
If a deviation or violation occurs, please follow the guidelines below: 
Protocol Deviations: In the event a deviation from protocol procedures is identified, record 
the deviation in OnCore®.  
Protocol Violations: Violations should be reported to the IRB of record by UNC personnel 
within one (1) week of the investigator becoming aware of the event.   
Unanticipated Problems: Any events that meet the criteria for “Unanticipated Problems” 
must be reported by the study personnel to the IRB of record.  
 
 

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8.1.5 
RNA Electroporation of T cells 
Following 7 – 12 days of expansion, T cells are washed, resuspended and transferred 
to electroporation cuvettes, where they are electroporated with RNA coding for the 
CAR.B7-H3 using a closed system electroporation device. Immediately after 
electroporation, the cells are washed and returned to culture for recovery. 
8.1.6 
Cryopreservation of T cells 
After recovery (typically overnight), cells will be harvested from culture and 
cryopreserved following previously validated SOPs. Cells will also be tested for 
expression of the gene construct and potency using an assay as discussed with FDA. 
All lines will be analyzed for phenotype and sterility. The results will be reviewed by 
Quality Assurance (QA) prior to issuing a Certificate of Analysis. 
 
8.1.7 
Testing 
Products that meet study specific release criteria, as detailed on the Certificate of 
Analysis that accompany each infusion product, will be infused as per section 4.1.6. 
Complete sterility test results are currently required for product release prior to 
infusion. However, if a positive sterility testing result is reported after the product was 
infused, the FDA and other relevant parties would be notified as per our manufacturing 
standard operating procedure (SOP) and our clinical research SOP. Subjects would be 
managed per established practice. 
8.1.8 
Potential Toxicities 
Potential toxicities may be categorized as those related to infusion of T cells: cross-
reactivity with normal tissues, cytokine release syndrome (CRS), immune effector cell-
associated neurotoxicity syndrome (ICANS), and macrophage activation syndrome 
(MAS). 
8.1.8.1 
Cross-Reactivity 
B7-H3 has limited expression on normal tissues. In addition, the intraperitoneal 
infusion of the CAR.B7-H3 T cells should further mitigate the potential systemic 
toxicity. 
8.1.8.2 
Cytokine Release Syndrome 
CRS is the most common side effect of CAR-T cell therapy and is potentially life 
threatening [72]. Symptoms can vary from mild flu-like symptoms to more severe 
toxicities such as vascular leak, hypotension, coagulopathy, pulmonary edema and 
multi-organ failure. CRS-associated toxicities, when severe, require intensive 
medical management including vasoactive pressors, mechanical ventilation, anti-
epileptics, and antipyretics [53]. Quite recently, tocilizumab, a monoclonal 

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antibody specific to the IL-6 receptor, has been approved by the FDA for the 
treatment of patients with CRS. Cytokine elevations are detectable in most patients; 
however, the degree of elevation does not correlate with the severity of CRS or 
response to therapy. The most significantly elevated cytokines associated with CRS 
are IL-10, IL-6, and IFN-γ. IL-6 is an inflammatory cytokine involved in a large 
number of immune processes, including neutrophil trafficking, acute phase 
response, angiogenesis, B cell differentiation, and auto-antibody production. In 
severe CRS with T-cell engaging therapies, IL-6 levels peak during maximal T cell 
proliferation. High levels of IL-6, present in the context of CRS likely initiates a 
pro-inflammatory IL-6-mediated signaling cascade. 
8.1.8.3 
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) 
The underlying pathophysiology for immune effector cell-associated neurotoxicity 
syndrome (ICANS) is not fully understood [54, 72]. CAR-T cells in the CNS may 
play a role. However, the heightened systemic inflammatory and cytokine state 
resulting from CAR-T therapy may also be a factor, as other therapies associated 
with increased cytokine levels have also been associated with neurologic toxicities, 
such as high-dose interleukin-2 (IL-2) and blinatumomab.  
The symptoms and manifestations of ICANS are broad and range from 
confusion/altered mental status to seizures. Routine monitoring is critical in 
subjects receiving CAR-T therapy to identify neurologic symptoms early and 
neurology should be consulted for any subjects who exhibit early signs/symptoms 
of neurotoxicity. Early interventions should be employed to prevent worsening, 
especially if therapies are already indicated such as corticosteroids. 
8.1.8.4 
Macrophage Activation Syndrome 
Macrophage activation syndrome (MAS) has been found previously in patients 
with acute lymphoblastic leukemia receiving CAR-T cell therapy [73]. Macrophage 
activation syndrome is characterized by pancytopenia, liver insufficiency, 
coagulopathy and neurological symptoms, and is thought to be mediated by 
uncontrolled proliferation and activation of T cells leading to macrophage 
activation and differentiation and cytokine production with hemophagocytosis. The 
pathophysiology of MAS is complex but appears to have some similarities to 
hemophagocytic lymphohistiocytosis (HLH). Correlative evaluations have shown 
that hepatic biopsy samples in patients with hemophagocytic lymphohistiocytosis 
including a subgroup with macrophage activation syndrome demonstrated the 
presence of CD8+ T cells generating IFNγ with macrophages generating IL-6 and 
TNF. There was overproduction of IL-18, which may play a role in the polarization 
of T cells.  
Diagnosis of macrophage activation syndrome: pancytopenia, fever, elevated AST, 
ALT, triglycerides and LDH, increased PT and PTT associated with increased 
number of fibrin split products and decreased fibrinogen.  

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Additionally, splenomegaly, hepatomegaly and CNS dysfunction characterized by 
lethargy, irritability, disorientation, headache, seizures and coma can be found. 
8.2 
Lymphodepleting Chemotherapy 
Subjects will receive lymphodepleting chemotherapy with cyclophosphamide 300 
mg/m2/day and fludarabine 30 mg/m2/day IV for three consecutive days administered 2-14 
days prior to initial cellular product administration. 
8.2.1 
Cyclophosphamide 
Cyclophosphamide is an alkylating agent that has anticancer activity. It is converted in 
the liver to active alkylating metabolites such as phosphoramide mustard by 
cytochrome-P450 enzymes. These alkylating metabolites interfere with the growth of 
susceptible rapidly proliferating malignant cells. Alkyl radicals intercalate into DNA 
strands and interfere with DNA replication. 
Cyclophosphamide is commercially available and will not be supplied free of charge 
to the patient. Cyclophosphamide should be handled and stored per institutional 
guidelines in accordance with the manufacturer’s prescribing information. 
8.2.1.1 
How Supplied 
Cyclophosphamide is supplied as 500 mg, 1 gm and 2 gm vials containing white 
powder for IV administration. 
8.2.1.2 
Storage Requirements/Stability 
Cyclophosphamide vials should be stored at or below 25°C (77°F). 
Cyclophosphamide does not contain any antimicrobial preservative and care must 
be taken to assure the sterility of prepared solutions. 
8.2.1.3 
Handling and Dispensing 
Cyclophosphamide must be dispensed by authorized personnel according to local 
regulations. Cyclophosphamide should be stored in a secure area according to local 
regulations. 
8.2.1.4 
Preparation 
Cyclophosphamide should be reconstituted in 25 mL (500 mg), 50 mL (1 gm) or 
100 mL (2 gm) normal saline or sterile water for injection, USP, for IV infusion 
(i.e., per institutional guidelines). Shake vigorously to dissolve the drug. To 
minimize risk of dermal exposure, always wear gloves when handling vials 
containing cyclophosphamide sterile powder for injection.   

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8.2.1.5 
Dosage and Administration 
Cyclophosphamide 300 mg/m2/day will be administered intravenously for 3 
consecutive days 2 – 14 days prior to initial cellular product administration. 
8.2.1.6 
Adverse Events Associated with Cyclophosphamide 
Please refer to the prescribing information for cyclophosphamide for complete 
information. 
Possible side effects: 
 Nausea, vomiting, diarrhea 
 Urinary bladder toxicity 
 Bone marrow suppression 
 Gonadal suppression 
 Myelodysplasia 
 Alopecia 
 Immunosuppression 
 Hyperpigmentation of the skin 
Full prescribing information on cyclophosphamide is available at: 
http://medlibrary.org/lib/rx/meds/cyclophosphamide-1/    
8.2.1.7 
Prohibited Medications 
Drugs that should not be administered concomitantly with cyclophosphamide: 
 Carbamazepine 
 Idarubicin 
 Natalizumab 
 Etanercept 
 Palifermin 
Consumption of alcohol should be avoided while the subject is receiving 
cyclophosphamide. In addition, subjects should avoid the consumption of 

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grapefruit or grapefruit juice during treatment with cyclophosphamide. Vaccination 
with live vaccines is prohibited (see product insert for details). In addition, there 
are 46 medications known to have major interactions with cyclophosphamide 
provided at this link: https://www.drugs.com/drug-interactions/cyclophosphamide-
index.html?filter=3&generic_only=.   
8.2.2 
Fludarabine 
Fludarabine phosphate for injection is a fluorinated nucleotide analog of the antiviral 
agent vidarabine, 9-β-D-arabinofuranosyladenine (ara-A) that is relatively resistant to 
deamination by adenosine deaminase. Fludarabine phosphate is indicated for the 
treatment of adult patients with B-cell chronic lymphocytic leukemia who have not 
responded to or whose disease has progressed during treatment with at least one 
standard alkylating agent containing regimen. Details on this product may be found in 
the Prescribing Information http://medlibrary.org/lib/rx/meds/fludarabine-phosphate-
10/ 
8.2.2.1 
Formulation 
Fludarabine is supplied in clear glass vials. Each vial of sterile lyophilized solid 
cake contains 50 mg of the active ingredient fludarabine phosphate, USP, 50 mg of 
mannitol, USP, and sodium hydroxide to adjust to pH to 7.7. The pH range for the 
final product is 7.2 to 8.2. Reconstitution with 2 mL of sterile water for injection, 
USP results in a solution containing 25 mg/mL of fludarabine phosphate, USP, 
intended for intravenous administration. 
8.2.2.2 
Storage 
Fludarabine should be stored in a secure area according to local regulations at 20° 
to 25°C (68° to 77°F). Excursions permitted between 15° to 30° C (59° to 86°F). 
Fludarabine should be retained in original package until time of use. 
8.2.2.3 
Handling and Dispensing 
Fludarabine is commercially available and will not be supplied free of charge to the 
subject. Fludarabine should be handled and stored per institutional guidelines in 
accordance with the manufacturer’s prescribing information. Local requirements 
for disposal of hazardous drugs should be followed per institutional policy. 
8.2.2.4 
Preparation 
Refer to the package insert for instructions on preparation for IV administration 
(see http://medlibrary.org/lib/rx/meds/fludarabine-phosphate-10/).  

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8.2.2.5 
Dose and Administration 
Fludarabine (30 mg/m2/day × 3 days) will be administered by IV infusion for 
lymphodepletion prior to cellular product infusion. 
8.2.2.6 
Adverse Events Associated with Fludarabine 
Please refer to the prescribing information for fludarabine for complete 
information. The information below summarizes the warnings and precautions 
from the prescribing information. 
8.2.2.6.1 
Dose Dependent Neurologic Toxicities 
There are clear dose dependent toxic effects seen with fludarabine for injection, 
USP. Dose levels approximately 4 times greater (96 mg/m2/day for 5 to 7 days) 
than that recommended for CLL (25 mg/m2/day for 5 days) were associated 
with a syndrome characterized by delayed blindness, coma, and death. 
8.2.2.6.2 
Bone Marrow Suppression 
Severe bone marrow suppression, notably anemia, thrombocytopenia, and 
neutropenia, has been reported in patients treated with fludarabine phosphate 
for injection. Cumulative myelosuppression may be seen. While chemotherapy-
induced myelosuppression is often reversible, administration of fludarabine 
phosphate for injection requires careful hematologic monitoring. 
8.2.2.6.3 
Autoimmune Reactions 
Instances of life-threatening and sometimes fatal autoimmune phenomena such 
as hemolytic anemia, autoimmune thrombocytopenia purpura, Evans 
syndrome, and acquired hemophilia have been reported to occur after one or 
more cycles of treatment with fludarabine. 
8.2.2.6.4 
Transfusion Associated Graft vs. Host Disease (GVHD) 
Transfusion-associated GVHD has been observed after transfusion of non-
irradiated blood in fludarabine-treated patients.   
8.2.2.6.5 
Pulmonary Toxicity 
A high incidence of fatal pulmonary toxicity has been observed when 
fludarabine is administered in combination with pentostatin for treatment of 
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8.2.2.6.6 
Pregnancy Category D 
Fludarabine can cause fetal harm when administered to a pregnant woman. 
Women of childbearing potential should be advised to avoid becoming pregnant 
if they are to receive therapy with fludarabine. 
8.2.2.6.7 
Male Fertility and Reproductive Outcomes 
Males with female partners of childbearing potential should use contraception 
during and after cessation of fludarabine. Possible sperm DNA damage raises 
concerns about loss of fertility and genetic abnormalities in fetuses. 
8.2.2.6.8 
Renal Impairment 
Subjects with creatinine clearance 30 to 79 mL/min should have their 
fludarabine dose reduced and monitored for excessive toxicity. Fludarabine 
should not be administered to patients with creatinine clearance < 30 mL/min. 
8.2.2.6.9 
Prohibited Concomitant Therapy 
Medications known to have major interactions with fludarabine are provided at 
this 
link: 
https://www.drugs.com/drug-interactions/fludarabine-
index.html?filter=3&generic_only=. These medications are prohibited while 
the subject is receiving fludarabine.   
Ensure that subjects are not receiving any of the prohibited medications listed 
at the links provided while they are undergoing lymphodepletion with 
bendamustine and fludarabine. 
 
 
 
 
 

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9 ADVERSE EVENTS 
9.1 
Definitions 
9.1.1 
Adverse Event (AE) 
An adverse event (AE) is any untoward medical occurrence (e.g., an abnormal 
laboratory finding, symptom, or disease temporally associated with the use of cellular 
product in a subject or clinical investigation subject administered a cellular product and 
which does not necessarily have a causal relationship with this treatment). An AE can, 
therefore, 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 related to the medicinal product.  
Hospitalization for elective surgery or routine clinical procedures that are not the result 
of an AE (e.g., surgical insertion of a central line) need not be considered an AE and 
should not be recorded as an AE. Disease progression should not be recorded as an AE, 
unless it is attributable by the investigator to the study therapy. 
9.1.2 
Suspected Adverse Reaction (SAR) 
A suspected adverse reaction (SAR) is any AE for which there is a reasonable 
possibility that the cellular product is the cause. Reasonable possibility means that there 
is evidence to suggest a causal relationship between the cell infusion and the AE. A 
suspected adverse reaction implies a lesser degree of certainty about causality than 
adverse reaction, which means any adverse event caused by cellular product.   
Causality assessment to a cellular product is a medical judgment made in consideration 
of the following factors: temporal relationship of the AE to cellular product exposure, 
known mechanism of action or side effect profile of study treatment, other recent or 
concomitant cellular product exposure, normal clinical course of the disease under 
investigation, and any other underlying or concurrent medical conditions. Other factors 
to take into account when considering whether cellular product is the cause of the AE:  
o Single occurrence of an uncommon event known to be strongly associated with 
cellular product exposure (e.g., angioedema, hepatic injury, Stevens-Johnson 
Syndrome). 
o One or more occurrences of an event not commonly associated with cellular 
product exposure, but otherwise uncommon in the population (e.g., tendon 
rupture); often more than one occurrence from one or multiple studies would 
be needed before the sponsor could determine that there is reasonable 
possibility that the cellular product caused the event.  

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o An aggregate analysis of specific events observed in a clinical trial that 
indicates the events occur more frequently in the cellular product treatment 
group than in a concurrent or historical control group. 
9.1.3 
Unexpected AE or SAR 
An AE or SAR is considered unexpected if the specificity or severity of it is not 
consistent with prior experience in CAR-T therapy trials or the applicable product 
information. 
9.2 
Documentation of Non-Serious Adverse Events or SARs 
For non-serious AEs or SARs, documentation must begin at the time of procurement when 
the consent form is signed by the subject prior to procurement and continues through the 3 
week follow-up period after cellular treatment is discontinued. Any AEs or SARs 
experienced by the subject related to these procedures (procurement, lymphodepletion, and 
cellular product administration) must be documented. Adverse event data collection will 
cease in subjects that receive therapy for relapse of their primary malignancy. The DLT 
assessment period will start at the time of the initial cellular product administration through 
the 3 week DLT follow up period after the final (third) cellular product administration. 
Subjects will be followed for safety and documentation of AEs for 4 weeks after the final 
cell infusion.   
Collected information should be recorded in the electronic case report forms (eCRF) for 
that subject. A description of the event, its severity or toxicity grade, onset and resolved 
dates (if applicable), and the relationship to the study drug should be included.  

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10 SERIOUS ADVERSE EVENT 
10.1 
Definition of Serious Adverse Event 
An AE or SAR is considered serious if, in the view of either the investigator or sponsor, it 
results in any of the following outcomes:  
• Death;  
• Is life-threatening (places the subject at immediate risk of death from the event as 
it occurred);  
• Requires inpatient hospitalization (>24 hours) or prolongation of existing 
hospitalization*;  
• Results in congenital anomaly/birth defect;  
• Results in a persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions;  
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse study treatment related 
experience when, based upon appropriate medical judgment, they may jeopardize 
the subject or subjects and may require medical or surgical intervention to prevent 
one of the outcomes listed in the definition. For reporting purposes, also consider 
the occurrences of pregnancy as an event which must be reported as an important 
medical event.  
*Hospitalization for anticipated or protocol specified procedures such as administration of 
chemotherapy, central line insertion, metastasis interventional therapy, resection of 
primary tumor, or elective surgery, will not be considered serious adverse events.   
Pregnancy that occurs during the study must also be reported as an SAE. 
10.2 
Documentation of SAEs or Serious SARs 
10.2.1 
Timing 
After informed consent but prior to initiation of study medications, only SAEs caused 
by a protocol-mandated intervention will be collected (e.g. SAEs related to invasive 
procedures such as biopsies, medication washout).   
For any other experience or condition that meets the definition of an SAE or a serious 
SAR, recording of the event must begin at procurement and continue through the 3 
week follow-up period after treatment with the final cell infusion is initiated. 

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10.2.2 
Documentation and Notification 
SAEs or Serious SARs must be recorded in the SAE console within OnCore® for that 
subject within 24 hours of learning of its occurrence. The Regulatory Associate and 
Medical Monitor must be notified via email of all SAEs within 24 hours of learning of 
its occurrence. 
10.3 
Adverse Event Reporting 
10.3.1 
IRB Reporting Requirements 
The IRB will be notified of all SAEs that qualify as an Unanticipated Problem as per 
the IRB’s Policies within 7 days of the Investigator becoming aware of the problem. 
These events must be reported to the sponsor within 24 hours of learning of the 
occurrence. 
10.3.1.1 
Pregnancy 
Pregnancies and suspected pregnancies (including a positive pregnancy test 
regardless of age or disease state) of a female subject occurring while the subject is 
on study, or within 4 weeks of the subject’s last dose of study treatment should be 
recorded as SAEs. The subject is to be discontinued immediately from the study.  
The female subject should be referred to an obstetrician-gynecologist, preferably 
one experienced in reproductive toxicity for further evaluation and counseling. 
The Investigator will follow the female subject until completion of the pregnancy 
and must document the outcome of the pregnancy (either normal or abnormal 
outcome) and report the condition of the fetus or newborn to the UNC Study 
Coordinator. If the outcome of the pregnancy was abnormal (e.g., spontaneous or 
therapeutic abortion), the Investigator should report the abnormal outcome as an 
AE. If the abnormal outcome meets any of the serious criteria, it must be reported 
as an SAE. 
10.3.2 
FDA Expedited Reporting Requirements for Studies Conducted Under an IND 
A sponsor must report any suspected adverse reaction that is both serious and 
unexpected and related to the cellular product to the FDA. The sponsor must report an 
adverse event as a suspected adverse reaction only if there is evidence to suggest a 
causal relationship between the cellular product and the adverse event. For the 
definition of SAR refer to Section 9.1.2.  
The sponsor must submit each IND safety report on the MedWatch Form 3500A.  

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10.3.2.1 
Timing  
FDA must be notified of potential serious risks within 15 calendar days after the 
sponsor determines the event requires reporting. FDA must be notified of 
unexpected fatal or life-threatening suspected adverse reactions as soon as possible 
but in no case later than 7 calendar days after the sponsor’s initial receipt of the 
information. As a result, the sponsor must be notified of the SAE by the investigator 
within 24 hours of the event. If the results of a sponsor’s investigation show that an 
adverse event not initially determined to be reportable is reportable, the sponsor 
must report such suspected adverse reaction in an IND safety report as soon as 
possible, but in no case later than 15 calendar days after the determination is made.   
10.3.2.2 
Follow-Up  
The sponsor must promptly investigate all safety information it receives. Relevant 
follow-up information to an IND safety report must be submitted as soon as the 
information is available and as such the sponsor should be updated within 24 hours 
of the information being available via a follow-up MedWatch Form 3500A. 
10.3.2.3 
Notification of Investigators  
The sponsor must notify all participating investigators (i.e., all investigators to 
whom the sponsor is providing cell infusion under its INDs or under any 
investigator’s IND) in an IND safety report of potential serious risks, from clinical 
trials or any other source, as soon as possible, but in no case later than 15 calendar 
days after the sponsor determines that the information qualifies for reporting.    
10.3.2.4 
Process  
If the sponsor deems that an event is both a serious adverse reaction (SAR) AND 
unexpected, it must also (in addition to OnCore®) be recorded on the MedWatch 
Form 3500A. Unexpected adverse events or adverse reaction refers to an event or 
reaction that is not listed in the Investigator’s Brochure/IND or is not listed at the 
specificity or severity that has been observed; or if an Investigator’s Brochure is 
not required or available, is not consistent with the risk information described in 
the general investigation plan or elsewhere in the current IND application.   
10.3.2.5 
Additional Reporting Requirements  
The following additional items must be reported via IND safety report:  
 Findings from other studies. The sponsor must report any findings from 
epidemiological studies, pooled analysis of multiple studies, or clinical 
studies, whether or not conducted under an IND, and whether or not 
conducted by the sponsor, that suggest a significant risk to humans exposed 
to the cell infusion.   

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 Findings from animal or in vitro testing. The sponsor must report any 
findings from animal or in vitro testing, whether or not conducted by the 
sponsor, that suggest a significant risk in humans exposed to the cell 
infusion, such as reports of mutagenicity, teratogenicity, or carcinogenicity, 
or reports of significant organ toxicity at or near the expected human 
exposure.  
 Increased rate of occurrence of serious suspected adverse reactions. 
 Grade 4 or 5 cellular production infusion reactions, CRS or ICANS. 
10.3.2.6 
Additional Guidance  
Please refer to 21CFR312.32 and “Guidance for Industry and Investigators: Safety 
Reporting Requirements for INDs and BA/BE Studies” for additional information 
and reporting requirements. All IND Safety Reports will be submitted in 
accordance with these regulations/guidances. 
10.3.3 
Institutional Biosafety Committee (IBC) Reporting Requirements 
In addition to the local IRB, any qualifying serious adverse events (SAEs) must be 
reported to the Institutional Biosafety Committee (IBC). The IBC is responsible for 
reviewing recombinant DNA research conducted at or sponsored by the institution for 
compliance with NIH Guidelines. Experiments covered by the NIH Guidelines and 
approving those research projects that are found to conform with the NIH Guidelines. 
As such, the IBC is charged with ensuring compliance with all surveillance, data 
reporting and adverse event reporting requirements set forth in the NIH Guidelines. 
The UNC study coordinator will be responsible for notifying the Regulatory Associate 
within 48 hours should any reportable event occur. 
 

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negative subjects and B7H3 positive subjects. For example, if none of the four B7H3 
negative subjects have disease control and 11 or more of the B7H3 positive subjects have 
disease control, we will conclude that the disease control rates are significantly different in 
the two subgroups and further investigation of the treatment in the B7H3 negative group is 
not warranted.  
The duration of accrual is expected to be 48 months. 
11.4 
Data Analysis Plans 
Descriptive statistics will be utilized to summarize toxicity overall and by dose. 
All subjects who receive an infusion of CAR.B7-H3 T cells will be included in the safety 
analysis. Adverse event data and corresponding toxicity grades through 4 weeks after the 
last CAR-T cell infusion and during long-term follow up will be summarized. Tables will 
be generated to summarize incidence of subjects experiencing at least one episode of each 
adverse event, incidence of adverse events causing withdrawal, and incidence of serious 
adverse events. The total number of episodes for each event reported, the severity, and 
attribution to study therapy of each episode reported will also be displayed.  
Listings of adverse events by subjects will include the time to onset, the duration of each 
event, the severity of each event, the relationship of the event to study therapy, whether it 
was a serious event, and whether it caused withdrawal. Safety data will be summarized by 
dose level.  
For laboratory data, descriptive statistics (means, standard deviations, medians and ranges) 
at each evaluation point through 6 weeks after initial cellular product administration will 
be calculated. Laboratory data collected intervals dictated by the Time & Events Table for 
the first year will also be summarized.  
Disease control rate will be estimated as a proportion of subjects with complete response 
(CR) + partial response (PR) + stable disease and 95% confidence interval computed. PFS 
applies to all subjects and will be measured from the time of lymphodepletion prior to 
infusion with CAR.B7-H3 to progression or death from any cause; subjects not known to 
have any of these events are censored on the date they were last examined.  OS will be 
measured from the date of lymphodepletion prior to CAR.B7-H3 T cell product 
administration to the date of death. PFS and OS will be estimated using the Kaplan-Meier 
method. 
Toxicity and durability of response to therapy will be modeled as a function of changes in 
the expression of genes and/or proteins from before to after treatment to find the genes 
and/or proteins with the strongest association with toxicity and durability of response. 
 

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12 STUDY MANAGEMENT 
12.1 
Required Documentation 
Before the study can be initiated at any site, the following documentation must be provided 
to the Clinical Protocol Office (CPO) at the University of North Carolina. 
• A copy of the official IRB approval letter for the protocol and informed consent  
• IRB membership list. 
• CVs and medical licensure for the principal investigator and any sub-investigators 
who will be involved in the study. 
• Form FDA 1572 appropriately filled out and signed with appropriate 
documentation. 
• Financial Disclosures. 
• CAP and CLIA Laboratory certification numbers and institution lab normal values. 
• Executed clinical research contract. 
12.2 
Institutional Review Board (IRB) Approval and Consent  
It is expected that the IRB will have the proper representation and function in accordance 
with federally mandated regulations. The IRB should approve the consent form and 
protocol.  
In obtaining and documenting informed consent, the investigator should comply with the 
applicable regulatory requirement(s) and should adhere to Good Clinical Practice (GCP) 
and to ethical principles that have their origin in the Declaration of Helsinki. 
Before recruitment and enrollment onto this study, the subject will be given a full 
explanation of the study and will be given the opportunity to review the consent form. Each 
consent form must include all the relevant elements currently required by the FDA 
Regulations and local or state regulations. Once this essential information has been 
provided to the subject and the investigator is assured that the subject understands the 
implications of participating in the study, the subject will be asked to give consent to 
participate in the study by signing an IRB approved consent form.  
Prior to a subject’s participation in the trial, the written informed consent form should be 
signed and personally dated by the subject and by the person who conducted the informed 
consent discussion. 

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12.3 
Institutional Biosafety Committee Approval 
In accordance with the NIH Guidelines, any experiments involving the deliberate transfer 
of recombinant or synthetic nucleic acid molecules, or DNA or RNA derived from 
recombinant or synthetic nucleic acid molecules, into human research participants (human 
gene transfer), no human gene transfer experiment shall be initiated until Institutional 
Biosafety Committee (IBC) approval (from the clinical trial site) has been obtained and all 
applicable regulatory authorization(s) and approvals have been obtained. 
12.4 
Registration Procedures 
All subjects must be registered (prior to procurement) by the Cellular Immunotherapy 
Study Coordinator at UNC before enrollment to the study. Prior to registration at the time 
of cell procurement, eligibility criteria must be confirmed with the Cellular Immunotherapy 
Study Coordinator. 
12.5 
Adherence to Protocol 
Except for an emergency situation in which proper care for the protection, safety, and well-
being of the study subject requires alternative treatment, the study shall be conducted 
exactly as described in the approved protocol. 
12.6 
Emergency Modifications 
UNC investigators may implement a deviation from, or a change of, the protocol to 
eliminate an immediate hazard(s) to trial subjects without prior IRB/IEC 
approval/favorable opinion.  
For any such emergency modification implemented, the IRB must be notified within five 
(5) business days of making the change. 
12.7 
Study Files and Record Retention 
Study documentation includes all eCRFs, data correction forms or queries, source 
documents, Sponsor correspondence to Investigators, monitoring logs/letters, and 
regulatory documents (e.g., protocol and amendments, IRB correspondence and approval, 
signed subject consent forms).  
Source documents include all recordings of observations or notations of clinical activities 
and all reports and records necessary for the evaluation and reconstruction of the clinical 
research study.  
Government agency regulations and directives require that all study documentation 
pertaining to the conduct of a clinical trial must be retained by the study investigator. In 
the case of a study with a cell infusion seeking regulatory approval and marketing, these 
documents shall be retained for at least two years after the last approval of marketing 

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application in an International Conference on Harmonization (ICH) region. In all other 
cases, study documents should be kept on file until three years after the completion and 
final study report of this investigational study. 
12.8 
Source Documentation 
The Principal Investigator is responsible for the conduct of the clinical trial at the site in 
accordance with Title 21 of the Code of Federal Regulations and/or the Declaration of 
Helsinki. The Principal Investigator is responsible for personally overseeing the treatment 
of all study subjects. The Principal Investigator must assure that all study site personnel, 
including sub-investigators and other study staff members, adhere to the study protocol and 
all FDA/GCP/NCI regulations and guidelines regarding clinical trials both during and after 
study completion.  
The Principal Investigator or site will be responsible for assuring that all the required data 
will be collected and entered into the eCRFs. Periodically, monitoring visits will be 
conducted, and the Principal Investigator will provide access to his/her original records to 
permit verification of proper entry of data. At the completion of the study, all eCRFs will 
be reviewed by the Principal Investigator and will require his/her final signature to verify 
the accuracy of the data. 
12.9 
Data and Safety Monitoring Plan 
The Principal Investigator will provide continuous monitoring of subject safety in this trial 
with periodic reporting to the Data and Safety Monitoring Committee (DSMC).    
Meetings/teleconferences will be held at a frequency dependent on study accrual. These 
meetings will include the investigators as well as study coordinators, data coordinators, 
regulatory associates, clinical data management associates and any other relevant personnel 
the principal investigator may deem appropriate. At these meetings, the research team will 
discuss all issues relevant to study progress, including enrollment, safety, regulatory, data 
collection, etc. Prior to dose escalation, dose escalation meetings will be held to determine 
whether enrollment should continue on the next dose level. These meetings will include 
investigators, the Medical Monitor, the people responsible for review and evaluation of 
information relevant to the safety of the drug, the biostatistician, study coordinators and 
clinical data management associates. 
The team will produce summaries or minutes of these meetings. These summaries will be 
available for inspection when requested by any of the regulatory bodies charged with the 
safety of human subjects and the integrity of data including, but not limited to, the oversight 
of the IRB, the Oncology Protocol Review Committee (PRC) or the North Carolina TraCS 
Institute Data and Safety Monitoring Board (DSMB).   
The UNC LCCC Data and Safety Monitoring Committee (DSMC) will review the study 
on a regular (quarterly to annually) basis, with the frequency of review based on risk and 
complexity as determined by the UNC Protocol Review Committee. The UNC PI will be 

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responsible for submitting the following information for review: 1) safety and accrual data 
including the number of subjects treated; 2) significant developments reported in the 
literature that may affect the safety of participants or the ethics of the study; 3) preliminary 
response data; and 4) summaries of team meetings that have occurred since the last report. 
Findings of the DSMC review will be disseminated by memo to the UNC PI, PRC, the 
UNC IRB and DSMB. 
 
 
 
  

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13 AUDITING AND MONITORING 
The UNC LCCC will serve as the coordinating center for this trial. Data will be collected 
through a web based electronic data capture system, Advarra EDC. All data will be collected 
and entered into Advarra by research coordinators from UNC LCCC.   
The sponsor will provide direct access to source data/documents for trial-related monitoring, 
audits, IRB/IEC review, and regulatory inspection. As an investigator initiated study, this trial 
will also be audited and reviewed by the LCCC compliance committee every six or twelve 
months. It will also be monitored according to LCCC SOPs, within 8 weeks of the first patient 
enrolled, and subsequently every 4 months while there are subjects in the treatment period. 
Monitoring will occur annually once the study is closed to accrual and all subjects are in the 
follow-up period. 
 

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14 AMENDMENTS 
Should amendments to the protocol be required, the amendments will be originated and 
documented by the Principal Investigator at UNC. It should also be noted that when an 
amendment to the protocol substantially alters the study design or the potential risk to the 
subject, a revised consent form might be required. 
  

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15 STUDY DISCONTINUATION  
Both Lineberger Comprehensive Cancer Center and the Principal Investigator reserve the 
right to terminate the study at the investigator’s site at any time. Should this be necessary, 
Lineberger Comprehensive Cancer Center or a specified designee will inform the appropriate 
regulatory authorities of the termination of the study and the reasons for its termination, and 
the Principal Investigator will inform the IRB/IEC of the same. In terminating the study, 
Lineberger Comprehensive Cancer Center and the Principal Investigator will assure that 
adequate consideration is given to the protection of the subjects’ interests. 

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16 CONFIDENTIALITY 
All information generated in this study is considered highly confidential and must not be 
disclosed to any person or entity not directly involved with the study unless prior written 
consent is gained from Lineberger Comprehensive Cancer Center. However, authorized 
regulatory officials, IRB/IEC personnel, Lineberger Comprehensive Cancer Center and its 
authorized representatives are allowed full access to the records. 
Identification of subjects and eCRFs shall be by initials, screening and treatment numbers 
only. If required, the subject's full name may be made known to an authorized regulatory 
agency or other authorized official. 

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17 REFERENCES 
1. 
Cannistra, S.A., Cancer of the ovary. N Engl J Med, 2004. 351(24): p. 2519-29. 
2. 
Parmar, M.K., et al., Paclitaxel plus platinum-based chemotherapy versus conventional 
platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-
OVAR-2.2 trial. Lancet, 2003. 361(9375): p. 2099-106. 
3. 
du Bois, A., et al., A randomized clinical trial of cisplatin/paclitaxel versus 
carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst, 2003. 
95(17): p. 1320-9. 
4. 
Ledermann, J.A. and R.S. Kristeleit, Optimal treatment for relapsing ovarian cancer. 
Ann Oncol, 2010. 21 Suppl 7: p. vii218-22. 
5. 
McGuire, W.P., et al., Cyclophosphamide and cisplatin versus paclitaxel and cisplatin: a 
phase III randomized trial in patients with suboptimal stage III/IV ovarian cancer (from 
the Gynecologic Oncology Group). Semin Oncol, 1996. 23(5 Suppl 12): p. 40-7. 
6. 
Ozols, R.F., et al., Phase III trial of carboplatin and paclitaxel compared with cisplatin 
and paclitaxel in patients with optimally resected stage III ovarian cancer: a 
Gynecologic Oncology Group study. J Clin Oncol, 2003. 21(17): p. 3194-200. 
7. 
Ledermann, J., et al., Olaparib maintenance therapy in patients with platinum-sensitive 
relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by 
BRCA status in a randomised phase 2 trial. Lancet Oncol, 2014. 15(8): p. 852-61. 
8. 
Markman, M. and M.A. Bookman, Second-line treatment of ovarian cancer. Oncologist, 
2000. 5(1): p. 26-35. 
9. 
ten Bokkel Huinink, W., et al., Topotecan versus paclitaxel for the treatment of recurrent 
epithelial ovarian cancer. J Clin Oncol, 1997. 15(6): p. 2183-93. 
10. 
Buda, A., et al., Randomised controlled trial comparing single agent paclitaxel vs 
epidoxorubicin plus paclitaxel in patients with advanced ovarian cancer in early 
progression after platinum-based chemotherapy: an Italian Collaborative Study from the 
Mario Negri Institute, Milan, G.O.N.O. (Gruppo Oncologico Nord Ovest) group and 
I.O.R. (Istituto Oncologico Romagnolo) group. Br J Cancer, 2004. 90(11): p. 2112-7. 
11. 
Gordon, A.N., et al., Recurrent epithelial ovarian carcinoma: a randomized phase III 
study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol, 2001. 19(14): 
p. 3312-22. 
12. 
Matsuo, K., et al., Overcoming platinum resistance in ovarian carcinoma. Expert Opin 
Investig Drugs, 2010. 19(11): p. 1339-54. 
13. 
Mutch, D.G., et al., Randomized phase III trial of gemcitabine compared with pegylated 
liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol, 
2007. 25(19): p. 2811-8. 
14. 
Vergote, I., et al., Phase 3 randomised study of canfosfamide (Telcyta, TLK286) versus 
pegylated liposomal doxorubicin or topotecan as third-line therapy in patients with 
platinum-refractory or -resistant ovarian cancer. Eur J Cancer, 2009. 45(13): p. 2324-32. 
15. 
Pujade-Lauraine, E., et al., Bevacizumab combined with chemotherapy for platinum-
resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. 
J Clin Oncol, 2014. 32(13): p. 1302-8. 
16. 
Coleman, R.L., et al., Rucaparib maintenance treatment for recurrent ovarian carcinoma 
after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-
controlled, phase 3 trial. Lancet, 2017. 390(10106): p. 1949-1961. 

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17. 
Domchek, S.M., et al., Efficacy and safety of olaparib monotherapy in germline BRCA1/2 
mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. 
Gynecol Oncol, 2016. 140(2): p. 199-203. 
18. 
Lee, J.M., J.A. Ledermann, and E.C. Kohn, PARP Inhibitors for BRCA1/2 mutation-
associated and BRCA-like malignancies. Ann Oncol, 2014. 25(1): p. 32-40. 
19. 
Mirza, M.R., et al., Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent 
Ovarian Cancer. N Engl J Med, 2016. 375(22): p. 2154-2164. 
20. 
Pujade-Lauraine, E., et al., Olaparib tablets as maintenance therapy in patients with 
platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-
Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol, 
2017. 18(9): p. 1274-1284. 
21. 
Swisher, E.M., et al., Rucaparib in relapsed, platinum-sensitive high-grade ovarian 
carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. 
Lancet Oncol, 2017. 18(1): p. 75-87. 
22. 
Brentjens, R.J., et al., CD19-targeted T cells rapidly induce molecular remissions in 
adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med, 
2013. 5(177): p. 177ra38. 
23. 
Dotti, G., et al., Design and development of therapies using chimeric antigen receptor-
expressing T cells. Immunol Rev, 2014. 257(1): p. 107-26. 
24. 
Maude, S.L., et al., Chimeric antigen receptor T cells for sustained remissions in 
leukemia. N Engl J Med, 2014. 371(16): p. 1507-17. 
25. 
Kakarla, S. and S. Gottschalk, CAR T cells for solid tumors: armed and ready to go? 
Cancer J, 2014. 20(2): p. 151-5. 
26. 
Newick, K., E. Moon, and S.M. Albelda, Chimeric antigen receptor T-cell therapy for 
solid tumors. Mol Ther Oncolytics, 2016. 3: p. 16006. 
27. 
Newick, K., et al., CAR T Cell Therapy for Solid Tumors. Annu Rev Med, 2017. 68: p. 
139-152. 
28. 
Chapoval, A.I., et al., B7-H3: a costimulatory molecule for T cell activation and IFN-
gamma production. Nat Immunol, 2001. 2(3): p. 269-74. 
29. 
Steinberger, P., et al., Molecular characterization of human 4Ig-B7-H3, a member of the 
B7 family with four Ig-like domains. J Immunol, 2004. 172(4): p. 2352-9. 
30. 
Hofmeyer, K.A., A. Ray, and X. Zang, The contrasting role of B7-H3. Proc Natl Acad 
Sci U S A, 2008. 105(30): p. 10277-8. 
31. 
Seaman, S., et al., Eradication of Tumors through Simultaneous Ablation of CD276/B7-
H3-Positive Tumor Cells and Tumor Vasculature. Cancer Cell, 2017. 31(4): p. 501-515 
e8. 
32. 
Inamura, K., et al., Tumor B7-H3 (CD276) expression and smoking history in relation to 
lung adenocarcinoma prognosis. Lung Cancer, 2017. 103: p. 44-51. 
33. 
Loos, M., et al., B7-h3 and its role in antitumor immunity. Clin Dev Immunol, 2010. 
2010: p. 683875. 
34. 
Picarda, E., K.C. Ohaegbulam, and X. Zang, Molecular Pathways: Targeting B7-H3 
(CD276) for Human Cancer Immunotherapy. Clin Cancer Res, 2016. 22(14): p. 3425-
3431. 
35. 
Yamato, I., et al., Clinical importance of B7-H3 expression in human pancreatic cancer. 
Br J Cancer, 2009. 101(10): p. 1709-16. 

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36. 
Benzon, B., et al., Correlation of B7-H3 with androgen receptor, immune pathways and 
poor outcome in prostate cancer: an expression-based analysis. Prostate Cancer Prostatic 
Dis, 2017. 20(1): p. 28-35. 
37. 
Loos, M., et al., Expression of the costimulatory molecule B7-H3 is associated with 
prolonged survival in human pancreatic cancer. BMC Cancer, 2009. 9: p. 463. 
38. 
Parker, A.S., et al., Evaluation of B7-H3 expression as a biomarker of biochemical 
recurrence after salvage radiation therapy for recurrent prostate cancer. Int J Radiat 
Oncol Biol Phys, 2011. 79(5): p. 1343-9. 
39. 
Qin, X., et al., B7-H3 is a new cancer-specific endothelial marker in clear cell renal cell 
carcinoma. Onco Targets Ther, 2013. 6: p. 1667-73. 
40. 
Roth, T.J., et al., B7-H3 ligand expression by prostate cancer: a novel marker of 
prognosis and potential target for therapy. Cancer Res, 2007. 67(16): p. 7893-900. 
41. 
Zang, X., et al., B7-H3 and B7x are highly expressed in human prostate cancer and 
associated with disease spread and poor outcome. Proc Natl Acad Sci U S A, 2007. 
104(49): p. 19458-63. 
42. 
Zang, X., et al., Tumor associated endothelial expression of B7-H3 predicts survival in 
ovarian carcinomas. Mod Pathol, 2010. 23(8): p. 1104-12. 
43. 
Fauci, J.M., et al., Monoclonal antibody-based immunotherapy of ovarian cancer: 
targeting ovarian cancer cells with the B7-H3-specific mAb 376.96. Gynecol Oncol, 
2014. 132(1): p. 203-10. 
44. 
Kasten, B.B., et al., B7-H3-targeted (212)Pb radioimmunotherapy of ovarian cancer in 
preclinical models. Nucl Med Biol, 2017. 47: p. 23-30. 
45. 
Kramer, K., et al., Compartmental intrathecal radioimmunotherapy: results for treatment 
for metastatic CNS neuroblastoma. J Neurooncol, 2010. 97(3): p. 409-18. 
46. 
Loo, D., et al., Development of an Fc-enhanced anti-B7-H3 monoclonal antibody with 
potent antitumor activity. Clin Cancer Res, 2012. 18(14): p. 3834-45. 
47. 
Institute, N.C., NCI Clinical Announcement: Intraperitoneal chemotherapy for ovarian 
cancer. 2006: p. 1-22. 
48. 
Armstrong, D.K., et al., Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N 
Engl J Med, 2006. 354(1): p. 34-43. 
49. 
van Driel, W.J., et al., Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. 
N Engl J Med, 2018. 378(3): p. 230-240. 
50. 
Verwaal, V.J., et al., Randomized trial of cytoreduction and hyperthermic intraperitoneal 
chemotherapy versus systemic chemotherapy and palliative surgery in patients with 
peritoneal carcinomatosis of colorectal cancer. J Clin Oncol, 2003. 21(20): p. 3737-43. 
51. 
Verwaal, V.J., et al., 8-year follow-up of randomized trial: cytoreduction and 
hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients 
with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol, 2008. 15(9): p. 
2426-32. 
52. 
Katz, S.C., et al., Regional CAR-T cell infusions for peritoneal carcinomatosis are 
superior to systemic delivery. Cancer Gene Ther, 2016. 23(5): p. 142-8. 
53. 
Lee, D.W., et al., Current concepts in the diagnosis and management of cytokine release 
syndrome. Blood, 2014. 124(2): p. 188-95. 

LCCC 1818-ATL 
CAR T-Cells Targeting B7-H3 Antigen in Recurrent Epithelial Ovarian Cancer 
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54. 
Lee, D.W., et al., ASTCT Consensus Grading for Cytokine Release Syndrome and 
Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow 
Transplant, 2019. 25(4): p. 625-638. 
55. 
Mirzaei, H.R., et al., Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: 
Challenges and Clinical Applications. Front Immunol, 2017. 8: p. 1850. 
56. 
Davila, M.L., et al., Efficacy and toxicity management of 19-28z CAR T cell therapy in B 
cell acute lymphoblastic leukemia. Sci Transl Med, 2014. 6(224): p. 224ra25. 
57. 
Lee, D.W., et al., T cells expressing CD19 chimeric antigen receptors for acute 
lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. 
Lancet, 2015. 385(9967): p. 517-528. 
58. 
Maus, M.V., et al., Antibody-modified T cells: CARs take the front seat for hematologic 
malignancies. Blood, 2014. 123(17): p. 2625-35. 
59. 
van der Stegen, S.J., M. Hamieh, and M. Sadelain, The pharmacology of second-
generation chimeric antigen receptors. Nat Rev Drug Discov, 2015. 14(7): p. 499-509. 
60. 
Beatty, G.L., et al., Mesothelin-specific chimeric antigen receptor mRNA-engineered T 
cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res, 2014. 2(2): 
p. 112-20. 
61. 
ACTEMRATM (tocilizumab) [package insert]. Genentech, San Francisco, CA; 2017. 
62. 
Porter, D.L., et al., Chimeric antigen receptor T cells persist and induce sustained 
remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med, 2015. 
7(303): p. 303ra139. 
63. 
Maude, S.L., et al., CD19-targeted chimeric antigen receptor T-cell therapy for acute 
lymphoblastic leukemia. Blood, 2015. 125(26): p. 4017-23. 
64. 
Neelapu, S.S., et al., Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large 
B-Cell Lymphoma. N Engl J Med, 2017. 377(26): p. 2531-2544. 
65. 
Koneru, M., et al., A phase I clinical trial of adoptive T cell therapy using IL-12 secreting 
MUC-16(ecto) directed chimeric antigen receptors for recurrent ovarian cancer. J Transl 
Med, 2015. 13: p. 102. 
66. 
Curran, K.J., H.J. Pegram, and R.J. Brentjens, Chimeric antigen receptors for T cell 
immunotherapy: current understanding and future directions. J Gene Med, 2012. 14(6): 
p. 405-15. 
67. 
Gill, S. and C.H. June, Going viral: chimeric antigen receptor T-cell therapy for 
hematological malignancies. Immunol Rev, 2015. 263(1): p. 68-89. 
68. 
Grupp, S.A., et al., Adoptive transfer of autologous T cells improves T-cell repertoire 
diversity and long-term B-cell function in pediatric patients with neuroblastoma. Clin 
Cancer Res, 2012. 18(24): p. 6732-41. 
69. 
Handolias, D., et al., Oral cyclophosphamide in recurrent ovarian cancer. Asia Pac J 
Clin Oncol, 2016. 12(1): p. e154-60. 
70. 
Garcia, A.A., et al., Phase II clinical trial of bevacizumab and low-dose metronomic oral 
cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and 
Princess Margaret Hospital phase II consortia. J Clin Oncol, 2008. 26(1): p. 76-82. 
71. 
Nehama, D., et al., B7-H3-redirected chimeric antigen receptor T cells target 
glioblastoma and neurospheres. EBioMedicine, 2019. 47: p. 33-43. 
72. 
Neelapu, S.S., et al., Chimeric antigen receptor T-cell therapy - assessment and 
management of toxicities. Nat Rev Clin Oncol, 2018. 15(1): p. 47-62. 

LCCC 1818-ATL 
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73. 
Maus, M.V. and B.L. Levine, Chimeric Antigen Receptor T-Cell Therapy for the 
Community Oncologist. Oncologist, 2016. 21(5): p. 608-17. 
74. 
Eisenhauer, E.A., et al., New response evaluation criteria in solid tumours: revised 
RECIST guideline (version 1.1). Eur J Cancer, 2009. 45(2): p. 228-47. 
75. 
Oken, M.M., et al., Toxicity and response criteria of the Eastern Cooperative Oncology 
Group. Am J Clin Oncol, 1982. 5(6): p. 649-55. 
 
 

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18.2 
APPENDIX II – Tumor Measurement Based on RECIST 1.1 
See the international criteria proposed by the Response Evaluation Criteria in Solid Tumors 
(RECIST) Committee, version 1.1 [74] for additional details on RECIST 1.1. 
Measurable disease will be defined as the presence of at least one measurable lesion that 
can be accurately measured in at least one dimension with the longest diameter a minimum 
size of: 
• >10 mm by CT scan (CT scan slice thickness no greater than 5 mm) 
• 10 mm caliper measurement by clinical exam (lesions which cannot be accurately 
measured with calipers should be recorded as non-measurable). 
• 20 mm by chest X-ray. 
For malignant lymph nodes to be considered pathologically enlarged and measurable, a 
lymph node must be ≥15mm in short axis when assessed by CT scan (CT scan slice 
thickness recommended to be no greater than 5mm). At baseline and in follow-up, only the 
short axis will be measured and followed.   
All other lesions, including small lesions (longest diameter <10mm or pathological lymph 
nodes with ≥10 to <15 mm short axis) as well as truly non-measurable lesions, will be 
considered non-measurable. Lesions considered truly non-measurable include: 
leptomeningeal disease; ascites; pleural/pericardial effusion; inflammatory breast disease; 
lymphangitic involvement of skin or lung, abdominal masses/abdominal organomegaly 
identified by physical exam that is not measurable by reproducible imaging techniques. 
All measurements should be recorded in metric notation, using calipers if clinically 
assessed. All baseline evaluations should be performed as close as possible to the treatment 
start and never more than 4 weeks before the beginning of the treatment.  The same method 
of assessment and the same technique should be used to characterize each identified and 
reported lesion at baseline and during follow-up.  Imaging based evaluation should always 
be done rather than clinical examination unless the lesion(s) being followed cannot be 
imaged but are assessable by clinical exam. Clinical lesions will only be considered 
measurable when they are superficial and ≥10 mm diameter as assessed using calipers (e.g. 
skin nodules). For the case of skin lesions, documentation by color photography including 
a ruler to estimate the size of the lesions is recommended. 
18.2.1 
Baseline Documentation of Target and Non-Target Lesions 
All measurable lesions up to a maximum of 5 lesions total (and a maximum of two 
lesions per organ) representative of all involved organs should be identified as target 
lesions and will be recorded and measured at baseline.   

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Target lesions should be selected on the basis of their size (lesions with the longer 
diameter), be representative of all involved organs, but in addition should be those that 
lend themselves to reproducible repeated measurements.  
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for 
all target lesions will be calculated and reported as the baseline sum diameters. If lymph 
nodes are to be included in the sum, only the short axis is added into the sum.  The 
baseline sum diameters will be used as reference to further characterize the objective 
tumor response of the measurable dimension of the disease. 
All other lesions (or sites of disease) including pathological lymph nodes should be 
identified as non-target lesions and should also be recorded at baseline. Measurements 
are not required, and these lesions should be followed as “present” or “absent”, or in 
rare cases “unequivocal progression”.   
18.2.2 
Evaluation of Target Lesions using RECIST 1.1 Criteria 
NOTE: In addition to the information below, also see section 4.3.2 in the international 
criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) 
Committee, version 1.1 [74] for special notes on the assessment of target lesions.  
Complete response (CR) − Disappearance of all target lesions.  Any pathological 
lymph node (LN) (whether target or non-target) must have decreased in short axis to 
<10mm. 
Partial response (PR) − At least a 30% decrease in the sum of the LD of the target 
lesions taking as reference the baseline sum LD. 
Progressive Disease (PD) − At least a 20% increase in the sum of the LD of the target 
lesions taking as reference the smallest sum LD recorded since the treatment started 
including baseline if that is the smallest on study.  In addition to the relative increase 
of 20%, the sum must also demonstrate an absolute increase of at least 5mm.  The 
appearance of one or more new lesions also constitutes PD. 
Stable disease (SD) − Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD taking as references the smallest sum LD since the treatment 
started. 
18.2.3 
Evaluation of Non-Target Lesions using RECIST 1.1 Criteria 
Complete response (CR) − Disappearance of all non-target lesions and normalization 
of tumor marker levels.  All LN must be non-pathological in size (<10mm short axis).   
Non-complete response (non-CR)/non-progression (non-PD) − Persistence of one 
or more non-target lesion(s) or/and maintenance of tumor marker level above the 
normal limits. 

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Progressive disease (PD) − Appearance of one or more new lesions and/or 
unequivocal progression of existing non-target lesions. 
18.2.4 
Evaluation of Best Overall Response using RECIST 1.1 Criteria 
The best overall response is the best response recorded from the start of the study 
treatment until the end of treatment provided the confirmation criteria are met.  To be 
assigned a status of PR or CR, changes in tumor measurements must be confirmed by 
repeat studies that should be performed > 4 weeks after the criteria for response are 
first met. If a CR/PR cannot be confirmed the original "response" should be considered 
stable disease.  The best overall response will be defined according to the following 
table (Table 4). 
 
Table 4 Best Overall Response 
Overall Response First 
Time Point 
Overall Response 
Subsequent Time Point 
BEST Overall Response 
CR 
CR 
CR 
CR 
PR 
SD, PD, or PR1 
CR 
SD 
SD provided minimum criteria for SD 
duration met, otherwise, PD 
CR 
PD 
SD provided minimum criteria for SD 
duration met, otherwise, PD 
CR 
NE2 
SD provided minimum criteria for SD 
duration met, otherwise, NE2 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD provided minimum criteria for SD 
duration met, otherwise, PD 
PR 
NE2 
SD provided minimum criteria for SD 
duration met, otherwise, NE2 
NE 
NE2 
NE2 
1 If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease 
meeting PR criteria relative to baseline, makes the disease PD at that point (since disease must have 
reappeared after CR).  Best response would depend on whether minimum duration for SD was met.  
However, sometimes ‘CR’ may be claimed when subsequent scans suggest small lesions were likely still 
present and in fact the subject had PR, not CR at the first time point.  Under these circumstances, the 
original CR should be changed to PR and the best response is PR.  
2 NE=unevaluable

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18.5 
APPENDIX V – Treatment Algorithm for Macrophage Activation Syndrome 
MAS can be diagnosed with any of the following criteria: 
• Laboratory (need 4 or more of these for diagnosis plus 2 or more clinical criteria) 
o Decreased platelet count < 150 × 109/L 
o Increased AST 
o Decreased WBC < 4 × 109/L.   
o Hypofibrinogenemia (< 250 mg/dL) 
o Increase in triglycerides 
o Increase in ferritin 
• Clinical Criteria: 
o CNS dysfunction (irritability, disorientation, lethargy, headache, seizures or 
coma) 
o Hemorrhage or easy bleeding 
o Hepatomegaly and/or splenomegaly (> 3 cm below the costal margin)  
o Fever (temperature > 38ºC) 
• Additional criteria include evaluating bone marrow for the presence of 
macrophages phagocytosing hematopoietic cells.  
 
Initial evaluation should include the following: 
• CBC with differential and reticulocyte count 
• AST, ALT, alkaline phosphatase, LDH, total bilirubin 
• Basic metabolic panel including sodium, creatinine, BUN 
• Ferritin level 
• Triglyceride level 

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• CT scan with contrast or MRI scan with contrast (if renal function permits) in the 
setting of CNS symptoms 
• Spinal tap with evaluation for infection and the presence of CAR-T cells + 
cytokines such as IL-6 if this can be done without significant concern for bleeding.  
Research evaluations which should be drawn and can assist in the diagnosis include: 
• Soluble IL-2 receptor 
• Soluble CD163 
Treatment will be either high dose corticosteroids at 2 mg/kg of prednisone or an equivalent 
+/- etoposide similar to institutional therapy for HLH.  Other therapies that should be 
considered in refractory cases include anakinra, cyclosporine A or tacrolimus, and 
therapies targeted to TNF such as etanercept, infliximab or adalimumab.

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18.6 
APPENDIX VI – ECOG Performance Status [75] 
Grade 
Description 
0 
Normal activity. Fully active, able to carry on all pre-disease performance 
without restriction. 
1 
Symptoms, but ambulatory. Restricted in physically strenuous activity, 
but ambulatory and able to carry out work of a light or sedentary nature 
(e.g., light housework, office work). 
2 
In bed <50% of the time. Capable of only limited self-care, confined to 
bed or chair more than 50% of waking hours. 
3 
In bed >50% of the time. Capable of only limited self-care, confined to 
bed or chair more than 50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any self-care. 
Totally confined to bed or chair. 
5 
Dead.