A Phase Ib/II Study of Leronlimab (PRO 140) Combined With Carboplatin in Patients With CCR5+ Metastatic Triple Negative Breast Cancer (mTNBC)
Phase: PHASE1
Conditions: Triple Negative Breast Neoplasms
Sponsor: CytoDyn, Inc.

 
 
CytoDyn Inc.    1111 Main Street, Suite 660, Vancouver, Washington 98660   T 360.980.8524  F 360.799.5954 
 
 
Protocol Cover Page 
 
 
Protocol Title: A Phase Ib/II Study of Leronlimab (PRO 140) Combined with Carboplatin in 
Patients with CCR5+ Metastatic Triple Negative Breast Cancer 
 
Protocol Number: CD07_TNBC 
 
Version: 4.0 
 
Document Date: 20-Jan-2021 
 
NCT Number: NCT03838367 
 

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A Phase Ib/II Study of Leronlimab (PRO 140) Combined with Carboplatin in 
Patients with CCR5+ Metastatic Triple-Negative Breast Cancer (mTNBC) 
Protocol Number:
CD07_TNBC
Version:
4.0
Date:
20-Jan-2021 
Sponsor:
CytoDyn, Inc.
1111 Main Street, Suite 660 
Vancouver, Washington 98660
(360) 980-8524-Work 
(360) 980-8549-Fax
www.cytodyn.com 
Lead Principal Investigator:
Confidentiality Statement
This document is a confidential communication of CytoDyn, Inc. It is provided for the conduct of a clinical 
research study. The information contained in this document is confidential and, except to the extent 
necessary to obtain informed consent or IEC/IRB approval, cannot be disclosed unless required by 
governmental regulation. Persons to whom any portion of the contents of this document is disclosed must 
be informed that the information is confidential and may not be further disclosed by them.

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PROTOCOL APPROVAL PAGE
Protocol Number:
CD07_TNBC
Version: 
 
4.0 
Date:
20-Jan-2021 
We, the undersigned, have reviewed this protocol and agree that it contains all relevant information required 
to meet FDA, GCP and all applicable regulatory guidelines and statutes.
PROTOCOL APPROVAL FOR USE
Date
Date
Date
Date
Date

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INVESTIGATOR’S SIGNATURE PAGE
 
 
Protocol Number:
CD07_TNBC
Version: 
 
4.0
Date:
20-Jan-2021 
I have read the protocol specified above and agree to participate in and comply with the procedures, as 
outlined herein for the conduct of this clinical trial. I also agree to comply with US Food and Drug 
Administration (FDA) regulations and Investigational Review Board/Institutional Ethics (IRB/IEC)
requirements for testing on human subjects. I agree to ensure that the requirements for obtaining informed 
consent are met.
Principal Investigator’s Signature
Date
Print Name
Site Number

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TABLE OF CONTENTS
PROTOCOL SYNOPSIS..............................................................................................................5
TABLE OF CONTENTS ............................................................................................................17
List of Tables .................................................................................................................................23
List of Figures ...............................................................................................................................24
List of Abbreviations .....................................................................................................................24
1
INTRODUCTION AND BACKGROUND ..........................................................................28
1.1
Statement of Intent ..............................................................................................................28
1.2
Background of the Disease ..................................................................................................28
1.2.1.
Triple Negative Breast Cancer (TNBC) ............................................................28
1.2.2.
C-C Chemokine Receptor Type-5 (CCR5) .......................................................28
1.2.3.
Circulating Tumor Cells (CTCs) in Metastatic Breast Cancer (MBC) .............31
1.2.4.
CCR5+ tumor-infiltrating leukocytes ................................................................31
1.3
Study Treatments .................................................................................................................34
1.3.1.
Leronlimab (PRO 140) ......................................................................................34
1.3.2.
Carboplatin ........................................................................................................35
1.4
Pre-Clinical Studies of leronlimab (PRO 140) ....................................................................36
1.4.1.
Effect of PRO140 on human CCR5 in breast cancer cells, MDA-MB-231 ......36
1.4.1.1
PRO140 binding to human CCR5 in human breast cancer cells .......................36
1.4.1.2
PRO140 blocks human CCR5 mediated signaling in human breast cancer cells.
37
1.4.1.3
PRO140 blocks human CCR5 mediated invasion of extracellular matrix in 
human breast cancer cells. .................................................................................38
1.4.2.
Effect of PRO 140 on Growth of SW480 Human Colon Carcinoma Xenografts
40
1.4.3.
Clinical Studies with leronlimab (PRO 140) .....................................................43
1.4.4.
PRO 140 1101 Study .........................................................................................43
1.4.5.
PRO 140 1102 Study .........................................................................................43
1.4.6.
PRO 140 1103 Study .........................................................................................44
1.4.7.
PRO 140 1302 Study .........................................................................................44
1.4.8.
PRO 140 2301 Study .........................................................................................44
1.4.9.
PRO 140 2101 Study .........................................................................................45

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1.4.10.
PRO 140_CD01 Study ......................................................................................45
1.4.11.
PRO 140_CD01 Extension Study .....................................................................46
1.4.12.
PRO 140_CD02 Study ......................................................................................47
1.4.13.
PRO 140_CD02 Extension Study .....................................................................48
1.4.14.
PRO 140_CD03 HIV Study ..............................................................................48
1.4.15.
PRO 140_CD03 HIV Extension Study .............................................................49
1.4.16.
PRO 140_CD06 Study ......................................................................................49
1.4.17.
CD08_mCRC Study ..........................................................................................49
1.5
Rationale for Target Population and Dose Selection ..........................................................52
1.6
Risks / Benefits Assessment ................................................................................................53
1.6.1.
Risks/Discomfort to Subjects and Precautions to Minimize Risk .....................53
1.6.2.
Intended Benefit for Subjects ............................................................................55
2
STUDY OBJECTIVES ..........................................................................................................56
3
STUDY DESIGN ....................................................................................................................57
3.1
Study Center ........................................................................................................................61
3.2
Study Population .................................................................................................................61
3.3
Eligibility Criteria ................................................................................................................62
3.3.1.
Inclusion Criteria ...............................................................................................62
3.3.2.
Exclusion Criteria ..............................................................................................63
4
STUDY SCHEDULE .............................................................................................................65
4.1
Pre-Screening Period ...........................................................................................................71
4.1.1.
Pre-Screening Visit............................................................................................71
4.2
Screening Period ..................................................................................................................71
4.2.1.
Screening Visit (SV) .........................................................................................71
4.3
Treatment Period .................................................................................................................73
4.3.1.
Treatment Cycle 1, Day 1 ..................................................................................73
4.3.2.
Treatment Cycle 1, Day 8 & Day 15 .................................................................74
4.3.3.
Subsequent Treatment Cycle(s), Day 1 .............................................................74
4.3.4.
Subsequent Treatment Cycle(s), Day 8 & Day 15 ............................................75
4.4
Follow-Up Period ................................................................................................................76
4.4.1.
End of Treatment Visit (EOT) ...........................................................................76

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4.4.2.
Survival Follow-up Visits .................................................................................77
4.5
Unscheduled Visits ..............................................................................................................77
5
SUBJECT COMPLETION, WITHDRAWAL AND CRITERIA FOR STOPPING THE 
STUDY ....................................................................................................................................79
5.1
Removal of Subjects from Study Treatment and/or Study as a Whole ...............................79
5.2
Subject Replacement ...........................................................................................................80
5.3
Data Collected from Withdrawn Subjects ...........................................................................80
5.4
Screen Failures ....................................................................................................................80
6
STUDY TREATMENT .........................................................................................................81
6.1
leronlimab (PRO 140) .........................................................................................................81
6.1.1.
Leronlimab (PRO 140) - Packaging and Labeling ............................................82
6.1.2.
Leronlimab (PRO 140) - Storage and Handling ................................................83
6.1.3.
Leronlimab (PRO 140) - Administration ..........................................................84
6.1.4.
Leronlimab (PRO 140) - Post Injection Monitoring .........................................84
6.1.5.
Leronlimab (PRO 140) - Dose Modifications ...................................................85
6.1.6.
Leronlimab (PRO 140) - Disposition ................................................................86
6.1.7.
Leronlimab (PRO 140) - Accountability ...........................................................86
6.2
Carboplatin ..........................................................................................................................86
6.2.1.
Other names .......................................................................................................86
6.2.2.
Classification – Type of agent ...........................................................................86
6.2.3.
Carboplatin - Mode of Action ...........................................................................86
6.2.4.
Carboplatin - Storage and stability ....................................................................87
6.2.5.
Carboplatin - Dose specification per protocol ...................................................87
6.2.6.
Carboplatin - Preparation ..................................................................................87
6.2.7.
Carboplatin - Route of administration ...............................................................87
6.2.8.
Carboplatin - Incompatibilities ..........................................................................87
6.2.9.
Carboplatin - Availability and Supply...............................................................88
6.2.10.
Carboplatin - Side effects ..................................................................................88
6.2.11.
Carboplatin - Nursing implications ...................................................................88
6.2.12.
Return and Retention of Study Drug .................................................................89
6.2.13.
Carboplatin - Toxicity Management & Dose Delays/Modifications ................89

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7
DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES ...................91
7.1
Informed Consent ................................................................................................................91
7.2
Assessment of Eligibility .....................................................................................................91
7.2.1.
Re-screening ......................................................................................................91
7.3
Demographic Information and Baseline Disease Characteristics .......................................91
7.4
Medical History ...................................................................................................................92
7.5
Concomitant Medication .....................................................................................................93
7.5.1.
Permitted Medications .......................................................................................93
7.5.2.
Prohibited Medications......................................................................................93
7.6
Vital Signs, Height and Weight ...........................................................................................94
7.7
Physical Examination ..........................................................................................................94
7.8
ECOG Performance Status ..................................................................................................95
7.9
Electrocardiogram (ECG) ....................................................................................................95
7.10 Toxicity Assessment ............................................................................................................95
7.11 Clinical Laboratory Assessments ........................................................................................96
7.11.1.
Correlatives/Special Studies ..............................................................................97
7.11.1.1
Sample Collection Guidelines ...........................................................................98
7.11.1.2
Sample Processing, Storage, and Shipment ......................................................98
7.11.1.3
Assay Methodology ...........................................................................................99
7.12 Study Treatment Application ..............................................................................................99
7.13 Post-Injection Evaluation and Injection Site Reaction Assessment ....................................99
7.14 Pain Assessment using Visual Analog Scale (VAS) .........................................................100
7.15 Tumor Imaging and Response Evaluation ........................................................................100
7.15.1.
Definition of Lesions .......................................................................................101
7.15.2.
Method of Assessment ....................................................................................102
7.15.3.
Baseline documentation of ‘target’ and ‘non-target’ lesions ..........................103
7.15.4.
Evaluation of target lesions .............................................................................104
7.15.5.
Evaluation of non-target lesions ......................................................................105
7.15.6.
Evaluation of Best Overall Response ..............................................................105
7.15.7.
Duration of Response ......................................................................................106
7.16 Survival Status ...................................................................................................................107

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8
STATISTICAL ANALYSIS ...............................................................................................108
8.1
Treatment Groups ..............................................................................................................108
8.2
Sample Size Determination and Rationale ........................................................................108
8.3
Randomization and Stratification ......................................................................................108
8.4
Blinding .............................................................................................................................108
8.5
Interim Analysis ................................................................................................................108
8.6
General Statistical Considerations .....................................................................................109
8.6.1.
Analysis Populations .......................................................................................110
8.6.1.1
Intent-to-Treat Population ...............................................................................110
8.6.1.2
Per Protocol Population ...................................................................................110
8.6.1.3
Safety Population ............................................................................................110
8.6.2.
Covariates ........................................................................................................110
8.6.3.
Missing Data....................................................................................................110
8.7
Analysis Methods ..............................................................................................................110
8.7.1.
Subject Disposition .........................................................................................110
8.7.2.
Demographic and Baseline Disease Characteristics .......................................110
8.7.3.
Study Analyses ................................................................................................111
8.7.3.1
Primary Analysis .............................................................................................111
8.7.3.2
Safety Analyses ...............................................................................................113
9
ADVERSE EVENTS (DEFINITIONS AND REPORTING) ..........................................115
9.1
Adverse event (AE) ...........................................................................................................115
9.2
Reporting and Follow-Up of Adverse Events ...................................................................115
9.2.1.
Impact on Study Treatment .............................................................................115
9.2.2.
CTCAE Grade (Intensity) Assessment ............................................................115
9.2.3.
Causality Assessment ......................................................................................116
9.2.4.
Treatment Given as a Result of the Event .......................................................117
9.2.5.
Outcome Assessment ......................................................................................117
9.2.6.
Injection-site reactions ....................................................................................117
9.3
Serious Adverse Events .....................................................................................................117
9.4
Reporting of Serious Adverse Events ...............................................................................118
9.5
SAE Follow-Up .................................................................................................................118

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10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION ....................................119
11 QUALITY CONTROL AND QUALITY ASSURANCE .................................................120
11.1 Monitoring Requirements ..................................................................................................120
11.2 Acceptability of Case Report Forms (CRFs) ....................................................................120
11.3 Modification of Protocol ...................................................................................................120
11.4 Reporting Protocol Deviations ..........................................................................................121
11.4.1.
Major Protocol Deviation or Violation ...........................................................121
11.4.2.
Minor Protocol Deviation or Violation ...........................................................121
12 DATA SAFETY MONITORING BOARD (DSMB) ........................................................123
13 ETHICS AND REGULATORY REQUIREMENTS .......................................................125
13.1 Institutional Review Board/Independent Ethics Committee (IRB/IEC) ...........................125
13.2 Investigator’s Responsibilities ..........................................................................................125
13.3 Subject Informed Consent Requirements ..........................................................................126
14 DATA HANDLING AND RECORD KEEPING ..............................................................127
14.1 Recording and Collection of Data .....................................................................................127
14.2 Clinical Data Management ................................................................................................127
14.3 Archiving ...........................................................................................................................128
15 PUBLICATION PLAN .......................................................................................................130
16 REFERENCES .....................................................................................................................131
17 APPENDIX ...........................................................................................................................136
17.1 Appendix 1:  Acceptable methods of Contraception .........................................................136
17.2 Appendix 2: Recommendations for HER-2 testing in breast cancer .................................137
17.3 Appendix 3: Common Terminology Criteria for Adverse Events v5.0 ............................138

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LIST OF TABLES
Table 1-1:
List of Completed Clinical Studies with leronlimab (PRO 140) .............................49
Table 1-2:
List of Ongoing Clinical Studies with leronlimab (PRO 140) ................................51
Table 4-1:
Schedule of Assessments .........................................................................................67
Table 6-1:
Treatment Administration Summary .......................................................................81
Table 6-2:
Investigational Product - leronlimab (PRO 140) .....................................................82
Table 6-3:
Leronlimab (PRO 140) Dose Modification and Management for Injection Site 
Reactions .................................................................................................................85
Table 6-4:
Carboplatin Dose Modification and Management ..................................................89
Table 7-1:
ECOG Performance Status Scale ............................................................................95
Table 7-2:
Central Lab Parameters ...........................................................................................97
Table 7-3:
Target Lesion Evaluation ......................................................................................104
Table 7-4:
Non-Target Lesion Evaluation ..............................................................................105
Table 7-5:
Time point response: subjects with target (± non-target) disease .........................106
Table 9-1: 
CTCAE v5.0 General Guidelines ..........................................................................116

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LIST OF FIGURES
Figure 1-1:
CCR5 over-expression correlates with poor survival). Immunohistochemical staining 
for CCR5 in 537 patients .........................................................................................29
Figure 1-2:
The CCR5 antagonist Maraviroc inhibits lung metastases in vivo .........................30
Figure 1-3:
Tumor Tregs (Stain with CD4, CD325, CD127, and CCR5) ..................................32
Figure 1-4:
IHC staining showing high predominance of CCR5+ tumor infiltrating leukocytes in 
TNBC (Subject 1) ....................................................................................................33
Figure 1-5:
IHC staining showing high predominance of CCR5+ tumor infiltrating leukocytes in 
TNBC (Subject 2) ....................................................................................................34
Figure 1-6:
PRO-140 binds human CCR5 in human breast cancer cells. .................................37
Figure 1-7:
 PRO140 blocks human CCR5 mediated signaling in human breast cancer cells. .38
Figure 1-8:
 PRO140 blocks CCL5-induced breast cancer cell invasion ...................................39
Figure 1-9:
 Part 1: SW480 Human Colon Carcinoma Xenografts Grown in NCr Nude Mice .41
Figure 1-10:  Part 2: SW480 Human Colon Carcinoma Xenografts Grown in NCr Nude Mice .42
Figure 1-11:  Part 3: SW480 Human Colon Carcinoma Xenografts Grown in NCr Nude Mice .42
Figure 1-12:  Part 4: SW480 Human Colon Carcinoma Xenografts Grown in NSG Mice .........43
Figure 3-1:
Study Schematic ......................................................................................................57
Figure 3-2:
3+3 Study Design ....................................................................................................59
Figure 4-1:
Study Flow Diagram ...............................................................................................66
Figure 6-1:
Investigational Product - Vial Label .......................................................................82
Figure 6-2:
Investigational Product - Syringe Label ..................................................................83
Figure 6-3:
Investigational Product - Kit Label .........................................................................83
Figure 7-1:
Visual Analog Scale ..............................................................................................100
LIST OF ABBREVIATIONS
Abbreviation
Term
AE 
Adverse Event 
ALP
Alkaline Phosphatase
ALT
Alanine  Aminotransferase
AST 
Aspartate Aminotransferase

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Abbreviation
Term
BUN
Blood Urea Nitrogen 
Cmax
Maximal Concentration
cART
Combination Antiretroviral Therapy
CBR
Clinical Benefit Rate
CCL5
C-C Chemokine Ligand Type-5 
CCR5
C-C Chemokine Receptor Type-5 
CFR
Code of Federal Regulations 
CHO
Chinese Hamster Ovary
CNS
Central Nervous System
CrCl
Creatinine Clearance
CRF
Case Report Form
CRO
Contract Research Organization
CS
Clinically Significant
CTC
Circulating Tumor Cells
CTCAE
Common Terminology Criteria for Adverse Events
DAPI
4,2-diamidino-2- phenylindole dihydrochloride 
DFS
Disease Free Survival
DLT
Dose Limiting Toxicities
DSMB
Data Safety Monitoring Board
ECG
Electrocardiogram
ECL2
ExtraCellular Loop 2
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic Case Report Form
EOT
End of Treatment
ER
Estrogen Receptor
FDA
U.S. Food and Drug Administration 
FI
Fluorescent Intensity   
FISH
Fluorescence in Situ Hybridization 
FOCBP
Females of Child-bearing Potential 
FUV
Follow-up Visit
GCP
Good Clinical Practice

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Abbreviation
Term
GMP
Good Manufacturing Practice 
HDR
Homology-Directed DNA Repair
HEENT
Head, Ears, Eyes, Nose, and Throat 
HER2
Human Epidermal Growth Factor Receptor-2
HIPAA
Health Insurance Portability Accountability Act
HIV-1 
Human Immunodeficiency Virus Type 1 
IA
Interim Analysis
ICF
Informed Consent Form 
ICH
International Conference on Harmonization 
IEC
Independent Ethics Committee
IHC
Immunohistochemistry assay
IND
Investigational New Drug 
IP
Investigational Product 
IRB
Institutional Review Board
ISR
Injection Site Reactions
ITT
Intent-to-Treat
IV
Intravenous 
LAR
Legally Authorized Representative
LTF
Lost to Follow-up 
mAb
Monoclonal Antibody
MTD
Maximum Tolerate Dose
Nt
N terminus
OBT
Optimized Background Therapy
ORR
Overall Response Rate
OS
Overall Survival 
OTC
Over the Counter 
PFS
Progression Free Survival
PI
Principal Investigator
PK
Pharmacokinetics
PP
Per Protocol
PR
Progesterone Receptor
RECIST
Response Evaluation Criteria in Solid Tumors 

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Abbreviation
Term
RP2D
Recommended Phase II Dose
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SC
Subcutaneous
SD
Stable Disease
SLD
Sum of the Longest Diameters
SOP
Standard Operating Procedure 
SV
Screening Visit
TEAE
Treatment Emergent Adverse Event
TNBC
Triple Negative Breast Cancer
TTNM
Time to New Metastasis
TV 
 
Treatment Visit
VAS
Visual Analog Scale
VF
Virologic Failure

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1
INTRODUCTION AND BACKGROUND
1.1
STATEMENT OF INTENT
The design, conduct and reporting of this study shall be conducted in compliance with the protocol, 
International Conference on Harmonization/Good Clinical Practice (ICH/GCP), and all appropriate 
regulatory requirements. Investigator(s) participating in this study will have documented training 
in GCP. Independent monitoring of the trial will be accomplished utilizing a Contract Research 
Organization (CRO).
1.2
BACKGROUND OF THE DISEASE
1.2.1. Triple Negative Breast Cancer (TNBC)
Clinical and molecular heterogeneity of breast cancer are translated in a diversity of clinical patterns 
of disease evolution and patient outcomes [Dawood, 2011] [Engstrom, 2013] [Harbeck, 2016].
TNBC is defined by the lack of estrogen receptor (ER), progesterone receptor (PgR) and human 
epidermal growth factor receptor-2 (HER-2) expression, which are known targets of endocrine 
therapies and anti-HER2 agents, respectively. Chemotherapy is still the main treatment option for 
TNBC patients. It accounts for 15-20% of breast cancer patients, a clinically highly relevant patient 
group that is characterized by younger age, unfavorable histopathological features including high 
histological grade, elevated mitotic count, high rate of p53 mutations and pushing margins of 
invasion with a shortened overall survival (OS) and disease free survival (DFS) compared to other 
breast cancer subgroups [Dawood, 2011] [Engstrom, 2013][Malorni, 2012]. For these reasons, 
TNBC account for a disproportionately high percentage of metastases, particularly distant 
recurrence, and death among patients with breast cancer. Moreover, in younger women TNBC has 
been described to occur more often with a high risk of recurrence and death, respectively, the latter 
with a peak incidence of 3 years after primary diagnosis. The pattern of recurrence involves more 
often visceral organs and less common bones compared to other breast cancer subtypes [Foulkes, 
2010].
1.2.2. C-C Chemokine Receptor Type-5 (CCR5)
The process of cancer cell metastasis in different organs is a complex biologic event. Each tumor 
type presents a unique pattern of dissemination that has been well recognized for over a century as 
the “soil and seed” hypothesis [Paget, 1889]. However, only recently factors involved in this 
process have started to be understood. Preclinical and clinical data have suggested that chemokine 
receptors and its ligands, also referred as chemoattractant or chemotactic cytokines, are involved in 
the process of cancer cells tropism by specific organs [Moser, 2001][Neagu, 2015][Velasco-
Velazquez, 2012][Chow, 2014]. Studies have correlated the altered expression of C-C Chemokine 
Ligand type-5 (CCL5) with disease progression in patients with breast cancer [Luboshits, 

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1999][Niwa, 2001][Zhang, 2009]. Immunofluorescence staining techniques are well established for 
CCR5 expression. Velasco-Velazquez et al have evaluated an analysis of a combined microarray 
database comprising 2,254 breast cancer samples and showed that expression of CCL5/CCR5 is 
higher in basal subtypes (over 58% of samples) of breast cancer compared to luminal subtypes
[Velasco-Velazquez, 2012]. 
Figure 1-1: 
CCR5 over-expression correlates with poor survival). Immunohistochemical 
staining for CCR5 in 537 patients
CCR5 is also associated with programmed death-ligand 1 (PD-L1) [Halama, 2016]. Anti-PD-L1
antibodies have shown outstanding efficacy in the clinic for melanoma, non-small cell lung cancer 
and other cancers [Moser, 2001] [Garon, 2015] [Borghaei, 2015][Brahmer, 2015][Larkin, 2015].
Upregulation of PD-L1 may allow cancers to evade the host immune system and also inducing 
apoptosis in activated T cells. Preclinical data have shown that PD-L1 present in cancer is correlated 
with CCR5 abundance. Thus, blocking CCR5 may also contribute to increased immune response 
against tumor cells.  
CCR5 has been shown to be sufficient to induce in vitro invasiveness and metastasis of breast 
cancer cells that is blocked by CCR5 inhibitors. Two distinct CCR5 inhibitors (Maraviroc, 
Vicriviroc) blocked CCR5 signaling and thereby blocked cells migration, invasion and metastasis in
mice (Figure 1-2) [Velasco-Velazquez]. The CCR5 inhibitors were shown to block homing of 
breast cancer cells to the lungs. The dose of CCR5 inhibitor used in these mouse models was the 
same as the dose used in patients for HIV treatment. Preclinical studies have also demonstrated that 
oncogenic transformation of immortal human breast cancer cells, with either Ha-Ras, c-Myc, ErbB2 

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(NeuT) or c-Src, induces the mRNA expression and protein abundance of CCR5 during the process 
of transformation [Velasco-Velazquez]. 
Figure 1-2: 
The CCR5 antagonist Maraviroc inhibits lung metastases in vivo 
Another cancer hallmark that CCR5 presents potential role is the DNA repair pathways. This cancer 
characteristic attenuates apoptosis and contributes to chemotherapy resistance and tumor cells 
immortality. Preclinical data have separated CCR5+ vs CCR5- SUM159 cells by FACS and 
conducted mRNA gene expression profiling. GO term pathway analysis demonstrated CCR5+ cells 
induced the expression of pathways governing DNA repair. QT- PCR was used to quantitate a 
number of these genes and showed endogenous CCR5 enhances expression of the DNA repair 
genes, (FANCB, LIG3, POLE and CRY1) governing both homologous and non-homologous DNA 
repair, nucleotide excision repair and base excision repair. SUM159 cells stably transfected with
CCR5 or control vector were
-radiation of 
SUM159 cells induced p-
-overexpressing cells showed reduced p-
at 24 hours. Treatment of SUM159 cells with the DNA intercalating anthracycline doxorubicin 
sphorylation, and CCR5-overexpressing cells showed less p-
control with 24 hours treatment. The DNA repair reporter, DR-GFP is used to measure homology-
directed DNA repair (HDR). In order to measure HDR activity CCR5+SUM159 cells, the cells were 
co-transfected with the plasmid encoding I-SceI and the I-SceI based DNA repair reporter DR-GFP 

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and stained with APC labeled anti-CCR5 antibody. GFP+cells, generated by HDR of I-SceI induced 
double-strand DNA, were sorted by FACS into CCR5- and CCR5+ populations. The percentage of 
DR-GFP+ cells was increased in CCR5+ or CCR5- overexpressing cells compared with CCR5- or 
vector control cells [Robert, 2015]. The dramatic enhancement of DNA repair signaling by CCR5 
activation may contribute to the resistance of a patient’s tumor to chemotherapeutic agents.
1.2.3. Circulating Tumor Cells (CTCs) in Metastatic Breast Cancer (MBC) 
The major treatment objectives in the advanced stage disease remain palliation of symptoms and
improvement of quality of life. Importantly, breast cancer is a heterogeneous disease and long-term
patient outcome can be influenced by various biological features, as well as by the extent and site of 
metastatic disease. Typically, widespread visceral disease is associated with symptomatic 
progression leading to deterioration of the performance status and short survival. Various molecular 
markers and blood-based tests have been investigated as surrogate for more aggressive disease, 
among them the most reliable appears enumeration of circulating tumor cells [Xuanmao, 2015].  
During the last decade, several techniques capable of detecting and quantifying circulating tumor
cells (CTCs) in cancer patients have been developed. It has been proposed that subpopulation of 
CTCs with tumor initiating potential act as a central mediator of metastatic dissemination, giving 
rise to the formation of distant micrometastases, which subsequently generate overt detectable and 
frequently measurable lesions [Foulkes, 2010]. In support of this theory, multiple studies have 
shown that a number of CTCs higher or equal than 5 per 7.5 mL of blood, evaluated before starting 
systemic treatment, is associated with poor outcome in patients with metastatic breast cancer
[Xuanmao, 2015]. In addition, high CTC counts are associated with greater metastatic tumor burden, 
expressed as number of metastatic sites [Moser,2001][Neagu, 2015]. Importantly, despite this
association, the prognostic value of CTCs is independent from the initial number of metastatic sites 
[Moser,2001][Neagu, 2015]. Moreover, a recent pooled analysis of 1944 patients was performed
confirming those data [Cristofanilli, 2004]. The authors created a clinicopathological prognostic 
model to determine the added impact of CTCs for PFS and OS. They found that adding CTC count 
The prognostic value of CTCs was consistent across all subtypes of disease. Finally, in the 
multivariate analysis, CTC count was the strongest prognosticator for PFS and OS. Furthermore, 
continued elevation of CTCs is known to be associated with a poor prognosis as well as a sign of 
chemoresistance [Bidard, 2014]. 
1.2.4. CCR5+ tumor-infiltrating leukocytes
The role of CCR5 blockade of the CCL5-CCR5 pathway in immune control of tumors have been 
defined in several publications in the peer-reviewed medical literature [Mañes, 2003]. CCR5 on 
tumor cells especially those that evade local immune control in the primary tumor leads to CCR5 
positive circulating tumor cells that have the capability to disseminate and migrate into distant 
tumor sites again through the CCL5-CCR5 axis. Previous research and current data has also 

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identified other immune mediated anti-tumor effects from CCR5 blockade [Lanitis, 2017, Halama, 
2016]. Previous published reports suggest CCR5 expression on Treg cells which migrate into 
tumors due to the expression of CCL5 by lymphocytes [de Oliveira, 2017, Del Prete, 2017, Lanitis, 
2017]. Tregs are responsible for minimizing or eliminating the anti-tumor effects of CD8 T-cells 
now restored by blockade of PD-L1/PD-1 by the new class of immune-oncology drugs [de Oliveira, 
2017]. Further, blocking CCR5 on tissue associated macrophages (TAMS), one of the major cells 
in the tumor microenvironment that suppresses the T-cell mediated anti-tumor immune response, 
restores the anti-tumor activity by re-programming the TAMs [Lanitis, 2017, Walens, 2019]. Data 
from novel 24-color flow cytometry assay performed on single cell suspensions created with IVD 
IncellPREP device, confirmed the expression of CCR5 on Tregs from the tumor microenvironment 
in lung, breast, and bladder cancer samples. This technology or CCR5 immunohistochemistry of 
biopsies already obtained has allowed to selectively choose patients with CCR5 expression not only 
on tumor but on intra-tumor immune cells in the tumor microenvironment.
Figure 1-3: 
Tumor Tregs (Stain with CD4, CD325, CD127, and CCR5)  
Because of the multitude of different mechanism CCR5 blockade may promote anti-tumor activity, 
immune control, and metastasis, the inclusion criteria has been expanded to encompass these varied 
mechanisms that may all lead to improved clinical response. 
Below are the representative IHC staining images showing high predominance of CCR5 positive 
tumor infiltrating leukocytes in Triple Negative Breast Cancer tissue samples:

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Figure 1-4: 
IHC staining showing high predominance of CCR5+ tumor infiltrating 
leukocytes in TNBC (Subject 1)
(A)Subject 1: Representative images of IHC for CCR5
(B) Negative Control CCR5
(C)Positive Control CCR5

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Figure 1-5: 
IHC staining showing high predominance of CCR5+ tumor infiltrating 
leukocytes in TNBC (Subject 2)
(A)Subject 2: Representative images of IHC for CCR5
(B) Negative Control CCR5
(C)Positive Control CCR5
1.3
STUDY TREATMENTS
1.3.1. Leronlimab (PRO 140) 
Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine 
receptor type 5 (CCR5), under development as a therapy for human immunodeficiency virus (HIV) 
infection.
Leronlimab (PRO 140) binds to the N terminus (Nt) and the extracellular loop 2 (ECL2) domain of 
the CCR5 cell surface receptor that HIV-1 uses to gain entry to a cell. Leronlimab (PRO 140) 

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(binding to CCR5 blocks viral entry by interfering with the final phase of viral binding to the cell 
surface prior to fusion of the viral and cell membranes. Leronlimab (PRO 140) has been 
administered intravenously or subcutaneously to more than 750 healthy and HIV-1 infected 
individuals in Phase I/II/III studies. The drug has been well tolerated following intravenous 
administration of single doses of 0.5 to 10 mg/kg or up to 700 mg weekly doses as subcutaneous 
(SC) injection. Overall, 324 subjects have been exposed to leronlimab (PRO 140) 350 mg SC weekly 
dose with the longest duration of exposure lasting 4 years. Similarly, more than 250  and 150 subjects 
have been exposed to leronlimab (PRO 140) 525 mg and 700 mg SC weekly dose, respectively.
1.3.2. Carboplatin 
Chemotherapy is the main treatment for TNBC, with clinical trials showing benefit in the 
neoadjuvant, adjuvant and metastatic settings [Smearge, 2014][Huang, 1996] [Lee, 1999][Samson, 
1996]. Platinum compounds are one of the most widely employed classes of anticancer drugs 
worldwide due to their broad spectrumof action and safety profile. Carboplatin is a platinum salt 
and, like cisplatin, leads to DNA crosslink strand breaks that result in apoptosis in cells with 
inefficient DNA repair system. Preclinical and clinical data have shown that TNBC presents higher 
sensitivity to these DNA- damaging agents when compared with other breast cancer subtypes which 
led carboplatin to be extensively studied and clinically used in breast cancer management [Gulick, 
2007][Lalezari, 2011][Lalezari, 2005][Landovitz, 2008][Nichols, 2008][Schurmann, 2007].
Carboplatin is administered intravenously with the major route of elimination of renal excretion. 
Bone marrow suppression is the dose-limiting toxicity of carboplatin. However, marrow 
suppression is usually more severe in patients with impaired kidney function. Additionally, patients 
with poor performance status have also experienced a higher incidence of severe leukopenia and 
thrombocytopenia. The hematologic effects, although usually reversible, have resulted in infectious 
or hemorrhagic complications in 5% of the patients treated with carboplatin, with drug related death
occurring in less than 1% of the patients. Fever has also been reported in patients with neutropenia. 
Bone marrow depression may be more severe when carboplatin is combined with other bone 
marrow suppressing drugs or with radiotherapy. However, since the inclusion criteria of this trial 
will only select subjects with adequate renal and bone marrow function, and leronlimab (PRO 140) 
has no overlap adverse effect in bone marrow or renal function, we do not expect any major increase 
in carboplatin toxicity. 
Due to its low rates of adverse events and unique mechanism of action, carboplatin has been 
combined with a variety of chemotherapy agents and targeted therapies such as taxanes, 
gemcitabine, trastuzumab, pertuzumab, bevacizumab and PARP inhibitors
[Lalezari, 
2005][Landovitz, 2008] [Suleiman, 2010][Cooper, 2010][Cooper, 2014] [Fatkenheuer, 2008].
Recent data have shown that in patients with TNBC, first line monotherapy with carboplatin 
presented similar results in RR, PFS and OS when compared to the standard arm docetaxel in a 
phase III trial. Moreover, in this trial patients with TNBC harboring BRCA mutation presented
superior response rate, PFS and OS survival when compared to the docetaxel arm [Guilick, 2014]. 

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1.4
PRE-CLINICAL STUDIES OF LERONLIMAB (PRO 140) 
In vitro and in vivo preclinical studies have been conducted to determine the pharmacokinetic, 
immunogenicity, and toxicity profiles of leronlimab (PRO 140) following IV and SC 
administration. Several acute and chronic toxicity studies have been conducted to support the 
clinical development plan.  
Acute toxicity of leronlimab (PRO 140) was evaluated in New Zealand rabbits, following IV 
administration of 5 or 15 mg/kg. Chronic toxicity was evaluated in cynomolgus monkeys 
following biweekly administration of IV doses up to 10 mg/kg for six months and biweekly 
administration of various SC doses up to 50 mg/kg for 24 weeks. The drug was generally well 
tolerated. Biweekly administration of IV doses up to 10 mg/kg for six months resulted in minimum 
to mild lymphoid hyperplasia in assorted lymph nodes and spleen, which was considered an 
expected immune response to a foreign protein. Biweekly administration of SC doses up to 50 
mg/kg for 24 weeks resulted in minimum injection-site reactions (minimal, multifocal, 
mononuclear cell infiltrates in the subcutis), which were considered due to an inflammatory 
response to the injected antigen. Monkeys tolerated treatment with leronlimab (PRO 140) for 24 
weeks without evidence of local or systemic toxicity. Leronlimab (PRO 140) caused no mortality, 
cageside observations, in-life injection-site observations, or gross pathologic findings. Chronic 
treatment with leronlimab (PRO 140) did not affect body weight, food consumption, hematology, 
clinical chemistry or coagulation parameters.
Both IV and SC administration resulted in elimination half-lives of approximately 200 hours, and 
overall exposure increased with increasing doses. Following SC administration of leronlimab 
(PRO 140) in monkeys, the maximal concentration (Cmax) was achieved within 56 hours and 
bioavailability for leronlimab (PRO 140) after SC dosing was approximately 70%. 
1.4.1. Effect of PRO140 on human CCR5 in breast cancer cells, MDA-MB-231 
1.4.1.1
PRO140 binding to human CCR5 in human breast cancer cells
In order to determine the binding of PRO140 with human CCR5 in breast cancer cells, MDA-MB-
231, a human triple-negative breast cancer cell line, was stably transfected with a human CCR5 
expression vector as a model system. A commercial APC conjugated mouse anti-human/mouse/rat 
CCR5 antibody was used as a positive control to assess CCR5 positive cells. MDA-MB-231-CCR5 
cells were stained with both APC-
1). Alexa Fluor 488 conjugated mouse anti-human IgG was used as secondary antibody to measure 
PRO140 binding cells. Analysis of PRO140 binding with CCR5 by FACS is shown in Figure 1. 
The efficiency of PRO140 binding with CCR5 was calculated as the ratio of Alexa Fluro 488 
positive cells to APC positive cells. The efficiency of PRO140 binding to CCR5 positive cells was 
62% at 1/800 dilution (Figure 1-6A, B). These results demonstrate that PRO140 binds with human 
CCR5. 

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Figure 1-6: 
 PRO-140 binds human CCR5 in human breast cancer cells.
Validation of PRO140 binding to CCR5 positive cells was assessed by FACS analysis. MDA-MB-231 stably 
expressing a human CCR5 expression vector was double stained with a commercial APC-conjugated mouse anti-
human/mouse/rat CCR5 antibody and PRO140. Alexa Fluor 488 conjugated anti-human IgG was used as secondary 
antibody of PRO140. PRO 140 was diluted from 1/50 to 1/3200. (B) The efficiency of PRO140 binding to the CCR5 
positive cells.
1.4.1.2
PRO140 blocks human CCR5 mediated signaling in human breast cancer cells.
CCR5 activation induces calcium flux [Mueller, 2002][Petkovic, 2004]. To assess the effects of 
PRO140 on CCR5 function, we measured the calcium responses induced by CCL5 in MDA-MB- 
231-CCR5 cells with or without PRO140 by living cell image (Figure 1-7). Fluo-4 was used as 

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calcium concentration indicator. The CCR5 antagonist, Vicriviroc, was used as a positive control 
(Figure 1-7). 
MDA-MB-231-CCR5 cells were labeled with calcium indicator Fluo-4 and monitored under 
fluorescent inverted microscope with the incubator chamber at 37ºC and 5% CO2. For treated 
samples, a CCR5 inhibitor, either PRO140 or Vicriviroc, was added 30 minutes prior to the 
experiments. Video of living cells was taken at 20 sec intervals. CCL5 was added after 6 frames of 
the video, and FBS induced calcium responses were used as positive control. A representative 
example is shown in Figure 1-7. Relative intracellular Ca2+ concentration was determined by the 
changes in fluorescent intensity (FI) of Fluo-4-
Quantitative analysis of calcium responses induced by CCL5 are represented in Figure 1-7 (B) 
control, (C) PRO140, and (D) Vicriviroc. Data is shown as mean ±SEM from 10-12 cells. 
The results showed that PRO140 can block CCL5 induced calcium responses in MDA-MB-231-
CCR5 cells at 1/100 dilution. (1.23±0.10, N=10 for control cells and 0.54±0.13 N=12 for PRO140 
treated cells. P<0.001 at calcium peak induced by CCL5). 
1.4.1.3
PRO140 blocks human CCR5 mediated invasion of extracellular matrix in human 
breast cancer cells. 
Our previous studies using CCR5 specific small molecule inhibitors demonstrated that CCR5 is 
required for the invasion of extra-cellular matrix in both breast and prostate tumor models [Sicolo, 
2014][Velasco-Velazquez, 2012]. Cancer cell invasion into the extra-cellular matrix is a key step 
of tumor metastasis [Zetter, 1990]).  
MDA-MB-231 cells were used to test the ability of PRO140 to block cell invasion in a 3D-matrigel 
assay. CCL5 was used as chemoattractant to induce the invasion. Vicriviroc, a small molecule 
inhibitor of CCR5, was used as a form of positive control.  
The results showed that PRO140 can block CCL5 induced MDA-MB-231 breast cancer cell 
invasion with similar efficacy as Vicriviroc (Figure 1-8A, B) (855±9, N=8 for control vs 855±9, 
N=9 for PRO140, P <0.001). We also tested the effects of different doses of PRO140 on breast 
cancer cell invasion, and the results showed that both a 1/500 and a 1/1000 dilution of PRO140 can 
effectively block MDA-MB-231 cell invasion (Figure 1-8C, D). Data is shown as mean ± SEM of 
the distance of cell invasion. 
Figure 1-7: 
 PRO140 blocks human CCR5 mediated signaling in human breast cancer 
cells.  
The effects of PRO140 on CCL5 induced Ca+2 responses. MDA-MB-231 stable expressing CCR5 cells was labeled
with Calcium indicator Fluo-4 and monitored under fluorescent inverted microscope with incubator chamber at 37oC 
and 5% CO2. Video of living cells was taken with 20 sec intervals. 30 minutes prior to the experiments, PRO140 or 
Vicriviroc was added. CCL5 was added after 6 frames of the video and FBS induced calcium responses were used as 
a positive control. A representative example is shown. (B-D) quantitative analysis of calcium responses induced by 
CCL5 in control (B), PRO140 (C) or Vicriviroc (D) treated cells. Data is shown as mean ±SEM from 10-12 cells.

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Figure 1-8: 
 PRO140 blocks CCL5-induced breast cancer cell invasion  
3D reconstruction of CCL5-induced invasion into collagen I gels by MDA-MB-231 breast cancer cells in presence of 
PRO140. CCL5 was used as chemoattractant. (A, B) The comparison of the effects of PRO14 and Vicriviroc. (C, D) 
The effects of different doses of PRO140 is shown. Data is shown as mean ± SEM of the distance of cell invasion.

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1.4.2. Effect of PRO 140 on Growth of SW480 Human Colon Carcinoma Xenografts 
A study was conducted to determine the anti-tumor activity of PRO 140 humanized monoclonal 
antibody against CCR5 in mouse xenograft models of SW480 human colon carcinoma grown in 
immunocompromised mice. The study was conducted in four parts, using different mouse strains, 
drug doses, and drug schedules.  
SW480 human colon carcinoma cells (ATCC) were expanded in culture (DMEM, 10%FBS, 
antibiotic, antimycotic) and were inoculated subcutaneously (2 million per site, s.c.) in the flanks 
of male NCr nu/nu mice (Taconic), and male NOD-scid-IL2Rg (NSG) mice (Jackson). Mice were 
randomized to receive Control human IgG or PRO 140 intraperitoneal injection (i.p.) twice per 
week (Mon, Thu). Tumor diameters were measured 3 times weekly (Mon, Wed, Fri) with calipers, 
and tumor volume calculated using the formula for a prolate spheroid. The body weight of mice 
was determined weekly (Wed). 

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In Part 1 (high dose, early Rx) of the study, 2 mg PRO 140 i.p. was administered twice weekly, 
starting at Day 1 in 16 athymic nude mice. Part 2 (high dose, late Rx) included 8 athymic nude mice 
receiving 2 mg PRO140 i.p administered twice weekly, beginning Day 21. 
In Part 3 (low dose, early Rx), 0.2 mg PRO 140 i.p was administered, beginning on Day 1, twice 
weekly in 16 athymic nude mice. Lastly, in Part 4 (high dose, early Rx), 16 NSG mice received 2 
mg PRO 140 i.p, twice weekly, beginning Day 1. 
PRO 140 dosage was calculated using “Representative Surface Area to Weight Ratios (km) for 
Various Species” from: Freireich EJ, Gehan EA, Rall DP, Schmidt LH, Skipper HE. Quantitative 
comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man, Cancer 
Chemother Rep. 1966;50:219-44; and the National Cancer Institute Developmental Therapeutics 
Program http://dtp.nci.nih.gov
Starting with the human dose of PRO 140 = 5.8 mg/kg x 12 (man-to-mouse conversion factor) =
69.6 mg/kg mouse dose. Average mouse = 0.025 kg, therefore 69.6 mg/kg x 0.025 kg = 1.74 mg
(mouse single dose). This was rounded up to 2.0 mg and designated as the high dose. A low dose 
(0.2 mg) was also tested. As control antibody, IgG derived from human serum was used (>95% 
SDS-PAGE, Sigma, I4506). 
In Part 1, administration of PRO 140 (2 mg i.p. twice a week) induced a 62.8% reduction in SW480 
tumor volume by day 42 (p=0.014). Mice receiving PRO 140 exhibited normal weight gain over 
the course of the study, whereas mice receiving non-specific IgG lost weight during the second half 
of the study (p=0.047). 
Figure 1-9: 
 Part 1: SW480 Human Colon Carcinoma Xenografts Grown in NCr Nude 
Mice
PRO 140 2 mg i.p. Twice/Wk, Started Day 1, n=16 Tumors/Group

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During Part 2, treatment of larger established tumors (volume: Cont 68.5 ± 47.25, PRO 140 47.25 
± 34.89 mm3) with PRO 140 (2 mg i.p. twice a week) commencing on day 21, did not result in 
significant inhibition of tumor growth (p=0.719). 
Figure 1-10:  Part 2: SW480 Human Colon Carcinoma Xenografts Grown in NCr Nude 
Mice
PRO 140 (2 mg i.p. Twice/Wk), Started Late (D21), n= 8 Tumors/Group
In Part 3 of the study, administration of PRO 140 at a reduced dose (0.2 mg i.p. twice a week) 
induced an 18.3% reduction in SW480 tumor volume by day 42, but did not reach statistical 
significance (p=0.272). During tumor progression in the second half of the study, both groups 
exhibited similar degree of weight loss (p=0.708). 
Figure 1-11:  Part 3: SW480 Human Colon Carcinoma Xenografts Grown in NCr Nude 
Mice
PRO 140 0.2 mg i.p. Twice/Wk, Started Day 1, n=16 Tumors/Group

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For Part 4, switching from nude mice (lack T cells) to a more immunosuppressed host (NSG lack 
T, B, NK cells) resulted in loss of PRO 140 anti-tumor efficacy. There was a 32% reduction in 
tumor volume in the PRO 140 groups compared to control, but this did not reach statistical 
significance (p=0.076). There was a similar degree of weight loss in both treatment groups (p=0.61).
Figure 1-12:  Part 4: SW480 Human Colon Carcinoma Xenografts Grown in NSG Mice 
PRO 140, 2 mg i.p. Twice/Wk Started Day 1, n=16Tumors/Group
1.4.3. Clinical Studies with leronlimab (PRO 140) 
Current human experience with leronlimab (PRO 140) consists of nine completed and five ongoing 
clinical trials, mostly on healthy subjects or HIV-1 positive subjects. These studies are summarized 
in Table 1-1 and Table 1-2 (pages 49-51). In all clinical trials, the majority of adverse events (AEs) 
have been mild or moderate. No dose-limiting toxicities or patterns of drug-related toxicities were 
observed. Antiviral activity was potent, rapid, prolonged, dose-dependent, and highly significant. 
1.4.4. PRO 140 1101 Study 
For the first-in-human trial, PRO 140 1101, the drug was administered IV at 0.1, 0.5, 2.0, or 5.0 
mg/kg to healthy subjects and was generally well tolerated, non-immunogenic, and without 
clinically relevant toxicity. Treatment Emergent Adverse Events (TEAEs) did not increase with 
rising PRO 140 dose levels. Seventy-five percent (75%) of subjects reported TEAEs, most of which 
were deemed unrelated to study treatment by the investigator. 
1.4.5. PRO 140 1102 Study 
For PRO 140 1102, the majority of AEs, other than injection-site reactions, were considered mild 
and possibly related to drug administration. The majority of injection-site reactions were considered 
mild, self-resolving, and definitely related to drug administration. PRO 140 derived from Chinese 
Hamster Ovary (CHO) cells and administered at 100 mg/mL was generally well tolerated in 

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healthy, normal volunteers. Overall, PRO 140 administered SC using Autoject® 2 appeared better 
tolerated than manual injection.
1.4.6. PRO 140 1103 Study  
In PRO 140-1103, administration of PRO 140 at 350 mg using Autoject® 2 appeared well tolerated. 
Manual injections, on the other hand, were associated with a greater number of AEs. There did not 
appear, however, to be any substantial difference in subject perception of pain or discomfort related 
to site of drug administration. No anti-PRO 140 antibodies were detected in any subjects in this 
study. There was a tendency of higher exposure associated with SC administration of PRO 140 at 
350 mg in the abdomen and the thigh. A higher number of AEs were associated with injections in 
the arm. Based on these observations, thigh and abdominal administration of PRO 140 were 
preferred over arm injection.
1.4.7. PRO 140 1302 Study 
The initial proof-of-concept study was a randomized, double-blind, placebo-controlled study in 
subjects with early-stage, asymptomatic HIV infection, only R5 HIV-1 detectable, and no
antiretroviral therapy for 12 weeks [Jacobson, 2008]. Subjects (n=39) were randomized to receive 
a single IV injection of placebo or PRO 140 at doses of 0.5, 2, or 5 mg/kg. Subjects were monitored 
for antiviral effects, safety, and PRO 140 pharmacokinetics (PK) for 58 days.  
PRO 140 demonstrated potent, rapid, prolonged, and dose-dependent antiviral activity. Intravenous 
PRO 140 was generally well tolerated. No drug-related serious events or dose-limiting toxicity was 
observed [Jacobson, 2008]. The most common adverse events (headache, lymphadenopathy, 
diarrhea, and fatigue) were observed at similar frequencies across the placebo and PRO 140 dose 
groups. There was no significant effect on QTc intervals or other electrocardiographic parameters, 
and there were no remarkably laboratory findings. 
1.4.8. PRO 140 2301 Study 
PRO 140 2301 was a multi-center, randomized, double-blind, placebo-controlled, parallel group 
study in 30 male and female adult subjects infected with HIV-1 [Jacobson, 2010]. Subjects were 
randomized to one of three groups (N=10/group), each receiving one of three treatments: (i) a single 
IV dose of 5 mg/kg by 30-minute IV infusion; (ii) a single IV dose of 10 mg/kg by 30-minute IV 
infusion; (iii) a single placebo dose by 30-minute IV infusion. The objective of the study was to 
assess and characterize the PK and PD of PRO 140 administered by IV infusion, assess efficacy at 
a new dosage level, and safety and tolerability of single doses of PRO 140. 
All PRO 140-treated subjects had more than 10-fold reduction in viral loads [Jacobson, 2010]. Both 
the 5 mg/kg and 10 mg/kg doses have shown favorable tolerability and no dose-limiting toxicity 

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has been observed. High levels of receptor occupancy (>85% reduction in the number of cells 
detected) were observed for 29 days after treatment with both 5 and 10 mg/kg doses.  
1.4.9. PRO 140 2101 Study 
A subcutaneous (SC) form of PRO 140 was tested in HIV-infected subjects. The trial was a 
randomized, double-blind, placebo-controlled study in subjects (n=44) with early-stage, 
asymptomatic HIV infection, only R5 HIV-1 detectable, and no antiretroviral therapy for 12 weeks 
[Thompson, 2009]. Placebo (n=10) and three PRO 140 doses were examined: 162 mg weekly for 
three weeks (n=11), 324 mg weekly for three weeks (n=11), and 324 mg biweekly (every other 
week) for two doses (n=12). Subjects were followed for 44 days after the final dose.  
Potent, dose-dependent and highly statistically significant antiviral activity was observed. The trial 
established the first antiviral proof of concept for a long-acting, self-administrable drug for HIV-1 
infection [Thompson, 2009]. 
Subcutaneous PRO 140 was generally well tolerated both locally and systemically. There was no 
obvious dose-related pattern of toxicity. The most common adverse events (diarrhea, headache, 
lymphadenopathy and hypertension) were mild to moderate and self-resolving. These events are 
common in HIV infection and were reported with similar frequencies in the placebo and PRO 140 
treatment groups. Administration-site reactions were mild, transient, and observed in a fraction of 
subjects.  
1.4.10. PRO 140_CD01 Study 
PRO 140_CD01 study (open-label, 43 subjects, multi-center) evaluated the efficacy, safety, and 
tolerability of PRO 140 monotherapy (350 mg subcutaneous injection weekly for up to 12 weeks) 
for the maintenance of viral suppression following substitution of antiretroviral therapy in HIV-1 
infected patients (with exclusive CCR5-tropic virus). Participants in this study were experienced 
HIV-infected individuals who were virologically suppressed on combination antiretroviral therapy. 
Consenting patients were shifted from combination antiretroviral regimen to PRO 140 monotherapy 
for 12 weeks.  
Forty-three (43) subjects (M/F: 37/3) with median age of 54.5 years (26-72) and median CD4 T-
cell count of 604.5 cells/mm3 (365-1240) were enrolled in the CD01 study. Overall, twenty-two 
out of 40 (55%) enrolled subjects completed 12 weeks of PRO140 monotherapy without 
experiencing virologic failure. Virologic failure was defined as two consecutive HIV-1 RNA levels 
to have Dual/Mixed (D/M) tropism [1 at baseline and 2 at the time of virologic failure] and 37 
subjects were found to have exclusive CCR5-tropic virus. A letter of amendment was filed to 
increase the planned number of subjects from 40 to 43 subjects to compensate for the 3 Dual/Mixed 
subjects enrolled in the study.

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All virologic failure subjects who had available lab data in both studies achieved viral suppression 
to < 400 HIV-1 RNA copies/mL, as well as viral suppression to ‘Non Detectable’ or < 50 HIV-1 
RNA copies/mL after re-initiation of ART. 
The by-subject analysis of PhenoSense® Entry Assay data for PRO140, maraviroc, and AMD3100 
shows no significant changes in the post-treatment IC50 and IC90 values were noted when 
compared with baseline values in virologic failure and non-virologic failure groups of subjects. As 
the aggregate analysis shows for initial 40 subjects, the subjects who experienced virologic failure 
had higher IC90 value for PR0140 at baseline compared to subjects without virologic failure. The 
mean IC90 for subjects who experienced virologic failure was higher (10.84 µg/mL) than the IC90 
for subjects without virologic failure (6.70 µg/mL) in the CD01 study (p=0.0115).  
Anti-PRO140 antibodies were not identified in any post-treatment sample and data derived from 
the CD01 study further supports the favorable PRO140 PK profile data generated from both pre-
clinical as well as prior Phase 1/2 clinical trials.
Safety data were analyzed for all 43 enrolled subjects. One (1) of 43 subjects experienced an SAE 
that was deemed not related to the study drug by the Principal Investigator. Twenty-eight (28) of 
43 subjects (67%) experienced one or more adverse events (AEs) after receiving at least one dose 
of PRO140. The most commonly occurring AEs were infections and infestation conditions which 
were reported by 14 of 43 (32.5%) subjects. The majority of the reported AEs (62/87; 71.2%) were 
deemed either unlikely or not related to study treatment by the Investigator. Similarly, the majority 
of the reported AEs (70/87; 80.4%) were deemed mild in nature.  
1.4.11. PRO 140_CD01 Extension Study 
PRO 140_CD01-Extension study (open-label, 28 subjects, multi-center) seeks to evaluate the 
efficacy, safety, and tolerability of PRO 140 monotherapy (350 mg subcutaneous injection weekly) 
for the continued maintenance of viral suppression following substitution of antiretroviral therapy 
in HIV patients (with exclusive CCR5-tropic virus). Participants in this study were HIV-infected 
individuals who were virologically suppressed on combination antiretroviral therapy and completed 
the first 12 weeks of CD01 study without experiencing virologic failure. As with the CD01 study, 
virologic failure was defined as two consecutive HIV-
by at least 3 days. Consenting patients may remain on PRO 140 monotherapy until PRO 140 
receives marketing approval or IND is withdrawn by Sponsor.  
A total of 17 subjects participated in the CD01-Extension study of which one subject was 
considered not eligible as subject experienced virologic failure prior to first extension treatment.
Sixteen (16) eligible subjects (M/F: 14/2) with median age of 54.9 years (26-68) and median CD4 
T-cell count of 593 cells/mm3 (365-1059) were enrolled in an extension study. One patient 
discontinued at week 37 (with viral load of <40 copies/mL) due to relocation. Two subjects were 

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withdrawn due to non-treatment related SAEs at week 140 and 149, respectively. One subject was 
withdrawn due to re-starting their ART at week 99. Two subjects withdrew consent at week 81 and 
139, respectively. Five (5) subjects experienced virologic failure (VF) (two consecutive viral load 
-691).  
Five (5) subjects are currently receiving weekly 350 mg PRO140 SC monotherapy and have 
completed more than three years of treatment (176 - 198 weeks). Overall, 12 subjects completed at 
least one year of treatment and 9 subjects completed at least two years of treatment in this study
PRO140 was generally well tolerated, and no drug-related SAEs were observed.  
This clinical study is currently ongoing. 
1.4.12. PRO 140_CD02 Study 
PRO 140_CD02 study (double blind, placebo controlled, 52 subjects, multi-center) seeks to 
evaluate the efficacy, safety, and tolerability of PRO 140 in combination with either existing ART 
(failing regimen) or Optimized Background Therapy (OBT) in patients infected with HIV-1. The 
study population includes 52 adult patients with a documented history of genotypic or phenotypic 
resistance to ART drugs within two or more drug classes who demonstrate evidence of HIV-1
replication despite ongoing antiretroviral therapy and have limited treatment options. The options 
may be limited as a result of drug antiviral class cross-resistance, documented treatment intolerance, 
documented objective assessments such as renal or hepatic insufficiency (e.g. high creatinine at 
baseline, limiting treatment options due to potential for toxicity), past adverse reactions such as 
hypersensitivity reactions or neuropsychiatric issues that could limit use of currently approved 
drugs. 
In Part 1 of double-blind treatment period, virally non-suppressed subjects will be randomized and 
treated with either PRO 140 or Placebo in combination with the failing ART regimen for 7 days 
until HIV-1 genotypic drug resistance assay results are available to construct an OBT. The primary 
-1 RNA viral load 
from baseline at the end of the 7 day functional monotherapy period. 
In Part 2 of double-blind treatment period, subjects will continue treatment with PRO 140 in 
combination with OBT within the 24-week open-label period.  
Fifty-two subjects with a mean age of 52.4 years, 73.1% male, 48.1% non-white and mean duration 
of HIV-1 infection of 20.4 years were randomized 1:1 to the PRO 140 SC or placebo arm. Subjects 
had been previously exposed to an average of 11 ART drugs and had documented resistance to >9 
ART drugs. Mean baseline VL and CD4 cell count were 21,104 c/mL and 297.8 c/mm3,
respectively. The primary efficacy endpoint- the propo
in HIV-1 VL from baseline at the end of the 1-week double-blind, randomized, placebo-controlled 

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treatment period- was met (16/25 vs 6/26 [p-value <0.0032, ITT population]). Forty seven (47) of 
52 patients have completed the 25-week study. Approximately 81% of patients completing 25-
weeks of PRO 140 SC treatment demonstrated HIV-1 VL <50 c/mL and 92% had HIV-1 VL <400 
c/mL. Continued access to PRO 140 SC was provided through a rollover study and 40 patients 
entered the extension protocol after completing the CD02 study. PRO 140 SC was generally well 
tolerated. No drug-related SAEs or treatment discontinuations were reported in the study.
This clinical study is completed pending final database lock.  
1.4.13. PRO 140_CD02 Extension Study
PRO 140_CD02 Extension study (open label, 40 subjects, multi-center) seeks to evaluate the long 
term efficacy, safety and tolerability of PRO 140 weekly injection in combination with Optimized 
Background Therapy (OBT) in patients infected with HIV-1. The study population includes 40 
treatment-experienced HIV-infected adult patients with CCR5-tropic virus who successfully 
completed PRO 140_CD02 study and continue to demonstrate HIV-1 viral suppression. 
This clinical study is currently ongoing. 
1.4.14. PRO 140_CD03 HIV Study 
PRO 140_CD03 HIV (open-label, 350 subjects, multi-center) is a three part study enrolling virally 
suppressed HIV-1 patients with CCR5-tropic HIV-1 receiving combination antiretroviral (cART)
therapy. Patients received weekly doses of PRO 140 on single-agent maintenance therapy following 
one week of overlap of the existing cART regimen that is then discontinued. In part 1, 156 
participants received 350 mg PRO 140 SC in a single-arm design. In part 2, 147 participants 
received 350 or 525 mg PRO 140 SC in a 1:1 ratio as randomized controlled, two-arm study. In an 
ongoing part 3, 51 participants have been randomized to receive 525 or 700 mg PRO 140 SC in a 
1:1 ratio.  
Despite reaching the enrollment target of 350 subjects for the PRO140_CD03 HIV study, the 
enrollment is ongoing as the goal of enrolling 20 subjects for the CNS sub-study have not achieved. 
As a result, sites that are currently participating in the CNS sub-study are permitted to continue 
enrollment in the CD03 HIV study. 
Of the 354 patients enrolled, median age was 51 yrs (21-77) with the majority reported as male 
(79%) and 37% were non-white. A total of 27 subjects have been randomized to 700 mg dose. In 
addition, another 18 subjects have been exposed to 700mg dose after rescuing from the lower doses 
(350 mg or 525mg). On average, participants were diagnosed with HIV-1 infection for 16.8 yrs and 
were on cART regimen for 14.8 yrs. The frequency and severity of injection site reactions were 
comparable between the three dose groups (350, 525 and 700mg) and the incidence or severity of 

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140); 3) Reduced CTCs along treatment period compared to baseline in patients with response to
therapy. 
Leronlimab (PRO 140) is currently under development for the indication of HIV in combination 
with other antiretroviral agents or as single agent maintenance therapy for the treatment of only 
CCR5-tropic human immunodeficiency virus type 1 (HIV-1) infection. The safety profile of 
leronlimab (PRO 140) has been extensively evaluated in clinical trials of HIV-positive patients. 
PRO 140 has been administered intravenously or subcutaneously to more than 750 healthy and 
HIV-1 infected individuals in Phase I/II/III studies. The drug has been well tolerated following 
intravenous administration of single doses of 0.5 to 10 mg/kg or up to 700 mg weekly doses as 
subcutaneous (SC) injection. Overall, 324 subjects have been exposed to PRO 140 350 mg SC 
weekly dose with the longest duration of exposure lasting 4 years. Similarly, more than 250 and 150
subjects have been exposed to PRO 140 525 mg and 700 mg SC weekly dose, respectively. We
anticipate a manageable safety profile with combination therapy since: 1) Leronlimab (PRO 140) 
is not metabolized by the liver, and therefore may have the potential for a better tolerability profile 
than many of the existing small-molecule therapies; 2) Unlike small molecules, monoclocal 
antibodies are too large to be filtered by the kidneys and are not eliminated in the urine, except in 
pathologic conditions. If low molecular weight antibody fragments are filtered, they are usually 
reabsorbed and metabolized in the proximal tubule of the nephron; 3) there is no major toxicity 
overlap between leronlimab (PRO 140) and Carboplatin. These pharmacodynamic characteristics 
led to the dose selection of 350mg, 525mg and 700mg of leronlimab (PRO 140) in a dose escalation 
manner for the phase Ib part of this study. Carboplatin target of AUC 5 is the recommended dose 
for carboplatin in combination with other chemotherapy agents. 
1.6
RISKS / BENEFITS ASSESSMENT
1.6.1. Risks/Discomfort to Subjects and Precautions to Minimize Risk
Allergic Reaction
Leronlimab (PRO 140) belongs to the monoclonal antibody class of drugs. Monoclonal antibodies 
are sometimes associated with allergic reactions or flu-like reactions (such as fever, chills, and 
aches) or injection-site reactions. These events are usually of short duration if they occur at all. 
Severe allergic reactions, however, can be life-threatening. Although anaphylaxis has not been 
observed in prior trials of leronlimab (PRO 140), infusion of proteins always carries with it the 
theoretical risk for anaphylactic shock. Accordingly, whenever leronlimab (PRO 140) is 
administered to subjects, there should be available and in place the procedures required to manage 
anaphylactic shock. 

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Immune Response
People who take leronlimab (PRO 140) or other monoclonal antibodies can also develop an immune 
response to leronlimab (PRO 140) that may affect their ability to receive monoclonal antibodies, or 
to benefit from diagnosis or therapy with a monoclonal antibody in the future. 
Pregnancy
Risks to unborn babies are unknown at this time; pregnant females will be excluded from this study. 
Females of childbearing potential must have a negative pregnancy test prior to enrollment. Both 
male and female patients and their partners of childbearing potential must agree to use appropriate 
birth control methods throughout the study duration (excluding women who are not of childbearing 
potential and men who have been sterilized).  
Venipuncture
Blood sampling is required as part of the study protocol. Blood sampling carries a minimal risk of 
minor discomfort and the possibility of minor bruising at the site of the needle puncture and, rarely, 
the possibility of infection at the needle puncture site.
Core or excisional biopsy 
A core or excisional biopsy may be necessary in order to evaluate the CCR5 receptor expression of 
the breast cancer tumor by Immunohistochemistry (IHC) assay. This assay will be performed in 
archival tissue from previous biopsy specimens. If archival tissue is not available then, fresh core 
or excisional biopsy will be done. Serious complications related to core biopsy are rare. The 
commonest problem is bleeding, which is usually easy to control at the time of the procedure. Rarer 
complications of core biopsy include infection and abscess formation, pneumothorax, milk fistula 
formation, cosmetic deformity and seeding of tumor along the biopsy track. Compared to a needle 
biopsy, a surgical biopsy is more invasive, has a longer, more uncomfortable recovery time and has 
a higher risk of infection and bruising. 
Unknown Risks
As with all research there is the remote possibility of risks that are unknown or that cannot be 
foreseen based on current information.  
Theoretical risk for increased severity of West Nile virus infection
Individuals who lack a functional CCR5 gene are at increased risk for severe infection by West Nile 
virus [Thompson, 2009]. Because of this, treatment with CCR5 co-receptor antagonists poses a 
theoretical risk for increased severity of West Nile virus infection. However, this concern is 
mitigated by several factors. First, no increased risk was observed for individuals who possess one 

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functional and one non-functional CCR5 gene, indicating that an intermediate amount of CCR5 is 
sufficient for defense against West Nile virus [Thompson, 2009]. Second, use of CCR5 co-receptor 
antagonists is unlikely to completely abrogate CCR5 function, and there has been no association 
reported to date between CCR5 co-receptor use and severe West Nile virus. Additionally, 
leronlimab (PRO 140) weakly antagonizes the natural activity of CCR5 and thus is less likely to 
adversely affect immune function. However, patients enrolled in this study may have immune 
suppression from chemotherapy and therefore, DSMB and the investigators will be alerted to risks 
of West Nile infections. Furthermore, this has not been established to be a risk with maraviroc, the
other FDA-approved anti-CCR5 drug already. 
Collectively, the experience with both IV and SC, simulation modeling and the recent confirmation 
that a higher concentration of leronlimab (PRO 140) synthesized using a highly efficient CHO cell 
line can be conveniently and safely administered has resulted in the design of the current study.  
1.6.2. Intended Benefit for Subjects
This study provides an opportunity for subjects with CCR5 + metastatic triple negative breast 
cancer who are naïve to chemotherapy in the metastatic setting (first-line) OR who have failed first-
line combination of chemotherapy and a checkpoint inhibitor in the metastatic setting (excluding 
carboplatin) to have once weekly SC treatment with leronlimab (PRO 140) in addition to 
carboplatin target of AUC 5 as a combination regimen. Subjects participating in the present study 
will contribute to the development of a drug which has the potential to become a treatment option 
for them and others in the future.

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2
STUDY OBJECTIVES 
Phase Ib
The primary objectives of this study are:
To determine the safety, tolerability and maximum tolerate dose (MTD) of leronlimab (PRO 
140) when combined with carboplatin in patients with CCR5+ mTNBC, to define a 
recommended Phase II dose of the combination. 
The secondary objective of this study is:
To determine the recommended Phase II dose for the combination of leronlimab (PRO 140) 
and carboplatin in patients with CCR5+ mTNBC. 
Phase II
The primary objective of this study is:
To evaluate the impact on progression-free survival (PFS) of the combination leronlimab 
(PRO 140) and carboplatin in patients with CCR5+ mTNBC. 
The secondary objectives of this study are:
To assess the overall response rate (ORR) and clinical benefit rate (CBR) of carboplatin – 
leronlimab (PRO 140) in patients with CCR5+ mTNBC;
To assess benefit, based on time to new metastasis (TTNM);
To assess the change in circulating tumor cells (CTCs) number after treatment; and 
To assess the safety and tolerability of the combination of leronlimab (PRO 140) and 
carboplatin in subjects with CCR5+ mTNBC.

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3
STUDY DESIGN  
This is a Phase Ib/II, multicenter study with a planned enrollment of up to 18 subjects in the Phase 
Ib portion of the study and 30 subjects in the Phase II portion of the study. The target population 
for this study is subjects with histologically confirmed diagnosis of CCR5 positive, metastatic 
triple-negative breast cancer (documentedas having HER-2 negative, ER<1%, PR<1% disease) 
who are naïve to chemotherapy in metastatic setting (first-line) OR have failed first-line 
combination of chemotherapy and checkpoint inhibitor in metastatic setting (excluding 
carboplatin). A study flow schematic is presented in Figure 3-1.
Figure 3-1: 
Study Schematic
Phase Ib:
3+3 Design
MTD to be established for the combination treatment
Up to 18 Subjects
Cohort A: 350 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
Cohort B: 525 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
Cohort C: 700 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
Phase II:
Single Arm
30 Subjects
MTD PRO 140 SC + AUC 5 Carboplatin
 Primary Endpoint: PFS
Secondary Endpoints: ORR, CBR, TTNM, and safety
Study Population: 
Phase 1: 
2 line of therapy in metastatic setting but untreated with 
carboplatin
Phase 2: TNBC patients who are naïve to chemotherapy or untreated with carboplatin in 
metastatic setting (first-line) OR excluding carboplatin chemotherapy, patients must 
have failed first-line combination of chemotherapy and checkpoint inhibitor in metastatic 
setting
HER-2 negative, ER<1%, PR <1%
CCR5-postive (>10% IHC)
PS ECOG 0-1
 Treatment may continue until one of the following 
occurs:
- Progressive disease
-  Unacceptable toxicity
- Withdrawal of consent
Follow-Up: Follow-up will be done for survival status, 
by clinic visits or phone or another method of contact 
every three months for two years after treatment 
discontinuation or until death, whichever occurs first. 
Note: 1 treatment cycle = 21 (± 3) days
Note: Scans to be done at the end of 2 cycles (prior to Cycle 3) for the first 12 months and at 
the end of every 3 cycles (9 weeks) thereafter and at EOT, by CT, PET/CT, or MRI with 
contrast.

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Phase Ib
Phase Ib is a dose escalation phase with 3 dose levels (cohorts) of leronlimab (PRO 140) 
administered in combination with a fixed dose of carboplatin at AUC 5. This dose finding portion 
of study will follow a “3+3” designed to determine the maximum tolerated dose (MTD) of 
leronlimab (PRO 140) administered as subcutaneous injection in subjects with histologically 
confirmed mTNBC that express CCR5. The MTD is defined as 1 dose level (cohort) below the dose 
The calculation of the sample size for the Phase Ib trial is based on the traditional 3 + 3 dose 
escalation scheme which is conducted as follows:
Subjects are treated in cohorts of three each receiving the same dose. For the assessment of a 
DLT subjects are observed for 3 weeks (Cycle 1) after the first application of the study 
treatment.
If none of the three subjects of a cohort exhibits a DLT, the next cohort of three subjects receives 
the next higher dose. 
Otherwise, if at least one subject of a cohort exhibits a DLT, a further cohort of three subjects
is treated at the same dose level (cohort) without escalating the dose.
If exactly one out of the six subjects treated at this dose exhibits a DLT, the trial continues as 
planned at the next higher dose level (cohort). 
If two or more subjects out of the six subjects treated at this dose exhibit a DLT, the dose 
escalation stops at that level and the next lower dose is considered as the MTD. When the 
escalation has stopped, additional subjects will be treated at the MTD to a total of six subjects.
A schematic of the “3 + 3” Dose Escalation Study Design is provided in Figure 3-2. 
Cohorts of 3 patients are entered at given dose level K. If no patients have a DLT, then the dose 
will be escalated to the next dose level, K +1. If more than 1 subject has a DLT then the previous 
dose level, K -1, will be considered as MTD. If 1 subject has a DLT an additional 3 patients will be 
treated at this dose level, K. If no further subjects suffer a DLT then the dose level will be escalated 
to K +1 and if any further subjects have a DLT then the previous dose level, K -1, will be considered 
the MTD. The MTD will be the maximum dose level with an observed toxicity rate of 0% or 17%.

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b. The occurrence in any subject of an anaphylactic reaction to leronlimab (PRO 140)
c.
The occurrence in any subject of a severe local injection site reaction (Grade 3 which is not 
resolved or recurs; or Grade 4) that precludes administration of consecutive leronlimab 
(PRO 140) doses.
d. The occurrence in any subject of a life-threatening SAE whose causal relationship to 
leronlimab (PRO 140) is judged to be probable or definite 
e.
The occurrence of one or more non-life-threatening SAEs whose causal relationship to 
leronlimab (PRO 140) is judged to be definite
f.
The occurrence, in one or more subjects, of Grade 4 laboratory abnormalities, judged to be 
probably or definitely related to receipt of leronlimab (PRO 140) 
g. The occurrence of hematologic and non-hematological adverse events, judged to be 
possibly, probably or definitely related to receipt of leronlimab (PRO 140) based on 
previous clinical experience and that are of CTCAE Grade 3 or greater severity. Permissible 
exceptions to this rule include Grade 3 fatigue of less than one week duration, and Grade 3 
nausea, vomiting, and diarrhea that resolve within 48 hours following institution of 
appropriate supportive care.
h. Hy's law 
i.
Neutropenic fever 
j.
Grade 4+ neutropenia or thrombocytopenia >7 days 
k. Grade 3+ thrombocytopenia with bleeding 
l.
Grade 3+ electrolyte abnormality that lasts >72 hours, unless the patient has clinical 
symptoms, in which case all grade 3+ electrolyte abnormality regardless of duration should 
count as a DLT.  Grade 3+ amylase or lipase elevation NOT associated with symptoms or 
clinical manifestations of pancreatitis does not need to be counted as a DLT
m. For patients with hepatic metastases, AST or ALT >8xULN or AST or ALT >5x ULN for 
If any of the SAEs or DLTs outlined above have occurred, the Data Safety Monitoring Board 
(DSMB) will conduct an independent review of the data and make a final decision for dose 
escalation to the next cohort.
The dosing regimen for each cohort is as follows: 
Cohort A: 350 mg leronlimab (PRO 140) SC weekly + AUC 5 Carboplatin every 3 weeks 
Cohort B: 525 mg leronlimab (PRO 140) SC weekly + AUC 5 Carboplatin every 3 weeks 
Cohort C: 700 mg leronlimab (PRO 140) SC weekly + AUC 5 Carboplatin every 3 weeks 

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Leronlimab (PRO 140) is administered as subcutaneous injection in the abdomen weekly. A total 
of 350 mg, 525 mg, or 700 mg (175 mg/mL) is delivered as two injections on opposite sides of the 
abdomen. The 350 mg dose will be delivered as two injections of 1 mL each, 525 mg dose will be 
delivered as two injections of 1.5 mL each and 700 mg dose will be delivered as two injections of 
2 mL each.
The final decision on the MTD will be made following a review of the study data by the DSMB.
Continuation into Phase II of the study will take place after the DSMB meeting.
Once the MTD has been determined, subjects enrolled in lower dose cohorts will be allowed to 
escalate the dose to the MTD, if acceptable per the Investigator’s discretion.
Phase II
Phase II is a single arm study with 30 patients in order to test the hypothesis that the combination 
of carboplatin AUC 5 intravenously and MTD of leronlimab (PRO 140) SC will increase PFS in 
patients with CCR5 + mTNBC. PFS in patients with newly recurred TNBC is approximately 5 
months. 
Leronlimab (PRO 140) will be administered subcutaneously at a weekly MTD dose determined in 
the Phase Ib portion of the study and carboplatin target of AUC 5 every 3 weeks as combination 
therapy until disease progression or intolerable toxicity. A de-escalation dose of carboplatin will be 
allowed based on the toxicity, efficacy evaluation, and clinical judgment by physician. 
In both the Phase Ib and Phase II portions of the study, patients will be evaluated for response at 
the end of 2 cycles (i.e., every 6 weeks) for the first 6 cycles (18 weeks) and at end of 3 cycles (i.e., 
every 9 weeks) thereafter and at EOT by CT, PET/CT or MRI with contrast (per treating 
investigator’s discretion) using the same method as at baseline. Tumor measurements will be done 
using RECIST v1.1.
3.1
STUDY CENTER
Up to five centers in the United States (US). 
3.2
STUDY POPULATION
The target population for this study is subjects with histologically confirmed mTNBC that express 
CCR5 (> 10% membranous staining completed at the laboratory at the Medical College of 
Wisconsin). Subjects should have measurable disease. Subjects must be naïve to chemotherapy in 
the metastatic setting (first-line) OR failed first-line combination of chemotherapy and a checkpoint 
inhibitor in the metastatic setting (excluding carboplatin). 
This will be a multicenter trial. A total of up to 18 subjects in Phase Ib and 30 subjects in Phase II 
will be needed for this trial.

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Eligibility will be evaluated by the study team according to the following criteria. Eligibility waivers
are not permitted. Subjects must meet all of the inclusion and none of the exclusion criteria to be 
registered to the study.  
3.3
ELIGIBILITY CRITERIA
3.3.1. Inclusion Criteria
Subjects are required to meet all of the following criteria for enrollment into the study:
1. Must have a histologically confirmed diagnosis of TNBC. Must demonstrate HER-2 
negative (IHC 0, 1+, or fluorescence in situ hybridization (FISH) negative and ER< 1%, 
and PR < 1%, per ASCO/CAP criteria); 
2. Demonstrate CCR5 + by IHC (>10% of primary or metastatic tumor cells shows
membranous staining and/or high predominance of CCR5+ tumor-infiltrating 
leukocytes completed at the reference laboratory of Dr. Hallgeir Rui at Medical College 
of Wisconsin).  
Note: This test will be done as part of the pre-screening period. It will be performed in 
archival metastatic tissue. If archival tissue is not available then, fresh biopsy will be 
done; 
3. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor 
lesion (in case archival tissue is not available);
4. Patients with stage IV de-novo disease or patients that develop recurrence after 
completion of neoadjuvant or adjuvant therapy are eligible; 
Note: Patients who have been exposed to carboplatin in neoadjuvant or adjuvant setting 
treatment.
5. Phase 1 study section:
Subjects must have disease 
metastatic setting but untreated with carboplatin
Phase 2 study section:
Subjects must be naïve to chemotherapy or untreated with carboplatin in metastatic 
setting (first-line) OR excluding carboplatin chemotherapy, subjects must have failed 
first-line combination of chemotherapy and a checkpoint inhibitor in metastatic setting;  
6. Patients must have measurable disease based on RECIST v1.1; 
7. Female patients,
of age; 

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8. Patients must exhibit a/an ECOG performance status of 0-1; 
9. Life expectancy of at least 6 months; 
10. Patients must have adequate organ and bone marrow function within 28 days prior to 
registration, as defined below:
absolute neutrophil 
 1,500/mcL; 
 100,000/mcL; 
total bilirubin: within normal institutional limits;
normal (ULN) 
(applicable to all patients, irrespective of liver disease or metastasis); and
creatinine: within normal institutional limits.
11. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered 
not clinically significant by the Principal Investigator.
12. Females of child-bearing potential (FOCBP) and males must agree to use two medically 
accepted methods of contraception with hormonal or barrier method of birth control, or 
abstinence, prior to study entry, for the duration of study participation and for 60 days 
after the last dose of study drug (Refer to Appendix 1). Should a female patient become 
pregnant or suspect she is pregnant while participating in this study, she should inform 
her treating physician immediately. NOTE: A FOCBP is any woman (regardless of 
sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) 
who meets the following criteria:
Has not undergone a hysterectomy or bilateral oophorectomy; and 
Has had menses at any time in the preceding 12 consecutive months (and 
therefore has not been naturally postmenopausal for > 12 months). 
13. FOCBP must have a negative serum pregnancy test at Screening Visit and negative urine 
pregnancy test prior to receiving the first dose of study drug; and
14. Patients must have the ability to understand and the willingness to sign a written 
informed consent prior to registration on study. 
3.3.2. Exclusion Criteria
Subjects meeting any of the following criteria will be excluded from enrollment:
1. HER-2 overexpressed/amplified MBC (Appendix 2 for guidelines from ASCO);
2. ER and or PR expressing tumors; 

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3. Is currently participating and receiving study therapy or has participated in a study of an 
investigational agent and received study therapy or used an investigational device within 
28 days prior to enrollment; 
4. Patients who have a history of allergic reactions attributed to compounds of similar 
chemical or biologic composition to leronlimab (PRO 140) are not eligible;
5. Patients who have had prior exposure to CCR5 antagonists are not eligible;
6. Patients who have a known additional malignancy that is progressing or requires active 
treatment are not eligible. Patients who have had a prior diagnosis of cancer and if it has 
been <3 years since their last treatment are not eligible. Exceptions include basal cell 
carcinoma of the skin or squamous cell carcinoma of the skin that has undergone 
potentially curative therapy or in situ cervical cancer; 
7. Has an active infection requiring systemic therapy. Note: Patients must complete any 
treatment with antibiotics prior to registration;
8. Patients who have a known HIV positive status or known/ active Hepatitis B and/or C 
infection are not eligible;
9. Has known active central nervous system (CNS) metastases and/or carcinomatous 
meningitis. Note: Subjects with previously treated brain metastases may participate 
provided they are stable (without evidence of progression by imaging for at least four 
weeks prior to the first dose of trial treatment and any neurologic symptoms have 
returned to baseline), have no evidence of new or enlarging brain metastases, and are 
not using steroids for at least 7 days prior to trial treatment. This exception does not 
include carcinomatous meningitis which is excluded regardless of clinical stability;
10. Has a history or current evidence of any condition, therapy, or laboratory abnormality 
that might confound the results of the trial, interfere with the subject’s participation for 
the full duration of the trial, or is not in the best interest of the subject to participate, in 
the opinion of the treating investigator; 
11. Has known psychiatric or substance abuse disorders that would interfere with 
cooperation with the requirements of the trial; and
12. Is pregnant or breastfeeding, or expecting to conceive or have children within the 
projected duration of the trial, starting with the pre-screening or screening visit through 
the duration of study participation. 

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4
STUDY SCHEDULE
The total study duration for each subject consists of pre-screening, screening, treatment, and follow-
up periods. A study flow diagram is presented in Figure 4-1.
(1) Pre-Screening Period: A separate Informed Consent Form (ICF) will be used for the pre-
screening. The pre-screening period is designed for evaluation of histologically confirmed 
diagnosis of mTNBC (documented by HER-2 negative, ER<1%, PR<1%) and CCR5 
positive expression by Immunohistochemistry (IHC) assay. This assay will be performed in 
archival tissue from previous biopsy specimens. If archival tissue is not available then, fresh 
core or excisional biopsy will be done. If patient qualifies, then they will undergo full 
screening.
(2) Screening Period: Screening assessments will commence after obtaining signed informed 
consent, and will include review of medical and medication history, demographic 
information
and baseline disease characteristics, eligibility evaluation, physical 
examination, vital signs, height and weight, concomitant medications, electrocardiogram 
(ECG), tumor imaging assessment, routine serum biochemical, hematologic, urinalysis, 
serum pregnancy (if applicable). These assessments must be conducted within 28 days of 
the first treatment visit.
(3) Treatment Period: Subjects who meet the eligibility criteria will have completed following 
evaluations and assessments before receiving treatment: a) review of medical and 
medication history; b) physical examination, vital signs and documentation of ECOG 
performance status; c) ECG; d) routine serum biochemical, hematologic, urine pregnancy 
(if applicable) and urine laboratory assessments. Additionally, a blood sample will be 
collected prior to treatment administration for CTCs PD-L1/CCR5 and CTC - CAMLs 
analysis.
Each treatment cycle will consist of 21 days. Leronlimab (PRO 140) will be administered 
subcutaneously weekly on Days 1, 8, and 15 in combination with carboplatin AUC 5 on 
Day 1 of each cycle (every 21 days). Day 1 of Cycle 2 begins at Day 22. The study treatment 
will be administered by a licensed medical professional at clinic site or self-administered by 
subjects at home.  
Note: All leronlimab (PRO 140) SC weekly injections at Cycle 1 (Days 1, 8, and 15) and at 
Day 1 of subsequent cycles must be administered at clinic. The remaining study treatment 
injections at Day 8 and Day 15 (beyond Cycle 1) may be self-administered by subjects at 
home after proper training by a healthcare professional. 
Subjects will be allowed to continue treatment under subsequent treatment cycles until any 
one of the following occurs: progressive disease or unacceptable toxicity or withdrawal of 
consent. 

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4.1
PRE-SCREENING PERIOD
4.1.1. Pre-Screening Visit
Sites are required to pre-screen subjects for study inclusion, evaluating CCR5 positive expression 
by Immunohistochemistry (IHC) assay prior to performing a full screening visit. This assay will be 
performed in archival tissue from previous biopsy specimens. If archival tissue is not available then, 
fresh core or excisional biopsy will be obtained. 
The subject will sign and date the pre-screening informed consent form (ICF) prior to any study-
related pre-screening procedures. A unique identification number will be assigned to each subject 
who has provided written pre-screening informed consent.  
The subject unique identification number will incorporate a three-digit Study Center number (701, 
702 or 703….) and a three-digit numeric ID assigned in successive order of entering the study after 
signing the pre-screening ICF at each center, beginning with 001 at each site (e.g. 701-001 or 702-
001).  
Subject Screening # :
XXX
-
YYY
XXX=Study Center
YYY=Subject Numeric ID
Once the pre-screening ICF has been signed, the following procedures and information will be 
obtained to confirm pre- eligibility including:
Review of prior medical records
CCR5+ expression confirmed by archival or fresh biopsy from primary or metastatic site
PD-L1 expression confirmed by archival or fresh biopsy from primary or metastatic site
A pre-screening log will be maintained to capture the following information: 
Subject unique identification number 
Patient initials
Date pre-screened
Initial eligibility
Date of re-consent (for the full consent form) or reason for ineligibility
4.2
SCREENING PERIOD
4.2.1. Screening Visit (SV)

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The subject (or Legally Acceptable Representative (LAR)) will sign and date the informed consent 
form (ICF) and Health Insurance Portability Accountability Act (HIPAA) authorization (according 
to site policy and practices) prior to any study-related procedures. 
All study centers will be instructed to maintain the study-specific screening and enrollment logs at 
their sites. If a subject initially fails to meet inclusion/exclusion criteria and is later reconsidered 
for participation, the subject will be re-consented and assigned a new unique identification number 
at the time of re-screening. Subjects who fail their first screening attempt may be re-screened a 
maximum of once and may be enrolled if they are found to meet all inclusion and no exclusion 
criteria when re-screened.
Once the Screening ICF has been signed, screening procedures and information will be obtained to 
confirm subject eligibility including:
Demographic information and baseline disease characteristics (see Section 7.3),  
Medical history (see Section 7.4),
Prior medications assessment (see Section 7.5),  
Vital Signs (see Section 7.6),
Body Weight & Height measurements (see Section 7.6),
Physical examination (see Section 7.7),
Eastern Cooperative Oncology Group (ECOG) Performance Review (see Section 7.8) 
12-lead Electrocardiogram (see Section 7.9) 
Tumor imaging assessment (see Section 7.15) 
Collection of lab specimens (see Section 7.11) for
o
Complete blood count 
o
Biochemistry
o
Serum pregnancy test, for female subjects of childbearing potential. 
o
Urine sample for urinalysis parameters
All screening information will be fully documented in the subject’s medical records (i.e., source 
documents).  
For consented subjects who do not meet eligibility criteria, a Screen Failure Case Report 
Form (CRF) will be completed. The Screen Failure CRF will contain the following details:
the subject identification number, the date of ICF signature, demographic information (see 

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Section 7.3), and the reason for screen failure. No additional information will be required 
for subjects who fail screening.  
For consented subjects who meet eligibility criteria, all required screening information will 
be transcribed onto the appropriate page of the CRF.
4.3
TREATMENT PERIOD
Subjects who meet all eligibility criteria, as per data gathered from Screening Period are to be 
treated. All subjects who fail to meet eligibility criteria will be considered screen failure and exit 
the study without further evaluation
Phase Ib
The dose finding portion of study will follow a “3+3” design. The maximum sample size for this 
portion of the study is 18 subjects that will be followed by treatment according to the schedule 
described above starting on Cycle 1, Day 1. 
Phase II
The maximum sample size for this portion of the study is 30 subjects that will be followed by 
treatment according to the schedule described above starting on Cycle 1, Day 1. 
During the Phase Ib and Phase II of the study, treatment may continue until one of the following 
criteria applies:
Disease progression,
Intercurrent illness that prevents further administration of treatment,
Unacceptable adverse event(s), or
Withdrawal of consent
Each treatment cycle consists of 21 days. Leronlimab (PRO 140) will be administered 
subcutaneously weekly on Days 1, 8, and 15 in combination with carboplatin AUC 5 on Day 1 of 
each cycle (every 21 days). Day 1 of Cycle 2 begins at Day 22. 
4.3.1. Treatment Cycle 1, Day 1 
The following assessments will be performed at the first treatment visit of Cycle 1:
Concomitant medications assessment (see Section 7.5),  
Vital Signs and body weight measurement (see Section 7.6),
Physical examination, including evaluation of all body systems (see Section 7.7) 
ECOG Performance Status (see Section 7.8) 

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12-lead Electrocardiogram (see Section 7.9) 
Collection of lab specimens (see Section 7.11 ) for
o
Complete blood count 
o
Biochemistry
o
Urine pregnancy test, for female subjects of childbearing potential.
o
Urine sample for urinalysis parameters
o
CTCs PD-L1/CCR5 analysis 
o
CTC and CAMLs analysis
Note: Complete blood count, biochemistry and urinalysis can be performed within 
3 days prior to each cycle start.
Leronlimab (PRO 140) Administration (see Section 6.1.3) 
Carboplatin Administration (see Section 6.2.5) 
Post Injection Site Evaluation (performed by Investigator) (see Section 7.13) 
Toxicity assessment (see Section 7.10) and Review of Adverse Events (see Section 9) 
4.3.2. Treatment Cycle 1, Day 8 & Day 15 
The following assessments will be performed at during the remaining visits (Day 8 and 15) in the 
first treatment cycle:
Concomitant medications assessment (see Section 7.5),  
Review of Adverse Events (see Section 9) 
Vital Signs (see Section 7.6),
Symptom-based physical examination (see Section 7.7) 
Leronlimab (PRO 140) Administration (see Section 6.1.3) 
Post Injection Site Evaluation by Investigator (see Section 7.13) 
Injection Site Pain Assessment (VAS) (see Section 7.14) 
4.3.3. Subsequent Treatment Cycle(s), Day 1 
The following assessments will be performed at Day 1 of each subsequent treatment cycles:
Concomitant medications assessment (see Section 7.5),  

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Leronlimab (PRO 140) Administration (see Section 6.1.3) 
Post Injection Site Evaluation by Investigator (see Section 7.13) 
Injection Site Pain Assessment (VAS) (see Section 7.14) 
Note: Vital signs, symptom-based physical examination, post injection site evaluation by 
Investigator, and injection site pain assessment (VAS) will not be applicable if leronlimab 
(PRO 140) is self-administered by subjects at home.
4.4
FOLLOW-UP PERIOD
Duration of Follow Up 
An End of Treatment (EOT) visit will be conducted 30 (± 3) days after the last treatment visit 
(i.e., after last dose of leronlimab (PRO 140) and carboplatin). 
All patients will be followed for adverse events for 30 days after last dose of leronlimab (PRO 
140) and Carboplatin, or until the patient starts a new treatment, whichever occurs first.
Subjects who discontinue treatment for unacceptable adverse event(s) will be followed until 
resolution or stabilization of the adverse event (i.e. the grade is not changing). 
If a subject stops treatment due to unacceptable adverse event(s) but has not demonstrated 
disease progression, then the subject will be followed with imaging studies every 9 weeks until 
the time of progression radiographically according to RECIST v1.1 criteria. In the event that a 
radiographic response is detected, then this event will be included as a response in the final 
analysis, and the time of progression used in calculation of the survival analysis. 
Subjects will be followed up by clinic visits or phone call or another method of contact, for 
survival status every 3 months (±1 month) for 2 years after treatment discontinuation or until 
death, whichever occurs first.
4.4.1. End of Treatment Visit (EOT)
An EOT visit will take place 30 (± 3) days from the last treatment visit. 
The following assessments will be performed at the EOT visit:
Concomitant medications assessment (see Section 7.5),  
Review of Adverse Events (see Section 9) 
Vital Signs (see Section 7.6),
Physical examination, including evaluation of all body systems (see Section 7.7), 
ECOG Performance Status (see Section 7.8),

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12-lead Electrocardiogram (see Section 7.9),
Toxicity Assessment (see Section 7.10),
Collection of lab specimens (see Section 7.11) for
o
Complete blood count 
o
Biochemistry
o
Urine sample for urinalysis parameters
o
CTCs PD-L1/CCR5 Analysis
o
CTC and CAMLs Analysis 
Survival status (see Section 7.16) 
4.4.2. Survival Follow-up Visits 
Survival follow-up visits will be performed every 3 months (±1 month) for 2 years after treatment 
discontinuation or until death, whichever occurs first. Subjects will be followed up by clinic visits 
or phone call or another method of contact, for survival status. During the visit, the following 
assessments will be performed:
Survival status 
Concomitant medications (limited to all subsequent anti-cancer treatments)
Toxicity assessment
Note: Subjects who discontinue treatment for unacceptable adverse event(s) will be 
followed until resolution or stabilization of the adverse event (i.e. the grade is not 
changing).
Tumor imaging assessment (see Section 7.15 and note below)  
Note: If a subject stops treatment due to unacceptable adverse event(s) but has not 
demonstrated disease progression, then the subject will be followed with imaging studies 
every 9 weeks until the time of progression radiographically according to RECIST v1.1 
criteria. In the event that a radiographic response is detected, then this event will be included 
as a response in the final analysis, and the time of progression used in calculation of the 
survival analysis.
4.5
UNSCHEDULED VISITS
In the event that the subject will return to clinic at a time other than a regularly scheduled study 
visit, the visit will be regarded as an unscheduled visit. Assessments at unscheduled visits are at 

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the discretion of the Investigator. All pertinent findings, including adverse events or changes in 
medications, will be noted in the eCRF.  
Any hospitalization or ER visits in between the scheduled visits should be promptly notified to the 
site staff. 

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5
SUBJECT COMPLETION, WITHDRAWAL AND CRITERIA FOR 
STOPPING THE STUDY
A subject is considered to have completed the study once all survival follow-up visit assessments up 
to 2 years after treatment discontinuation have been performed or until death, whichever occurs first.
While subjects are encouraged to complete all study evaluations, they may withdraw from the study 
at any time and for any reason. Reasonable effort will be made to determine why any subject 
withdraws from the study prematurely. This information will be recorded. If a subject withdraws 
prematurely after dosing, subjects will be monitored until they are stable for discharge from the clinic. 
All data normally collected at the scheduled Post-Study (Follow-up) Visit should be recorded at the 
time of premature discontinuation.
5.1
REMOVAL OF SUBJECTS FROM STUDY TREATMENT AND/OR STUDY AS A WHOLE
Subjects can be taken off the study treatment and/or study as a whole at any time at their own 
request, or they may be withdrawn at the discretion of the investigator for safety, behavioral or 
administrative reasons. The reason(s) for discontinuation must be clearly documented on the 
appropriate eCRF and may include: 
Subject voluntarily withdraws from treatment (follow-up permitted) 
Subject withdraws consent (no follow-up permitted) 
Subject is unable to comply with protocol requirements
Subject demonstrates disease progression
Subject experiences unacceptable toxicity
Treating physician determines that continuation on the study would not be in the subject’s 
best interest
Subject becomes pregnant 
Subject develops a second malignancy that requires treatment which would interfere with 
this study 
Subject becomes lost to follow-up (LTF)
If a subject fails to return for the scheduled study visit or is discontinued from the study, an attempt 
will be made to determine the reason(s). If the subject is unreachable by telephone, a registered 
letter will be sent to the subject requesting that he/she contact the clinic. 
All patients with an ongoing SAE at the Post-Study (Follow-up) Visit (scheduled or premature) 
must be followed until the event is resolved (with or without sequelae) or deemed stable.

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5.2
SUBJECT REPLACEMENT
Three subjects within a dose level must be observed for one cycle (21 days) before accrual to the 
next higher dose level may begin. If a subject is withdrawn from the study prior to completing one 
cycle of therapy without experiencing a DLT prior to withdrawal, an additional subject may be 
added to that dose level. 
Subjects missing leronlimab (PRO 140) administration (during the DLT period i.e., Cycle 1) due 
to toxicity will not be replaced since these subjects will be considered to have experienced a dose 
limiting toxicity.
5.3
DATA COLLECTED FROM WITHDRAWN SUBJECTS
Every attempt should be made to collect follow-up information. The reason for withdrawal from 
the study will be recorded in the source documents and on the appropriate page of the CRF. 
Before a subject is identified as lost-to-follow up, the site should make all reasonable efforts to 
contact the subject. These attempts must be documented and should include at a minimum one 
phone call and one certified letter.  
In the event that a subject is withdrawn from the study at any time due to an adverse event or SAE, 
the procedures stated in Sections 9.2 and 9.4 must be followed.
5.4
SCREEN FAILURES
A subject who signed a consent form, but did not meet the inclusion/exclusion criteria is classified 
as a screen failure. Subject number, demographics and reason for screen failure will be recorded.
In the event that a subject initially fails to meet inclusion/exclusion criteria and is later reconsidered 
for participation, will be re-consented and assigned a new unique identification number at the time 
of re-screening. Subjects who fail their first screening attempt may be re-screened again (i.e., up to 
two screenings) and may be enrolled if they are found to meet all inclusion and no exclusion criteria 
at the subsequent screening visit.

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Figure 6-2: 
Investigational Product - Syringe Label
Protocol: PRO 140_CD07                                      Contents of Kit No. xxx
This syringe contains 1/1.5/2 mL PRO 140 (175 mg/mL) solution for 
subcutaneous injection
USE AS PER STUDY PROTOCOL
Caution: New Drug – Limited by Federal (or United States) Law to 
Investigational Use
CytoDyn Inc., Vancouver, WA, USA
Figure 6-3: 
Investigational Product - Kit Label
Protocol: PRO 140_CD07                                                          Kit No. xxx
Site No. ____________                           Subject No.  ________________   
This kit contains 2/3/4 single-use vials
Each 3 mL vial contains 1.4 mL of PRO 140 (175 mg/mL) solution for subcutaneous 
injection
Store at 2oC to 8oC (36oF to 46oF)
USE AS PER STUDY PROTOCOL
Caution: New Drug – Limited by Federal (or United States) Law to Investigational Use
CytoDyn Inc., Vancouver, WA, USA
The pharmacy manual provides the criteria regarding vial acceptance or rejection, as well as 
instructions for the preparation of the IP syringes to be used to administer drug. 
6.1.2. Leronlimab (PRO 140) - Storage and Handling
Study drug will be shipped at 2°C to 8°C (refrigerated [36°F to 46°F]) to the investigator’s site. 
Upon receipt at the site, the responsible site staff or pharmacist should verify the integrity of the 
vials. Study drug should be stored at 2°C to 8°C (refrigerated [36°F to 46°F]). The contents of the 
vial should appear as a clear to opalescent, colorless to yellow solution; fine translucent particles 
may be present. This is normal.  
The investigator must maintain an accurate record of the shipment, storage, and dispensing of the 
study drug in a drug accountability log. An accurate record including the date and amount of study 
drug dispensed to each subject must be available for inspection at any time. A study CRA assigned 

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to monitor the investigational site will review these documents once study drug has been received 
by the investigational site. Study drug will be accounted for on an ongoing basis during the study. 
6.1.3. Leronlimab (PRO 140) - Administration
Guidelines for dose preparation can be found in the pharmacy manual. 
Leronlimab (PRO 140) will be provided to the administering personnel in single-use syringes 
prepared from vials of study drug stored at 2-8°C at the site pharmacy prior to use. Each of two 
syringes is filled to deliver 1.0, 1.5 or 2 mL of study drug (per assigned dose).  
Equivalent volumes of PRO 140 will be administered subcutaneously on opposite sides of the 
abdomen.  
A 21-guage needle should be used to remove PRO 140 from vial and a 25-guage needle is used for 
administration to subjects. 
IP should be administered slowly over 15 seconds per mL. Leronlimab (PRO 140) should not be 
kept in syringe for longer than 60 minutes. 
Following each SC delivery of drug, careful examination will be made to assess the appearance of 
any study drug Injection Site Reactions (ISRs) as per CTCAE v5.0 
All doses of study drug will be prepared by either the credentialed pharmacist or qualified medical 
professional and will be administered as SC injection by a licensed medical professional when 
leronlimab (PRO 140) is administered at clinic site. Self administration by subjects at home is 
allowed at certain visits.
All leronlimab (PRO 140) SC weekly injections at Cycle 1 (Days 1, 8, and 15) and at Day 1 of 
subsequent cycles must be administered at clinic. The remaining study treatment injections at Day 
8 and Day 15 (beyond Cycle 1) may be self-administered by subjects at home after proper training 
by a healthcare professional.
Note: It is preferred that the same injection site be used throughout the study. At the same time, it 
is not recommended to inject the study drug into areas where skin shows signs of a previous 
injection site reaction. It is advised to change the injection site if any previous injection site reaction 
remains unresolved. 
6.1.4. Leronlimab (PRO 140) - Post Injection Monitoring
Subject will be observed at approximately 30 minutes post-injection or longer if necessary for 
injection site reaction as per CTCAE v5.0. 
In addition, the tolerability of repeated subcutaneous administration of PRO 140 is evaluated based 
on assessment of subject-perceived injection site pain using the Pain Visual Analog Scale (VAS).  

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Cohort C (PRO 140 700 mg): 
Dose de-escalation: If a dose-response relationship for toxicity is observed at leronlimab 
(PRO 140) 700 mg dose, the dose can be de-escalated to 525 mg. If no toxicity is observed 
at reduced dose (525 mg), the subjects will receive the reduced dose until disease 
progression, consent withdraw or death. One more dose de-escalation (to 350 mg) will be 
allowed as per discretion of the treating physician.
Permanent discontinuation of Treatment: If Dose Limiting Toxicity (DLT) is reported at 350mg 
dose.  
6.1.6. Leronlimab (PRO 140) - Disposition
All drug supplies are to be used only for this protocol and not for any other purpose. The investigator 
must not destroy any drug labels or any partially used or unused drug supply until instructed by the 
Sponsor. At the conclusion of the study and as appropriate during the course of the study, the 
investigator will return all used and unused drug containers and drug labels to the drug distributor 
as directed by the Sponsor. A copy of the completed drug disposition form will be sent to CytoDyn, 
Inc. or to its designee.
6.1.7. Leronlimab (PRO 140) - Accountability
Study drug must be used in accordance with this protocol and only under the direction of the 
responsible investigator. The investigational site must maintain complete and accurate records 
showing receipt and disposition of all study drug, including master records listing the date of 
receipt, the number and nature of medication units received, and a dispensing record which includes 
each quantity dispensed, identification of the staff member/subject to whom dispensed, the date of 
dispensing, the intended study participant, and the identification of the preparer. All used and 
unused study kits will be retained by the investigational site until drug accountability can be 
confirmed by study CRA during the monitoring visits. Instructions will be provided by Sponsor 
regarding final disposition of all study drug in compliance with applicable regulations. 
6.2
CARBOPLATIN
6.2.1. Other names
CBDCA, Paraplatin, JM-8, NSC-241240 
6.2.2. Classification – Type of agent 
Second-generation tetravalent organic platinum compound
6.2.3. Carboplatin - Mode of Action 

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Like cisplatin, carboplatin binds to DNA, thereby inhibiting DNA synthesis, in a cell cycle 
nonspecific manner. Carboplatin must first undergo activation to produce antineoplastic activity. 
Bidentate carboxylate ligands of carboplatin are displaced by water forming (aquation) positively 
charged platinum complexes which bind to nucleophilic sites in DNA, such as the O-6 position on 
guanine. Carboplatin produces predominantly interstrand DNA crosslinks rather than DNA-protein 
crosslinks. Intrastrand crosslinks result from the formation of adducts between the activated 
platinum complexes of the drug and the N-7 atom (not exclusively) atom on guanine to produce 1,2 
intrastrand links between adjacent guanine molecules, between neighboring guanine and adenosine 
molecules, or between neighboring guanine molecules. Interstrand cross-linking within the DNA 
helix also occurs. 
Platinum adducts may inhibit DNA replication, transcription and ultimately cell division.
6.2.4. Carboplatin - Storage and stability
Store according to package insert recommendations 
6.2.5. Carboplatin - Dose specification per protocol
Carboplatin will be IV infused at AUC 5 on D1 of each cycle, every 3 weeks Routine premedication 
should include at least a 5 – HT3 antagonist and dexamethasone.
Other pre-medications, such as NK1 receptor antagonists can be given per institutional guidelines. 
The dose of carboplatin based on target AUC is calculated using the Calvert equation:
Dose (total mg) = Target AUC X (GFR + 25). The patient’s creatinine clearance (GFR) in 
mL/minute is calculated by the Cockgraft Gault equation.
6.2.6. Carboplatin - Preparation 
Per package insert or institutional guidelines.
Add 5, 15, or 45 mL sterile water, normal saline, or 5% dextrose to the 50, 150, or 450 mg vial, 
respectively. The resulting solution contains 10 mg/mL. The desired dose is further diluted, usually 
in 5% dextrose. Aluminum displaces platinum from the carboplatin molecule, resulting in the 
formation of a black precipitate and loss of potency. Carboplatin solutions should not be prepared 
with needles, syringes, catheters, or IV administration sets containing aluminum parts that might 
be in contact with the drug. 
6.2.7. Carboplatin - Route of administration
Intravenous (IV) over 60 (±15) minutes or per institutional guidelines
(Note: the 60 minutes duration is for Carboplatin infusion at AUC 5. If Carboplatin is given at AUC 
4, then institutional standards should be followed). 
6.2.8. Carboplatin - Incompatibilities

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Aluminum displaces platinum from the carboplatin molecule, resulting in the formation of a black 
precipitate and loss of potency. Carboplatin solutions should not be prepared or administered with 
needles, syringes, catheters, or IV administration sets containing aluminum parts that might be in 
contact with the drug. 
Concomitant myelosuppressive drugs or radiation therapy may potentiate the hematologic toxicity 
of carboplatin. Concomitant nephrotoxic drugs may potentiate the nephrotoxicity of carboplatin, 
particularly when carboplatin is given in high-dose chemotherapy regimens.
6.2.9. Carboplatin - Availability and Supply
Carboplatin will be given as standard of care therapy. Commercial supply of Carboplatin will be 
used for this study. 
6.2.10. Carboplatin - Side effects
1. Hematologic: Thrombocytopenia (dose limiting), neutropenia, leukopenia, anemia. 
2. GI: Nausea and vomiting (frequent but less severe than with cisplatin), treatable with 
appropriate antiemetic prophylaxis.
3. Anorexia, diarrhea and constipation have also been reported. 
4. Dermatologic: Rash, urticaria. Rarer reactions include alopecia, mucositis, and hypersensitivity 
reactions.
5. Hepatic: Abnormal liver function tests, usually reversible with standard doses.
6. Neurologic: Rarely peripheral neuropathy is seen. May be more common in patients greater 
than 65 years of age. May also be cumulative, especially in patients with prior cisplatin 
treatment.
7. Ototoxicity (rare).
8. Renal: Elevations in serum creatinine, BUN; electrolyte loss (Mg, K, Na, Ca).
9. Miscellaneous: Pain, asthenia, flu-like syndrome. 
6.2.11. Carboplatin - Nursing implications
1. Aluminum displaces platinum from the carboplatin molecule, resulting in the formation of a 
black precipitate and loss of potency. Carboplatin solutions should not be prepared with needles, 
syringes, catheters, or IV administration sets containing aluminum parts that might be in contact 
with the drug.
2. Monitor CBC and platelet count at least every 21 days or earlier if warranted per institutional 
standard of care. 

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7
DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES
7.1
INFORMED CONSENT
A written informed consent will be obtained for this study for pre-screening and screening by the 
Investigator or designee from all subjects prior to performance of any protocol-specific procedure. 
This study will be conducted in accordance with the provisions of the Declaration of Helsinki.  
The Investigator must comply with applicable regulatory requirements and must adhere to the Good 
Clinical Practice (GCP) in the process of obtaining and documenting the informed consent. The 
Investigator, or designee, must also inform subjects of all pertinent aspects of the study. Before 
written informed consent is obtained from the subject, the Investigator or a person designated by 
the Investigator, must provide the subject enough time and opportunity to inquire about the details 
of the study and to decide whether or not to participate in the trial. All questions addressed by the 
subject about the study must be answered to the satisfaction of the subject. Prior to the subject’s 
participation in the trial, the written informed consent must be signed and personally dated by the 
subject and by the person who conducted the informed consent discussion. Authorization for release 
of protected health information must also be obtained, as per local policies.
7.2
ASSESSMENT OF ELIGIBILITY
The Investigator must assess subject’ continued eligibility for the study as per the Inclusion and 
Exclusion criteria, during the Screening Period. The eligibility criteria are described in Section 3.3.1
(Inclusion Criteria) and Section 3.3.2 (Exclusion Criteria). In the event that the subject is not 
suitable or eligible for the study, the subject will be considered “screen failure”.  
7.2.1. Re-screening
If a subject fails initially to meet the eligibility criteria, and is later reconsidered for participation, 
the subject will be re-consented and assigned a new unique identification number at the time of re-
screening. Subjects who fail their first screening attempt may be re-screened a maximum of once 
and may be enrolled in the study only if they meet all Inclusion and no Exclusion criteria when re-
screened.
7.3
DEMOGRAPHIC INFORMATION AND BASELINE DISEASE CHARACTERISTICS
In this study the demographic information will include: 
Dates of ICF signature 
Date of birth
Gender 

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Race (American Indian/Alaskan Native, Asian, Black/African American, Native 
Hawaiian/Pacific Islander, Caucasian, or other)
Ethnicity (Hispanic/Latino or Not Hispanic/Latino)
In addition, the following baseline disease characteristics will be collected:
Year of initial diagnosis,
Tumor morphology (Ductal/NOS, Lobular, Medullary, Tubular, Other, or Unknown),  
Histologic grade (I, II, III, or Unknown), 
BRCA 1/2 status,
Menstrual status, 
Location of metastasis (Brain, Visceral, Nonvisceral)
7.4
MEDICAL HISTORY
A complete review of the subject’s past medical history (including all prior anti-tumoral therapy 
related to breast cancer), past surgeries, and current therapies (medications and non-medications) 
will be undertaken by the Investigator to check that all inclusion and no exclusion criteria have been 
met.
Events that emerge prior to the first treatment (C1D1) will be recorded in the medical history and 
not as AEs. Aside from being used to determine subject eligibility, this information will permit the 
Investigator to record the nature, duration and severity of any ongoing baseline medical conditions 
prior to the subject’s receiving investigational product treatment. 
Medical histories will be recorded using the body system categories outlined below: 
Cardiovascular 
Lymphatic 
Respiratory
Hematologic
Gastrointestinal
Immunologic 
Renal
Dermatologic
Hepatic
Psychiatric
Neurological 
Genitourinary 
Endocrine 
Other
For each relevant history, the following will be documented:  
Disease/disorder/condition

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Date of diagnosis 
History status (resolved or ongoing). 
7.5
CONCOMITANT MEDICATION
The subject may be applied any medications judged necessary by the Investigator, provided such 
medications are not listed in Section 7.5.2.
All concomitant medication administered or taken by the subject beginning 30 days prior to 
Screening Visit and throughout the study will be recorded in the source documents and on the 
appropriate page of the Case Report Form (CRF) including all prescription, over-the-counter 
(OTC), herbal supplements, and IV medications and fluids. If changes occur during the trial period, 
documentation of drug dosage, frequency, route, and date may also be included on the CRF. 
Subjects must be questioned at each study visit concerning any new medications or changes in 
current medications including over-the-counter medication and topical medication.
For each medication and non-study treatment, the following will be documented: 
Medication/treatment name (generic name may be used if trade name is unknown)
Dose, unit, and frequency of dosing (individual dosages, not total daily dose).  
Note: Each new dose of medication should be recorded as a separate entry, with the 
exception of medications that are given on a sliding scale. For these, it is acceptable to enter 
the range of the dosage, including the start and stop dates for which the specified dosage 
range was used.
Route of dosing 
Indication for use
The start date 
The stop date (if medication/therapy is not ongoing).  
7.5.1. Permitted Medications
All treatments that the investigator considers necessary for a subject’s welfare may be administered 
at the discretion of the investigator in keeping with the community standards of medical care. 
Patients will be permitted to receive granulocyte-colony stimulating factor (G-CSF) therapy as part 
of support medication for carboplatin.   
7.5.2. Prohibited Medications
Subjects are prohibited from receiving the following therapies during the Screening and Treatment 
Period of this trial:

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Anti-cancer systemic chemotherapy or biological therapy not specified in this protocol
Investigational agents other than leronlimab (PRO 140) 
Radiation therapy
7.6
VITAL SIGNS, HEIGHT AND WEIGHT
The following will be collected: 
Vital signs:
o
Seated blood pressure (taken after the subject has been seated for at least 5 minutes)
o
Pulse
o
Temperature (oral or tympanic)
o
Respiratory Rate
Height (at Screening Visit only) and Weight 
BMI (derived from the height and weight measurements). 
7.7
PHYSICAL EXAMINATION
The physical examination will include routine examinations for the following:
Head, Ears, Eyes, Nose, Throat (HEENT) 
Abnormalities of the extremities
Neurologic abnormalities
Heart/cardiovascular abnormalities
Musculoskeletal abnormalities
Dermatologic abnormalities
Any other body system for which an abnormality is noted and which, in the opinion of the 
Investigator, is relevant to the safety of the subject or could impact safety or efficacy results 
for the subject; i.e., the abnormality is clinically significant. 
Each abnormality will be recorded and the Investigator will record an assessment of its clinical 
significance. 

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refer to Table 6-3 and Table 6-4 for the dose modification and management of leronlimab (PRO 
140) and carboplatin for any toxicity.  
All subjects will be followed for adverse events for 30 days after last dose of leronlimab (PRO 140)
and carboplatin, or until the subject starts a new treatment, whichever occurs first.
Subjects who discontinue treatment for unacceptable adverse event(s) will be followed until 
resolution or stabilization of the adverse event (i.e. the grade is not changing). If a subject stops 
treatment due to unacceptable adverse event(s) but has not demonstrated disease progression, then 
the subject will be followed with imaging studies every 9 weeks until the time of progression 
radiographically according to RECIST v1.1 criteria.  
7.11 CLINICAL LABORATORY ASSESSMENTS
Blood samples will be collected for analysis of the following parameters:
Biochemistry and Complete Blood Count (CBC) Parameters: At Screening and Day 1 of 
each treatment cycle and at the end of treatment (EOT).
Serum pregnancy test (for female subjects of childbearing potential): At Screening
Urine pregnancy test (for female subjects of childbearing potential): At Day 1 of each 
treatment cycle
CTCs PD-L1/CCR5 Analysis: At Day 1 of each treatment cycle and at the end of treatment 
(EOT).
CTC and CAMLs Analysis: At Day 1 of each treatment cycle and at the end of treatment 
(EOT).
All laboratory reports will be reviewed by the Investigator. Abnormal results that are considered by 
the Investigator to be clinically significant, will be recorded as adverse events. If in the 
Investigator’s judgment, in order to make the determination of clinical significance the testing may 
be needed to be repeated. Validated, quality-controlled laboratory data will be transferred to the 
main database for analyses.

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7.11.1.3 Assay Methodology 
CTCs Enumeration and PD-L1
CTC isolation and enumeration will be performed using the US Food and Drug Administration-
approved CellSearch™ technology (Janssen Diagnostics). This technology consists of a semi-
automated system for the preparation of a sample [Al-Kateb, 2015] and is used with the 
CellSearch™ Epithelial Cell Kit. The procedure enriches the sample for cells expressing the 
epithelial-cell adhesion molecule with antibody- coated magnetic beads, and labels the cells with 
the fluorescent nucleic acid dye 4,2-diamidino-2- phenylindole dihydrochloride (DAPI). 
Fluorescently labeled monoclonal antibodies specific for leukocytes (CD45-allophycocyan) and 
epithelial cells (cytokeratin 8, 18, 19-phycoerythrin) are used to distinguish epithelial cells from 
leukocytes. A PD-L1 expression kit has been developed and is currently tested in clinical trial 
evaluating PD-L1 or PD-1 therapeutic targeting antibodies. 
CTCs and CAMLs using CellSieve™
The CellSieve Microfiltration assay isolates CTCs and CAMLs by size exclusion, identifying CTCs 
or CAMLs by their morphological features and the phenotypic expression of CD14, cytokeratins 8, 
18, and 19, CD45 and DAPI. The low-pressure vacuum system uses a specialized, holder attached 
to a syringe pump, to provide steady state flow of samples. Peripheral blood (7.5 mL) collected in 
CellSave preservative tubes is prefixed for 15 min, placed into the 30-mL syringe, and drawn 
through the filter in 3 min. The filter is then washed, postfixed, and permeabilized for 15 min. 
The filter and cells are stained with an antibody mixture and blocking buffer of FITC-conjugated 
anti-cytokeratin 8, 18, 19, phycoerythrin (PE)-conjugated CD14, and Cy5-conjugated CD45 
(Creatv MicroTech, Inc.).
CTCs are CD45/CD14 negative cells with a pleomorphic nucleus and a filamentous cytokeratin 
positive phenotype. CAMLs are morphologically identified as single cells with an enlarged nuclear 
profile (14–
iameter) or separated polymorphic nuclei contained within the cell. In 
addition, the nuclei had to be surrounded by a larger CD14 signal (21–
can be identified further by vacuoles containing DAPI+ and/or cytokeratin. 
7.12 STUDY TREATMENT APPLICATION
Refer to Section 6.1 and 6.2 for details.
7.13 POST-INJECTION EVALUATION AND INJECTION SITE REACTION ASSESSMENT
At each treatment visit, an injection site reaction assessment will be made for the current and 
previous injection sites. Injection site reaction assessments are recorded by the Investigator starting 
after the first injection is given. Subject will be observed at approximately 30 minutes post-injection 

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or longer if necessary for injection site reaction as per CTCAE v5.0. Refer to Sections 9.2.6 for 
more details.
7.14 PAIN ASSESSMENT USING VISUAL ANALOG SCALE (VAS)
Tolerability of repeated subcutaneous administration of leronlimab (PRO 140) is evaluated based 
on assessment of subject-perceived injection site pain using the Pain Visual Analog Scale (VAS). 
This assessment will be performed each time subjects arrive to the clinic for the study treatment 
visit.
Before and immediately after each study treatment administration, subjects will be asked to mark 
the point that best represents the pain intensity over the past week at the time of injection 
administration on a horizontal line (100 mm in length) anchored by the following word descriptors 
at each end, “no pain" on the left side and "pain as bad as it could possibly be" on the right side of 
the line. The subject marks on the line or by pointing to a position on the line the point that they 
feel represents their perception of their pain state. The VAS score is determined by measuring in 
millimeters from the left-hand end of the line to the point that the patient marks. 
Figure 7-1: 
Visual Analog Scale 
7.15 TUMOR IMAGING AND RESPONSE EVALUATION
For the purposes of this study, patients should be re-evaluated for response every 6 weeks for the 
first 13 months of treatment, and every 9 weeks thereafter. In addition to a baseline scan, 
confirmatory scans should also be obtained 6 weeks following initial documentation of objective 
response greater than Stable Disease (SD).
Response and progression will be evaluated in this study using the new international criteria 
proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 
1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the 
shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
High resolution CT with oral/intravenous contrast or contrast-enhanced MRI is the preferred 
imaging modalities for assessing radiographic tumor response. If a subject has a known allergy to 

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contrast material, please use local prophylaxis standards to obtain the assessment with contrast if at 
all possible, or use the alternate modality. In cases where contrast is strictly contraindicated, a non-
contrast scan will suffice. Screening assessments should be performed within 28 days of 
registration. Brain MRI is the preferred imaging method for evaluating CNS metastasis, and 
assessment is required during screening in all eligible subjects. All known or suspected sites of 
disease (including CNS if history of CNS metastases) should be assessed at screening and at 
subsequent assessments using the same imaging method and technique. If more than one method is 
used at screening, then the most accurate method according to RECIST v1.1 should be used when 
recording data, and should again be used for all subsequent assessments. Previously treated CNS
metastases are not considered measurable lesions for purposes of RECIST determined response. 
Subjects with a history of brain metastasis should have surveillance MRI approximately every 12 
weeks, or sooner if clinically indicated.
Radiographic tumor assessments will be conducted at the end of 2 cycles (i.e., every 6 weeks) for 
the first 6 cycles (18 weeks) and at end of 3 cycles (i.e., every 9 weeks) thereafter, and at End of 
Treatment (EOT) visit by CT or MRI (per treating investigator’s discretion); the same modality 
used at baseline should be used throughout. Tumor measurements will be done using RECIST v1.1. 
Tumor assessments for all subjects should continue as per protocol even if dosing is interrupted. 
Tumor measurements should be made by the same investigator or radiologist for each assessment 
whenever possible. Changes in tumor measurements and tumor responses to guide ongoing study 
treatment decisions will be assessed by the investigator using RECIST.
7.15.1. Definition of Lesions
Tumor response will be assessed according to the RECIST (version 1.1; Eisenhauer et al. 2009). 
At baseline, tumor lesions/lymph nodes will be categorized measurable or non-measurable as 
follows:
Measurable disease
Measurable lesions are defined as those that can be accurately measured in at least one dimension 
-
CT scan, MRI, or calipers by clinical exam (such measurements must be clearly documented). All 
tumor measurements must be recorded in millimeters (or decimal fractions of centimeters).
Malignant lymph nodes:
axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm). 
At baseline and in follow-up, only the short axis will be measured and followed. 

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Non-measurable disease
All other lesions (or sites of disease), including small lesions (longest diameter < 10mm or 
5mm short axis) as well as truly non-measurable lesions. 
Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis 
cutis/pulmonitis, inflammatory breast disease, and abdominal masses (not followed by CT or MRI), 
are considered as non-measurable.
Special considerations regarding lesion measurability
Bone lesions, cystic lesions, and lesions previously treated with local therapy require particular 
comment:
Bone lesions:
Bone scan, PET scan or plain films are not considered adequate imaging techniques to measure 
bone lesions. However, these techniques can be used to confirm the presence or disappearance 
of bone lesions. 
Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that
can be evaluated by cross sectional imaging techniques such as CT or MRI can be considered 
as measurable lesions if the soft tissue component meets the definition of measurability 
described above.
Blastic bone lesions are non-measurable.
Cystic lesions:
Lesions that meet the criteria for radiographically defined simple cysts should not be considered 
as malignant lesions (neither measurable nor non-measurable) since they are, by definition, 
simple cysts.
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable lesions, 
if they meet the definition of measurability described above. However, if noncystic lesions are 
present in the same patient, these are preferred for selection as target lesions.
Lesions with prior local treatment:
Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-
regional therapy, are usually not considered measurable unless there has been demonstrated 
progression in the lesion. Study protocols should detail the conditions under which such lesions 
would be considered measurable. 
7.15.2. Method of Assessment

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The same method of assessment and the same technique have to be used to characterize each 
identified and reported lesion at screening, at end of treatment and during follow-up. 
Clinically detected lesions will only be considered measurable when they are superficial (e.g., skin 
nodules and palpable lymph nodes). 
Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined and 
surrounded by aerated lung. However, CT is preferable. 
Conventional CT and MRI should be performed with contiguous cuts of 5 mm or less in slice 
slice thickness, if the slice thickness is > 5 mm].
Ultrasound may only be used as a possible alternative to clinical measurements for superficial 
palpable lymph nodes, subcutaneous lesions, and thyroid nodules. 
7.15.3. Baseline documentation of ‘target’ and ‘non-target’ lesions
Only subjects with measurable disease at baseline should be enrolled in this study. For evaluation 
of tumor response, lesions present at screening will be separated into target and non-target lesions 
according to the following criteria:
Target Lesions: 
All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, 
representative of all involved organs, should be identified as target lesions and recorded and 
measured at baseline. 
Target lesions should be selected on the basis of their size (lesions with the longest diameter), 
be representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on occasion, the largest lesion 
does not lend itself to reproducible measurement in which circumstance the next largest lesion 
which can be measured reproducibly should be selected.
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. This is the “sum of 
the longest diameters” (SLD). If lymph nodes are to be included in the sum, then only the short 
axis is added into the sum. The baseline sum diameters will be used as reference to further 
characterize any objective tumor regression in the measurable dimension of the disease.
Non-Target Lesions 
All other lesions (or sites of disease) including any measurable lesions over and above the 5 
target lesions should be identified as non-target lesions and should also be recorded at baseline. 

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when no lesions can be measured is not advised for CR until the first date that progressive disease 
is objectively documented. 
Duration of stable disease: Stable disease is measured from the start of the treatment until the 
criteria for progression are met, taking as reference the smallest measurements recorded since the 
treatment started, including the baseline measurements. 
7.16 SURVIVAL STATUS
Subjects will be followed up by clinic visits or phone call or another method of contact, for survival 
status every 3 months (±1 month) for 2 years after treatment discontinuation or until death, 
whichever occurs first. 

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8
STATISTICAL ANALYSIS 
This section presents general information about statistical considerations and concepts and a brief 
discussion on analysis methodology, as well as some data conventions. Detailed descriptions of the 
statistical analysis methods and data conventions that will be used in this study will be in a separate 
document; i.e., the Statistical Analysis Plan (SAP).
8.1
TREATMENT GROUPS
The following treatment groups will be assessed in the dose-finding portion of the study: 
350 mg leronlimab (PRO 140) + AUC 5 Carboplatin
525 mg leronlimab (PRO 140) + AUC 5 Carboplatin
700 mg leronlimab (PRO 140) + AUC 5 Carboplatin
8.2
SAMPLE SIZE DETERMINATION AND RATIONALE
Up to 18 patients will be enrolled in the Phase Ib portion of the study. A total of 30 subjects will be 
enrolled in the Phase II portion. 
8.3
RANDOMIZATION AND STRATIFICATION
Not applicable. 
8.4
BLINDING
Not applicable.  
8.5
INTERIM ANALYSIS
No interim analysis (IA) will be performed for efficacy. There will be a safety review, once all three 
(or six) subjects from each cohort complete the DLT evaluation period (defined as cycle 1 or the 
first 21 days of treatment).
The Sponsor’s Medical Monitor, CRO Medical Monitor and study investigators must be satisfied 
with data obtained in Cohort A before allowing subsequent enrollment of Cohort B. Likewise, they 
must be satisfied with data obtained in Cohort B before allowing subsequent enrollment in Cohort 
C. 
In addition, should any of the following events occur in any cohort during the DLT evaluation 
period, the Data Safety Monitoring Board (DSMB) will meet to review available study data and 
make a final decision for dose escalation to the next cohort: 

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a.
Death in any subject in which the cause of death is judged to be possibly, probably or 
definitely related to leronlimab (PRO 140) 
b. The occurrence in any subject of an anaphylactic reaction to leronlimab (PRO 140)
c.
The occurrence in any subject of a severe local injection site reaction (Grade 3 which is not 
resolved or recurs; or Grade 4) that precludes administration of consecutive leronlimab 
(PRO 140) doses.
d. The occurrence in any subject of a life-threatening SAE whose causal relationship to 
leronlimab (PRO 140) is judged to be probable or definite 
e.
The occurrence of one or more non-life-threatening SAEs whose causal relationship to 
leronlimab (PRO 140) is judged to be definite
f.
The occurrence, in one or more subjects, of Grade 4 laboratory abnormalities, judged to be 
probably or definitely related to receipt of leronlimab (PRO 140) 
g.
The occurrence of hematologic and non-hematological adverse events, judged to be 
possibly, probably or definitely related to receipt of leronlimab (PRO 140) based on 
previous clinical experience and that are of CTCAE Grade 3 or greater severity. Permissible 
exceptions to this rule include Grade 3 fatigue of less than one week duration, and Grade 3 
nausea, vomiting, and diarrhea that resolve within 48 hours following institution of 
appropriate supportive care.
h. Hy's law 
i.
Neutropenic fever 
j.
Grade 4+ neutropenia or thrombocytopenia >7 days 
k. Grade 3+ thrombocytopenia with bleeding 
l.
Grade 3+ electrolyte abnormality that lasts >72 hours, unless the patient has clinical 
symptoms, in which case all grade 3+ electrolyte abnormality regardless of duration should 
count as a DLT.  Grade 3+ amylase or lipase elevation NOT associated with symptoms or 
clinical manifestations of pancreatitis does not need to be counted as a DLT
m. For patients with hepatic metastases, AST or ALT >8xULN or AST or ALT >5x ULN for 
8.6
GENERAL STATISTICAL CONSIDERATIONS
All collected study data will be presented in subject data listings. Statistical analyses will be 
performed using SAS® for Windows, version 9.3 or later. Descriptive statistics (n, mean, standard 
deviation, median, minimum and maximum) will be presented by treatment group for continuous 

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variables. Frequencies and percentages will be presented by treatment group for categorical 
variables.
8.6.1. Analysis Populations
8.6.1.1
Intent-to-Treat Population
The Intent-to-Treat (ITT) population is defined as the set of subjects who have received at least 
one dose of leronlimab (PRO 140) and have measurable disease at baseline. The ITT population 
will be used as the primary analysis population. 
8.6.1.2
Per Protocol Population
The Per Protocol (PP) population is defined as the set of subjects who meet the ITT population 
requirements, were not associated with any major protocol violations and have received at least 2 
cycles of treatment. This population will be identified before the database lock. 
The PP analysis of primary and secondary endpoints will be considered supportive 
8.6.1.3
Safety Population 
The Safety Population will include all subjects who have received one dose of leronlimab (PRO 
140). This population will be used for the analysis of safety parameters.
8.6.2. Covariates 
For efficacy analyses, the baseline values will be used as covariates in the analysis models. Other 
important prognostic factors will be specified in the SAP for the study.
8.6.3. Missing Data
All data will be used as observed, and no imputations will be made for any missing data point for
early phase study.
8.7
ANALYSIS METHODS
A SAP will be developed and approved before the database is locked. The SAP will present the 
detailed statistical methodology to be used in analyzing the data from this trial.
8.7.1. Subject Disposition
The disposition of all subjects who sign an ICF will be provided. The numbers of subjects screened, 
enrolled, completed, and discontinued during the study, as well as the reasons for all post-
enrollment discontinuations will be listed and/or summarized by treatment group. Disposition and 
reason for study discontinuation will also be provided as a by-subject listing.
8.7.2. Demographic and Baseline Disease Characteristics

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Demographics and baseline disease characteristics including medical history, prior and concomitant 
medications/therapies will be listed and/or summarized by treatment group using appropriate 
descriptive statistics.
8.7.3. Study Analyses 
8.7.3.1
Primary Analysis  
The primary analysis will be conducted on the Intent-to-treat (ITT) population.  
Primary Outcome (Endpoints) Measures: 
Phase Ib
Maximum Tolerated Dose (MTD) by evaluation of dose-limiting toxicities (DLTs) of 
leronlimab (PRO 140) when combined with carboplatin AUC5.  
Note: The MTD is defined as 1 dose level below the dose in which dose limiting toxicities (DLTs) 
33% of the participants during Cycle 1. 
Phase II
Progression free survival (PFS) defined as time in months from the date of first study treatment 
to the date of disease progression or death from any cause, whichever comes first.
Note: All patients who receive at least one dose of leronlimab (PRO 140) and carboplatin 
combination will be included in the primary analyses of PFS. The Response Evaluation Criteria 
in Solid Tumors (RECIST v1.1) criteria will be used for objective tumor response assessment 
(when disease is measurable and non- measurable); 
The time in months from start of treatment to progression or death will be measured for all 
patients who receive at least one dose of study drug. Patients will be followed up to 2 years 
after completion of treatment.
Secondary Outcome (Endpoints) Measures:
Phase Ib
The number, frequency, and severity of adverse events (AEs) collected from the time of 
first treatment until 12 weeks after study treatment completion to evaluate safety of 
leronlimab (PRO 140) and carboplatin in subjects with CCR5+ mTNBC. 
Note: Adverse events will follow National Cancer Institute Common Terminology Criteria 
for Adverse Events (CTCAE) version 5.0
Phase II

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PFS according to RECIST v1.1 in participants with Detectable Programmed Death-Ligand 
1 (PD-L1)
Note: The PD-L1 expression testing will be performed at baseline. Breast tissue (primary 
or metastatic site) collected to analyze for the presence of CCR5 at pre-screening will 
additionally be used for evaluating PD-L1 expression levels.
Overall response rate (ORR, defined as Complete Response (CR) + Partial Response (PR)), 
and clinical benefit rate (CBR, defined as CR + PR + Stable Disease (SD)) in subjects with 
CCR5+ mTNBC treated with leronlimab (PRO 140) and carboplatin. 
Note: Overall response rate defined as the proportion of patients who achieve an overall 
response of complete response or partial response in the total number of evaluable patients, 
assessed by RECIST v1.1. Clinical benefit rate is defined as the proportion of patients who 
achieve an overall response of complete response or partial response or stable disease in 
the total number of evaluable patients, assessed by RECIST v1.1. Imaging scans to be done 
at the end of 2 cycles (i.e., every 6 weeks) for the first 6 cycles (18 weeks) and at the end of 
3 cycles (i.e., every 9 weeks) thereafter.
Time to new metastases (TTNM);
Note: Recorded time from baseline metastatic disease (at time of enrollment) to the time of 
development of new metastasis in different site. New metastases in same site will be also 
recorded.
The change from baseline in circulating tumor cells (CTC) level in the peripheral blood. 
Note: Reported unit of measure will be the number of CTCs/milliliter. CTCs enumeration will 
be performed at baseline and at the time of response assessment. Fraction of baseline positive and 
Overall survival defined as time in months from the date of first study treatment to the date 
of death; 
Note: Patients will be followed from the start of treatment until 2 years post-treatment or 
death, whichever occurs first, and average survival time will be measured.
The number, frequency, and severity of AEs collected from the time of first treatment until 
12 weeks after study treatment completion to evaluate safety of leronlimab (PRO 140) and 
Carboplatin in subjects with CCR5+ mTNBC. 
Exploratory Outcome (Endpoints) Measures:
Measure immune biomarkers (PD-L1) in CTCs, metastatic tissue and immune cells such as
CAMLs and correlate with therapeutic benefit (PFS); and

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Correlation between CCR5 expression (CTCs, CAMLs) and PD- L1 expression. 
PFS will be calculated using Kaplan-Meier curves and the median PFS will be read from this curve. 
Response rates (overall response rate, clinical benefit rate) will be calculated using proportions and 
95% confidence intervals. Time to new metastases and overall survival will also be analyzed using 
Kaplan-Meier curves. Exploratory serial blood markers will be related to PFS using Cox regression, 
and to response using logistic regression. 
8.7.3.2
Safety Analyses  
Safety will be assessed by close monitoring and timely assessment of adverse events (AEs), 
laboratory parameters (blood tests, urinalysis), vital signs (blood pressure, heart rate), subject’s 
medical condition (physical examination including weight), general well-being and activities of 
daily life (Eastern Cooperative Oncology Group (ECOG) performance status). Each subject will be 
regularly assessed in each cycle for potential AEs and disease related signs and symptoms. The 
CTCAE v5.0 will be used to grade toxicities / AEs.
The Safety population will be used for the analysis of safety endpoints.  
Descriptive statistics (n, mean, standard deviation, median, minimum, and maximum) will be 
calculated for continuous variables. Frequencies and percentages will be presented for categorical 
variables.  
Adverse Events:
Adverse events will be coded using the most recent version of Medical Dictionary for Regulatory 
Activities (MedDRA). Treatment Emergent AE’s (TEAE) are defined as events with an onset on 
or after the first treatment. TEAEs will be summarized by study phase, treatment group, System 
Organ Class, and preferred term. The following TEAE summaries will be provided: 
Overall (i.e., regardless of severity or relationship to treatment)
By severity grade (mild, moderate, severe, or life threatening for SAEs)
By relationship to clinical trial treatment according to the mapping scheme below:
o
Potentially related: will include all adverse events with a relationship rating of 
“definitely”, “probably” or “possibly”.  
o
Unlikely/not related: will include all adverse events with a relationship rating of 
“unlikely” or “unrelated”. 
In addition, separate summaries of serious adverse events, and adverse events resulting in 
discontinuation of study treatment will be presented. 
Clinical Laboratory Data 

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All laboratory values will be listed. Laboratory measurements will also be summarized as 
continuous variable and presented by treatment group and time point.  
Physical Examination 
All physical examination findings will be listed and/or summarized. 
Vital Signs
All vital sign findings will be listed and summarized. 
Electrocardiograms (ECGs)
All ECG findings will be listed and summarized. 
Eastern Cooperative Oncology Group (ECOG) performance status
All ECOG performance status findings will be listed and summarized. 

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9
ADVERSE EVENTS (DEFINITIONS AND REPORTING)
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE, as provided in this protocol. During the study when there is a safety 
evaluation, the Investigator or site staff will be responsible for detecting, documenting and reporting 
AEs and SAEs as detailed in this Section of the protocol.  
9.1
ADVERSE EVENT (AE)
An adverse event (AE) is defined as any unfavorable or unintended sign, symptom, or disease that 
occurs or is reported by the subject to have occurred, or a worsening of a pre-existing condition. 
An adverse event may or may not be related to the study treatment.  
AEs will be elicited through direct questioning and subject reports. Any abnormalities in visit 
evaluations, physical examination findings or laboratory results that the investigator believes are 
clinically significant to the research subject and that occurred after initiation of the first study 
treatment will be reported as AEs. Abnormal findings that are NOT clinically significant should be 
not be recorded as an AE  
9.2
REPORTING AND FOLLOW-UP OF ADVERSE EVENTS
Report initiation for all AEs and serious adverse events (SAEs), (see Section 9.3), will begin at the 
time of the first treatment and continue up to the final study visit. All events will be followed to 
resolution or until 30 days after the subject completes the study. A final assessment of outcome will 
be made at that time.
All AEs must be recorded in the subject’s medical records and on the CRF. AEs will be reported 
using customary medical terminology along with the following information: the onset and end 
dates, whether the event is considered to be a SAE (see Section 9.3), the impact the event had on 
study treatment (see Section 9.2.1), the CTCAE grade (intensity) of the event (see Section 9.2.2), 
the causality of the event (see Section 9.2.3), whether treatment was given as a result of the event 
(see Section 9.2.4), and the outcome of the event (see Section 9.2.5).
9.2.1. Impact on Study Treatment
The impact the event had on the study treatment will be assessed as either: none, study treatment 
interrupted, study treatment discontinued, or not applicable. The “not applicable” assessment will 
be used only when the subject is no longer in the treatment period of the protocol or died.
9.2.2. CTCAE Grade (Intensity) Assessment
The guidelines outlined in CTCAE v5.0 will be used for assessing the intensity of the event. The 
general guidelines for assessing the AE grade appear below. Full guidelines may be obtained at 

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5. Definitely – The event follows a reasonable temporal sequence from the study biologic or 
control, abates upon discontinuation and cannot be explained by known characteristics of 
the patient’s clinical state.
9.2.4. Treatment Given as a Result of the Event
The event impact in terms of treatment provided will be as either: none, medication administered, 
non-drug therapy administered, surgery performed, hospitalization, or other (with a specification).
9.2.5. Outcome Assessment
The outcome of the event will be assessed as either: resolved, resolved with sequelae, ongoing, or 
death. Only one AE per subject is allowed to have an outcome assessment as “death.” If there are 
multiple causes of death for a given subject, only the primary cause of death will have an outcome 
of death.  
9.2.6. Injection-site reactions
Injection-site reactions thought to be directly related to the injection are considered to be AEs of 
special interest, and will be assessed as per CTCAE v5.0. 
For subjects who develop Grade 1 or Grade 2 events, therapy will be continued as per protocol. If 
a subject chooses to discontinue study treatment, the site should notify the protocol team leadership, 
and encourage the subject to complete any remaining study visits until the toxicity resolves. 
For subjects who develop Grade 3 events following study drug injection, the subject should be 
reevaluated closely until the AE returns to Grade 1 or less, at which time study treatment may be 
reintroduced at the discretion of the site investigator. If the same Grade 3 AE recurs following the 
next administration of study drug, study treatment must be permanently discontinued. Subjects 
experiencing Grade 3 AEs requiring permanent discontinuation of study treatment should be 
followed closely for resolution of the AE to Grade 1 or less and the team leadership must be notified.
For Grade 4 events permanently discontinue therapy.  
9.3
SERIOUS ADVERSE EVENTS
A SAE is defined as any AE that:
Results in death
Is life threatening (the subject is at immediate risk of dying from the adverse experience)
Requires subject hospitalization or prolongs existing hospitalization
Results in persistent or significant disability/incapacity 
Is a congenital anomaly/birth defect

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Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse device effect when, based upon appropriate 
medical judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition
9.4
REPORTING OF SERIOUS ADVERSE EVENTS
The Investigator is required to report all SAEs that occur during the time period specified in 
Section 9.2. Once the Investigator becomes aware of an SAE, he/she must report the SAE to 
Amarex Safety and Pharmacovigilance Department within 24 hours: 
CRO Medical Monitor
A written SAE reports must include a full description of the event as described in Section 9.2 and 
must follow within 24 hours from the time the Investigator first learned of the event. The Amarex 
Medical Monitor may request additional supporting documentation as it becomes available, such 
as lab reports, electrocardiogram [ECG] reports, discharge summary, hospital notes, etc, if 
applicable.  
The Investigator is also responsible for reporting all SAEs to the appropriate Institutional Review 
Board (IRB) in accordance with local laws and regulations. The Investigator is responsible for 
maintaining documentation in the study file that indicates the IRB has been properly notified.  
9.5
SAE FOLLOW-UP
All subjects experiencing an SAE, including the discontinued subjects, must be closely followed 
until sufficient information is obtained to indicate a return to normal status or until the event 
stabilizes at a level acceptable to the investigator (i.e., recovery, return to baseline status, no further 
improvement expected, or death).
For each SAE indicated as an unresolved event on the initial report, regardless of whether the 
subject completed the study or withdrew, the site should submit a follow-up report with updated 
information. 

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10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION
Subjects will be identified on eCRFs by a unique subject identification number and on source 
documents by name and date of birth. No personal identifier will be used in any publication or 
communication used to support this research study. The subject identification number will be used 
if it becomes necessary to identify data specific to a single subject. 
The local IRB, FDA, the monitors, auditors and personnel authorized by the Sponsor are eligible to 
review the medical and research records related to this study as part of their responsibility to protect 
human subjects in clinical research. They will be given direct access to source data and 
documentation (e.g., medical charts/records, printouts etc.) for source data verification, provided 
that subject confidentiality is maintained in accordance with local requirements. Access to 
electronic medical records may be governed by institution policy and each site will be required to 
ensure access while remaining compliant with institutional requirements.

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11 QUALITY CONTROL AND QUALITY ASSURANCE
11.1 MONITORING REQUIREMENTS
The specific obligations outlined in 21 Code of Federal Regulations (CFR) and ICH guidelines 
require the Sponsor to maintain current personal knowledge of the progress of a study. Therefore,
the Sponsor's designated monitor will visit the site during the study as well as maintain frequent 
telephone and written communication. The Investigator will permit the Sponsor to monitor the 
study as frequently as is deemed necessary and provide access to medical records to ensure that 
data are being recorded adequately, that data are verifiable and that protocol adherence is 
satisfactory. 
As delineated above, the Investigator will permit representatives of the Sponsor and/or designated 
CRO to inspect all CRFs and corresponding study subject original medical records (source 
documents) at regular intervals throughout the study. Subject original medical records and other 
relevant data must be available to support all data recorded in the eCRF. In addition to the original 
medical records, these data may include but are not limited to study, laboratory reports, etc.  
In accordance with federal regulations, site inspections will serve to verify strict adherence to the 
protocol and the accuracy of the data that is being entered on the case report forms. A Monitoring 
Log will be maintained at each study site. The Monitoring Log will be signed by the monitor, dated 
and stated the type of visit. The Investigator should be aware that the study site and subject records
may be inspected by the Sponsor and or representatives of the designated CRO, FDA or other 
regional regulatory authority.
11.2 ACCEPTABILITY OF CASE REPORT FORMS (CRFS) 
For each subject who has signed an informed consent form, a CRF must be completed. For subjects 
who are screen failures, this would be limited to the screen failure CRF page. All source documents 
and CRFs will be completed as soon as possible after the subject's visit and corrections to data on 
the CRFs will be documented, if applicable. The Investigator will review the CRFs to indicate that, 
to his/her knowledge, they are complete and accurate. CRFs will be reviewed by the Sponsor’s or 
designated CRO’s monitor, who will make a decision as to their acceptability.
11.3 MODIFICATION OF PROTOCOL
The Investigator will not modify or alter this protocol without first obtaining the concurrence of the 
Sponsor. Approval by the Investigator’s IRB must also be obtained prior to implementation of the 
change, with two exceptions: 
1. When necessary to eliminate apparent immediate hazard to the subject; or

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2. When the modification does not involve the subject’s participation in the trial. 
An amendment may also require modification of the informed consent form. The Investigator will 
provide an approval letter for the amendment and revised informed consent form, if applicable, to 
the Sponsor. An amendment must be provided in writing and it must be dated by both the Sponsor 
and the Investigator. If necessary, the Sponsor will submit protocol amendments to FDA and other 
appropriate regulatory authorities and notify other Investigators using this protocol.
11.4 REPORTING PROTOCOL DEVIATIONS
The Investigator is obligated to follow the protocol without departure from the requirements written 
in the protocol. If the Investigator deviates from the protocol requirements, the Sponsor will make 
the determination as to whether the subject will continue in the study. The Sponsor also has the 
right to discontinue the subject for protocol violations. The IRB may also have to be contacted if 
safety to the subject or if the scientific soundness of the study is involved. All protocol deviations 
must be documented in the CRFs. 
11.4.1. Major Protocol Deviation or Violation 
A major protocol deviation or violation is a deviation from the IRB approved protocol that may 
affect the subject's rights, safety, or well being and/or the completeness, accuracy and reliability of 
the study data. Examples of this include:
Failure to obtain informed consent prior to initiation of study-related procedures 
A research subject does not meet the protocol's eligibility criteria but was enrolled without 
prior approval from the sponsor.
A research subject received the wrong treatment or incorrect dose.
A research subject met withdrawal criteria during the study but was not withdrawn. 
A research subject received a prohibited concomitant medication.
Failure to treat research subjects per protocol procedures that specifically relate to primary 
efficacy outcomes.
Changing the protocol without prior sponsor and IRB approval. 
Multiple minor violations of the same nature after multiple warnings.
11.4.2.  Minor Protocol Deviation or Violation 
A minor protocol deviation is any change, divergence, or departure from the study design or 
procedures of a research protocol that has not been approved by the IRB and which DOES NOT 

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have a major impact on the subject's rights, safety or well-being, or the completeness, accuracy and 
reliability of the study data. Examples of this include: 
Follow-up visits that occurred outside the protocol required time frame because of the 
participant’s schedule.
Blood samples obtained at times close to but not precisely at the time points specified in the 
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12 DATA SAFETY MONITORING BOARD (DSMB) 
The study will be monitored by an independent DSMB to ensure patient safety. The CRO is
responsible for the overall management of DSMB, including development of its charter and
membership selection. The DSMB will be managed in conformance with the FDA guidelines
for DSMB independence, management, and oversight.
The DSMB will consist of at least three members and will review unexpected AEs, related AEs, 
SAEs, and deaths, according to the study’s phase and risk level, as outlined in the DSMB charter.
If any of the SAEs or dose limiting toxicities outlined below occurs, the DSMB will conduct an 
independent review of the data and will make a final decision for dose escalation to the next 
cohort: 
a.
Death in any subject in which the cause of death is judged to be possibly, probably or 
definitely related to leronlimab (PRO 140) 
b. The occurrence in any subject of an anaphylactic reaction to leronlimab (PRO 140)
c.
The occurrence in any subject of a severe local injection site reaction (Grade 3 if not 
resolved or recurs or Grade 4) that preclude administration of consecutive leronlimab (PRO 
140) doses.
d. The occurrence in any subject of a life-threatening SAE whose causal relationship to 
leronlimab (PRO 140) is judged to be probable or definite 
e.
The occurrence of one or more non-life-threatening SAEs whose causal relationship to 
leronlimab (PRO 140)is judged to be definite 
f.
The occurrence, in one or more subjects, of Grade 4 laboratory abnormalities, judged to be 
probably or definitely related to receipt of leronlimab (PRO 140) 
g.
The occurrence of hematologic and non-hematological adverse events, judged to be 
possibly, probably or definitely related to receipt of leronlimab (PRO 140) based on 
previous clinical experience and that are of CTCAE Grade 3 or greater severity. Permissible 
exceptions to this rule include Grade 3 fatigue of less than one week duration, and Grade 3 
nausea, vomiting, and diarrhea that resolve within 48 hours following institution of 
appropriate supportive care.
h. Hy's law 
i.
Neutropenic fever 
j.
Grade 4+ neutropenia or thrombocytopenia >7 days 
k. Grade 3+ thrombocytopenia with bleeding 

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l.
Grade 3+ electrolyte abnormality that lasts >72 hours, unless the patient has clinical 
symptoms, in which case all grade 3+ electrolyte abnormality regardless of duration should 
count as a DLT.  Grade 3+ amylase or lipase elevation NOT associated with symptoms or 
clinical manifestations of pancreatitis does not need to be counted as a DLT
m. For patients with hepatic metastases, AST or ALT >8xULN or AST or ALT >5x ULN for 
All expedited safety reports will be provided in real time to the DSMB chair upon being reported 
to FDA.
Note: For the purpose of expedited safety reporting, all adverse events except skin reactions will 
be considered unexpected. 
The DSMB will make the following recommendations at each safety evaluation:
Continue the study as planned; 
Assess a specific aspect of safety that is not conclusive; 
Gather more data to address a specific safety issue; and
Stop the study due to safety concerns. 
The Sponsor retains the responsibility to contact FDA and the final decision regarding the
recommendation to continue or to terminate the study.

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13 ETHICS AND REGULATORY REQUIREMENTS
This study is to be conducted in accordance with the specifications of this protocol and in 
accordance with principles consistent with Declaration of Helsinki, GCP, 21 CFR, ICH E6, HIPAA 
regulations in 45 CFR Part 164 (US only), and the Belmont Principles of respect for persons, 
beneficence, and justice. No protocol changes will be implemented without the prior review and 
approval of the IRB, except when the modification does not involve the subject’s participation in 
the trial or where it may be necessary to eliminate an immediate hazard to a research subject. In the 
latter case, the change will be reported to the IRB as soon as possible, according to IRB regulations. 
Additionally, the study product used in this study is manufactured, handled and stored in accordance 
with applicable GMP. The study product provided for this study will be used only in accordance 
with this protocol.
13.1 INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC)
The Principal Investigator (PI) at the site will provide the Institutional Review Board/Independent 
Ethics Committee (IRB/IEC) with all appropriate materials as required by their IRB/IEC, including 
but not limited to the clinical study protocol, informed consent form, and any advertising materials. 
The study will not be initiated until the IRB/IEC provides written approval of the aforementioned 
documents and until approval documents have been obtained by the Principal Investigator and 
Sponsor or Sponsor designee. The Investigator will not participate in the decision. If the 
Investigator is an IRB or IEC member, documentation must be provided indicating recusal from 
the approval process. Appropriate reports on the progress of this study by the Principal Investigator 
will be made to the IRB/IEC as required by local and applicable government regulations and in 
agreement with policy established by the Sponsor. The Investigator is required to maintain an 
accurate and complete record of all written correspondence to and received from the IRB/IEC, and 
must agree to share all such documents and reports with the Sponsor. 
No changes from the final approved protocol will be initiated without the IRB/IEC’s prior written 
approval or favorable opinion of a written amendment, except when necessary to eliminate 
immediate hazards to the subjects or when the modification does not involve the subject’s 
participation in the trial.  
13.2 INVESTIGATOR’S RESPONSIBILITIES
The Investigators are responsible for performing the study in full accordance with the protocol and 
the current revision of the Declaration of Helsinki, the Good Clinical Practice: Consolidated 
Guideline, approved by the ICH, and any applicable national and local laws and regulations. 

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Information regarding to the study center participating in this study that cannot comply with these
standards will be documented.
13.3 SUBJECT INFORMED CONSENT REQUIREMENTS
All subjects participating in this study will be given to by the Investigator and/or designee, written 
and oral information about the study in a language understandable by the subject. Written informed 
consent will be obtained from each subject prior any procedures or assessments that would not 
otherwise be required for the care of the subject are done and after the aims, methods, anticipated 
benefits, potential hazards, and insurance arrangements in force are explained and the subject has 
been given sufficient time to ask questions and consider participation in the study. It will also be 
explained to the subjects that they are free to refuse entry into the study and free to withdraw from 
the study at any time without prejudice to future treatment. It is permissible for a third person (e.g., 
a family member) to be present during the explanation of the study. 
The written Informed Consent Form ICF will be in compliance with CFR 21 Part 50.27 and GCP 
guidelines. The Sponsor and/or designated CRO will approve the ICF and all amendments to the 
ICF prior to submission to the IRB/IEC. A copy of the ICF to be used will be submitted by the 
Investigator to the IRB/IEC for review and approval prior to the start of the study. The study site 
must provide the Sponsor with an unsigned copy of IRB/IEC-approved ICF along with applicable 
documentation to support this approval. The original signed ICF is retained in the subject's study 
records, and a copy is provided to the subject. A second copy may be filed in the subject’s medical 
record, if allowed by institutional policy.  

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14 DATA HANDLING AND RECORD KEEPING
14.1 RECORDING AND COLLECTION OF DATA
The primary source document for this study will be the subject's medical record. If separate research 
records are maintained by the Investigator(s), the medical record and the research records will be 
considered the source documents for the purposes of auditing the study.  
Applicable source data will be manually transcribed to approve case report forms (CRF). The 
Investigator is ultimately responsible for the accuracy of the data transcribed on the forms. All 
source documents and CRFs will be completed as soon as possible after the subject's visit.
The Investigator will review the CRFs to indicate that, to his/her knowledge, they are complete and 
accurate. Designated source documents will be signed and dated by the appropriate study personnel. 
The Investigator must agree to complete and maintain source documents and CRFs for each subject 
participating in the study.
All research data will be entered, either electronically or manually, into a computerized database. 
The clinical database will be designed by the clinical data manager in accordance with 21 CFR Part 
11 and based on protocol requirements defined by the Sponsor in association with the Lead 
Investigator. 
The Investigator will maintain a confidential list of study subjects that will include each subject’s 
study number, name, date of birth, and unique hospital identification number if applicable. This list 
will be kept by the Investigator and will not be collected by the Sponsor. A notation will be made 
in the subject’s case history/medical chart that he/she is participating in a clinical study and has 
provided a signed and dated ICF as well as a release for protected health information as required 
by local policies. The Investigator must also maintain a separate screening log of all the subjects 
screened for participation in the study; it should include gender, age, eligibility status, reason for 
ineligibility, if applicable; and study allocated subject number, if applicable. 
14.2 CLINICAL DATA MANAGEMENT
The Sponsor and/or designated CRO will be responsible for the processing and quality control of 
the data. Data management will be carried out as described in the Sponsor’s or CRO’s standard 
operating procedures (SOPs) for clinical studies. 
The handling of data, including data quality control, will comply with regulatory guidelines 
(e.g., ICH E6 GCP, and local regulations where applicable) and the Sponsor’s or the CRO’s SOPs 
as well as provisions of the study-specific Data Management Plan.

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14.3 ARCHIVING
All study documentation at the Investigator site and Sponsor site will be archived in accordance 
with ICH GCP E6 and the Sponsor’s quality standards and SOPs. 
The Investigator will maintain all research records, reports, and case history reports for a period of 
two (2) years after regulatory approval of the investigational product. If no application is filed or if 
the application is not approved, records must be maintained for two (2) years after all investigations 
have been completed, terminated or discontinued and the FDA has been notified.  
These documents should be retained for a longer period however, if required by the applicable 
regulatory requirements or if needed by Sponsor or its authorized representative (as per 
GCP 5.5.11). 
At the completion of the study, details of the archival process must be provided to the Sponsor. 
Study records are subject to inspection by applicable health and regulatory agencies at any time.  
Records to be retained by the Investigator include, but are not restricted to: 
Source data and the primary records upon which they are based (e.g., subject’s progress 
notes, adverse event data, test results, and any other diagnostic procedures required to 
evaluate the progress of the study) 
Completed CRFs
Signed protocols and protocol amendments 
Laboratory results, ranges, and certifications
IP and accountability records
Study personnel signature log 
Monitoring logs 
Correspondence to and from the Sponsor, designee and IRB 
Investigator and sub-investigator CVs
Signed informed consent and protected health information consent forms 
Subject screening  
SAE reports
IRB approval and re-approval letters
Completed quality of life questionnaire 
Other documents pertaining to the conduct of the study 
These documents must be maintained and kept on file by the Investigator so that the conduct of the 
study can be fully documented and monitored. 

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Study records should not be transferred from site or destroyed without prior written agreement 
between the Sponsor and the study Investigator. Study records are subject to inspection by 
applicable health and regulatory agencies at any time.  

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15 PUBLICATION PLAN
All information supplied by CytoDyn in connection with this study and not previously published, 
is considered confidential information. This information includes, but is not limited to, the 
Investigator’s Brochure, clinical protocol, case report forms and other scientific data. Any data
collected during the study are also considered confidential. This confidential information shall
remain the sole property of CytoDyn, shall not be disclosed to others without the written consent
of CytoDyn, and shall not be used except in the performance of this study.
It is understood by the Investigator that the Sponsor will use the information collected in this clinical 
trial in connection with the development of CytoDyn. Therefore, this information may be disclosed
as required to other Investigators or appropriate regulatory authorities. By agreeing to participate 
in this clinical trial, the Investigator understands that he/she has an obligation to provide the Sponsor 
with complete test results and all data developed during this trial.
Publication and Disclosure: The site and Investigator agree to submit any proposed manuscript, 
presentation or other public disclosure regarding the study to Sponsor for review at least thirty (30) 
days prior to submitting such proposed manuscript to a publisher or delivering or making such 
presentation or other public disclosure to any third party. Within thirty (30) days of its receipt, 
Sponsor shall advise the site and/or Investigator, as the case may be, in writing of any information
contained therein that is confidential information (other than research results included in a proposed 
manuscript) or that may impair Sponsor’s ability to obtain patent protection. Sponsor shall have the 
right to require the site and/or Investigator, as applicable, to remove specifically identified 
confidential information (but may not require removal of research results from a proposed 
manuscript) and/or to delay the proposed submission or delivery of the proposed manuscript or 
presentation, or other public disclosure, for an additional sixty (60) days to enable Sponsor to seek 
patent protection. The site and Investigator shall not publish, publicly disclose, present or discuss 
any results of or information pertaining to the site’s and Investigator’s activities prior to completion 
of the trial, even if the multi-center trial or the study is terminated before its completion and the 
final clinical study report is signed off, or with respect to any endpoints or analyses other than those 
specified in this protocol.

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17 APPENDIX
17.1 APPENDIX 1:  ACCEPTABLE METHODS OF CONTRACEPTION
Barrier Methods
Intrauterine Device Methods
Hormonal Methods
Male condom plus 
spermicide
Cap plus spermicide 
Diaphragm plus 
spermicide
Copper T 
Progesterone T 
Levonorgestrel-releasing
Implants
Hormone shot or 
injection
Combined pill 
Minipill
Patch
NOTE: choice of contraception should be discussed with primary treating oncologist to 
discuss the risks and benefits of different modalities of contraception.

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17.2 APPENDIX 2: RECOMMENDATIONS FOR HER-2 TESTING IN BREAST CANCER
Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: 
American Society of Clinical Oncology/College of American Pathologists clinical practice 
guideline update.
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett 
JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, 
Spears PA, Vance GH, Viale G, Hayes DF; American Society of Clinical Oncology; College of 
American Pathologists.
J Clin Oncol. 2013 Nov 1;31(31):3997-4013. doi: 10.1200/JCO.2013.50.9984. Epub 2013 Oct 7. 
For complete detailed information please refer to the link below: 
http://ascopubs.org/doi/full/10.1200/JCO.2013.50.9984

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17.3 APPENDIX 3: COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS V5.0
For complete detailed information please refer to the link below: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Re
ference_8.5x11.pdf