A Phase 1/2 Trial of X4P-001 as Single Agent and in Combination With Axitinib in Patients With Advanced Renal Cell Carcinoma
Phase: PHASE1
Conditions: Clear Cell Renal Cell Carcinoma
Sponsor: X4 Pharmaceuticals

This study will be conducted according to the protocol and in compliance with 
Good Clinical Practice, the ethical principles stated in the Declaration of Helsinki, 
and other applicable regulatory requirements. 
Study Title: 
A Phase 1/2 Trial of X4P-001 as Single Agent and in 
Combination with Axitinib in Patients with Advanced Renal 
Cell Carcinoma 
Investigational Drug: 
X4P-001 
IND #: 
124194 
ClinicalTrials.gov ID: 
NCT02667886 
Sponsor: 
X4 Pharmaceuticals, Inc. 
955 Massachusetts Avenue, 4th Floor 
Cambridge, MA 02139 
Protocol Number: 
X4P-001-RCCA 
Protocol Version, Date: 
7.0, 08 June 2018 
Replaces Version, Date: 
6.0, 01 Feb 2017 
CONFIDENTIALITY NOTE: 
The information contained in this document is privileged and confidential. Any distribution, copying, or disclosure 
is strictly prohibited unless such disclosure is required by regulations or local law. Persons to whom the 
information is disclosed must know that it is confidential and that it may not be further disclosed by them 

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-RCCA, Version 7.0 (08 June 2018) 
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INVESTIGATOR STATEMENT 
I understand that all documentation provided to me by X4 Pharmaceuticals, Inc. (X4), or its 
designated representative(s) concerning this study that has not been published previously will be 
kept in the strictest confidence. This documentation includes the study protocol, investigator 
brochure, case report forms, and other scientific data. 
This study will not commence without the prior written approval of a properly constituted 
Institutional Review Board/Independent Ethics Committee (IRB/IEC). No changes will be made 
to the study protocol without the prior written approval of X4 and the IRB/IEC, except where 
necessary to eliminate an immediate hazard to the patient. 
Prior to study start, the investigator is required to sign a protocol signature page confirming 
his/her agreement to conduct the study in accordance with all of the instructions and procedures 
found in this protocol and to give access to all relevant data and records to X4 as required. If an 
inspection of the clinical site is requested by a regulatory authority, the investigator must inform 
X4 immediately that this request has been made. 
I have read, understood, and agree to abide by all the conditions and instructions contained in 
this protocol. 
Investigator Signature 
Date 
Printed Name 

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-RCCA, Version 7.0 (08 June 2018) 
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TABLE OF CONTENTS 
INVESTIGATOR STATEMENT .................................................................................................. 2 
TABLE OF CONTENTS ................................................................................................................ 3 
LIST OF TABLES IN THE TEXT ................................................................................................. 7 
LIST OF FIGURES IN THE TEXT ............................................................................................... 8 
LIST OF ABBREVIATIONS ......................................................................................................... 9 
PROTOCOL SYNOPSIS.............................................................................................................. 13 
SCHEMATIC OF THE STUDY DESIGN................................................................................... 26 
1.
KEY ROLES ..................................................................................................................... 27 
2.
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC
RATIONALE .................................................................................................................... 28 
2.1.
Background Information ....................................................................................... 28 
2.2.
Overview of X4P-001 ........................................................................................... 29 
2.2.1.
Prior Clinical Studies Conducted Using X4P-001 ............................... 30 
2.2.2.
Clinical Pharmacology of X4P-001 ..................................................... 32 
2.2.3.
Clinical Safety Experience with X4P-001............................................ 34 
2.2.4.
Treatment Effect of X4P-001 in Prior Clinical Studies ....................... 35 
2.2.5.
Nonclinical Toxicity Studies of X4P-001 ............................................ 35 
2.3.
Clinical Experience with Related Compounds ..................................................... 36 
2.4.
Rationale ............................................................................................................... 36 
3.
OBJECTIVES AND PURPOSE ....................................................................................... 37 
3.1.
Primary Objective ................................................................................................. 37 
3.2.
Secondary Objectives ............................................................................................ 37 
3.3.
Exploratory Objective ........................................................................................... 37 
4.
STUDY DESIGN AND ENDPOINTS ............................................................................. 38 
4.1.
Description of the Study Design ........................................................................... 38 
4.1.1.
Part A (Phase 1): X4P-001 with Axitinib – Dose-escalation Cohorts .. 38 
4.1.2.
Part B (Phase 2): An Expansion Cohort of the RP2D of X4P-001 in 
Combination with Axitinib .................................................................. 42 
4.1.3.
Part C: X4P-001 as a Single Agent (Monotherapy) ............................. 42 
4.2.
Rationale for the Study Design, Including the Choice of Control Groups ........... 43 

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4.2.1. 
Rationale for the Study Design ............................................................ 43 
4.2.2. 
Rationale for the Dose Regimen .......................................................... 43 
4.3. 
Endpoints .............................................................................................................. 44 
4.3.1. 
Safety Endpoints .................................................................................. 44 
4.3.2. 
Efficacy Endpoints ............................................................................... 44 
4.3.3. 
PK and PD Endpoints........................................................................... 45 
4.3.4. 
Exploratory Endpoints ......................................................................... 45 
5. 
STUDY ENROLLMENT AND WITHDRAWAL .......................................................... 45 
5.1. 
Inclusion Criteria .................................................................................................. 45 
5.2. 
Exclusion Criteria ................................................................................................. 46 
5.3. 
Strategies for Recruitment and Retention ............................................................. 48 
5.4. 
Participant Withdrawal or Termination ................................................................ 48 
5.4.1. 
Reasons for Withdrawal or Termination .............................................. 48 
5.4.2. 
Handling of Participant Withdrawals or Termination .......................... 49 
5.5. 
Premature Termination or Suspension of Study ................................................... 49 
6. 
STUDY DRUG(S) ............................................................................................................ 50 
6.1. 
Study Drug(s) and Control Description ................................................................ 50 
6.1.1. 
Acquisition ........................................................................................... 50 
6.1.2. 
Formulation, Appearance, Packaging, and Labeling ........................... 50 
6.1.3. 
Product Storage and Stability ............................................................... 50 
6.1.4. 
Preparation ........................................................................................... 51 
6.1.5. 
Dosing and Administration .................................................................. 51 
6.1.6. 
Route of Administration ....................................................................... 52 
6.1.7. 
Dose Adjustments/Modifications/Delays ............................................ 52 
6.1.8. 
Duration of Therapy ............................................................................. 54 
6.1.9. 
Treatment Compliance ......................................................................... 55 
6.2. 
Study Drug Accountability Procedures ................................................................. 55 
7. 
STUDY PROCEDURES AND SCHEDULE ................................................................... 56 
7.1. 
Study Procedures/Evaluations ............................................................................... 56 
7.1.1. 
Baseline and Safety Assessments......................................................... 56 
7.1.2. 
Pharmacokinetic Assessments ............................................................. 58 
7.1.3. 
Pharmacodynamic Assessments .......................................................... 59 
7.1.4. 
Efficacy Assessments ........................................................................... 60 
7.2. 
Laboratory Procedures/Evaluations ...................................................................... 63 
7.2.1. 
Clinical Laboratory Evaluations ........................................................... 63 
7.2.2. 
Other Assays or Procedures ................................................................. 64 

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7.2.3.
Specimen Preparation, Handling, and Storage..................................... 64 
7.2.4.
Specimen Shipment .............................................................................. 64 
7.3.
Study Schedule ...................................................................................................... 64 
7.4.
Concomitant Medications, Treatments, and Procedures ...................................... 65 
7.4.1.
Precautionary Medications, Treatments, and Procedures .................... 65 
7.4.2.
Prohibited Medications, Treatments, and Procedures .......................... 66 
7.4.3.
Prophylactic Medications, Treatments, and Procedures ...................... 66 
7.4.4.
Rescue Medications, Treatments, and Procedures ............................... 66 
7.4.5.
Precautions Regarding Axitinib ........................................................... 67 
7.4.6.
Patient Restrictions during the Conduct of the Study .......................... 67 
7.5.
Appropriateness of Measurements ........................................................................ 68 
8.
ADVERSE EVENTS ........................................................................................................ 68 
8.1.
Definitions............................................................................................................. 68 
8.1.1.
Adverse Events (AE) ........................................................................... 68 
8.1.2.
Serious Adverse Events (SAE) ............................................................ 69 
8.1.3.
Adverse Drug Reaction ........................................................................ 70 
8.1.4.
Suspected, Unexpected Serious Adverse Reaction (SUSAR) ............. 70 
8.1.5.
Clinical Laboratory Adverse Events .................................................... 70 
8.2.
Classification of Adverse Events .......................................................................... 71 
8.2.1.
Severity ................................................................................................ 71 
8.2.2.
Grading of Laboratory Safety Tests for Reporting and Analysis ......... 71 
8.2.3.
Relationship to Study Drug .................................................................. 71 
8.2.4.
Expectedness ........................................................................................ 72 
8.2.5.
Date and Time of Onset........................................................................ 72 
8.2.6.
Actions Taken for Management of AE ................................................... 73 
8.2.7.
Follow-up and Outcome of AEs .......................................................... 73 
8.2.8.
Date and Time of Outcome .................................................................. 74 
8.3.
Time Period and Frequency for Event Assessment and Follow-Up ..................... 74 
8.4.
Reporting Procedures ............................................................................................ 74 
8.4.1.
Adverse Event Reporting ..................................................................... 74 
8.4.2.
Serious Adverse Event Reporting ........................................................ 75 
8.4.3.
Events of Special Interest ..................................................................... 76 
8.4.4.
Reporting of Pregnancy ........................................................................ 76 
8.5.
Study Halting Rules .............................................................................................. 77 
8.6.
Safety Oversight .................................................................................................... 77 
8.6.1.
Procedures for Monitoring Risks Associated with X4P-001 ............... 77 
8.6.2.
Additional Procedures for Monitoring Patient Safety .......................... 78 

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8.6.3.
Data Review Committee (DRC) .......................................................... 78 
9.
CLINICAL MONITORING ............................................................................................. 79 
9.1.
External Review of the Study Conduct at Participating Sites ............................... 79 
9.2.
Study Monitoring Visits ........................................................................................ 80 
9.2.1.
Site Qualification and Initiation Visits ................................................. 80 
9.2.2.
Interim Monitoring Visits .................................................................... 80 
9.2.3.
Study Closeout Visit ................................................................................. 81 
10.
STATISTICAL CONSIDERATIONS.............................................................................. 82 
10.1.
Statistical and Analytical Plans ............................................................................. 82 
10.2.
Statistical Hypotheses ........................................................................................... 82 
10.3.
Analysis Datasets .................................................................................................. 82 
10.4.
Description of Statistical Methods ........................................................................ 83 
10.4.1.
General Approach ................................................................................ 83 
10.4.2.
Baseline Descriptive Statistics ............................................................. 83 
10.4.3.
Analysis of the Safety Analyses ........................................................... 83 
10.4.4.
Analysis of the Efficacy Endpoint(s) ................................................... 84 
10.4.5.
Planned Interim Analyses .................................................................... 84 
10.4.6.
Multiple Comparison/Multiplicity ....................................................... 84 
10.4.7.
Tabulation of Individual Response Data .............................................. 85 
10.4.8.
Exploratory Analyses ........................................................................... 85 
10.4.9.
Pharmacokinetic Analyses ................................................................... 85 
10.5. 
Sample Size ........................................................................................................... 85 
10.6. 
Measures to Minimize Bias .................................................................................. 86 
10.6.1.
Enrollment/ Randomization/ Masking Procedures .............................. 86 
10.6.2.
Evaluation of Success of Blinding ....................................................... 86 
10.6.3.
Breaking the Study Blind/Participant Code ......................................... 86 
11.
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .......... 87 
11.1.
Medical Records ................................................................................................... 87 
11.2.
Study-Specific Source Documents ....................................................................... 87 
11.3.
Source Documents Requirements ......................................................................... 88 
11.4.
Electronic Case Report Forms (eCRFs) ................................................................ 88 
12.
QUALITY ASSURANCE AND QUALITY CONTROL ................................................ 89 
12.1.
Study Monitoring .................................................................................................. 89 
12.2.
Case Report Form Completion ............................................................................. 89 
12.3.
Computerized Systems / Medical Records as Source Data .................................. 89 

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12.4.
Audits and Inspections .......................................................................................... 89 
12.5.
Resolution of Deficiencies .................................................................................... 90 
13.
ETHICS/PROTECTION OF HUMAN SUBJECTS ........................................................ 90 
13.1.
Ethical Standard .................................................................................................... 90 
13.2.
Institutional Review Board/Independent Ethics Committee ................................. 90 
13.3.
Informed Consent Process .................................................................................... 91 
13.3.1.
Consent/assent and Other Informational Documents Provided to 
Participants ........................................................................................... 91 
13.3.2.
Consent Procedures and Documentation ............................................. 91 
13.4.
Participant and Data Confidentiality..................................................................... 91 
14.
DATA HANDLING AND RECORD KEEPING ............................................................ 92 
14.1.
Data Collection and Management Responsibilities .............................................. 92 
14.2.
Study Records Retention ....................................................................................... 92 
14.3.
Protocol Deviations ............................................................................................... 92 
14.4.
Publication and Data Sharing Policy .................................................................... 92 
15.
STUDY ADMINISTRATION.......................................................................................... 93 
16.
CONFLICT OF INTEREST POLICY ............................................................................. 93 
17.
LITERATURE REFERENCES ........................................................................................ 94 
18.
APPENDICES .................................................................................................................. 97 
18.1. 
Revision History and Sponsor Signature .............................................................. 97 
18.2. 
Potential CYP-Related Drug-Drug Interactions ................................................... 99 
LIST OF TABLES IN THE TEXT 
Table 1-1: 
Schedule of Events ................................................................................................... 23 
Table 1-2: 
Estimated Blood Volumes ........................................................................................ 25 
Table 2-1: 
Prior Clinical Studies Conducted using X4P-001 – Protocol Number, Study Title, 
and Publication1 ........................................................................................................................................................ 31
Table 2-2: 
Prior Clinical Studies Conducted using X4P-001 – Study Population, Objectives, 31 

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Table 6-1: 
Physical and Chemical Properties of Active Ingredient (Drug Substance) .............. 50 
Table 6-2: 
Formulation of Drug Product ................................................................................... 50 
Table 6-3: 
Dose Modification Levels for X4P-001 ................................................................... 53 
Table 7-1: 
ECOG PS Definitions ............................................................................................... 58 
Table 7-2: 
Candidate Blood Biomarkers ................................................................................... 59 
Table 7-3: 
RECIST – Definitions of Response Categories for Target and Non-Target Lesions62 
Table 7-4: 
RECIST – Overall Responses Based on Target Lesions, Nontarget Lesions, and 
New Lesions ............................................................................................................. 62 
Table 7-5: 
Safety Laboratory Tests ............................................................................................ 63 
Table 8-1: 
Reporting the Date and Time of Onset of AE for Different Types of Events .......... 72 
Table 8-2: 
Date and Time of Outcome for AE by Outcome Class ............................................ 74 
Table 8-3: 
Monitoring Procedures for Risks Identified in Prior Studies of X4P-001 
(AMD11070) ............................................................................................................ 77 
Table 10-1: Relationship between Underlying DLT Rate and Probability of Dose Escalation ...85  
Table 18-1:   Protocol Revision History ........................................................................................ 97 
 
 
LIST OF FIGURES IN THE TEXT 
 
Figure 1-1: Overview of Study Design ....................................................................................... 26 
Figure 4-1: Study Design for Part A ........................................................................................... 39 

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LIST OF ABBREVIATIONS 
Abbreviation Explanation 
AE 
Adverse event 
AIDS 
Acquired Immune Deficiency Syndrome 
ALT 
Alanine amino-transferase 
ANC 
Absolute neutrophil count 
AST 
Aspartate transaminase 
AUC 
Area under the concentration-versus-time curve 
BID 
Twice daily 
ccRCC 
clear cell Renal Cell Carcinoma 
CI 
Confidence interval 
Cmax
Maximum concentration 
Cmin[12 hr]
Minimum concentration at 12 hours 
CNS 
Central nervous system 
CR 
Complete response 
CRA 
Clinical Research Associate 
CRO 
Contract research organization 
CS 
Clinically significant 
CT 
Computed tomography 
CV 
Coefficient of variation 
CXCL12 
C-X-C chemokine ligand type 12 (also designated SDF-1)
CXCR4 
C-X-C chemokine receptor type 4
CYP 
Cytochrome P450 
DBP 
Diastolic blood pressure 
DLT 
Dose-limiting toxicity 
DCR 
Disease Control Rate 
DDI 
Drug-drug interaction 
DRC 
Data Review Committee 
EC 
Effective concentration 

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Abbreviation Explanation 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
Emax 
Maximum exposure 
EOS 
End-of-study 
EOT 
End-of-treatment 
FDA 
Food and Drug Administration (U.S.) 
FGFR 
Fibroblast growth factor receptor 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
GMP 
Good Manufacturing Practice 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HIF-α 
hypoxia-inducible factor1 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
iRECIST 
Modified RECIST 1.1 for immune based therapeutics 
ITT 
Intent-to-treat 
IUD 
Intrauterine device 
LFT 
Liver function tests 
MDSC 
Myeloid-derived suppressor cell 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic resonance imaging 
MS/MS 
Tandem mass spectrometry 
MTD 
Maximum tolerated dose 

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mTKI 
Multi-tyrosine kinase inhibitor 
mTOR 
Mechanistic target of rapamycin 
NA 
Not applicable 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NCS 
Not clinically significant 
NOAEL 
No observed adverse effect level 
ORR 
Objective response rate 
PBMC 
Peripheral blood mononuclear cells 
PD 
Pharmacodynamics 
PDGFR 
Platelet-derived growth factor receptor 
PFS 
Progression-free survival 
PHB 
p-hydroxybenzoate 
PlGF 
Placental growth factor 
PK 
Pharmacokinetics 
PO 
Per Oral 
PR 
Partial response 
PS 
Performance Status 
QD 
Once daily 
RCC 
Renal cell carcinoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP-HPLC 
Reversed-phase high performance liquid chromatography 
RP2D 
Recommended phase 2 dose 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic blood pressure 
SD 
Stable disease 
SDF-1α 
Stromal-derived-factor 1α (also designated CXCL12) 
SOD 
Sum of diameters 
SUSAR 
Suspected unexpected serious adverse reaction 
T1/2 
Half-life 
T4 
Thyroxin 

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TKI 
Tyrosine kinase inhibitor 
Tmax 
Time to maximum concentration 
TME 
Tumor microenvironment 
TMF 
Trial master file 
Treg 
T regulatory 
TSH 
Thyroid stimulating hormone 
TTP 
Time to progression 
ULN 
Upper limit of normal 
US 
United States 
VEGF 
Vascular endothelial growth factor 
VEGFR 
Vascular endothelial growth factor receptor 
 
Abbreviation 
Explanation 
VHL 
Von Hippel-Lindau syndrome 
VL 
Volume of distribution 
WBC 
White blood cell 
WOCP 
Women of childbearing potential 
β-hCG 
Beta-human chorionic gonadotropin 

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PROTOCOL SYNOPSIS 
 
Study title 
A Phase 1/2 Trial of X4P-001 as Single Agent and in Combination with 
Axitinib in Patients with Advanced Renal Cell Carcinoma 
Study number 
X4P-001-RCCA 
Sponsor 
X4 Pharmaceuticals, Inc. 
955 Massachusetts Avenue, 4th Floor 
Cambridge, MA 02139 
Phase 
1 / 2 
Study centers / 
countries 
Multiple study centers globally 
Planned study period 
First patient enrolled: Q2 2016 
Last patient enrolled: Q1 2018 
Last patient last visit: Q1 2019 (anticipated) 
Study objectives 
The primary objective is: 
• 
To evaluate the safety and tolerability of escalating dose levels of 
X4P-001, both in combination with axitinib and as single agent, in 
patients with advanced clear cell Renal Cell Carcinoma (ccRCC). 
Secondary objectives are: 
• 
To assess the treatment effect (clinical activity) of X4P-001, both in 
combination with axitinib and as single agent, in patients with 
advanced ccRCC using Response Evaluation Criteria in Solid 
Tumors (RECIST) v1.1 [Eisenhauer 2009], including progression 
free survival (PFS). 
• 
To characterize the pharmacokinetics (PK) of escalating dose levels 
of X4P-001 administered orally. 
The exploratory objectives are: 
• 
To investigate associations between the treatment effect of X4P- 
001 (in combination with axitinib and as a single agent) and 
selected pharmacodynamic and disease-related biomarkers (e.g., 

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circulating CD34+ cells, plasma levels of soluble VEGF [vascular 
endothelial growth factor] receptor). 
• 
To assess the treatment effect (clinical activity) of X4P-001, both in 
combination with axitinib and as single agent, in patients with 
advanced ccRCC using modified Response Evaluation Criteria in 
Solid Tumors for immune-based therapeutics (iRECIST) 
[Seymour 2017].  
Study design and plan 
This study will be conducted in patients with advanced ccRCC and will 
comprise 3 parts. 
• 
Part A (Phase 1) will assess the safety and tolerability of 
escalating dose levels of X4P-001 in combination with axitinib, a 
TKI approved for use in this setting [Axitinib US prescribing 
information, 2014]. The X4P-001 dose level for the initial cohort is 
200 mg twice daily (BID). Subsequent cohorts will be administered 
X4P-001 once daily (QD). The initial QD dose level will be 400 
mg QD (representing the same total daily exposure as 200 mg 
BID), and then progressing to 600, 800, and 1200 mg. A safe 
maximum tolerated dose (MTD) and/or recommended phase 2 
dose (RP2D) will be identified in Part A. The RP2D may be the 
same as the MTD or may be lower (see Section 4.1.1). 
• 
Part B (Phase 2) is an expansion cohort assessing the safety, 
tolerability, and treatment effect of the RP2D of X4P-001 in 
combination with axitinib in approximately 45 patients. If the 
RP2D is determined before reaching the MTD, Part B may be 
initiated while Part A is ongoing (see Section 4.1.2). 
• 
Part C will assess the safety, tolerability, and treatment effect of 
X4P-001 as monotherapy in patients with advanced ccRCC and 
may be initiated after the MTD of X4P-001 with axitinib is defined 
in Part A. If that MTD was ≤800 mg QD, then the MTD as 
monotherapy will be defined by enrolling additional dose- 
escalation cohorts to receive X4P-001 as a single agent up to, but 
not exceeding, 1200 mg QD (see Section 4.1.3). 
Planned number of 
patients 
• 
Part A: Dose-escalation cohorts for X4P-001 in combination with 
axitinib; estimated to enroll approximately 15 patients. 
• 
Part B: Expansion cohort at the RP2D of X4P-001 in combination 
with axitinib; approximately 45 patients will be enrolled. 

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• 
Part C: Dose-escalation (if needed after Part A) cohorts of X4P-001 
as single agent (monotherapy); Expansion cohort of approximately 
15 patients. 
Schedule of visits and 
assessments 
The overall study schedule is as follows: 
• 
Screening will be done within 28 days prior to Day 1 (the first dose 
of study drug). 
• 
Treatment is scheduled to be administered continuously; one cycle 
is 28 days. Missed doses will be considered skipped. 
• 
Assessments for treatment response (or disease progression) are 
scheduled for every 8 weeks (± 4 calendar days) starting from 
Cycle 1 Day 1 for 80 weeks (20 cycles) and then every 12 weeks 
thereafter. 
• 
The End-of-Treatment (EOT) visit will be performed within 6 days 
after the last dose of study drug or the decision to terminate 
treatment prematurely. 
• 
End-of-Study (EOS) visit, the final study event, will be performed 
30 days (± 4 calendar days) after the last dose of study drug. In the 
event the EOT visit is delayed, the EOS visit will be performed at 
least 14 days after the EOT visit. 
Safety Assessments: 
Safety assessments include ongoing monitoring for clinical adverse events 
(AEs); and regularly scheduled measurement of vital signs; physical 
examinations; ophthalmologic examinations; laboratory tests (hematology 
and clinical chemistry); thyroid function tests (free thyroxin and thyroid 
stimulating hormone) (Parts A and B only); and electrocardiograms 
(ECG). Additional unscheduled assessments may be conducted at 
Investigator’s discretion. 
Efficacy Assessments: 
Tumor Response assessments will be conducted every 8 weeks for 80 
weeks (20 cycles) and then every 12 weeks thereafter, at EOT, and as 
indicated based on new signs, symptoms or laboratory findings. Disease 
status, time to progression, duration of response will be determined based 
on RESIST v1.1 criteria [Eisenhauer 2009]. Treatment decisions will be 
made by the Investigator incorporating the local radiology interpretation 
and consultation with the Medical Monitor. For data analysis, scans will be 
reviewed and interpreted by a blinded central review committee comprising 

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up to 3 experienced radiologists. 
Tumor Response assessments may be explored by using modified 
Response Evaluation Criteria in Solid Tumors for immune-based 
therapeutics (iRECIST) [Seymour 2017]. Patients enrolled with a 
history or current evidence of central nervous system (CNS) disease 
should have brain imaging by magnetic resonance imaging (MRI) at 
baseline and, thereafter, as clinically indicated. 
Pharmacokinetics 
PK samples will be obtained on all patients in Part A and Part C, and at 
least 15 patients in Part B as follows: 
• 
Cycle 1 Day 1: pre-dose (-30 min); post-dose at 30, 60, 90 min 
(each ±5 min) and 2, 3, 4 hr (each ±15 min) 
• 
Cycle 1 Day 15: pre-dose (-10 min); post-dose at 30, 60, 90 min 
(each ±5 min) and 2, 3, 4, 8 hr (each ±15 min) 
• 
Cycle 2 Day 1 and Day 15: pre-dose (-10 min) 
In Part B, for patients who will not collect extensive PK samples on Cycle 1 
Day 1 and Day 15, pre-dose (-10 min) samples will be collected on Cycle 1 
Day 1, Cycle 1 Day 15, Cycle 2 Day 1, and Cycle 2 Day 15. 
All PK samples will be used to analyze X4P-001. PK samples collected in 
Part B may be used to analyze axitinib as well. 
These visits will be scheduled for early in the day and patients will be 
instructed to arrive at the clinic fasting and having not taken their morning 
dose of study drug(s). 
Pharmacodynamics 
Whole blood samples will be obtained concurrently with scheduled PK 
samples on Cycle 1 Day 1 and Cycle 1 Day 15 only (see above) for total 
white blood cell (WBC) counts and counts of circulating CD34+ positive 
cells. 
If sample yields permit, additional investigational immunomodulatory 
subsets may be analyzed. Pharmacodynamic samples will not be drawn at 
Cycle 2 Day 1 and Cycle 2 Day 15. 
Biomarkers 
Blood samples for biomarker assessment [serum and peripheral blood 
mononuclear cells (PBMC)] will be collected as scheduled for potential 
treatment- and tumor-related biomarkers that reflect the pharmacologic 

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effects of CXCR4 antagonism on angiogenesis and immunomodulatory 
subsets of circulating PBMC. Additional investigational blood studies may 
be performed using the collected samples. 
Diagnosis and main 
Inclusion criteria 
Patients must meet all of the following criteria to be eligible for study 
participation: 
1. Be at least 18 years of age. 
2. Have signed the current approved informed consent form. 
3. Have a histologically confirmed diagnosis of predominant ccRCC. 
4. Have received at least one prior course of treatment for ccRCC (see 
Section 5.2. for specific exclusions). 
5. Have on computed tomography (CT) imaging done within 28 days 
of Day 1 findings consistent with advanced ccRCC, including at 
least one extra-renal measurable target lesion meeting the criteria of 
RECIST v1.1 [Eisenhauer 2009]. 
6. Agree to use contraception as follows: 
• 
For women of childbearing potential (WOCP, see Section 
7.4.1.2 for definition), agree to use highly effective 
contraceptive methods from screening, through the study, and 
for at least 4 weeks after the last dose of study drug. 
• 
For males, agree to use a condom with any WOCP sexual 
partner from Day 1 of study treatment, through the study, and 
at least 4 weeks after the last dose of study drug. 
7. For women of childbearing potential (WOCP), have a negative 
pregnancy test (serum or urine) on Day 1 prior to initiating study 
treatment. 
8. Be willing and able to comply with this protocol. 
Exclusion criteria 
Patients with any of the following will be excluded from participation in the 
study: 
1. Has life expectancy of less than 3 months. 
2. Has performance status Grade >2 (Eastern Cooperative 
Oncology Group [ECOG] criteria). 
3. Has New York Heart Association Class III or IV heart failure or 
uncontrolled hypertension (systolic blood pressure [SBP] ≥160 mm 
Hg; diastolic blood pressure [DBP] ≥100 mm Hg). 
4. Has previously received X4P-001. 
5. Parts A and B only: Has received a prior course of axitinib. 
Parts A and B only: Has received mechanistic target of rapamycin 

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(mTOR) inhibitor(s) as their only prior treatment for ccRCC. 
7. Has a prior history or current evidence of intracranial (CNS) 
metastatic RCC, except for ≤3 lesions treated by CyberKnife 
(or any type of radiation) or excisional surgery, clinically 
stable for at least 4 weeks, and without evidence of recurrence 
on MRI imaging at screening. 
8. Has ongoing acute clinical AEs of National Cancer Institute (NCI) 
Common Terminology Criteria for Adverse Events (CTCAE) 
Grade >1 resulting from prior cancer therapies (except alopecia, 
TKI-related hand-foot syndrome, or thyroid dysfunction). 
9. Has had within the past 6 months the occurrence or persistence of 
one or more of the following medical conditions that could not be 
controlled with usual medical care (e.g., required emergency care 
or hospitalization): hypertension, angina, congestive heart failure, 
diabetes, seizure disorder. 
10. Has had within the past 6 months the occurrence of one or more of 
the following events: myocardial infarction, cerebrovascular 
accident, deep vein thrombosis, pulmonary embolism, hemorrhage 
(CTCAE Grade 3 or 4), chronic liver disease (meeting criteria for 
Child-Pugh Class B or C), a second active malignancy (excluding 
malignancies that were treated curatively and have not recurred 
within 2 years prior to study treatment; completely resected basal 
cell and squamous cell skin cancers; any malignancy considered 
to be indolent and that has never required therapy; and completely 
resected carcinoma in situ of any type), organ transplantation. 
11. Has had within the 4 weeks prior to initiation of study drug, or is 
expected to have during the study period, surgery requiring general 
anesthesia. 
12. Has a known history of a positive serology or viral load for HIV or 
a known history of AIDS. 
13. Has, at screening, serologic laboratory tests meeting one or more of 
the following criteria: 
• 
An indeterminate or positive test for antibody to hepatitis C 
virus (HCV), unless documented to have no detectable viral 
load on 2 independent samples. 
• 
A positive test for hepatitis B surface antigen (HBsAg). 
14. Has, at screening, safety laboratory tests meeting one or more of the 
following criteria: 
• 
Hemoglobin <8.0 g/dL 

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• 
Absolute neutrophil count (ANC) <1,500/μL 
• 
Platelets <75,000/μL 
• 
Creatinine >2.0x ULN 
• 
Serum aspartate transaminase (AST) >2.5x upper limit of 
normal (ULN) 
• 
Serum alanine transaminase (ALT) >2.5x ULN 
• 
AST and ALT >5x ULN for patients with liver metastasis 
• 
Total bilirubin >1.5x ULN (unless due to Gilbert’s Syndrome, 
total bilirubin > 3.0x ULN and direct bilirubin > 1.5x ULN) 
15. Has received other anti-cancer therapy within the following specified 
intervals prior to Day 1: 
• 
TKI within 2 weeks. 
• 
Radiation therapy within 2 weeks. 
• 
Bevacizumab within 4 weeks. 
• 
Other chemotherapy (e.g., mitomycin-C, nitrosourea) or 
immunotherapy (e.g., antibody, cytokine) within 4 weeks. 
• 
For investigational anti-cancer therapies, the interval will be 
determined in consultation with the Medical Monitor. 
16. Has, within 2 weeks prior to Day 1, received a medication prohibited 
based on CYP3A4 interaction (see Section 7.4.1.1 for details). 
17. Has, within 2 weeks prior to Day 1, received systemic 
corticosteroids exceeding prednisone 10 mg per day or equivalent; 
for other immunosuppressive agents, the exclusionary dose and 
duration will be determined in consultation with the Medical 
Monitor. 
18. Is nursing. 
19. Has, at the planned initiation of study drug, an uncontrolled 
infection. 
20. Has any other medical or personal condition that, in the opinion of 
the Investigator, may potentially compromise the safety or 
compliance of the patient, or may preclude the patient’s successful 
Investigational 
Medicinal Product: 
dose/mode of 
administration/dosing 
schedule 
The investigational agent is X4P-001. X4P-001 will be provided as 100 mg 
capsules. XP4-001 is to be administered orally, at a consistent time each 
morning (±2 hours) with no food or drink (except water) for at least 1 hr pre-
dose and continuing for at least 2 hr post-dose. 
• 
For first cohort in Part A, taken as 2 capsules (representing 200 mg) 
twice daily. The morning dose should be taken at a consistent time 

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(±2 hr). The second daily dose should be taken 12 hr later (±3 hr). 
• 
For subsequent cohorts in Part A and for Parts B and C, taken as 4 
to 12 capsules (representing 400 - 1200 mg) once daily in the 
morning at a consistent time (±2 hr). 
Manufacturing of a 200 mg capsule formulation is under development and 
may be introduced into the clinic when released. 
All patients enrolled in Parts A and B also will receive treatment with 
axitinib at 5 mg orally BID in addition to X4P-001 at the assigned dose level. 
Axitinib will be supplied as 5 mg tablets, with one tablet administered orally 
BID (continuous dosing). 
Reference therapy: 
dose/mode of 
administration/dosing 
schedule 
None. 
Planned treatment 
duration per patient 
Patients who do not experience a DLT in Cycle 1 (Parts A and C) and 
patients in Part B will remain on study treatment until they experience 
progression of disease, unacceptable toxicity, or other specified reason for 
discontinuation (Section 5.4.1). In Part A and Part C, patients who 
experience a DLT during Cycle 1 will be withdrawn from the study and will 
not receive further study treatment. 
Safety and Efficacy 
Endpoints: 
Safety endpoints are: 
• 
AEs 
• 
Clinical observations (e.g., vital signs, physical examination) 
• 
Laboratory tests, (e.g., clinical chemistry, hematology, and thyroid 
function tests [Part A and Part B only]) 
• 
ECGs 
• 
Ophthalmologic examination 
Treatment effect (tumor response) will be analyzed using RECIST v1.1 
[Eisenhauer 2009] to determine the following efficacy endpoints: 
• 
Objective response rate (ORR) (Complete Response [CR] + Partial 
Response [PR]) 
• 
Time to objective response 
• 
Duration of objective response 
• 
Disease control rate (CR + PR + Stable Disease) 
• 
Time to progression 
• 
PFS 
• 
Treatment effect (tumor response) and efficacy endpoints may be 
explored using the iRECIST assessment [Seymour 2017]. 

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Statistical methods 
(includes sample size 
calculation) 
Sample Size: 
The maximum numbers of patients planned to be enrolled in Parts A and C 
are as follows: 
• 
Part A, Dose-escalation: up to 30 patients in total (up to 6 patients 
per dose level; 5 planned dose levels) 
• 
Part B, RP2D expansion cohort: approximately 45 patients will be 
enrolled; 
• 
Part C, Dose-escalation: up to 18 patients in total (up to 6 
patients per single agent dose-escalation level; maximum 3 dose 
levels); 
• 
Part C, Single agent Expansion: maximum 15 patients 
Dose-escalation in Part A (and, if needed, in Part C) employs the standard 
3+3 design. 
In Part B, approximately 45 patients will be enrolled and dosed with X4P- 
001 in the combination of axitinib to provide a preliminary assessment of 
both safety and anti-tumor activity. With 45 subjects at the RP2D, the two- 
sided 90% confidence interval width for any binary response rate (e.g., DLT 
or binary PD markers) will be approximately 0.24, assuming a 40% response 
rate. If a dose de-escalation occurs after the first 12 patients, the remaining 
33 patients will be dosed at a lower dose level. With 33 patients, the 
confidence interval width will be approximately 0.28 for a binary response 
rate. 
Part C has an expansion cohort at or below the MTD to further assess the 
toxicity at that dose level. With 15 patients, there is a 79% chance of 
observing at least one AE with the true underlying rate of 10%, and a 54% 
chance of observing at least one AE with true underlying rate of 5%. 
 
Statistical Methods: 
The primary objective of the study is safety and tolerability. AEs will be 
coded using Medical Dictionary for Regulatory Activities (MedDRA) 
version 16.0 (or later) and tabulated by event, grade, and relationship to 
study therapy. Laboratory results, vital signs, and ECG parameters will be 
summarized using descriptive statistics. Laboratory values will also be 
graded according to NCI CTCAE, Version 4.03, and summarized in shift 
tables. Dose-limiting toxicity (DLT) events will be summarized by dose 
level for Part A and identified in the listings. 
Safety observations will be analyzed using descriptive statistics and 
tabulation. No formal statistical comparisons are planned. All safety data 
will be presented in listings. 
Analysis of Tumor Response, ORR and Disease Control Rate (DCR) will 
be tabulated using best overall response, by dose level, incorporating 95% 
exact Clopper-Pearson confidence intervals (CI) for ORR and disease 
control rate. The analysis will be based on intent-to-treat (ITT) and 
Clinically Evaluable patient populations. 

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Median time to objective response, TTP, PFS as well as the proportion of 
patients with PFS at 6 and 12 months (with 95% CI) will also be derived 
from Kaplan-Meier estimates. 
Duration of ORR will be summarized as median (with 95% CI) and 
interquartile range estimated using Kaplan- Meier method with 
corresponding 95% CIs. 
Tumor Response and endpoints listed above may also be explored by using 
may be explored using the modified Response Evaluation Criteria in Solid 
Tumours for immune-based therapeutics (iRECIST) [Seymour 2017]  
Schedules of events: 
The schedule of events and estimated blood volume collections are 
presented in Table 1-1 and Table 1-2. Each Cycle represents 28 days. Pre- 
and post-dose intervals are relative to the time of oral administration of 
X4P-001, designated 0 hr. 

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Table 1-1: 
Schedule of Events 
Procedure1 
Screening 
Visit2 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Subsequent 
Odd- 
Numbered 
Cycles 5-19 
Subsequent 
Even- 
Numbered 
Cycles 6-20 
Repeats every 12 weeks4 
EOT5 
EOS6 
Cycle 
21 
Cycle 
22 
Cycle 
23 
D13 
D15 
D1 
D15 
D1 
D15 
D1 
D15 
D1 
D1 
D1 
D1 
D1 
Informed Consent 
X 
Inclusion/Exclusion Criteria 
X 
Medical History 
X 
History of Renal Cell 
Carcinoma 
X 
Vital Signs7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Body weight & height8 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG PS 
X 
X 
X 
X 
X 
Physical Examination 
X 
X 
X 
X 
X 
X 
X 
X 
Ophthalmologic Examination9 
X10 
X 
X 
X 
X 
X 
X 
12-Lead ECG 
X 
X 
X11 
X 
X 
X 
X 
X 
Safety Laboratory Tests12, 13 
X14 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serology 
X14 
Pregnancy Test13, 15 
X14 
X15 
X 
X 
Thyroid Function Test13, 16 
X14 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Biomarker Collection13, 17 
X 
X 
X 
X 
X 
X 
X 
X 
PK Collection18 
X19 
X19 
X20 
X20 
PD Collection18 
X19 
X19 
CT Imaging21 
X 
X 
X 
X 
X22 
Administration of Study 
Drug(s) in clinic23 
X 
X 
X 
X 
Dispense eye drops and nasal 
spray24 
X 
AE & Concomitant Med 
Monitoring25 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X26 
X26 
X 
X 

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1. 
The schedule is presented relative to Study Cycle, Day within Cycle, and Time of Dosing. The calendar day of the first administration of study drug is designated Day 1. Each 
Cycle represents 4 weeks (28 days). Pre- and post-dose intervals are relative to the time of oral administration, designated 0 hr. 
2. 
Screening activities may be initiated up to 28 days prior to Day 1. 
3. 
To allow for holidays and scheduling flexibility, on-treatment visits may be performed within ± 3 calendar days of the day indicated; ophthalmology exams and CT imaging 
within ± 4 calendar days. 
4. 
For cycles >23, perform assessments as indicated for Cycle 21-23 every 12 weeks until EOT visit. 
5. 
The EOT visit will be performed within 6 days after the last dose of study drug or the decision to terminate treatment prematurely. 
6. 
The EOS visit is scheduled for 30 days (± 4 days) after the last dose of study drug. In the event the EOT visit is delayed, the EOS visit will be performed at least 14 days after 
the EOT visit. 
7. 
Vital signs comprise heart rate, blood pressure, and temperature. For patients dosed in clinic on PK collection days, vital signs will be performed pre-dose. 
8. 
Body height needs to be measured at screening only. 
9. 
Ophthalmologic exam – see Section 7.1.1.5. for details. Note: an optometrist may complete the exam if all requirements can be met, including use of appropriate equipment to 
obtain the retinal photographs. 
10. Screening ophthalmologic exam reports and retinal photos must be submitted to the sponsor at least 5 business days prior to Cycle 1 Day 1 to allow central review for 
eligibility 
11. ECG should be performed at 2 hr (± 15 mins) post-dose 
12. Safety laboratory tests – hematology and chemistry (see Section 7.2.1 for details). 
13. Safety laboratory tests should be drawn and sent to central laboratory for analysis. 
14. All laboratory tests required for screening will be performed by the central laboratory. Specimens should be submitted no more than 14 days prior to Day 1. 
15. Women of child-bearing potential only (see Section 7.4.1.3). On Day 1, a urine or serum pregnancy test will be done at the site and the results obtained prior to dosing. 
16. Thyroid Function Tests are performed for Parts A and B only; Section 7.2.1 for details. 
17. Blood samples for tumor-related biomarkers; see Section 7.1.3.2 for details. 
18. PK and PD samples will be collected for all patients in Part A and Part C, and for at least 15 patients in Part B. 
19. PK and PD samples to be taken from 0-4 hr on Cycle 1 Day 1 and from 0-8 hr on Cycle 1 Day 15. See Section 7.1.2 and Section 7.1.3.1 for details of times for PK and PD 
dense sampling. For Part B subjects who do not complete PK/PD dense sampling (e.g. after the minimum 15 patients’ samples are collected), a pre-dose PK sample will 
be collected at these visits. 
20. PK sample is collected at Pre-dose only. 
21. CT imaging of chest, abdomen, and pelvis; see Section 7.1.4.1 for details. Patients with history or current evidence of CNS disease should also have brain imaging by MRI. 
22. CT imaging is not required at the EOT visit if performed within the previous 4 weeks and patient is being terminated for disease progression. 
23. Study drugs will be self-administered by the patient daily, except at PK visits, when study drugs will be administered in the clinic. 
24. See Section 7.4.4.1 for details. 
25. Concomitant illnesses that worsen or illnesses with onset in screening period will be recorded as AEs (see Section 8). 
26. Can be completed via telephone. 

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Table 1-2: 
Estimated Blood Volumes 
 
 
 
Tests 
MAX 
Vol 
(mL) 
per 
sample(s) 
 
 
Screening2 
Visit 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Odd-Numbered Cycles 
5 through 19 
 
 
Even-
Numbered 
Cycles 6 
through 20 
Cycle 21 
and every 
3rd cycle 
until EOT8 
 
 
 
EOT 
 
 
 
EOS 
D1 
D15 
D1 
D15 
D1 
D15 
D1 
D15 
Safety Laboratory 
7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
          X 
X 
X 
X 
Pharmacokinetics 
6 
 
X3 
X4 
X5 
X5 
 
 
 
 
 
Pharmacodynamic 
6 
 
X3 
X4 
 
 
 
 
 
 
 
Blood Biomarker 
11 
- 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Pregnancy test 6,7 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
Serology7 
2.5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total mL blood draw
1
 
9.5 
86 
82.5 
24 
10.5 
18 
5 
18 
5 
18 
5 
18 
18 
18 
1. The volumes shown are estimates; final volumes may vary, but will not be more than 15% greater than shown. 
2. The schedule is presented relative to Study Cycle, Day within Cycle, and Time of Dosing. The calendar day of the first administration of study drug is designated Day 1. 
Each Cycle represents 4 weeks (28 days). Pre- and post-dose intervals are relative to the time of oral administration, designated 0 hr. 
3. PK and PD samples taken at 7 different time points. See Section 7.1.2 and Section 7.1.3 for sampling times. 
4. PK and PD samples taken at 8 different time points. See Section 7.1.2 and Section 7.1.3 for sampling times. 
5. PK samples taken at pre-dose. 
6. Pregnancy testing will be done on WOCP only. 
7. Done at the central lab; extra blood volume is not required. 
8. The samples are taken on Cycle 21, 24, 27, etc. (every 3 cycles) until EOT. 

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SCHEMATIC OF THE STUDY DESIGN 
 
Figure 1-1 presents an overview of the design of Parts A, B, and C of the study. 
 
Figure 1-1: 
Overview of Study Design 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Part A 
X4P-001 with axitinib 
Part B 
X4P-001 with axitinib 
Dose Escalation Cohort 
RP2D Dose-Expansion Study 
X4P-001 planned dose levels: 
200 mg BID; 
400, 600, 800, 1200 mg QD, 
in combination with axitinib 
Approximately  45 patients 
to receive: X4P-001 at 
RP2D in 
Part C 
X4P-001 monotherapy 
 
Dose Escalation and 
Expansion Cohort 
 
If MTD with axitinib (Part A) 
is ≤800 mg QD, then 
additional monotherapy dose 
escalation cohorts may be 
enrolled to define the MTD of 
X4P-001 as single agent. 
 
Expansion Cohort: 
X4P-001 at or below MTD* 

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1. 
KEY ROLES 
 
 
Study Sponsor: 
X4 Pharmaceuticals, Inc. 
955 Massachusetts Ave, 4th Floor 
Cambridge, MA 02139 
 
 
 
Primary Sponsor Contact: 
 
  
X4 Pharmaceuticals, Inc.  
Telephone: 
 
E-mail: 
  
Sponsor Signatory: 
 
 
 X4 Pharmaceuticals, Inc. 
E-mail: 
 
 
 
 
  
X4 Pharmaceuticals, Inc. 
E-mail:  
 
 

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2. 
INTRODUCTION: BACKGROUND INFORMATION AND 
SCIENTIFIC RATIONALE 
2.1. 
Background Information 
In ~75% of patients with sporadic clear-cell renal cell carcinoma (ccRCC) there is functional loss 
of the VHL gene, typically by mutation, but also silencing by hypermethylation. VHL encodes the 
von Hippel-Lindau tumor suppression protein which mediates proteolytic degradation of the 
hypoxia-inducible factor (HIF)-α [Turner 2002]. Loss of this function results in increased levels 
of HIF-α, increased expression of vascular endothelial growth factor (VEGF), tumor 
angiogenesis, and, ultimately, the hypervascularity characteristic of these malignancies. Multiple 
agents that block the activation of the VEGF pathway have been shown to improve outcomes, 
including: 
• Tyrosine kinase inhibitors (TKIs), such as sunitinib, axitinib, sorafenib or pazopanib, that 
block the VEGF signaling pathway. 
• Bevacizumab, a monoclonal antibody, that binds circulating VEGF and thus prevents the 
ligand from binding to the VEGF receptor. 
Despite the demonstrated benefits of angiogenesis inhibitors in ccRCC, the approach is not 
curative. Although many patients respond initially, most of them experience relapse and 
progression. There is clear unmet need for agents that improve outcomes by preventing or 
delaying treatment resistance. 
CXCR4 (C-X-C chemokine receptor type 4) is the receptor for CXCL12 (C-X-C chemokine 
ligand type 12; also referred to as SDF-1α, stromal-derived-factor 1α). CXCL12 has potent 
chemotactic activity for lymphocytes and MDSCs (myeloid-derived suppressor cells), and is 
important in homing of hematopoietic stem cells to the bone marrow. CXCR4 is also expressed 
and active on multiple types of human cancers, including ccRCC, ovarian cancer, and melanoma, 
and increased expression of CXCR4 on tumor cells has been associated with significantly 
decreased overall patient survival [Staller 2003; Sekiya 2012; Ejtesja, 2008; Maréchal 2009]. 
Multiple observations implicate the CXCL12/CXCR4 axis in contributing to the lack (or loss) of 
tumor responsiveness to angiogenesis inhibitors (also referred to as “angiogenic escape”). In 
animal cancer models interference with CXCR4 function has been demonstrated to disrupt the 
tumor microenvironment (TME) and unmask the tumor to immune attack by multiple 
mechanisms, including 
• Eliminating tumor re-vascularization [Righi 2011; Kioi 2010]. 
• Decreasing the infiltration of MDSCs. 

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• Increasing the ratio of CD8+ T cells to T regulatory (Treg) cells [Righi 2011; Feig 2013; 
Fearon 2014]. 
These effects result in significantly decreased tumor burden and increased overall survival in 
xenograft, syngeneic, as well as transgenic, cancer models [Righi 2011; Feig 2013; Kioi 2010]. 
X4P-001 is a potent, orally bioavailable CXCR4 antagonist [Stone 2007], that has demonstrated 
activity in solid and liquid tumor models [Parameswaran 2011], and unpublished data] and has 
previously (under the designations AMD070 and AMD11070) been in Phase 1 and 2a studies 
involving a total of 71 healthy volunteers [Stone 2007; Cao 2008; Nyunt 2008] and human 
immunodeficiency virus (HIV)-infected patients [Moyle 2009; Study ACTG (DIAIDS) Protocol 
A5210]. These studies demonstrated the following: 
• Oral administration of up to 400 mg twice daily (BID) for 3.5 days (healthy volunteers) 
and 200 mg BID for 8-10 days (healthy volunteers and HIV patients) was generally safe 
and well-tolerated with no serious or severe treatment-related adverse events and no 
pattern of clinically significant laboratory changes. 
• Pharmacodynamic activity, with dose- and concentration-related changes in circulating 
white blood cells (WBCs). 
• High volume of distribution (VL) suggesting high tissue penetrance. 
We postulate that effective CXCR4 antagonism by X4P-001 would be of potential benefit in 
patients with advanced ccRCC and other cancers by multiple mechanisms: 
• Decreased recruitment of MDSC, resulting in increased anti-tumor immune attack. 
• Sustained decrease in neoangiogenesis and tumor vascular supply. 
• Interference with the autocrine effect of increased expression by ccRCC of both CXCR4 
and CXCL12, its only ligand, thereby, potentially reducing cancer cell metastasis. 
This clinical study in patients with advanced ccRCC will evaluate X4P-001 both as a single 
agent (monotherapy) and also in combination with axitinib, a small molecule TKI approved for 
second-line treatment of patients with ccRCC. We hypothesize that the combination has the 
potential to further improve outcomes by reducing the angiogenic escape that typically occurs 
with TKI therapy. 
2.2. 
Overview of X4P-001 
X4P-001 was previously under development for the treatment of HIV infection based on the role 
of CXCR4 in viral entry into the cell. That program, which is presented in detail in the 
Investigator Brochure, included nonclinical toxicology studies and clinical studies using the free 

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base formulation, then designated AMD11070 and here X4P-001. Throughout the prior clinical 
development program, the drug product used was capsules containing 100 mg of the free base. 
The same formulation will be used in this protocol (see Section 6.1.2). 
During the earlier clinical studies, a p-hydroxybenzoate (PHB) salt form of the drug (designated 
AMD11070PHB) was identified for future manufacturing and development purposes. Animal 
toxicology studies (13- and 26-week duration) conducted with AMD11070PHB demonstrated 
unexpected findings, including retinal changes in albino rats treated for 26 weeks and notable 
gastrointestinal (GI) intolerance and liver changes in Beagle dogs treated for 13 weeks (see 
Investigator’s Brochure). 
Although AMD11070PHB was never administered to humans and is not proposed for use in any 
clinical studies in this program, these observations were carefully considered in the safety 
monitoring plans for clinical studies of X4P‑001. 
2.2.1. 
Prior Clinical Studies Conducted Using X4P-001 
The 4 clinical studies conducted under the prior development program included Phase 1 and 2a 
studies involved a total of 55 healthy volunteers [Cao 2008; Nyunt 2008] and 16 HIV-infected 
patients [Moyle 2009; ACTG (DIAIDS) Protocol A5210]. Table 2-1 shows the protocol 
numbers, titles, and related publications; Table 2-2 summarizes the study populations, objectives, 
numbers, dose administered, and duration. 
These studies demonstrated the following: 
• Oral (PO) administration of up to 400 mg BID for 3.5 days (healthy volunteers) and 200 
mg BID for 8-10 days (healthy volunteers and HIV patients) was generally safe and well- 
tolerated with no pattern of adverse events (AEs) or clinically significant laboratory 
changes. 
• T1/2 of X4P-001 is ~23 hours, supporting the use of QD dosing (see Investigator’s 
Brochure). 
• Pharmacodynamic activity, as assessed by increases in circulating WBC, was related to 
dose and duration of treatment. 

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Table 2-1: 
Prior Clinical Studies Conducted using X4P-001 – Protocol Number, Study 
Title, and Publication1 
Protocol No. 
Study Title 
Publications 
A5191 
A Phase I, Dose-Rising Study of AMD11070 In HIV-Seronegative Men To 
Assess the Safety and Pharmacokinetics After Single or Multiple Doses 
Stone 2007 
AMD-1001 
Multicenter, dose-finding safety and activity study of AMD11070 in HIV- 
infected patients carrying X4-tropic virus 
Moyle 2009 
AMD-1002 
A Study of the Pharmacokinetic Interaction between AMD11070 and Substrates 
of CYP 3A4 and 2D6 Enzymes in Healthy Volunteers 
Nyunt 2008 
A5210 
Phase IB/IIA Dose-Finding Safety and Activity Study of AMD11070 (An Orally 
Administered CXCR4 Entry Inhibitor) in HIV-Infected Patients 
(unpublished) 
1 
All studies were conducted between 3 Sep 2003 and 13 Jul 2006. 
 
Table 2-2: 
Prior Clinical Studies Conducted using X4P-001 – Study Population, 
Objectives, and Exposures 
Study ID 
Study 
Population 
Study 
Objective 
Cohort 
(A5191 
only) 
N 
Gender 
M/F2 
Dose & Regimen 
(All oral) 
Duration 
A51911 
Healthy 
Volunteers 
Dose escalation: 
Safety, PK 
A-D 
121 
43 M, 0 Fa 
Single Dose 
50 to 400 mg 
1 day 
F, G, I 
181 
100 to 400 mg, BID 
3.5 days (7 doses) 
Effect of food, 
DDI of ritonavir 
H, J, K 
321 
≤3 doses, 200 mg or 
400 mg each 
≤3 doses over 6 to 
17 days 
A5210 
HIV-infected 
Safety 
Viral load 
reduction 
6 
3 M, 3 F 
200 mg, BID 
10 days 
AMD-1001 
HIV-infected 
Safety 
Viral load 
reduction 
10 
9 M, 1 F 
100 mg, BID (N=2) 
200 mg, BID (N=8) 
10 days 
AMD-1002 
Healthy 
Volunteers 
Safety 
Drug-drug 
interaction 
12 
9 M, 3 F 
200 mg, BID 
8 days 
1. 
Study A5191 enrolled 10 cohorts totaling 68 subjects representing 43 unique individuals. There were 3 subjects in each of 
the 4 single dose escalation cohorts (A-D) and 6 subjects in each of the 3 multiple dose escalation cohorts (F, G, I). No 
subject was enrolled in more than one of the dose escalation cohort. 
2. 
Within each study the median age was ~40 years; overall age range was 19 to 58 years. 

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2.2.2. 
Clinical Pharmacology of X4P-001 
2.2.2.1. 
Clinical Pharmacokinetics 
In the 4 previous clinical studies conducted by AnorMed and NIH (Studies AMD1001, AMD1002, 
A5191, and A5210) using the freebase formulation in normal healthy volunteers and patients with 
HIV. Drug was administered PO in all studies; multiple dose studies were conducted using BID 
dosing. In single and multiple dose escalation studies, maximum concentration (Cmax) and AUC 
increased more than dose-proportionally over 50 - 400 mg dose range. Mean terminal half-life 
(T1/2) was 22.9 hr, supporting the QD dosing regimen. 
Steady-state PK parameters were similar in healthy volunteers (AMD-1002) and in HIV infected 
patients (A5210 and AMD-1001). The results (mean ± standard deviation) were derived from 26 
subjects, including both healthy volunteers and HIV-infected subjects, who received X4P-001 at 
200 mg BID for 8 to 10 days. 
• AUC(0-12hr):  3735 ± 1755 nghr/mL 
• Cmax:  1223 ± 600 ng/mL 
• Minimum concentration (Cmin) at 12 hours: 74.3 ± 47.3 ng/mL 
• Time to maximum concentration (Tmax):  2.2 ± 0.9 hr 
For 13 subjects, daily Cmin(trough) concentrations were determined. Overall, subjects reached steady 
state by Day 6, which is consistent with the T1/2 of ~23 hr. Further, Cmin and AUC(0-12) were strongly 
correlated suggesting that monitoring Cmin may provide a practical means for assessing drug 
exposure. 
X4P-001-REGA study was a phase I study in 15 healthy volunteers comparing two different dosing 
regimens: 200 mg BID and 400 mg QD (10-day treatment). The study was prematurely 
discontinued on Day 3 due to an insufficient number of patients remaining on the trial to assess 
the statistical endpoints. In this study, PK samples were collected from 0-12 hr for BID dosing and 
0-24 hr for QD dosing. Preliminary PK results are listed below. 
Following administration of X4P-001 200 mg BID and 400 mg QD on Day 1, the mean Cmax were 
1070 ng/mL and 2662 ng/mL, respectively; the median Tmax were 2.5 hr and 1.5 hr respectively.  
AUC0-12 was 3682 ng*hr/mL after 200 mg  BID  dose and AUC0-24 was 9421 ng*hr/mL after 400 
mg QD dose. Comparing with results from Study A5191, the exposure in REGA study is higher. 
2.2.2.2. 
Effect of Food on Absorption 
In a food-effect study (A5191), 9 male subjects received X4P-001 in the fasted stated (fasting 
overnight after midnight until 2 hours post-dose) and in the fed state (low fat meal within 30 

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minutes prior to dosing), food had a significant negative effect on the bioavailability of X4P-001. 
Cmax and AUC0-12 in the fed state was 0.33x and 0.44x of that observed in the fasted state, 
respectively. Tmax was delayed from 1 hr (fasted) to 3 hr (fed). T1/2 was not changed. 
2.2.2.3. 
Potential for Drug-Drug Interactions Based on CYP Metabolism 
Two clinical studies (A5191, AMD-1002) were conducted to assess the potential for drug-drug 
interactions (DDI). Ritonavir (a strong CYP3A4 inhibitor, P-gp inhibitor) resulted in a modest 
increase in X4P-001 plasma concentrations [A5191, Cao et al., 2008]. The mean Cmax and AUC of 
X4P-001 coadministered with the first dose of ritonavir were increased by 39% and 60%, 
respectively, compared to the administration of X4P-001 alone. Similar effects were seen after 
ritonavir had been administered twice daily for 14 days. 
Study AMD-1002 assessed the effect of X4P-001 on metabolism of CYP3A4 and CYP2D6 
substrates, using midazolam and dextromethorphan as substrates [Nyunt et al., 2008]. 
Administration of X4P-001 had the following effects. 
• The Cmax for midazolam (a CYP3A4 substrate) was unaffected; AUC was 1.33x baseline. 
• The Cmax for dextromethorphan (a CYP2D6 substrate) was 2.5x baseline; the AUC, 2.86x. 
The magnitude of the midazolam interaction was modest. The magnitude of the effect on 
dextromethorphan has significant potential to result in changes in clinical drug response, affecting 
either efficacy or toxicity. The clinical study protocols include detailed restrictions on concomitant 
medications to minimize the potential for drug-drug interactions. 
2.2.2.4. 
Clinical Pharmacodynamics 
A primary pharmacodynamic effect of CXCR4 antagonism is mobilization of WBC (including 
both myeloid and lymphoid cells) from the bone marrow into the peripheral circulation. The 
relationship between plasma drug levels and concurrent peripheral blood WBC counts was 
examined in phase 1 studies with dense sampling [Stone et al., 2007]. After dosing, circulating 
WBC counts increased from baseline in all subjects, peaking between 2 and 4 h following dosing. 
The distribution of concurrent WBC-fold change from baseline versus drug concentration best fit 
a sigmoid maximum exposure (Emax) model. 
• The estimated Emax was WBC increase to 2.03x baseline (95% confidence interval [CI], 
1.95x to 2.11x). 
• The estimated half maximal effective concentration (EC50) was 39 ng/mL (95% CI, 28 to 
50 ng/mL), which is below the observed steady-state Cmin(12h) for X4P-001 at 200 mg BID, 
the starting dose in the proposed oncology studies. 

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2.2.3. 
Clinical Safety Experience with X4P-001 
2.2.3.1. 
Safety Experience – X4 Pharmaceuticals Clinical Development Program 
As of July 05, 2017, the following studies have been initiated or completed: 
• X4P-001-RCCA – the study detailed in this protocol. 
• X4P-001-RCCB - a study adding X4P-001 to patients receiving nivolumab for treatment 
of advanced ccRCC. 
• X4P-001-MELA – a phase 1b study of X4P-001 alone and in combination with 
pembrolizumab in patients with advanced melanoma. 
• X4P-001-MKKA – a phase 2/3 randomized, double-blind, placebo-controlled 
trial of X4P-001 in patients with WHIM (Warts, Hypogammaglobulinemia, 
Infections and Myelokathexis) Syndrome 
• X4P-001-REGA – a phase 1 study in healthy volunteers comparing 2 different dosing 
regimens: 200 mg BID versus 400 mg QD. 
Please refer to the current Investigator’s Brochure for more information related to X4P-001’s 
clinical safety data. 
2.2.3.2. 
Safety Experience – Prior Development Program 
A total of 71 individuals were exposed to X4P-001 in 4 prior clinical studies. Across these 
4 studies: 
• The most common AEs across studies were mild to moderate GI events. 
• There were no deaths and no discontinuations due to AEs. Two subjects discontinued for 
personal reasons after receiving 1 or 2 doses of X4P-001. 
• There was one SAE, a grand mal seizure in a subject with a history of epilepsy; there 
were no events of seizure reported in other subjects. This SAE was the only clinical AE 
assessed as severe (Grade 3). 
• There was one other clinically notable AE. A subject with baseline bradycardia 
experienced an episode of syncope upon standing rapidly. The episode resolved promptly 
without lying down. There were no events of syncope reported in other subjects. 
• There were no laboratory abnormalities assessed as clinically significant. The primary 
treatment-related laboratory abnormalities observed were the pharmacologically expected 
increase in circulating neutrophils and lymphocytes. Treatment-emergent elevation in 
lipase was observed in one asymptomatic patient; the source of the enzyme (pancreas or 
salivary glands) was unclear. 

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• A detailed by-subject analysis of abnormal liver function tests (LFTs) revealed no pattern 
of treatment-emergent LFT abnormalities suggesting a drug effect. 
2.2.4. 
Treatment Effect of X4P-001 in Prior Clinical Studies 
As of July 05, 2017, there are no efficacy data with X4P-001 to report in patients with 
malignancy (including ccRCC or melanoma). 
2.2.5. 
Nonclinical Toxicity Studies of X4P-001 
Pivotal nonclinical toxicity studies were conducted in rats and Beagle dogs with X4P-001 
administered orally in divided doses, BID. The no observed adverse effect level (NOAEL) in the 
4-week rat study was 125 mg/kg/day. Adverse effects at 250 mg/kg/day included decreases in 
food consumption, body weight, and reticulocyte counts and minimal bone marrow 
hypocellularity; all except body weight were resolved following a 14-day recovery period. 
The dose levels in the 13-week toxicity study in dogs were 10, 20, 35, and 70 mg/kg/day. 
Microscopic liver findings of pigment deposition and inflammation were reported in all dose 
groups and across males and females; these findings were typically assessed as minimal and not 
associated with histopathologic findings of necrosis or with LFT changes. The NOAEL 
(<10 mg/kg/day) reflected the finding of an isolated focus of liver necrosis (slight) in a single 
male animal dosed at 10 mg/kg/day. None of the remaining 11 animals (5 males and 6 females) 
in the 2 lowest dose groups had other liver-related findings and none, including the male with 
focal necrosis, had treatment-emergent increases in LFTs. 
At the 2 highest dose levels (35 and 70 mg/kg/day), 4 of 12 animals were reported to have 
microscopic liver changes of multifocal necrosis (minimal to slight), further characterized as 
single cell necrosis in 2 animals. Two of the 12 animals in those dose groups (both 
70 mg/kg/day) showed post-treatment increased ALT, rising to 1.4x above the upper range of 
controls in a male with no histologic findings, and to 2.4x in a female with multifocal single cell 
necrosis (slight). There were no elevations in bilirubin in any animal. One male (35 mg/kg/day) 
had “focally extensive (moderate)” necrosis and inflammation associated with macroscopic 
discoloration of the liver; transaminases were normal. On review, this lesion was qualitatively 
different from the microscopic multifocal lesions in other animals and had a subcapsular 
location, consistent with being secondary to external trauma. 
The original development program of AMD11070 identified an alternative salt form of the drug 
substance for manufacturing purpose, PHB salt (designated AMD11070PHB). Toxicology 
studies of AMD11070PHB included unexpected findings of retinal degeneration in Albino rats 
treated for 26 weeks. This was not seen in Beagles administered either PHB or free base (X4P- 

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001) drug forms for up to 13 weeks. AMD11070PHB was never administered to humans and is 
not proposed for use in any clinical studies in this program. 
2.3. 
Clinical Experience with Related Compounds 
Mozobil® (plerixafor) is the only approved agent that blocks the CXCR4 receptor, which is an 
injectable drug with a very short half-life, and is approved in combination with granulocyte- 
colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSCs) to the peripheral 
blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s 
lymphoma and multiple myeloma. 
In tumor models in mice the drug has been administered by continuous infusion using 
subcutaneous osmotic reservoirs. The results of those nonclinical studies indicate that CXCR4 
receptor blockade has an anti-tumor treatment effect and thereby support the hypothesis that an 
orally administered agent such as X4P-001 could have clinical benefit. 
2.4. 
Rationale 
Agents directed against the VEGF pathway have demonstrated clinical benefit in patients with 
advanced ccRCC. Targets of multi-tyrosine kinase inhibitors (mTKI) include vascular 
endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), 
fibroblast growth factor receptor (FGFR), and cytokine receptor (kit). 
While these agents have demonstrated benefit in progression-free and overall survival, tumors 
typically develop resistance to therapy within 5-11 months [Wang 2011]. Consequently, 
strategies to improve or prolong the effects have been actively investigated, including dose- 
intensification, variations in the sequencing and scheduling of agents, and the use of more 
selective agents [Amato 2007; Houk 2010; Rini 2011a; Rini 2011b]. 
Animal studies of ccRCC xenografts implicate increased infiltration of MDSC as a central factor 
in acquired resistance to VEGF-targeted therapies [Panka 2013] as well as other anti-cancer 
therapies [Shojaei 2007; Zea 2005; Nagaraj 2007; Finke 2011]. MDSC trafficking into tumor 
tissue is regulated by chemokines, many of which (e.g. SDF-1/CXCL12) are produced in 
response to hypoxia in a HIF-dependent manner. Agents such as X4P-001 that directly block 
CXCL12/CXCR4 signaling should decrease MDSC trafficking and, thereby, prevent the 
emergence of resistance to mTKI. This approach would be expected to introduce comparatively 
little additional toxicity since CXCR4-targeted drugs do not induce cell-cycle arrest in normal 
proliferating cell populations and have been well tolerated in short-term (10-day) clinical studies 
[Moyle 2009]. This protocol is designed to test this hypothesis systematically by evaluating the 
effects of the CXCR4 inhibitor X4P-001 on MDSC trafficking and differentiation, tumor 

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vascularization, and disease progression in RCC in combination with axitinib, the most selective 
mTKI currently approved. 
This protocol represents the first use of X4P-001 in patients with RCC. 
3. 
OBJECTIVES AND PURPOSE 
 
3.1. 
Primary Objective 
The primary objective is: 
• To evaluate the safety and tolerability of escalating dose levels of X4P-001, both in 
combination with axitinib and as single agent, in patients with advanced ccRCC. 
3.2. 
Secondary Objectives 
Secondary objectives are: 
• To assess the treatment effect (clinical activity) of X4P-001, both in combination with 
axitinib and as single agent, in patients with advanced ccRCC using Response Evaluation 
Criteria in Solid Tumors (RECIST) v1.1 [Eisenhauer 2009], including progression free 
survival (PFS). 
• To characterize the pharmacokinetics of escalating dose levels of X4P-001 administered 
orally. 
3.3. 
Exploratory Objective 
The exploratory objectives are: 
• To investigate associations between the treatment effect of X4P-001 (in combination with 
axitinib and as a single agent) and selected pharmacodynamic and disease-related 
biomarkers (e.g., circulating CD34+ cells, plasma levels of soluble VEGFR). 
• To assess the treatment effect (clinical activity) of X4P-001, both in combination with 
axitinib and as single agent, in patients with advanced ccRCC using modified Response 
Evaluation Criteria in Solid Tumors for immune-based therapeutics (iRECIST) 
[Seymour 2017]. 

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4. 
STUDY DESIGN AND ENDPOINTS 
 
4.1. 
Description of the Study Design 
This study will be conducted in patients with advanced ccRCC and will comprise 3 parts. 
• Part A (Phase 1) will assess the safety and tolerability of escalating doses levels of X4P-
001 in combination with axitinib, a TKI approved for use in this setting [Axitinib US 
prescribing information, 2014]. The X4P-001 dose level for the initial cohort is 200 mg 
BID. Subsequent cohorts will be administered X4P-001 QD. The initial QD dose level 
will be 400 mg QD (representing the same total daily exposure as 200 mg BID), and then 
progressing to 600, 800, and 1200 mg. A safe maximum tolerated dose (MTD) and/or 
recommended phase 2 dose (RP2D) will be identified in Part A. The RP2D may be the 
same as the MTD or may be lower (see Section 4.1.1). 
• Part B (Phase 2) is an expansion cohort assessing the safety, tolerability, and treatment 
effect of X4P-001 at RP2D in combination with axitinib in approximately 45 patients. If 
the RP2D is determined before the MTD is reached in Part A, Part B may be initiated 
while Part A is ongoing (see Section 4.1.2). 
• Part C will assess the safety, tolerability, and treatment effect of X4P-001 as 
monotherapy in patients with advanced ccRCC and may be initiated after the MTD of 
X4P-001 with axitinib is defined in Part A. If that MTD was ≤800 mg QD, then the MTD 
as monotherapy will be defined by enrolling additional dose-escalation cohorts to receive 
X4P-001 as a single agent up to, but not exceeding, 1200 mg QD (see Section 4.1.3). 
4.1.1. 
Part A (Phase 1): X4P-001 with Axitinib – Dose-escalation Cohorts 
Part A will evaluate the safety and tolerability of X4P-001 at increasing dose levels –specifically, 
200 mg orally BID, then 400, 600, 800, 1200 mg QD – in combination with axitinib (Figure 4-1). 
Axitinib is given at 5 mg orally BID in addition to X4P-001 at the assigned dose level. While 
proceeding with further dose escalation, additional patients may be enrolled at preceding dose 
levels that have been declared to be safe at a prior Data Review Committee (DRC) meeting to 
better understand the safety, tolerability and PK of X4P-001. 
• Provision is made for a contingency cohort (escalation or de-escalation) receiving an 
additional dose level of X4P-001(e.g. 1000 mg QD) plus axitinib with the approval of the 
Data Review Committee (DRC; see Section 8.6.3). 

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Figure 4-1: 
Study Design for Part A 
 
 
1200 mg QD + axi 
n=3-6 
 
 
 
 
 
 
4.1.1.1. 
Dose Escalation Process 
 
Dose-escalation will proceed using a standard “3+3” design with careful monitoring and review 
by the DRC. The review will include all available safety data. To facilitate standardizing the 
dose-escalation reviews across different cohorts, the focus will be on the observations at that 
dose level from the start of treatment (C1D1) through the visit scheduled for the beginning of 
C2D1 (Week 5). (Hereafter, this period will be referred to as “the first 4 weeks of treatment”). 
Each dose-escalation cohort is expected to enroll at least 3 patients, with a maximum of 
6 patients. 
• If 3 patients at the dose level complete the first 4 weeks of treatment without a DLT 
event, the DRC will conduct a dose-escalation review. 
• If 1 patient at the dose level experiences a DLT event during the first 4 weeks of 
treatment, then enrollment at that dose level will continue to a total of 6 patients and the 
dose-escalation review will be done when all 6 patients have completed the first 4 weeks 
treatment. 
400 mg QD + axi 
n=3-6 
200 mg BID + axi 
n=3-6 
n=3-6 
X4P-001 in Combination with Axitinib (axi) 
Part A - Dose Escalation 
800 mg QD + axi 
n=3-6 
600 mg QD + axi 

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• If 2 patients at a dose level experience DLT events during the first 4 weeks of treatment, 
then no further dosing will occur at that or higher dose levels. 
The expected outcomes of the DRC review include: 
• Dose-escalation – progression to the next planned dose level. 
• Continued enrollment at the dose level under review (applicable only after 3 patients) – 
enroll up to 6 patients at the current dose level to obtain additional safety data for 
subsequent review. 
• No further dose-escalation cohorts – at this time the DRC will indicate the dose level 
they consider represents the maximum tolerated dose (MTD) for X4P-001 in combination 
with axitinib. 
• The MTD will be applicable for proceeding to Part C or RP2D is determined to proceed 
to Part B. 
Replacement of Non-evaluable Patients. A maximum of 6 evaluable patients will be enrolled 
per dose-escalation cohort in Part A. An evaluable patient is defined as a patient who either (a) 
successfully completes 4 weeks treatment, receiving at least 75% of the assigned treatment 
(Section 6.1.9); or (b) experiences a dose-limiting toxicity (DLT) event in that period. 
To assure that the required number of evaluable patients is available for DRC review, non- 
evaluable patients (i.e., those who discontinue treatment prior to completion of the C2D1 (Week 
5) visit for reasons other than a DLT) may be replaced within a cohort; the replacement will be 
assigned the same dose level. 
4.1.1.2. 
Treatment Cycle 2 and Beyond 
Patients who do not experience a DLT in Cycle 1 will stay on study treatment. If during Cycle 2 
or later treatment cycles, a patient experiences an unacceptable toxicity (defined with the same 
criteria of DLT for Cycle 1), then, based on the judgment of the Investigator, the patient may 
continue treatment per dose modification recommendations (Sections 6.1.7.1 and 6.1.7.2). 
4.1.1.3. 
Definition of a Dose-Limiting Toxicity (DLT) 
A DLT event is defined as an adverse event occurring in Cycle 1 (i.e., in the first 4 weeks of 
treatment) that meets both of the following criteria: 
a) Is assessed by the Investigator as possibly or probably related to study drug (X4P-001) (see 
Section 8.2.2 for details). 
b) Represents one of the following events (grading as defined by NCI CTCAE, Ver. 4.03) (see 
Section 8.2.1): 

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• Is a Grade 3 or Grade 4 clinical event 
- Exception: Grade 3 nausea, vomiting, or diarrhea lasting <48 hrs in patients who 
have received suboptimal medical management 
• Is a confirmed Grade 3 or Grade 4 laboratory event (confirmatory sample to be submitted 
within 48 hrs of receiving initial lab report) 
- Exception: Grade 3 electrolyte events that persist <72 hrs and do not require 
hospitalization. 
- Exception: Grade 3 AST/ALT increases that persist <5 days and with Total 
Bilirubin ≤1.5x ULN. 
• Results, during the first 4 weeks of treatment, in the patient being unable to receive at 
least 75% of the intended dose (Section 6.1.9). 
• Is one of the following, which are designated as critical DLT events 
- AST/ALT increased >3x ULN with Total Bilirubin increased >2x ULN in the 
absence of cholestasis. 
- Febrile neutropenia (Grade ≥3) — defined as ANC <1000/mm3 with a single 
temperature of >38.3°C (101°F) or a sustained temperature of ≥38°C (100.4°F) 
for more than one hour. 
- Retinopathy – confirmed treatment-emergent retinopathy (see Section 7.1.1.5). 
4.1.1.4. 
Definition of Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose 
(RP2D) 
The MTD is the highest dose level meeting both of the following criteria: 
• It is below the level at which 2 or more patients in a dose-escalation cohort experienced 
DLTs during the first 4 weeks of treatment; 
• It is a dose level at which no more than 1 patient in a dose-escalation cohort experienced 
a DLT during the first 4 weeks of treatment. 
The RP2D is defined as the dose which will be assigned in Part B based on Sponsor and DRC 
review of all available data of X4P-001, including safety and tolerability as well as PK, 
pharmacodynamic, and anti-tumor activity. The RP2D may be the same as the MTD or may be 
lower. The RP2D may not exceed the MTD. 

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4.1.2. 
Part B (Phase 2): An Expansion Cohort of the RP2D of X4P-001 in Combination with 
Axitinib 
The goal of Part B is to assess the safety, tolerability, and treatment effect of X4P-001 at the 
RP2D dose level in approximately 45 patients with advanced ccRCC. If the RP2D is determined 
before the MTD is reached in Part A, Part B may be initiated while Part A is still ongoing. 
Safety at the RP2D will be verified by monitoring DLTs as follows: if ≤ 4 DLTs are observed in 
the first 12 patients during the first 4 weeks of treatment, this RP2D dose will be considered safe 
to proceed for the remaining patients in this study. If 5 or more DLTs are observed in the first 12 
patients during the first 4 weeks of treatment, the trial may continue with dose de-escalation after 
DRC review. The dose will be reduced at least one dose level lower, according to the dose levels 
presented in Figure 4-1. To further protect patient safety, if additional DLTs are observed 
anytime during the trial, dose de-escalation can be enforced based on DRC recommendation, or 
the trial can be stopped at the sponsor’s discretion. 
 
Patients in Part B will be followed for safety and tumor response per RECIST 1.1 guidance. 
Patients will remain on study treatment until experiencing disease progression, unacceptable 
toxicity, or other specified reasons for discontinuation (see Section 5.4.1). In addition, a subset of 
patients will have PK/PD evaluations performed (at least 15 patients). 
 
4.1.3. 
Part C: X4P-001 as a Single Agent (Monotherapy) 
The goal of Part C is to assess the safety, tolerability, and treatment effect of single agent X4P- 
001 in patients with advanced ccRCC. Part C may be initiated after the DRC determines the 
MTD for X4P-001 in combination with axitinib (i.e., may enroll in parallel with Part B); if 
enrollment for Part B closes before the Part C MTD is reached, the Sponsor may elect to 
terminate the study for administrative reasons. 
The MTD of X4P-001 as single agent will be determined as follows: 
• If the MTD in Part A using combination treatment with axitinib is 1200 mg QD, then that 
dose of X4P-001 will be used for the single agent expansion cohort. Higher doses will not 
be assessed. 
• If the MTD in Part A using combination treatment with axitinib is ≤800 mg QD, then 
additional single agent, dose-escalation cohorts – that is, X4P-001 administered alone 
without axitinib – will be enrolled. The starting dose level will be one step above the 
MTD established in combination with axitinib in Part A; the maximum dose evaluated 
will be 1200 mg QD. Escalation will proceed as detailed for Part A; the same potential 
dose levels (Figure 4-1), the same “3+3” design, and the same dose-escalation review 
procedures will be applied (see Section 4.1.1). 

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Number of Patients. After establishing the MTD for single agent X4P-001, approximately 15 
patients may be enrolled at that dose level as expansion cohort. 
4.2. 
Rationale for the Study Design, Including the Choice of Control Groups 
 
4.2.1. 
Rationale for the Study Design 
The open-label study design is consistent with both the study objectives and current principles 
for the evaluation of investigational drugs in patients with advanced malignancy. 
• Part A: The dose-escalation design with enrollment guided by safety experience and 
reviewed by a DRC serves to minimize the number of patients required and to assure 
patient safety is protected. 
• Part B provides assessment of the safety and tolerability of X4P-001 in combination with 
axitinib at the RP2D dose level to guide further development of that regimen in the 
treatment of ccRCC and other malignancies. A DRC review of the initial 12 patients 
provides an additional safety assessment of the RP2D. 
• Part C provides assessing X4P-001 as a single agent to guide further development of 
X4P-001 monotherapy in ccRCC and other malignancies. 
4.2.2. 
Rationale for the Dose Regimen 
Starting dose / Safety. The proposed starting dose (200 mg BID) is selected based on 
experience in prior clinical studies demonstrating that dose was (a) pharmacologically active 
(Section 2.2.2.4) and (b) generally safe and well-tolerated in 26 healthy volunteers and HIV- 
infected patients treated for 8 to 10 days (Section 2.2.3), with no treatment-related 
discontinuations and no pattern of significant laboratory abnormalities. See Section 2.2.5 for 
discussion of anticipated clinical exposure relative to findings seen in nonclinical studies. 
Dosing interval. BID dosing is supported by clinical experience with BID dosing as detailed 
above. In the prior development program, 400 mg BID was generally safe and well tolerated for 
3.5 days and the T1/2 of X4P-001 is ~23hr. The once daily dosing regimen is easier and more 
reliable, particularly in patients with cancer, for whom avoiding food for two 3-hour periods each 
day may be difficult. 
In consideration of the advantages of once daily dosing, provision is made for patients in the 
initial cohort administered X4P-001 at 200 mg BID to convert to 400 mg QD, contingent on the 
following: 
• Successful DRC review of the 600 mg QD dose level with approval for further dose 
escalation. 
• Request of the patient’s Investigator and approval of the Medical Monitor. 

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Dose Escalation. Dose-escalation will proceed conservatively with increases never exceeding 
1.5x the prior dose level (see Section 4.1.1). Conversion of the dose escalation program from 
BID to QD will be accomplished as follows: 
• Following successful DRC review of the 200 mg BID cohort, once daily dosing regimens 
will be applied to subsequent cohorts. 
• The first once daily cohort will be 400 mg QD, representing the same total daily dose as 
200 mg BID. 
• Dose escalation will then proceed through the planned daily doses, which will be 
administered as 600, 800, and 1200 mg QD, the last being the highest dose level that will 
be given. 
4.3. 
Endpoints 
4.3.1. 
Safety Endpoints 
Safety endpoints are: 
• AEs. 
• Clinical observations (e.g., vital signs, physical examination). 
• Laboratory tests, (e.g., clinical chemistry, hematology, and   thyroid function tests [Part 
A and Part B only]). 
• ECGs. 
• Ophthalmologic examination 
4.3.2. 
Efficacy Endpoints 
Treatment effect (tumor response) will be analyzed using RECIST v1.1 [Eisenhauer 2009] to 
determine the following efficacy endpoints: 
• Objective response rate (ORR) (Complete Response [CR] + Partial Response [PR]) 
• Time to objective response 
• Duration of objective response 
• Disease control rate (CR + PR + Stable Disease) 
• Time to progression 
• PFS 

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4.3.3. 
PK and PD Endpoints 
PK samples will be collected from 0-4hr on Cycle 1 Day 1 (C1D1) and from 0-8 hr on C1D15. 
Pre-dose PK samples are also collection on C2D1 and C2D15. 
White blood cell counts and counts of circulation CD34+ positive cells are PD samples. 
 
4.3.4. 
Exploratory Endpoints 
Exploratory endpoints are blood biomarkers, including serum biomarkers and PBMC, as well 
as tumor response assessed possibly using modified Response Evaluation Criteria in Solid 
Tumors for immune-based therapeutics (iRECIST) [Seymour 2017]. 
5. 
STUDY ENROLLMENT AND WITHDRAWAL 
 
5.1. 
Inclusion Criteria 
Patients must meet all of the following criteria to be eligible for study participation: 
1. Be at least 18 years of age. 
2. Have signed the current approved informed consent form. 
3. Have a histologically confirmed diagnosis of predominant ccRCC. 
4. Have received at least one prior course of treatment for ccRCC (see Section 5.2 for 
specific exclusions). 
5. Have on computed tomography (CT) imaging done within 28 days of Day 1 findings 
consistent with advanced ccRCC, including at least one extra-renal measurable target 
lesion meeting the criteria of RECIST v1.1 [Eisenhauer 2009]. See Section 7.1.4.1 for 
details regarding specific imaging technology. 
6. Agree to use contraception as follows: 
• For women of childbearing potential (WOCP, see Section 7.4.1.2 for definition) agree 
to use highly effective contraceptive methods from screening, through the study, and 
for at least 4 weeks after the last dose of study drug. Acceptable methods are described 
in Section 7.4.1.3 
• For males, agree to use a condom with any WOCP sexual partner from Day 1 of study 
treatment, through the study, and at least 4 weeks after the last dose of study drug. 
7. For women of childbearing potential, have a negative pregnancy test (serum or urine) on 
Day 1 prior to initiating study treatment. 
8. Be willing and able to comply with this protocol. 
 

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5.2. 
Exclusion Criteria 
Patients meeting any of the following criteria are excluded from study participation: 
1. Has life expectancy of less than 3 months. 
2. Has performance status Grade >2 (Eastern Cooperative Oncology Group [ECOG] 
criteria). 
3. Has New York Heart Association Class III or IV heart failure or uncontrolled 
hypertension (systolic blood pressure [SBP] ≥160 mm Hg; diastolic blood pressure 
[DBP] ≥100 mm Hg). 
4. Has previously received X4P-001. 
5. Parts A and B only: Has received a prior course of axitinib. 
6. Parts A and B only: Has received mechanistic target of rapamycin (mTOR) inhibitor(s) as 
their only prior treatment for ccRCC. 
7. Has a prior history or current evidence of intracranial (CNS) metastatic RCC, except for 
≤3 lesions treated by CyberKnife (or any type of radiation) or excisional surgery, 
clinically stable for at least 4 weeks, and without evidence of recurrence on MRI 
imaging at screening. 
8. Has ongoing acute clinical AEs of National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) Grade >1 resulting from prior cancer 
therapies (except alopecia, TKI-related hand-foot syndrome, or thyroid dysfunction). 
9. Has had within the past 6 months the occurrence or persistence of one or more of the 
following medical conditions that could not be controlled with usual medical care (e.g., 
required emergency care or hospitalization): hypertension, angina, congestive heart 
failure, diabetes, seizure disorder. 
10. Has had within the past 6 months the occurrence of one or more of the following events: 
myocardial infarction, cerebrovascular accident, deep vein thrombosis, pulmonary 
embolism, hemorrhage (CTCAE Grade 3 or 4), chronic liver disease (meeting criteria for 
Child-Pugh Class B or C), a second active malignancy (excluding: malignancies that 
were treated curatively and have not recurred within 2 years prior to study treatment; 
completely resected basal cell and squamous cell skin cancers; any malignancy 
considered to be indolent and that has never required therapy; and completely resected 
carcinoma in situ of any type), organ transplantation. 
11. Has had within the 4 weeks prior to initiation of study drug, or is expected to have during 
the study period, surgery requiring general anesthesia. 
12. Has a known history of a positive serology or viral load for HIV or a known history of 
AIDS. 
13. Has, at screening, serologic laboratory tests meeting one or more of the following 
criteria: 

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• An indeterminate or positive test for antibody to hepatitis C virus (HCV), unless 
documented to have no detectable viral load on 2 independent samples. 
• A positive test for hepatitis B surface antigen (HBsAg). 
14. Has, at screening, safety laboratory tests meeting one or more of the following criteria: 
• Hemoglobin <8.0 g/dL 
• Absolute neutrophil count (ANC) <1,500/μL 
• Platelets <75,000/μL 
• Creatinine >2.0x ULN 
• Serum aspartate transaminase (AST) >2.5x upper limit of normal (ULN) 
• Serum alanine transaminase (ALT) >2.5x ULN 
• AST and ALT >5x ULN for patients with liver metastasis 
• Total bilirubin >1.5x ULN (unless due to Gilbert’s Syndrome, total bilirubin > 3.0x 
ULN and direct bilirubin > 1.5x ULN) 
15. Has received other anti-cancer therapy within the following specified intervals prior to 
Day 1: 
• TKI within 2 weeks. 
• Radiation therapy within 2 weeks. 
• Bevacizumab within 4 weeks. 
• Other chemotherapy (e.g., mitomycin-C, nitrosourea) or immunotherapy 
(e.g., antibody, cytokine) within 4 weeks. 
• For investigational anti-cancer therapies, the interval will be determined in 
consultation with the Medical Monitor. 
16. Has, within 2 weeks prior to Day 1, received a medication prohibited based on CYP3A4 
interaction (see Section 7.4.1.1 for details). 
17. Has, within 2 weeks prior to Day 1, received systemic corticosteroids exceeding 
prednisone 10 mg per day or equivalent; for other immunosuppressive agents, the 
exclusionary dose and duration will be determined in consultation with the Medical 
Monitor. 
18. Is nursing. 
19. Has, at the planned initiation of study drug, an uncontrolled infection. 
20. Has any other medical or personal condition that, in the opinion of the Investigator, may 
potentially compromise the safety or compliance of the patient, or may preclude the 
patient’s successful completion of the clinical study. 
Patients taking medications prohibited on the basis of CYP 3A4 interactions (see Section 

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7.4.1.1), may, after discussion with the prescribing physician, be changed to a functionally 
equivalent, non-prohibited medication, and, after at least 2 weeks off the prohibited medication, 
reassessed for enrollment, including rescreening, if necessary. 
5.3. 
Strategies for Recruitment and Retention 
Following receipt of IRB/IEC approval, the Investigator may initiate patient recruitment (see 
Section 13). To reach an economically and socially diverse population, the study may be 
announced publicly, including on relevant Internet websites; prior to use, the form and content of 
such announcements will be submitted to the IRB/IEC for approval (see Section 13). 
5.4. 
Participant Withdrawal or Termination 
 
5.4.1. 
Reasons for Withdrawal or Termination 
To provide for consistent accounting of patient disposition, when study treatment is discontinued 
in an individual patient for any reason, the Investigator will complete the appropriate electronic 
case report form (eCRF) and select the primary reason from the following standard categories: 
• DLT event – see Section 4.1.1.3. 
- For any DLT event occurring during the first 4 weeks of treatment, study treatment 
will be discontinued permanently. 
- For one of the critical DLT events (see Section 4.1.1.3) occurring after successful 
completion of 4 weeks of treatment, study treatment will be discontinued 
permanently. 
- For other unacceptable toxicity (defined with the same criteria of DLT for Cycle 1) 
occurring after successful completion of 4 weeks of treatment, provision is made for 
dose reduction (see Sections 6.1.7.1 and 6.1.7.2). 
• Disease progression – Patients will be assessed at study entry and every 8 weeks for 80 
weeks (20 cycles) and then every 12 weeks thereafter while on treatment; unscheduled 
assessments may be conducted in response to new clinical observations. Disease status 
will be classified according to RECIST v1.1 [Eisenhauer 2009] (see Section 7.1.4.2 for 
details). 
- Study treatment will be discontinued in patients who demonstrate disease 
progression. For patients who have radiological disease progression, but haven’t 
experienced clinical progression/deterioration, the patient may stay on study if the 
Investigator considers that the patient may still derive benefit from this study and 
have consulted with Medical Monitor. 
Removal of the subject for clinical progression/deterioration will be at the discretion of 
the Investigator. The decision needs to be consulted with Medical Monitor. 

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• Adverse Event, other than DLT – This includes any AE (clinical or laboratory; serious or 
non-serious; regardless of relation to study drug), that represents the reason study drug 
was discontinued, including: 
- The medical judgment of the Investigator based on the best interests of the patient. 
• The patient’s request based on any AE. 
• Withdrawal of Consent – The patient desired to withdraw from further participation in the 
study in the absence of a clinical issue. If the patient gave a reason for withdrawing (e.g., 
leaving area), it should be recorded in the eCRF. 
• Lost to Follow-Up – The patient stopped coming for visits. 
• Study Termination – by the Sponsor, for any reason. 
5.4.2. 
Handling of Participant Withdrawals or Termination 
When study treatment is discontinued for any reason, the End-of-Treatment (EOT) and End-of- 
Study (EOS) visits will be performed as specified. If a patient cannot be seen, attempts will be 
made to contact the patient by telephone to inquire about reasons for stopping participation and 
get updated information on any unresolved AEs. 
5.5. 
Premature Termination or Suspension of Study 
The Sponsor reserves the right to terminate the study or particular study center at any time. If the 
Sponsor or Investigator discovers conditions arising during the study that suggest the study 
should be halted, then study termination can occur only after appropriate consultation between 
the Sponsor and Investigators. Conditions that may warrant study or study center termination 
include, but are not limited to: 
• The discovery of any unexpected, significant, or unacceptable risk to the patients enrolled 
in the study. 
• Failure of the Investigator to enter patients at an acceptable rate. 
• Insufficient adherence to the protocol requirements. 
• A decision on the part of the Sponsor to suspend or discontinue development of study 
drug. 
Should the study be closed prematurely, all study materials (study drug, etc.) must be returned to 
the Sponsor or designee (or disposed of as directed by the Sponsor or designee). 

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6. 
STUDY DRUG(S) 
 
6.1. 
Study Drug(s) and Control Description 
6.1.1. 
Acquisition 
Study drug will be supplied by the Sponsor 
 
6.1.2. 
Formulation, Appearance, Packaging, and Labeling 
All manufacture, packaging and labeling operations will be performed according to ICH Good 
Manufacturing Practice (GMP) and Good Clinical Practice (GCP) guidelines. 
 
Table 6-1: 
Physical and Chemical Properties of Active Ingredient (Drug Substance) 
Name 
X4P-001 
Drug Class 
Chemokine (C-X-C motif) receptor 4 (CXCR4) antagonist 
INN 
Not Assigned 
Molecular Formula 
C21H27N5 
Molecular Weight 
349.48 amu 
Appearance 
white to pale yellow solid 
Solubility 
X4P-001 is freely soluble in the pH range 3.0 to 8.0 (>100 mg/mL), sparingly soluble at pH 9.0 (10.7 
mg/mL) and slightly soluble at pH 10.0 (2.0 mg/mL). X4P-001 is only slightly soluble in water. 
Melting Point 
111 °C 
 
Table 6-2: 
Formulation of Drug Product 
Name 
X4P-001 100 mg or 200 mg Capsule 
Active ingredient 
X4P-001 
Excipients 
Microcrystalline cellulose, dibasic calcium phosphate dihydrate, croscarmellose sodium, 
sodium stearyl fumarate, colloidal silicon dioxide, sodium lauryl sulfate 
How supplied 
Refer to the Pharmacy Manual. 
Storage 
5°C ± 3°C; Protect from light and humidity 
Administration 
Oral 
 
6.1.3. 
Product Storage and Stability 
Refer to the Pharmacy Manual. 

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6.1.4. 
Preparation 
None. 
6.1.5. 
Dosing and Administration 
6.1.5.1. 
X4P-001 
X4P-001 at the assigned dose level is administered orally QD or BID. Patients will be instructed 
about both dosing schedule and requirements relating to food or drink near the time of dosing. 
Dosing Schedule. 
For BID dose, it is expected that the first daily dose will be taken in the morning and the second 
daily dose approximately 12 hours later using the following guidelines: 
• Dosing should be at the same times each day ± 2 hr. 
• The interval between successive doses should not be <9 hours nor >15 hours. It the 
interval would be >15 hrs, the dose should be omitted and the usual schedule resumed at 
the next dose. 
For QD dose, it is expected that the daily dose will be taken as follows: 
• The daily dose should be taken in the morning, at the same times each day ± 2 hr. 
• The interval between successive doses should not be < 20 hrs. 
• If the interval between successive doses is delayed to > 30 hrs, the dose should be 
omitted and the usual schedule resumed the next day. 
Restrictions relating to food. Absorption is impacted by food and patients will be instructed as 
follows for all doses: 
• No food or drink (except water) for 1 hour before dosing 
• No food or drink (except water) for 2 hours after dosing. 
Patients for whom the scheduling requirements and eating restrictions represent significant 
difficulties should be discussed with the Medical Monitor to develop the most effective regimen 
possible. 
6.1.5.2. 
Axitinib 
Axitinib may be taken at the same time as X4P-001. Alternatively, since axitinib has been 
associated with GI AEs and its absorption is not altered by food (see current product label), 
patients may, with the approval of their Investigator, take the axitinib separately, following the 
same BID dosing schedule guidelines noted in Section 6.1.5.1. 

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Investigators should review and be familiar with the current US prescribing information for 
axitinib. 
6.1.6. 
Route of Administration 
X4P-001 will be administered PO. 
6.1.6.1. 
Axitinib 
 
Axitinib will be administered PO. 
 
6.1.7. 
Dose Adjustments/Modifications/Delays 
Treatment modifications should be implemented as described below. Any plan to deviate from 
the following guidelines in the interest of patient safety must be previously discussed with the 
Medical Monitor unless there is an urgent need for action. Investigators always have the option 
to discontinue study treatment based on their judgment of the patient’s best interests. For dose 
modifications due to concomitant use of strong inhibitors and inducers of CYP3A4, see Section 
7.4.1.1. 
After dose modification, the reduced doses of X4P-001 and axitinib can be re-escalated to the 
initial assigned dose levels if treatment related AEs remain ≤ Grade 1 over 4 weeks. 
A patient with a Grade 4 AE may resume treatment at the next lower dose level if the AE 
recovers to ≤ Grade 1 and, if in the opinion of the investigator and medical monitor, the 
patient can be monitored for recurrence of AE. 
6.1.7.1. 
X4P-001 Administered in Combination with Axitinib (Part A and Part B) 
1. Patients will be discontinued from this study if AEs (defined with the same criteria of critical 
DLT event; Section 4.1.1.3) occur and are considered to be related to X4P-001. 
 
2. If a patient receiving X4P-001 in combination with axitinib successfully completes the first 4 
weeks of treatment, and subsequently has a unacceptable toxicity (defined with the same 
criteria of DLT for Cycle 1, other than those designated critical) 
a. And the event is (possibly) related to both X4P-001 and axitinib, study treatment may be 
managed as follows. 
• Both X4P-001 and axitinib will be held (dosing interrupted). Note that the Schedules of 
Events are based on calendar days following the first dose and will not change. 
• If the event does not improve to Grade ≤1 within the next 14 days, study treatment will 
be discontinued. 
• If the event improves to Grade ≤1 within 14 days of holding study treatment, the patient 
may resume axitinib alone at the next lower dose level (see Section 6.1.7.3 for axitinib 

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dose adjustment guidelines). 
- If during the first 7 days on axitinib alone at the reduced dose, the event recurs or 
worsens to Grade >2, the dose modification procedure may be applied again, with 
the dose of axitinib being reduced one additional level. 
- If during the first 7 days on axitinib alone at the further reduced dose, the event 
recurs or worsens to Grade >2 again, study treatment will be discontinued. 
• If after 7 days on axitinib alone at reduced dose, the event does not recur or worsen, then 
X4P-001 will be resumed at the next lower dose level (see Table 6-3). 
b. And the event is (possibly) related to X4P-001 and not related to axitinib, study treatment 
may be managed as follows. 
• X4P-001 will be held (dosing interrupted) without dose modification of axitinib. 
• If the event does not improve to Grade ≤1 within the next 14 days, study treatment will be 
discontinued. 
• If the event improves to Grade ≤1 within 14 days of holding study treatment, the patient 
may resume X4P-001 at the next lower dose level (Table 6-3). 
• If the event recurs or worsens to Grade >2 at any time, the dose modification procedure 
may be applied again, with the dose of X4P-001 being reduced one additional level. 
• If there are any further Grade >2 recurrences, study treatment will be discontinued. 
 
c. And the event is (possibly) related to axitinib, but not X4P-001, dose modification of axitinib 
is described in Section 6.1.7.3 without any dose change for X4P-001. 
 
Table 6-3: 
Dose Modification Levels for X4P-001 
 
Current Dose (mg) 
200 BID 
400 QD 
600 QD 
800 QD 
1200 QD 
Modified Dose (mg) 
200 QD 
200 QD 
400 QD 
600 QD 
800 QD 
 
6.1.7.2. 
X4P-001 Administered as a Single Agent (Part C) 
If a patient receiving X4P-001 as single agent successfully completes the first 4 weeks of 
treatment, and subsequently has an unacceptable toxicity (defined with the same criteria of DLT 
for Cycle 1, other than those designated critical), study treatment may, with the agreement of the 
patient, the Investigator, and the Medical Monitor, be managed as follows. 
• X4P-001 will be held (dosing interrupted). 

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• If the event does not improve to Grade ≤1 within the next 14 days, X4P-001 will be 
discontinued. 
• If the event improves to Grade ≤1 within 14 days of holding X4P-001, the patient may 
resume X4P-001 as single agent at the next lower dose level (see Table 6-3). 
• If the event recurs at Grade >2 at any time after resuming X4P-001, one (and only one) 
additional level of dose reduction may be implemented using the above procedure. 
• If there are any further Grade >2 recurrences, study treatment will be discontinued. 
6.1.7.3. 
Axitinib 
Dose modifications of axitinib are recommended based on individual safety and tolerability and 
are permitted in this protocol. However, to minimize potential confounding of assessing 
concomitant X4P-001, the guidelines are adapted as follows. 
• Axitinib dose increases 
- There will be no axitinib dose increases during the first 8 weeks of treatment. 
- Thereafter, dose increases may be made during the first week of a cycle after 
completion of all procedures scheduled for the visit that week, including AE and 
con med review, drug compliance, physical exam, and safety laboratory tests. 
- Dose increases will be done as recommended: Patients must have no AEs Grade 
>2 for at least 2 weeks, be normotensive, and not be receiving anti-hypertensives. 
Dose increases will proceed from 5 mg BID to 7 mg BID to a maximum of 10 mg 
BID. 
• Axitinib dose decreases 
- These may be made at any time based on the Investigator’s judgment and 
following the label recommendations – decreasing from 5 mg BID to 3 mg BID to 
2 mg BID. 
- In the event of an unacceptable toxicity (defined with the same criteria of DLT for 
Cycle 1), dose reduction will be made as detailed above. 
6.1.8. 
Duration of Therapy 
Patients will remain on study treatment until disease progression, unacceptable toxicity, or other 
specified reasons for discontinuation (see Section 5.4). 

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6.1.9. 
Treatment Compliance 
Treatment compliance will be monitored by 2 procedures. 
• Patients will be provided with a treatment diary to record time and dose taken for both 
X4P-001 and axitinib, as well as time of last food prior to and after dosing X4P-001. 
Diaries will be reviewed with the patient at each clinic visit. 
• Both X4P-001 and axitinib will be dispensed in bottles, which will be examined visually 
at each clinic visit; non-destructive pill counts will be performed if indicated. 
For DLT evaluation, treatment compliance is required for both X4P-001 and axitinib during 
Cycle 1. The percentage of compliance is calculated using the following equation for doses taken 
at the intended dose level: 
% Compliance = 
Number of  X4P-001 or Axitinib doses actually taken 
Number of X4P-001 or Axitinib doses that should have been taken 
 
6.2. 
Study Drug Accountability Procedures 
× 100 
Regulatory authorities require accounting of all investigational drug received by each study 
center. Records of drug disposition required include the date received by the center, date 
administered, quantity administered, and the patient to whom study drug was administered. The 
Investigator is responsible for the accountability of all used and unused study drug containers 
and unused study drug. For the Combination Cohort(s), the study center also will maintain 
records for the combination anticancer agent, including the date administered, quantity 
administered, and the patient to whom the agent was administered. 
Each study center is to use a study drug accountability log to document study drug disposition. 
All items on this form are to be completed in full. The Sponsor’s clinical research associate 
(CRA) is to approve the area where study drug is to be stored and accountability records are to 
be maintained. 
The investigator identification number and patient initials (as allowed by local regulations) and 
identification number are to be recorded on each study drug accountability log. Each time study 
personnel dispense study drug for a patient, he or she is to record the date dispensed, amount of 
study drug dispensed, and his or her initials. Study personnel are to monitor the inventory of 
clinical supplies and maintain a count of all used and unused study drug. The CRA is to review 
study drug accountability records and remaining drug supplies during routine monitoring visits. 
At the completion of the study, the site must obtain written authorization from the Sponsor 
regarding the final disposition of any remaining X4P-001; that disposition must be appropriately 
documented. Typical procedures for handling any remaining study drug include the following: 

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• Returning study drug to the Sponsor. 
• Destroying study drug at the study site according to the site’s institutional standard 
operating procedure. 
Supplies of axitinib that have been distributed to the patient should be returned to the study site 
and destroyed as per institutional procedures. Supplies of axitinib that have not been distributed 
may be returned to the Sponsor, destroyed, or used for clinical purposes in accordance with 
institutional procedures. The final disposition will be agreed to in writing between the Sponsor 
and the study site. 
7. 
STUDY PROCEDURES AND SCHEDULE 
 
7.1. 
Study Procedures/Evaluations 
Written informed consent and, as applicable, assent will be obtained and the consent procedure 
recorded in source documentation before any other study-specific procedures are performed. 
7.1.1. 
Baseline and Safety Assessments 
7.1.1.1. 
Medical History 
General Medical History 
A complete medical history is to be documented during Screening, including relevant general 
medical and surgical history, current or past abnormalities or diseases of the following systems: 
allergic (including drug sensitivity), cardiovascular, dermatologic, endocrine/metabolic, 
gastrointestinal, gynecologic, hematologic/lymphatic, hepatic/biliary, immunologic, infectious, 
musculoskeletal, neurologic/psychiatric, renal, and respiratory. 
The medical history should include all significant illnesses and hospitalizations that occurred in 
the past 6 months, whether active or resolved. Illnesses active at the time of informed consent 
will be recorded in the medical history. 
History of Renal Cell Carcinoma (RCC) 
Detailed history of the course of the patient’s RCC will be recorded, including: 
• Prior surgical procedures, diagnostic or therapeutic. 
• Results (positive and negative) of prior tissue biopsies. 
• Prior medical treatments (including supportive therapy) – agent, duration, best clinical 
response, adverse events related to treatment, and reason for discontinuation. 
• Hospitalizations for clinically significant complications of the treatments or the 

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malignancy, e.g., systemic infections, bleeding. 
7.1.1.2. 
Enrollment Procedure 
All patients in this study will be treated open-label. To minimize the potential for patients being 
enrolled but not treated, patients will be enrolled (i.e., treatment assigned) as close as feasible to 
the scheduled date for first dose of study drug. 
7.1.1.3. 
Vital Signs 
Vital signs include heart rate (HR), SBP, DBP, and temperature. Where feasible, vital signs 
should be measured before blood is drawn and after the patient has been sitting comfortably for 
5 minutes with the BP cuff in place on the non-dominant arm. BP and HR measurements will be 
taken first and may be done manually or by automated recorder. Temperature will be obtained 
using an electronic (rapid reading) device. 
Vital sign measurements will be assessed by the Investigator as either ‘normal’, ‘abnormal, not 
clinically significant’, or ‘abnormal, clinically significant’. Clinically significant abnormal vital 
sign measurements will be reported as an AE, and, if possible, should be repeated at clinically 
relevant intervals until resolved or stabilized. 
7.1.1.4. 
Physical Examination, Body Weight, and Height 
Complete physical examinations will include measurement of body weight and examination of 
general appearance, skin, neck (including thyroid), eyes, nose, throat, heart, lungs, abdomen, 
lymph nodes, extremities, and nervous system. Body height will be measured at screening only. 
• For palpable lymph nodes, the location and maximal linear dimension will be recorded at 
each examination. 
• Examination of the reproductive system, breast, and rectal will be performed if there are 
related symptoms, adverse events, or recent history; the exam may be performed by the 
Investigator or delegated to a specialist. 
Physical examination findings will be assessed by the Investigator as either ‘normal’, ‘abnormal, 
not clinically significant’, or ‘abnormal, clinically significant’. Any clinically significant changes 
identified after the baseline (screening) examination will be recorded as AEs (see Section 8). 
7.1.1.5. 
Ophthalmologic Examination 
Ophthalmologic examination will be performed as scheduled and include the following 
elements: assessment of visual acuity (using Snellen test or local equivalent in countries outside 
the U.S.), refraction (at screening only), assessment of color vision, slit lamp examination, and 
retinal examination with photographs. All examination reports and photographs will be 
submitted to a central repository as soon as feasible after being performed to be reviewed for 
quality and completeness (see study operations manual for details). Note: an optometrist may 
complete the exam if all requirements can be met, including use of appropriate equipment to 

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obtain the retinal photographs. 
Retinal abnormalities noted at screening will be discussed with the Medical Monitor. 
Examination by a second ophthalmologist may be requested to confirm the description of the 
findings and the adequacy of the photographs. Enrollment may proceed with the approval of the 
Medical Monitor. 
Any patient reported to have treatment-emergent findings of retinopathy may be examined by 
a second ophthalmologist. 
All examination reports and photographs may be reviewed by an independent, blinded 
ophthalmologist designated by the Sponsor. 
7.1.1.6. 
ECOG Performance Status (PS) 
 
The ECOG PS will be obtained by questioning the patient about their functional capabilities, 
according to the table below. 
 
Table 7-1: 
ECOG PS Definitions 
Grade ECOG Performance Status 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about 
more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 
5 
Dead 
7.1.1.7. 
Electrocardiogram (ECG) 
Standard 12-lead ECG will be obtained after the patient has been semi-recumbent for ~10 
minutes. The following ECG parameters will be recorded: ventricular rate, RR interval, 
PR interval, QRS interval, QT interval, QTc interval, and QTc method. 
7.1.2. 
Pharmacokinetic Assessments 
PK samples (i.e.: “PK dense sampling’) will be obtained on all patients in Part A and Part C and 
at least 15 patients in Part B as follows: 
• Cycle 1 Day 1: pre-dose (-30 min); post-dose at 30, 60, 90 min (each ±5 min) and 2, 3, 
4 hr (each ±15 min) 
• Cycle 1 Day 15: pre-dose (-10 min); post-dose at 30, 60, 90 min (each ±5 min) and 2, 
3, 4, 8 hr (each ±15 min) 
• Cycle 2 Day 1 and Cycle 2 Day 15: pre-dose (-10 min) 

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These visits will be scheduled for early in the day and patients will be instructed to arrive at the 
clinic fasting and having not taken their morning dose of study drug(s). 
 
At a minimum, all subjects in Part B should have pre-dose PK samples collected at the visits 
above (e.g. Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15) if subjects are not 
required to complete the PK dense sampling.  
All samples will be analyzed for X4P-001 concentration and some samples in Part B may be 
analyzed to measure axitinib concentration using reversed-phase high performance liquid 
chromatography (RP-HPLC) with tandem mass spectrometry (MS/MS) detection. 
7.1.3. 
Pharmacodynamic Assessments 
Investigational biomarker and pharmacodynamic assays will be performed by a central 
laboratory designated by the Sponsor; to maximize consistency, tests may be batched. The 
clinical significance of these tests is unknown at this time, and the results will not be assessed 
by the Investigator. 
7.1.3.1. 
Pharmacodynamics 
Whole blood samples will be obtained concurrently with scheduled PK samples on Cycle 1 Day 1 
and Cycle 1 Day 15 only (see above) for: 
• WBC counts 
• Counts of circulating CD34+ positive cells. 
PD samples will be obtained on all patients in Part A and Part C and at least 15 patients in Part B. 
If sample yields permit, additional investigational immunomodulatory subsets may be analyzed 
(Table 7-2). PD samples will not be drawn at Cycle 2 Day 1 and Cycle 2 Day 15. 
7.1.3.2. 
Blood Biomarkers 
Blood samples (serum and PBMC) will be collected as scheduled for potential treatment- 
and tumor-related biomarkers that reflect the pharmacologic effects of CXCR4 antagonism 
on angiogenesis and immunomodulatory subsets of circulating PBMC (Table 7-2). 
Additional investigational blood studies may be performed using the collected samples. 
 
Table 7-2: 
Candidate Blood Biomarkers 
Serum factors associated with angiogenesis 
[DePrimo 2007] 
Immunomodulatory subsets of circulating PBMC 
[Tarhini 2014] 
CXCL12 
VEGF-A 
Soluble VEGFR-2 (sVEGFR-2) 
Placenta growth factor (PGF) 
Treg lymphocytes 
Activated T cells 
MDSC 
 

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7.1.4. 
Efficacy Assessments 
7.1.4.1. 
Radiologic Assessment of ccRCC 
Radiologic imaging of chest, abdomen and pelvis for assessing tumor status and treatment effect 
will be performed as indicated in the Schedules of Events. Interim assessments may be done at 
the request of the Investigator based on new findings. Patients enrolled with a history or current 
evidence of CNS disease will have brain imaging by magnetic resonance imaging (MRI) with 
contrast at baseline and, thereafter, as clinically indicated. 
Imaging will be interpreted using RECIST v1.1 [Eisenhauer 2009] (see Section 7.1.4.2). The 
expected imaging technology is CT with slice thickness ≤5 mm and contrast. The use of 
alternative technologies (e.g., CT scan with slice thickness >5 mm or MRI) requires the approval 
of the Medical Monitor and must be performed in a manner consistent with RECIST. For each 
patient, the imaging modality should be consistent throughout the study. If there is a need to 
change modality (e.g., a patient cannot receive radiologic contrast), an alternative modality may 
be used with the approval of the Medical Monitor. 
For clinical management during the study, imaging will be interpreted by the radiologist at the 
site and a written report provided. Patients who, in the judgment of the Investigator, have 
Progressive Disease, which is a protocol endpoint, will be reviewed with the Medical Monitor. 
As soon as feasible after an imaging study is performed, the images (with indication of the 
modality used) will be submitted to a central repository to be reviewed for quality and for central 
reading; the written report will be submitted to the eCRF. 
For endpoint analysis, after a patient completes the EOT visit, all imaging studies for that patient 
will be reviewed together and outcomes assigned by one or more radiologists designated by the 
Sponsor and experienced applying RECIST; they will be blinded to treatment allocation and 
clinical outcome. 
7.1.4.2. 
Evaluation of Response to Treatment and Disease Status 
Tumor response assessments will be conducted every 8 weeks (2 cycles) for 80 weeks (20 
cycles) and then every 12 weeks thereafter, at EOT, and as indicated based on new signs, 
symptoms or laboratory findings. Disease status, time to progression, duration of response will 
be determined based on RECIST v1.1 [Eisenhauer 2009]. Treatment decisions will be made by 
the Investigator incorporating the local radiology interpretation and consultation with the 
Medical Monitor. For data analysis, scans will be reviewed and interpreted by a blinded central 
review committee comprising up to 3 experienced radiologists; see Section 7.1.4.1 for details. 
Patients enrolled with a history or current evidence of CNS disease should have brain imaging by 
MRI at baseline and, thereafter, as clinically indicated. 

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The current (v1.1) RECIST provide a detailed process for using sequential CT imaging to 
classify tumor response [Eisenhauer 2009]. Key elements of the process are summarized below; 
details provided in the guideline [Eisenhauer 2009] remain determinative. NOTE: all 
specifications assume use of CT with slice thickness ≤5 mm. Modifications are required for 
other technologies [Eisenhauer 2009]. 
Definitions of key terminology: 
• Measurable non-nodal lesions – ≥10 mm in longest diameter. 
• Measurable nodal lesions – ≥15 mm in short axis 
• Nonmeasurable lesions – lesions that are smaller, including those that cannot be 
measured. 
• Measurable disease – presence of at least one measurable lesion. [NOTE: Entry into this 
study requires at least one measurable extra-renal lesion.] 
• Target lesions – At baseline, a maximum of 5 measureable lesions, no more than 2 for 
any individual organ, should be identified, documented, and the appropriate diameter of 
each recorded. Lesions should be selected based on size, be representative of disease, and 
be suitable for reproducible repeat measurement. Target lesions may include measurable 
lymph nodes. 
• The baseline sum of diameters (SOD) – The sum of the longest diameters for all non- 
nodal target lesions plus the sum of the short axis diameter for all nodal target lesions. 
• Non-target lesions – All other lesions present at baseline, including pathologic nodes 
(defined as nodes >10 mm in short axis). These should be documented (quantitative 
measurements are not required) so that they can be classified on follow-up as present, 
absent, or unequivocal progression. 
• New lesions – a new lesion should be unequivocal (e.g., not attributable to variation in 
technique); includes lesions in a location not scanned at baseline. 
• Definitions of response criteria for target and non-target lesions are summarized in Table 
7-3; these are integrated into an overall response assessment as summarized in Table 7-4. 

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Table 7-3: 
RECIST – Definitions of Response Categories for Target and Non-Target 
Lesions 
Target Lesions 
Complete Response (CR) (a) Disappearance of all non-nodal lesions, and (b) Absence of pathologic lymph nodes1. 
Partial Response (PR) 
≥30% decrease from baseline in the SOD of the target lesions 
Stable Disease (SD) 
Persisting disease that does not meet criteria for either PR or PD 
Progressive Disease (PD) a) ≥20% increase in the SOD of the target lesions, compared to the smallest sum on study, 
which may be either at baseline or while on treatment; 
and (b) an absolute increase of ≥5 mm in the SOD. 
Non-Target Lesions 
Complete Response (CR) (a) Disappearance of all non-target lesions, and (b) Absence of pathologic lymph nodes1. 
Non-CR/non-PD 
Persistence of one or more non-target lesions 
Progressive Disease (PD) Unequivocal progression of existing non-target lesions. 
1. 
All lymph nodes, whether or not designated target or non-target lesions, have short axis diameter ≤10 mm 
 
Table 7-4: 
RECIST – Overall Responses Based on Target Lesions, Nontarget Lesions, 
and New Lesions 
Target 
Lesions 
Non-target 
Lesions 
New 
Lesions 
Overall 
Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all evaluated 
No 
SD 
Non-PD or not all evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
Non-evaluable 
CR, PR, or SD 
PDa 
No 
PD 
Any 
Yes or no 
PD 
Any 
Any 
Yes 
1. 
“The designation of overall progression solely on the basis of change in non-target disease” in the face of CR, PR, or SD of 
target lesions is expected to be “extremely rare” [Eisenhauer 2009]. 
 
7.1.4.3. 
Exploratory Analysis of Efficacy Using iRECIST 
Tumor Response assessments may be explored by using modified  Response Evaluation 
Criteria in Solid Tumors for immune-based therapeutics (iRECIST) [Seymour 2017]. Details of 
this assessment will be defined in statistical analysis plan (SAP) and/or central imaging review 
documents. 

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7.2. 
Laboratory Procedures/Evaluations 
 
7.2.1. 
Clinical Laboratory Evaluations 
The laboratory safety tests below will be performed as scheduled by a central laboratory facility. 
The Investigator may order additional local laboratory tests consistent with their routine standard 
of care. 
 
Table 7-5:       Safety Laboratory Tests 
Hematology Panel 
Hematocrit 
WBC differential and absolute cell counts: 
Hemoglobin 
Basophils 
Platelet count 
Eosinophils 
WBC 
Lymphocytes 
 
Monocytes 
 
Neutrophils 
Clinical Chemistry Panel 
ALT 
Lipase 
Albumin 
Magnesium 
Alkaline phosphatase 
Potassium 
Amylase 
Total bilirubin** 
AST 
Total protein 
Bicarbonate 
Sodium 
Calcium 
Urea 
Chloride 
Uric acid 
Creatine kinase 
 
Creatinine* 
 
Glucose  
 
Inorganic phosphorus  
 
*Creatinine clearance will be calculated using the method of Cockcroft and Gault (Cockroft, Gault, 1976). 
** If the total bilirubin concentration is above 1.5 times the upper limit of normal, direct and indirect bilirubin should be 
differentiated. 
 
Thyroid Function Tests (Parts A and B only) 
Free thyroxin (Free T4) 
Thyroid stimulating hormone (TSH) 
Pregnancy tests (WOCP only)* 
beta-human chorionic gonadotropin 
*WOCP are required to take a pregnancy test if their period is late. 
 
 

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Serologic tests (Screening only) 
HBsAg 
 
Antibody to HCV 
 
7.2.1.1. 
Reporting of Safety Laboratory Tests 
Results of safety laboratory tests (except serology) are expected to be available to the 
Investigator within 48 hours. Procedures for the Investigator assessment of the results are 
detailed in Section 8.1.5. Procedures for the analysis of laboratory data are described in 
Section 8.2.2. 
7.2.1.2. 
Repeating Abnormal Laboratory Tests 
Laboratory tests showing abnormal or exclusionary values at Screening may be repeated no 
more than once; however, exclusionary serologic results may not be repeated. 
After dosing, abnormal laboratory tests assessed as “clinically significant” values may be 
repeated as often as deemed clinically necessary by the Investigator until the test values 
are clinically acceptable or until an explanation other than drug effect is given. 
7.2.2. 
Other Assays or Procedures 
None. 
7.2.3. 
Specimen Preparation, Handling, and Storage 
Laboratory samples are to be prepared, handled, and stored as instructed in the laboratory 
manual. 
7.2.4. 
Specimen Shipment 
Laboratory samples are to be prepared, handled, and stored as instructed in the laboratory 
manual. 
7.3. 
Study Schedule 
The overall study schedule is as follows: 
• Screening will be done within 28 days prior to Day 1 (the first dose of study drug). See 
Section 7.1.1.2 for details of the enrollment process. 
• Laboratory tests required for screening will be performed with 14 days prior to Day 1. 
• Treatment is scheduled to be administered continuously. Missed doses will be considered 
skipped. 
• Assessments for treatment response (or disease progression) are scheduled every 8 weeks 
(± 4 calendar days) of treatment for 80 weeks (20 cycles) and every 12 weeks thereafter. 

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• The EOT visit is will be performed within 6 days after the last dose of study drug or the 
decision to terminate treatment prematurely. 
• EOS visit, the final study event, will be performed 30 days after the last dose of study 
drug. In the event the EOT visit is delayed, the EOS visit will be performed at least 14 
days after the EOT visit. 
A detailed schedule of events is presented in Table 1-1. 
 
7.4. 
Concomitant Medications, Treatments, and Procedures 
Prior treatments for ccRCC will be recorded as detailed in Section 7.1.1.1. 
Any concomitant medication used from time of screening through last study visit will be 
recorded in the eCRF, including dose, regimen, and indication (reason for its prescription). 
7.4.1. 
Precautionary Medications, Treatments, and Procedures 
7.4.1.1. 
Restrictions related to CYP Interactions 
X4P-001 is metabolized through, and interacts with, the CYP metabolic enzymes found in the 
hepatic and intestinal microsomes (see Section 2.2.2.3 for details). Based on these observations, 
the following restrictions are placed on concomitant medications: 
• Strong inhibitors and inducers of CYP3A4 are prohibited. If a strong inhibitor or inducer 
cannot be avoided, the dose of X4P-001 can be reduced with approval of Medical 
Monitor. 
• Grapefruit and/or starfruit products, variable inhibitors of CYP3A4, are prohibited. 
• Moderate inhibitors and inducers of CYP3A4 are to be prescribed only with the approval 
of the Medical Monitor; additional monitoring of X4P-001 drug levels may be required. 
• Sensitive CYP2D6 substrates should be avoided and other CYP2D6 substrates should be 
administered only with the approval of the Medical Monitor. 
Appendix Section 18.2 provides a list of commonly prescribed drugs that are inhibitors or 
inducers of CYP3A4 and substrates of CYP2D6. Known strong inducers and inhibitors are 
indicated. This list of drugs may not be a complete list, consultation with the Medical Monitor is 
requested for any concerns about concomitant medication use. 
7.4.1.2. 
Non-childbearing Potential 
Non-childbearing potential is defined as a female who meets either of the following criteria: 
• Age ≥50 years and no menses for at least 1 year. 
• Documented hysterectomy, bilateral tubal ligation, or bilateral oophorectomy. 
7.4.1.3. 
Effective Birth Control (Contraception) Methods 

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Women of Childbearing Potential (WOCP) must use a highly effective method of contraception 
during the study and through 4 weeks after the last dose of study drug. Acceptable methods 
include: 
• hormonal contraceptives when used with an additional barrier method (e.g., a male 
condom): 
o combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation 
▪ oral 
▪ intravaginal 
▪ transdermal 
• progestogen-only hormonal contraception associated with inhibition of ovulation: 
o oral 
o injectable 
o implantable 
• intrauterine device (IUD)  
• intrauterine hormone-releasing system (IUS) 
• bilateral tubal occlusion 
• vasectomized partner who has received a medical assessment of surgical success (when 
the partner is the sole partner) 
• sexual abstinence (when in agreement with the lifestyle and preference of the WOCP) 
Males are required to use a condom with any WOCP sexual partner from Day 1 of study 
treatment, through the study, and at least 4 weeks after the last dose of study drug. 
7.4.2. 
Prohibited Medications, Treatments, and Procedures 
The exclusion criteria specify treatments prohibited at the time of study entry (Section 5.2). 
While patients are receiving study treatment, other treatments for ccRCC are prohibited. Patients 
who discontinue treatment prematurely and have completed the End-of-Treatment visit, may 
receive available or investigational treatment for their disease at any time based on the judgment 
of their physician. If such treatment is initiated prior to the EOS visit, this will be recorded in 
concomitant medications and considered in assessment of any new AE. 
7.4.3. 
Prophylactic Medications, Treatments, and Procedures 
None. 
7.4.4. 
Rescue Medications, Treatments, and Procedures 
7.4.4.1. 
Treatment of Expected Adverse Events 
Based on prior clinical experience (as detailed in Section 2.2.3), the following treatments are 
recommended for symptomatic relief of “red eye”, “dry eye”, nasal congestion (in some 

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instances with nosebleed), and facial pains, which may occur within 48 hours of initiation of 
treatment: 
• Lubricant eye drops containing carboxymethylcellulose sodium (0.5%), such as 
Refresh™ Tears 
• Non-medicated saline nasal spray, such as Simply Saline™ Nasal Mist (Arm & Hammer) 
• Acetaminophen (Tylenol™) 
7.4.5. 
Precautions Regarding Axitinib 
Drug metabolism. Axitinib is metabolized primarily by CYP3A4 and 3A5 and to a lesser extent 
by CYP1A2 and CYP2C19. Co-administration of strong CYP3A4 inhibitors and inducers, and of 
grapefruit or starfruit products, is prohibited. 
• The requirements detailed in Section 7.4.1.1 are consistent with this. Administration of 
X4P-001 caused only a modest increase in exposure to midazolam (also a CYP3A4 
substrate). 
Exclusions: Moderate to severe hepatic impairment; pregnancy. 
• Both of these are also exclusions under this protocol. 
Warnings and Precautions. The following events are listed: hypertension and hypertensive 
crisis; arterial thromboembolism; venous thromboembolism; hemorrhage; cardiac failure; 
gastrointestinal perforation; thyroid dysfunction; wound healing complications; reversible 
posterior leukoencephalopathy syndrome; proteinuria. 
• None of these events was observed in prior studies using X4P-001. Recent uncontrolled 
hypertension, uncontrolled congestive heart failure, and thromboembolic events are all 
exclusions. 
Elevation of liver enzymes. Grade 1 and 2 elevations of ALT (up to 5x ULN) were observed in 
~20% of patients with advanced RCC treated with axitinib. The incidence of Grade 3/4 events 
was <1%. 
• LFTs are being monitored closely in this protocol, and clinically significant abnormalities 
are explicitly defined (Section 4.1.1.3). 
7.4.6. 
Patient Restrictions during the Conduct of the Study 
In the interest of their safety and to facilitate assessment of both safety and treatment effect, the 
patients participating in this study will be requested to agree to the following restrictions during 
the study: 
• Not start any new prescription medications, except as prescribed or approved by their 
Investigator or if required in an emergency; 

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• Not take any over-the-counter medications, except as instructed or approved by their 
Investigator. 
• Not drink grapefruit juice or eat grapefruit/starfruit. 
• Use effective contraception as defined in Section 7.4.1.3. 
7.5. 
Appropriateness of Measurements 
Planned assessments are standard measurements for this type of study and are considered 
appropriate. Per regulatory guidance, demographic data, complete medical histories, including 
cancer treatment history, and Baseline disease status are to be documented for all patients at 
Baseline (FDA Guidance for Industry 2001). 
AEs and SAEs are monitored in this study in accordance with International Conference on 
Harmonisation (ICH) GCP guidelines to ensure the safety of patients. Furthermore, additional 
safety assessments conducted during this study, including physical examinations, ECGs, vital 
signs assessments, and clinical laboratory tests, are widely used and generally recognized as 
reliable, accurate, and relevant. These tests and procedures also will be monitored in accordance 
with ICH GCP guidelines. 
Tumor response and progression will be assessed using standard criteria for the assessment of 
disease response in solid tumors, RECIST, v1.1. 
 
8. 
ADVERSE EVENTS 
 
8.1. 
Definitions 
8.1.1. 
Adverse Events (AE) 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product, and which does not necessarily have to have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including abnormal laboratory findings), symptom, or disease temporally associated with the 
use of an investigational product, whether or not related to the investigational product. 
An AE in a clinical study may be any of the following: 
• An unfavorable and unintended symptom reported by the patient. Patients will be 
encouraged to report treatment-emergent AEs spontaneously; general, non-directed 
questioning may also be used to elicit reports of AEs. 
• Clinical sign detected by the Investigator. Observations by other study personnel will be 
reported to the Investigator for evaluation. 
• Abnormal result from a laboratory study or other diagnostic procedure that meets at least 

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one of the following criteria: 
- Results in termination of study drug; 
- Leads to treatment; 
- Leads to further diagnostic tests (other than a single repeat for confirmation); 
- Is assessed as “clinically significant” by the Investigator. 
8.1.2. 
Serious Adverse Events (SAE) 
An AE or suspected adverse reaction is considered serious if, in the view of either the 
Investigator or Sponsor, it: 
• Results in death. 
• Is life-threatening. Life-threatening means that the patient was at immediate risk of death 
from the reaction as it occurred, i.e., it does not include a reaction which hypothetically 
might have caused death had it occurred in a more severe form. 
• Requires in-patient hospitalization or prolongation of existing hospitalization. 
Hospitalization admissions and/or surgical operations scheduled to occur during the study 
period, but planned prior to study entry are not considered AEs if the illness or disease 
existed before the patient was enrolled in the study, provided that it did not deteriorate in 
an unexpected manner during the study (e.g., surgery performed earlier than planned). 
Additional exclusions to SAE reporting include hospitalizations for: 
- Elective procedures. 
- Social/administrative reasons in the absence of an AE. 
- Expected deterioration caused by progression of the disease under study. 
• Results in persistent or significant disability/incapacity. Disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions. 
• Is a congenital anomaly/birth defect. 
• Is an important medical event. An important medical event is an event that may not result 
in death, be life-threatening, or require hospitalization but may be considered an SAE 
when, based upon appropriate medical judgment, it may jeopardize the patient and may 
require medical or surgical intervention to prevent one of the outcomes listed in the 
definitions for SAEs. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in in-patient hospitalization, or the development of drug 
dependency or drug abuse. 
 

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8.1.3. 
Adverse Drug Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered adverse drug reactions. The phrase "responses to a medicinal products" means that a 
causal relationship between a medicinal product and an adverse event is at least a reasonable 
possibility, i.e., the relationship cannot be ruled out. 
8.1.4. 
Suspected, Unexpected Serious Adverse Reaction (SUSAR) 
A SUSAR is defined as an SAE that meets both the following criteria with respect to study drug: 
• Suspected — is assessed as related or possibly related to study drug (see Section 8.2.2); 
• Unexpected — compared to the study drug-related AEs described in Investigator’s 
Brochure, the event meets any of the following criteria: 
- The event was not previously described; 
- The event is now characterized as more severe (see Section 8.2.1); 
- The event is now characterized more specifically (e.g., an event of “interstitial 
nephritis” in a patient receiving an agent previously described as associated with 
“acute renal failure”). 
In clinical studies involving ill patients, events considered related to the natural history of the 
disease under study or to lack of efficacy (that is, the event is considered more likely related to 
those factors than to other factors, including study drug) are not considered "unexpected". 
8.1.5. 
Clinical Laboratory Adverse Events 
The Investigator will review the results of all Safety Laboratory tests (see Section 7.2.1) and 
designate any results outside of the reference range as either of the following: 
• Abnormal, not clinically significant (NCS) 
• Abnormal, clinically significant (CS). 
In making this judgment, the Investigator will consider all available information, including the 
patient’s clinical condition, all available laboratory results, and the potential for false positive test 
results. In addition, laboratory studies that result in the actions specified in Section 8.1.1 will be 
classified as “abnormal, clinically significant”. 
Any result assessed as “abnormal, clinically significant” will be recorded as an AE unless it is 
consistent with one or more of the following: 
• Process noted in the medical history: 
• Ongoing adverse event already recorded; 
• Expected course of the primary disease under study. 

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8.2. 
Classification of Adverse Events 
 
8.2.1. 
Severity 
The intensity (synonym: severity) of clinical AEs (i.e., symptoms reported by the patient and/or 
signs observed by the Investigator) will be assessed by the Investigator using the NCI CTCAE 
(v4.03) five-level grading system, available on-line (see 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf). 
If the AE is not included in the NCI CTCAE, then the Investigator is to determine the intensity 
of the AE according to the following criteria: 
• Mild (Grade 1):  AE that disappears or is easily tolerated on continuation of study drug. 
• Moderate (Grade 2): AE sufficiently discomforting to cause interference with usual 
work activities. 
• Severe (Grade 3): AE that is incapacitating, with inability to work or perform daily 
activities. 
• Life-Threatening (Grade 4):  AE that is potentially life threatening. 
• Death (Grade 5):  Death related to AE. 
8.2.2. 
Grading of Laboratory Safety Tests for Reporting and Analysis 
Treatment-emergent abnormal laboratory results will be reported as AEs when assessed as 
“clinically significant” using the procedures and criteria detailed in Section 8.1.5. 
For purposes of analyzing laboratory data, all laboratory results will be graded using NCI CTCAE 
v4.03 and then summarized as “shift tables” comparing baseline and treatment-emergent results. 
This process will assure that the final study report contains complete and consistent analyses of 
safety laboratory tests. 
8.2.3. 
Relationship to Study Drug 
This determination is based on the Investigator’s clinical judgment regarding the likelihood that 
the study drug caused the AE and may include consideration of some or all of the following 
factors: 
• Alternative possible causes of the AE, including the patient’s underlying disease or 
co-morbid conditions, other drugs, other host and environmental factors; 
• Temporal sequence between the exposure to study drug and the AE; 
• Whether the clinical or laboratory manifestations of the AE are consistent with known 
actions or toxicity of the study drug; 
• Whether the AE resolved or improved with decreasing the dose or stopping the study 

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drug (i.e., dechallenge); or recurred or worsened with re-exposure to the drug 
(i.e., rechallenge). 
The relationship between the study drug and the AE will be described using one of the following 
categories: 
• Related:  the study drug is more likely the cause of the AE than other factors; 
• Possibly related: there is a reasonable possibility that the study drug is the cause of the 
AE, including that the study drug and another factor(s) are equally likely as causes of the 
AE; 
• Unlikely related: another factor is considered more likely the cause of the AE than the 
study drug; 
• Not related:  another factor is considered to be the cause of the AE. 
Related and possibly related AEs may result during the use of the study drug as planned (per 
protocol), or from abuse, withdrawal or over-dosage of the agent. 
8.2.4. 
Expectedness 
AEs meeting the criteria in Section 8.1.4 are to be considered unexpected. 
 
8.2.5. 
Date and Time of Onset 
The date and time at which the event was first apparent. Table 8-1 summarizes the basis for 
reporting the date and time of onset for the different types of AEs. 
 
Table 8-1: 
Reporting the Date and Time of Onset of AE for Different Types of Events 
Type of Event 
Examples 
Source of Date and Time of Onset 
Symptom 
Headache, feverish, paresthesia 
When first experienced by the patient 
Sign (Finding) 
Elevated BP, enlarged liver on physical exam When first observed by the Investigator or other study 
staff 
Laboratory / 
diagnostic result 
Neutropenia, hyperglycemia, 
lesions on brain scan 
When lab sample was obtained or diagnostic study 
performed 
 
The time of onset of symptoms may be appreciably earlier than the date and time the Investigator 
becomes aware of the event. Some events may be apparent to the patient and Investigator 
independently, and information from each may contribute to the final report. For example, a 
patient may report the onset of a rash 2 days before being seen by a physician who makes a 
diagnosis of herpes zoster based on appearance and laboratory confirmation. In that case, there is 
a single AE, with the date of onset based on the date of the initial observation by the patient and 
a specific description (herpes zoster) based on the clinical examination and tests. 

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8.2.6. 
Actions Taken for Management of AE 
AEs will be followed and managed by the Investigator, including obtaining any supplemental 
studies needed to define the nature and/or cause of the event (e.g., laboratory tests, diagnostic 
procedures, consultation with other health care professionals). 
For each AE the Investigator will categorize as follows the actions taken to manage the AE: 
• Concomitant medication — one or more medications (prescription or over-the-counter) 
were started or increased in dose; non-medication actions may also have been ordered. 
• Other action — only non-medication action(s) were ordered as management of the AE 
(e.g., bed placed in Trendelenburg position). 
• No action — no actions were ordered for management of the AE. 
8.2.7. 
Follow-up and Outcome of AEs 
If possible, AEs will be followed until resolved (synonyms: recovered, recuperated, ended) either 
with or without sequelae, including for patients who prematurely discontinue study participation. 
For AEs that are assessed as not drug-related and are not resolved at the EOS visit, follow-up 
may be limited with the approval of the Medical Monitor. 
The outcome of each event will be described using the following categories: 
• Resolved without sequelae — the event resolved and patient returned to baseline; 
• Resolved with sequelae — the event resolved but the patient is left with residual 
problems (e.g., functional deficits, pain); 
• Resolving — at the last observation, the event was improving; 
• Not Resolved — at the last observation, the event was unchanged; 
• Death (Fatal) — to be used for the one AE which, in the judgment of the Investigator, 
was the primary cause of death; 
• Unknown — there were no observations after the onset (initial observation or report) of 
the event. 
Note: Resolving and Not Resolved may also be used for AEs that were unresolved at the time a 
patient died, but were not assessed as the primary cause of death. 

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8.2.8. 
Date and Time of Outcome 
For each class of outcome as defined above, Table 8-2 indicates the date and time to be recorded. 
As discussed in detail for date / time of onset (see Section 8.2.5), determining the date / time an 
event resolved (ended) should reflect the type of event and the source of the information. 
 
Table 8-2: 
Date and Time of Outcome for AE by Outcome Class 
Outcome assigned to AE 
Date and Time to be Recorded 
Resolved (with or without sequelae) 
Date and time event observed or reported as resolved 
Death 
Date and time of death 
Resolving or Not Resolved 
Date and time of last observation 
Unknown 
None (see definition above) 
 
8.3. 
Time Period and Frequency for Event Assessment and Follow-Up 
Procedures for the collection and recording of AEs are as follows: 
• From obtaining informed consent through EOS, there will be active surveillance to 
identify all AEs. Events will be recorded in the AE portion of the eCRF, with particular 
attention to whether the onset of the event was before or after the administration of the 
first dose of study drug. 
• After EOS, surveillance will be passive (only events brought to the Investigator’s 
attention will be considered) and only events assessed as SUSARs (see Section 8.1.4) 
will be recorded. 
8.4. 
Reporting Procedures 
8.4.1. 
Adverse Event Reporting 
Each patient must be carefully monitored for the development of any AEs. This information 
should be obtained in the form of non-leading questions (e.g., “How are you feeling?”) and from 
signs and symptoms detected during each examination, observations of study personnel, and 
spontaneous reports from patients. 
All AEs (serious and non-serious) spontaneously reported by the patient and/or in response to an 
open question from study personnel or revealed by observation, physical examination, or other 
diagnostic procedures occurring within the time frame specified in Section 8.3 will be 
documented in the patient’s source documents and recorded in the eCRF. Any clinically relevant 
(as determined by the Investigator) deterioration in laboratory assessments or other clinical 

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finding is considered an AE and must be recorded in the patient’s source documents and in the 
eCRF. 
The AE term should be reported in standard medical terminology when possible. Also when 
possible, signs and symptoms indicating a common underlying pathology should be noted as one 
comprehensive event. For each AE, the investigator will evaluate and report the onset, 
resolution, intensity, causality, action taken, serious outcome (if applicable), and whether or not 
it caused the patient to discontinue the study. 
8.4.2. 
Serious Adverse Event Reporting 
SAE reporting, including supporting materials, will be performed by the site using a system 
approved by the Sponsor; detailed training will be provided during site initiation. Contact 
information for guidance and assistance with SAE reporting will be provided in the Study 
Manual. 
8.4.2.1. 
Procedures for Reporting SAEs to the Sponsor 
The initial notification of each SAE will be reported within 24 hours of the time the Investigator 
(or the Investigator's designee) becomes aware that the event has occurred and will include the 
following items of information (any items not available should be explicitly noted): 
• Protocol number, study site, patient number; 
• Investigator’s name, address, and contact information (phone, fax, email); 
• Description of the event (i.e., date and time of onset, initial assessment, treatments and 
course); 
• Current status of the patient and the event; 
• Criteria by which the event was assessed as serious; 
• Date of the first administration of study drug; 
• Date of the last administration of study drug prior the event; 
• Assessment of relationship of study drug to the event; 
• Whether the study drug was discontinued or adjusted as a result of the event. 
A narrative summary of the event will be reported within 2 days for death and life-threatening 
events and within 4 days for all other SAEs. The narrative summary will include specific 
information that will assist in understanding the event, e.g., relevant medical history, co-morbid 
conditions, physical exam, diagnostics, assessment, treatments (including concomitant 
medications), response to treatment, course, and outcome (if known). 

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Thereafter, signed supplemental (follow-up) information will be provided as it becomes 
available to the Investigator (either directly or as a result of investigation into a query). Such 
information includes but is not limited to: 
• Copies of relevant medical reports — including diagnostic procedures (e.g., laboratory 
tests), surgical procedures, and consultations 
• More definitive outcome for events previously reported as ongoing or unknown outcome 
8.4.2.2. 
Requirements for Expedited and Periodic Reporting of Adverse Events 
SUSARs are required to be reported rapidly to regulatory authorities and to IRB/IECs (typically 
within 7 days for fatal or life-threatening SUSARs; within 15 days for all other SUSARs). The 
Sponsor and the Investigator will work together to meet these reporting requirements. 
8.4.2.3. 
Notification of SAEs to the Investigator by the Sponsor 
In accordance with regulatory requirements, the Sponsor will notify the Investigator of the 
occurrence of SUSARs reported by other Investigators in this or in other studies involving the 
study drug. The Investigator will promptly inform his/her IRB/IEC of such communications 
from the Sponsor and will document that notification in the Investigator’s Regulatory Binder. 
8.4.3. 
Events of Special Interest 
None. 
8.4.4. 
Reporting of Pregnancy 
Pregnancies occurring in the patient or patient’s partner while the patient is receiving study drug 
or within 1 month after the patient’s last dose of study drug will be reported using the same 
procedures as for SAEs described in Section 8.4.2. 
Study drug must be discontinued immediately in the event of a pregnancy in the patient. The 
patient should be referred to an obstetrician/gynecologist experienced in reproductive toxicity for 
further evaluation and counseling. 
The Investigator will follow the patient / patient’s partner until completion of the pregnancy, and 
must notify the Medical Monitor of the outcome within 5 days. The Investigator will provide this 
information as a follow-up to the initial report. 
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE (i.e., 
spontaneous abortion [any congenital anomaly detected in an aborted fetus is to be documented], 
stillbirth, neonatal death, or congenital anomaly), then the Investigator should report it as such. 
Furthermore, all neonatal deaths that occur within 30 days of birth should be reported, without 

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regard to causality, as SAEs. In addition, any infant death after 30 days that the Investigator 
suspects is related to the in-utero exposure to the study drug should also be reported. 
8.5. 
Study Halting Rules 
Stopping Rules may be developed if unexpected SAEs with causal relationship to study drug, 
including delivery procedure, appear during the study. 
The study also may be stopped based on a decision on the part of the Sponsor to suspend or 
discontinue development of study drug. 
8.6. 
Safety Oversight 
8.6.1. 
Procedures for Monitoring Risks Associated with X4P-001 
Table 8-3 indicates specific procedures in this protocol for managing these previously identified 
risks. 
 
Table 8-3: 
Monitoring Procedures for Risks Identified in Prior Studies of X4P-001 
(AMD11070) 
Prior Findings 
Clinical Monitoring Procedures 
X4P-001 is predominantly metabolized through CYP-3A4a 
Avoid concomitant medications that are strong CYP3A4 
inhibitors or inducers; If a strong inhibitor or inducer can not 
be avoided, the dose of X4P-001 can be reduced with 
approval of Medical Monitor. 
X4P-001 is a moderate inhibitor of CYP-2D6a1 
Avoid sensitive CYP2D6 substrates. Closely monitor other 
CYP2D6 substrates 
Beagles, 13-week toxicology study with X4P-001 (free-base)2 
-- ALT: mild (1.4x–2.4x), exposure-related increases 
-- Total bilirubin: no increases in any animal 
-- Microscopic liver findings: multifocal necrosis (single cell) in 4 
of 12 animals dosed at 35 or 70 mg/kg/d 
Safety laboratory tests, including aspartate transaminase, 
alanine transaminase, total bilirubin, every 4 weeks during 
treatment. 
Rats, 26-week toxicology study with AMD11070PHB (salt)c3 
-- retinal degeneration (20, 50, 100 mg/kg bid) 
-- retinal atrophy (100 mg/kg BID only) 
An ophthalmology evaluation every 12 weeks: 
visual acuity assessment; color vision assessment; 
slit lamp exam; retinal examination with photographs. 
1. 
A detailed listing of agents with potential for CYP-related interaction is provided in Appendix Section 18.2. 
2. 
The liver findings in beagles treated for 13 weeks with the PHB salt were greater than those observed with the free base 
drug. This (and all prior) clinical studies use only the free base drug. 
3. 
The retinal changes were observed only in albino rats treated for 26 weeks with the PHB salt. No retinal changes were 
observed in beagles treated for 13 weeks with either the free base or the PHB salt. 

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8.6.2. 
Additional Procedures for Monitoring Patient Safety 
Additional procedures for patient safety are summarized below: 
• The first dose of study drug will be administered by study personnel; in Part A, the 
patients will be observed over the next several hours while PK samples are obtained. 
• Ongoing monitoring for adverse events. 
• Regularly scheduled safety laboratory tests. 
• Ongoing monitoring of all concomitant medications (prescription and over-the-counter) 
to avoid potential drug-drug-interactions mediated through alterations in CYP- 
metabolism. 
• Detailed procedures for monitoring and review during dose-escalation, including: 
- Constitution of a DRC to make recommendations regarding dose-escalation and 
determination of the MTD (Section 8.6.3). 
- Definitions for DLT events (Section 4.1.1.3) 
- Definition for MTD (Section 4.1.1.4). 
- DRC will also review the data from the first 12 patients participating in Part B to 
confirm the safety of the RP2D selection (Section 4.1.2 and 8.6.3 ). 
• Detailed provisions for management of study drug in individual patients based on safety, 
tolerability, and disease response. In brief, each enrolled patient is planned to receive 
study treatment until the earliest of: 
- DLT event – see Section 4.1.1.3. 
- Disease progression – based on CT imaging scan results or as prompted by new 
signs, symptoms, and laboratory findings, and classified according to RECIST 
v1.1 [Eisenhauer 2009](see Section 7.1.4.2 for details). 
8.6.3. 
Data Review Committee (DRC) 
Members of the DRC will have appropriate experience treating patients with advanced ccRCC 
and/or conducting early phase studies of investigational drugs and will include the following: 
• An independent physician not otherwise involved with the study. 
• The Medical Monitor for the study. 
• Participating Investigator(s). 

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• A physician representative of the Sponsor. 
The functions of the DRC are: 
• Perform the dose-escalation review (see Section 4.1.1.3). 
• Make specific recommendations for the progress of the study, including confirming the 
RP2D selection in Part B by planned safety review (see Section 4.1). 
• Determine the MTD (see Section 4.1.1.4). 
The DRC comprises experienced clinicians, who will make recommendations based on their 
judgment. In consideration of the dynamic nature of early phase studies, those recommendations 
may include alternative courses of action not anticipated here. 
9. 
CLINICAL MONITORING 
 
9.1. 
External Review of the Study Conduct at Participating Sites 
All study-related materials at the site are subject to external review to ensure the safety of the 
patients, the integrity of the study data, and compliance with all applicable regulatory and 
oversight requirements. 
There are several different classes of review: 
• Monitoring — review by the Sponsor or authorized representatives, typically from the 
contract research organization (CRO) coordinating the clinical conduct of the study. As 
detailed below, visits may be conducted before, during, and after the conduct of the 
study. 
• Audits — systematic, independent review by the quality assurance department of the 
Sponsor or authorized representatives, potentially from an organization not involved in 
the clinical conduct of the study; 
• Regulatory review — performed by representatives of regulatory authorities with 
responsibility for oversight of the study or approval of the investigational agent. These 
authorities may be from the country where the site is located or from another country. 
Monitoring and auditing visits on behalf of the Sponsor will be scheduled with the Investigator 
in advance and will be conducted at a reasonable time. To facilitate these visits, the Investigator 
will assure that the following are available: 
• Appropriate space, facilities and access to all source documents (including access to 
computerized records either electronically or as complete print outs). 
• Consent/assent forms, eCRFs, SAE forms, and medical records for all screened and 

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enrolled patients. 
• Timely access to site personnel, including the Investigator, sub Investigator(s), and other 
study personnel on the day of the visit to resolve any questions that arise. 
Regulatory authorities may visit and review the site and/or Investigator during or after the study 
and may or may not notify the Investigator or the Sponsor in advance. The Investigator will fully 
cooperate with regulatory audits conducted at a reasonable time in a reasonable manner. The 
Investigator will notify the Sponsor immediately of any contact by or communication from 
regulatory authorities regarding the study. 
 
9.2. 
Study Monitoring Visits 
 
9.2.1. 
Site Qualification and Initiation Visits 
Before an investigational site can enter a patient into the study, a representative of X4 will visit 
the site to perform the following: 
• Inspect the facilities (e.g., clinical and administrative areas, pharmacy, laboratory). 
• Discuss with the Investigator(s) and other personnel their responsibilities with regards 
to protocol adherence, as well as the responsibilities of X4 and its representatives. 
• Review the site trial master file (TMF), including documentation related to the protocol, 
the Investigator, and other study site personnel; correspondence to and from the IRB/IEC 
the Sponsor, and their representatives. 
• Review the standard operating procedures and current practices relating to clinical and 
pharmacy activities, data handling, the IRB/IEC oversight and the informed consent 
process. 
9.2.2. 
Interim Monitoring Visits 
During the study, a CRA from or representing X4 will visit the investigational site, for the 
following: 
• Provide information and support to the Investigator(s). 
• Confirm that facilities remain acceptable. 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the case report forms, and that investigational product is being 
appropriately handled and accounted. 
• Perform source data verification, including verifying the data in the eCRFs against the 
relevant source documents (see Section 11.3) and resolving any discrepancies noted. 
• Record and report any protocol deviations. 

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• Confirm that AEs and SAEs have been properly documented on eCRFs; that any SAEs 
have been forwarded to X4; and that SAEs meeting criteria for reporting have been 
forwarded to the IRB/IEC. 
Between visits the CRA will be available as needed to provide information or support to the 
Investigator(s) or other staff. 
9.2.3. 
Study Closeout Visit 
The study will be considered complete when all of the following have occurred: 
• All treated patients have completed all scheduled visits plus any unscheduled follow-up 
required by AEs; 
• All eCRFs have been completed, submitted and all queries resolved; 
• The study database has been locked. 
• The Sponsor or designee will then conduct a study closeout visit, which may include, but 
is not limited to, the following: 
• Review the site TMF to assure all required regulatory documents are current and 
complete. 
• Resolve any open issues from prior monitoring, audit or inspection visits. 
• Review the site’s provisions for meeting the requirements for retention study records. 
• Discuss possible future site audits. 
• Review the Sponsor’s publication policy. 
• Confirm compliance with requirements for notifying the IRB/IEC of study events, 
including closure. 
• Collect any unused study materials for either return to the Sponsor or disposal in a 
manner approved by the Sponsor. 

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10. 
STATISTICAL CONSIDERATIONS 
 
10.1. 
Statistical and Analytical Plans 
A detailed statistical analysis plan (SAP) will be developed. The SAP will define populations for 
analysis, outline all data handling conventions, including software, and specify additional 
statistical methods to be used for analysis of safety, efficacy and pharmacokinetics. 
Consistent with the primary objective, the study design represents a pragmatic assessment of 
safety and tolerability across different dose levels of X4P-001 both in combination with axitinib 
and as single agent based upon clinical evaluations and laboratory tests. Secondary objectives 
relating to treatment effect are intended to guide further development of X4P-001 and aid in the 
design of appropriately controlled studies. 
10.2. 
Statistical Hypotheses 
Not applicable. 
 
10.3. 
Analysis Datasets 
Analyses will be performed using the following populations: 
• Safety / Intent-to-Treat (ITT) Population — all patients who received at least one dose of 
study drug. 
• PK – all patients who have at least one evaluable concentration. 
• Clinically Evaluable Population –All patients who receive at least one dose of study 
medication, who have at least one valid post-baseline response (CR/PR/SD/PD), and 
have no major protocol deviations which will impact the efficacy assessment.  
The clinically evaluable population may be omitted from the final analysis if clinically 
evaluable and ITT population  are similar and there are no clinically meaningful 
differences in outcomes between the 2 populations. 

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10.4. 
Description of Statistical Methods 
 
10.4.1. 
General Approach 
Study events will be recorded using the calendar date and (where applicable) the time to the 
nearest minute. 
For purposes of post-study analysis (e.g., tables and listings), study days will be designated as 
follows: 
• Day 1 is defined as the calendar day of the first dose of study drug. 
• The days prior to Day 1 are designated Day –1, Day –2, etc; there is no Day 0. 
• The days following the day of the first dose of study drug are designated Day 2, Day 3, 
etc. 
• The day of each dose of study drug is indicated by adding the suffix "L", e.g., if the 
last dose is administered on Day 43, it will be displayed as "Day 43L". 
• The days following the last administration of study drug are designated Day 1P, Day 2P, 
etc. 
The times of events related to dosing of study drug will be designated as minutes or hours before 
or after the time of dosing, which is designated as t = 0 (zero). Thus, 15 minutes prior to dosing 
is t = –15 min; 2 hour after dosing is designated t = 2 h. 
Missing and partial dates will be imputed. Full details will be given in the SAP. 
Missing baseline data will be imputed with screening data where available. No further 
imputations of missing data will be made.  
10.4.2. 
Baseline Descriptive Statistics 
Descriptive statistics will be used to summarize demographics and baseline characteristics. In 
addition, a summary will be presented for patient disposition, including number of patients 
enrolled into and completing each study part. 
Medical history, medications used prior to treatment, and concomitant medications will be 
summarized by study part. Please refer to the SAP for details. 
10.4.3. 
Analyses of Safety Endpoint 
The primary objective of the study is safety and tolerability. AEs will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA) version 16.0 (or later) and tabulated by event, 
grade, and relationship to study therapy. Laboratory results, vital signs, and ECG parameters will 
be summarized using descriptive statistics. Laboratory values will also be graded according to

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NCI CTCAE, Version 4.03, and summarized in shift tables. DLT events will be listed and 
summarized. 
Safety observations will be analyzed using descriptive statistics and tabulation. No formal 
statistical comparisons are planned. All safety data will be presented in listings. 
10.4.4. 
Analysis of the Efficacy Endpoint(s) 
The secondary objective of treatment effect (tumor response) will be analyzed using RECIST 
v1.1 criteria [Eisenhauer 2009] as identified by the central review committee to determine the 
following metrics: 
• ORR (CR + PR) 
• Time to objective response 
• Duration of objective response 
• Disease control rate (CR+PR+ Stable Disease) 
• Time to progression 
• PFS 
Analysis of Tumor response, ORR and Disease Control Rate (DCR) will be tabulated using Best 
overall response, by dose level, incorporating 95% exact Clopper-Pearson confidence intervals 
(CI) for ORR and disease control rate.. The analysis will be based on intent-to-treat (ITT) and 
Clinically Evaluable patient populations. 
Duration of ORR will be summarized as median (with 95% CI) and interquartile range estimated 
using Kaplan-Meier method with corresponding 95% CIs. 
Median time to objective response, TTP, PFS as well as the proportion of patients with PFS at 6 
and 12 months (with 95% CI) will also be derived from Kaplan-Meier estimates. 
Tumor Response and endpoints listed above may also be explored by using modified Response 
Evaluation Criteria in Solid Tumors for immune-based therapeutics (iRECIST) [Seymour 
2017].  Details of the analysis plan will be defined in the SAP. 
10.4.5. 
Planned Interim Analyses 
There is no formal provision for an interim analysis in this early phase study. 
 
10.4.6. 
Multiple Comparison/Multiplicity 
Not applicable. 

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10.4.7. 
Tabulation of Individual Response Data 
The individual response data will be provided in patient data listings and the details will be 
described in SAP. 
10.4.8. 
Exploratory Analyses 
The details of exploratory analyses will be described in SAP. 
 
10.4.9. 
Pharmacokinetic Analyses 
PK data will be analyzed (a) by patient and dose level using descriptive statistics for AUC, Cmax, 
and Tmax, and (b) across dose levels testing for dose proportionality of AUC and Cmax. 
10.5. 
Sample Size 
The maximum numbers of patients planned to be enrolled in Parts A and C are as follows: 
• Part A, Dose-escalation: 6 patients per dose level (5 planned dose levels) 
• Part B, A RP2D expansion cohort: approximately 45 patients will be enrolled; 
• Part C, Dose-escalation (to be done only if the MTD for X4P-001 from Part A 
(combination treatment) is ≤800 mg QD): up to 6 patients per single agent dose- 
escalation level (maximum 3 dose levels); 
• Part C, Expansion: maximum 15 patients 
Dose-escalation in Part A (and, if needed, in Part C) employs the standard 3+3 design. Table 
10-1 presents the probability of escalation from a lower dose to the next higher dose, for true 
rates of DLT ranging from 10% to 90%. For example, if the true DLT rate were 0.20 (20%), then 
the chance of dose escalation would be 0.71 (71%). 
 
Table 10-1: 
Relationship between Underlying DLT Rate and Probability of Dose 
Escalation 
Underlying DLT Rate 
10% 
20% 
30% 
40% 
50% 
60% 
70% 
80% 
90% 
Probability of Dose Escalation 
91% 
71% 
49% 
31% 
17% 
8% 
3% 
1% 
0.1% 
 
In Part B, approximately 45 patients will be enrolled and dosed with X4P-001 in the combination 
of axitinib to provide a preliminary assessment of both safety and anti-tumor activity. With 45 
subjects at the RP2D, the two-sided 90% confidence interval width for any binary response rate 
(e.g., DLT or binary PD markers) will be approximately 0.24, assuming a 40% response rate. If a 
dose de-escalation occurs after the first 12 patients, the remaining 33 patients will be dosed at a 

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lower dose level. With 33 patients, the confidence interval width will be approximately 0.28 for a 
binary response rate. 
Safety at RP2D will be verified by monitoring DLTs as follows: if ≤ 4 DLTs are observed in the 
first 12 patients during the first 4 weeks of treatment, this RP2D dose will be considered safe to 
proceed for the remaining patients in this study. If 5 or more DLTs are observed in the first 12 
patients during the first 4 weeks of treatment, the trial may continue with dose de-escalation after 
DRC review. The dose will be reduced at least one dose level lower, according to the dose levels 
presented in Figure 4-1. To further protect patient safety, if additional DLTs are observed 
anytime during the trial, dose de-escalation can be enforced based on DRC recommendation, or 
the trial can be stopped at the sponsor’s discretion. 
In Part C, dose-escalation (if needed after Part A) cohorts of X4P-001 as single agent 
(monotherapy) will employ the traditional 3+3 design. When the potential MTD is identified, an 
expansion cohort of approximately 15 patients will used to further assess MTD. With 15 
subjects, there is a 79% chance of observing at least one AE with the true underlying rate of 
10%, and a 54% chance of observing at least one AE with true underlying rate of 5%. 
10.6. 
Measures to Minimize Bias 
10.6.1. 
Enrollment/ Randomization/ Masking Procedures 
No randomization or blinding methods will be employed in this study. 
 
10.6.2. 
Evaluation of Success of Blinding 
Not applicable. 
10.6.3. 
Breaking the Study Blind/Participant Code 
Not applicable. 

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11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
Source documents are the originals of any documents used by the Investigator, hospital, or 
institution that verify the existence of the patient and substantiate the integrity of the data 
collected during the study. 
11.1. 
Medical Records 
Medical records related to the patient’s routine clinical care, including prior to or during the 
study: 
• Information obtained from the patient’s personal physicians or other third parties 
regarding the patient’s medical history or prior physical condition. 
• Medication prescription and administration records. 
• Laboratory reports, including clinical pathology and diagnostic histologic pathology. 
• Reports of imaging studies. 
• Data and reports from automated instruments (e.g., vital signs). 
• Medical records relating to scheduled and unscheduled clinical visits 
11.2. 
Study-Specific Source Documents 
Study-specific source documents include, but are not limited to, the following: 
• The informed consent form, signed and dated by the patient. 
• The site screening log. 
• Any clinical reports noted above that are scheduled as part of the protocol and have been 
annotated to indicate the significance of any abnormal findings. 
• Concomitant medication prescription and administration records. 
• Records relating to scheduled and unscheduled study visits, including, but not limited to, 
results of examinations, observations relating to AEs, and concomitant medications. 

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11.3. 
Source Documents Requirements 
The following document characteristics are essential to assuring data quality and are required of 
all documents generated by the Investigator and the study team during the course of the study. 
• Be prepared at the time of the events or activities described (i.e., contemporaneously); 
• Indicate both the date and time recorded; 
• Identify the source of all recorded information (e.g., the patient, direct observations of the 
recorder, laboratory reports, external / historical sources). 
• Text should be readable and unambiguous, including application of best medical record 
practices (e.g., minimal use of abbreviations; proper numerical, dose and posology 
formats). 
Electronic health record systems must be compliant with current regulatory requirements for 
systems containing “protected health information”, including, but not limited to: 
• Security requirements for restricted access and electronic signatures 
• Electronic timestamp 
• Audit trails for  any changes or amendment 
Paper documents must meet the following requirements: 
• Be written legibly in dark (preferably black) ink, including signature and date. 
• Be signed (or initialed), with date and time, by the recorder. The site must maintain a 
formal log showing for all study personnel printed name, full signatures, and initials. 
• In the event that any entry needs to be changed, a single line will be made through the 
original entry, the correct information entered (or referenced) on the same page, and the 
action initialed, dated, and (if appropriate) explained. The original entry must not be 
obscured or obliterated by multiple cross-out, correction fluid or overlay of other 
material. 
Study-specific source document forms created by the site must be reviewed by the Sponsor prior 
to use. 
11.4. 
Electronic Case Report Forms (eCRFs) 
The Sponsor will provide a regulatory-compliant electronic data capture (EDC) system for 
reporting study data to a central facility holding the study database. All study personnel will be 
trained on the system and each will have a unique login password and electronic signature. 

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The Investigator (or qualified sub-Investigator approved by the Sponsor) will review all eCRFs 
and indicate their concurrence by (electronic) signature. 
12. 
QUALITY ASSURANCE AND QUALITY CONTROL 
 
12.1. 
Study Monitoring 
Monitoring and auditing procedures developed by the Sponsor or designee will be followed, in 
order to comply with ICH GCP guidelines, as described in Section 9.2. 
12.2. 
Case Report Form Completion 
The Sponsor or designee will provide the study centers with eCRFs for each patient. 
eCRFs will be completed for each study patient. It is the Investigator’s responsibility to ensure 
the accuracy, completeness, and timeliness of the data reported in the patient’s eCRF. Source 
documentation supporting the eCRF data should indicate the patient’s participation in the study 
and should document the dates and details of study procedures, AEs, and patient status. 
The Investigator, or designated representative, should complete the eCRF as soon as possible 
after information is collected, preferably on the same day that a patient is seen for an 
examination, treatment, or any other study procedure. Any outstanding entries must be 
completed immediately after the final examination. An explanation should be given for all 
missing data. 
The Investigator must electronically sign and date the Investigator’s Statement at the end of the 
eCRF to endorse the recorded data. 
12.3. 
Computerized Systems / Medical Records as Source Data 
All study data recorded on source documents are to be transcribed into the eCRFs. Any 
electronic study data are to be entered into a secure, validated data processing system and a 
backup maintained. Any changes to electronic study data will be documented. 
12.4. 
Audits and Inspections 
Authorized representatives of Sponsor or designee, a regulatory authority, or IRB/IEC may visit 
the study center to perform audits or inspections, including source data verification. The purpose 
of a Sponsor audit or inspection is to systematically and independently examine all study-related 
activities and documents to determine whether these activities were conducted, and data were 
recorded, analyzed, and accurately reported according to the protocol, ICH GCP, and any 
applicable regulatory requirements. 
The investigator should contact the Sponsor immediately if contacted by a regulatory agency 

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about an inspection. 
12.5. 
Resolution of Deficiencies 
The Investigator agrees to take promptly any reasonable steps requested by the Sponsor to 
resolve any deficiencies identified as a result of monitoring, audits, inspections, protocol 
deviations, or review of any other study documentation. Failure to take adequate remedial action 
can result in suspension or termination of the study at the site. 
13. 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
 
13.1. 
Ethical Standard 
The Sponsor and any third party to whom aspects of the study management or monitoring have 
been delegated will undertake their assigned roles for this study in compliance with all applicable 
industry regulations, the ethical principles stated in the Declaration of Helsinki, and ICH GCP 
Guideline E6. 
ICH GCP Guideline E6 is available at: 
https://www.fda.gov/downloads/drugs/guidances/ucm073122.pdf 
13.2. 
Institutional Review Board/Independent Ethics Committee 
The IRB/IEC will review all appropriate study documentation in order to safeguard the rights, 
safety, and well-being of the patients. The study will only be conducted at study centers where 
IRB/IEC approval has been obtained. The protocol, Investigator’s Brochure, informed consent, 
advertisements (if applicable), written information given to the patients (including diary cards), 
safety updates, annual progress reports, and any revisions to these documents will be provided to 
the IRB/IEC by the Investigator. 
The final study protocol, including the final version of the Informed Consent Form, must be 
approved or given a favorable opinion in writing by an IRB/IEC as appropriate. Written IRB/IEC 
approval must be received by the Sponsor or designee before a site can enroll any patient into the 
study. 
The Investigator is responsible for informing the IRB/IEC of any amendment to the protocol in 
accordance with local requirements. In addition, the IRB/IEC must approve all advertising used 
to recruit patients for the study. The protocol (and other amended study documents) must be re- 
approved by the IRB/IEC upon receipt of amendments and annually, as local regulations require. 
The Investigator is also responsible for providing the IRB/IEC with reports of any reportable 
serious adverse drug reactions from any other study conducted with the investigational product. 
The Sponsor will provide this information to the Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the 
IRB/IEC according to local regulations and guidelines. 

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13.3. 
Informed Consent Process 
 
13.3.1. 
Consent/assent and Other Informational Documents Provided to Participants 
The Investigator(s) at each center will ensure that the patient is given full and adequate oral and 
written information about the nature, purpose, possible risk and benefit of the study. Patients 
must also be notified that they are free to discontinue from the study at any time. The patient 
should be given the opportunity to ask questions and allowed time to consider the information 
provided. This process should be recorded in the patient’s source documentation. 
The patient’s signed and dated informed consent must be obtained before conducting any study 
procedures. Documentation of the consenting process must be recorded in the patient’s source 
documents. 
13.3.2. 
Consent Procedures and Documentation 
The Investigator(s) must maintain the original, signed Informed Consent Form. A copy of the 
signed Informed Consent Form must be given to the patient, and this must be documented in the 
patient’s source documents. 
13.4. 
Participant and Data Confidentiality 
In order to maintain patient privacy, all eCRFs, study drug accountability records, study reports, 
and communications will identify the patient by initials (as allowed by local regulations) and the 
assigned patient number. The Investigator will grant monitor(s) and auditor(s) from the Sponsor 
or its designee and regulatory authority(ies) access to the patient’s original medical records for 
verification of data gathered on the eCRFs and to audit the data collection process. The patient’s 
confidentiality will be maintained and will not be made publicly available to the extent permitted 
by the applicable laws and regulations. 

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14. 
DATA HANDLING AND RECORD KEEPING 
 
14.1. 
Data Collection and Management Responsibilities 
All study data recorded on source documents are to be transcribed into the eCRFs. Any 
electronic study data are to be entered into a secure, validated data processing system and a 
backup maintained. Any changes to electronic study data will be documented. 
14.2. 
Study Records Retention 
The Investigator will maintain all study records according to ICH GCP and applicable regulatory 
requirement(s). Records will be retained for at least 2 years after the last marketing application 
approval or 2 years after formal discontinuation of the clinical development of the investigational 
product or according to applicable regulatory requirement(s). If the Investigator withdraws from 
the responsibility of keeping the study records, custody must be transferred to a person willing to 
accept the responsibility. The Sponsor must be notified immediately by telephone or e-mail and 
the notification confirmed in writing if a custodial change occurs. 
14.3. 
Protocol Deviations 
A protocol deviation is defined as an event in which the Investigator or site personnel did not 
conduct the study according to the Protocol, including compliance requirements and agreements. 
Guidelines for minor procedural variations (e.g., collection time of blood samples) will be agreed 
to and documented by the Investigator and the Sponsor prior to starting the study. Events 
conforming to those guidelines will not be considered deviations. 
For protocol deviations relating to individual patients, the event and relevant circumstances will 
be recorded on source documents and on the appropriate eCRF; reported to the Sponsor in a 
timely manner; and presented in the Clinical Study Report. 
Deviations that are not patient-specific (e.g., unauthorized use of an investigational agent outside 
the protocol, either human administration or laboratory use) will be reported to the Sponsor in 
writing and copies placed in the TMF. 
Deviations that can be anticipated should, if possible, be discussed with the Sponsor before being 
implemented. 
14.4. 
Publication and Data Sharing Policy 
X4 recognizes the importance of communicating the results of scientific studies, including 
clinical studies, and, therefore, encourages their publication in reputable scientific journals and 
presentation at seminars or conferences. X4 also has legitimate corporate and shareholder 

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responsibilities, including, but not limited to, protecting confidential information about its 
proprietary products and obtaining patent protection for its intellectual property. 
Therefore, the following procedures apply to any communication (including written, oral, or 
electronic; manuscript, abstract, other publication, or presentation) of results or information 
arising from this study (including any ancillary studies involving study patients) to any third 
parties: 
• The proposed communication will be prepared in collaboration with the Sponsor. 
• The final proposed version must be submitted to X4 for review and comment at least 
30 days prior to presentation, submission for publication or other dissemination. 
• In the event X4 reasonably determines that a proposed communication contains 
confidential or patentable material, they may require either of the following: 
- The material be removed from the communication; 
- The communication be delayed for up to 60 additional days to permit filing the 
appropriate intellectual property protection. 
These procedures apply regardless of whether the study is completed as planned or is terminated 
prematurely for any reason. 
 
15. 
STUDY ADMINISTRATION 
 
Key personnel, along with relevant contact information, are provided in the Study Manual. 
 
16. 
CONFLICT OF INTEREST POLICY 
 
The conflict of interest policy is addressed in the Clinical Trial Agreement. 
 
 

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17. 
LITERATURE REFERENCES 
 
ACTG (DIAIDS) Protocol A5210. Unpublished data. See Section 5.2.1 for details. 
Amato RJ, Harris P, Dalton M, Khan M, Alter R, Zhai Q, Brady RJ, Jac J, Hauke R, Srinva S: A 
Phase II trial of the intra-patient dose-escalated sorafenib in patients (pts) with metastatic renal 
cell cancer (mRCC) [abstract]. J. Clin Oncol 2007; 25(18S; June 20 Supplement):5026. 
Cao YJ, Flexner CW, Dunaway S, et al. Effect of Low-Dose Ritonavir on the Pharmacokinetics 
of the CXCR4 Antagonist AMD070 in Healthy Volunteers. Antimicrob Agents Chemother. 
2008; 52:1630-1634. 
Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0, 28 May 2009. U.S. 
Department of Health and Human Services, National Institutes of Health, National Cancer 
Institute. NIH Publication No. 03 5410. 
DePrimo SE, Bello CL, Smeraglia J, et al. Circulating protein biomarkers of pharmacodynamic 
activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and 
VEGF-related proteins. J Translational Med 2007; 5:32. 
Ehtesham M, Stevenson CB, Thompson RC. [Letter] Preferential Expression of Chemokine 
Receptor CXCR4 by Highly Malignant Human Gliomas and Its Association with Poor Patient 
Survival. Neurosurgery 2008; 63:E820 
Eisenhauer EA,Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: 
Revised RECIST guideline (version 1.1). Eur J Cancer. 2009; 45:228-247. 
Fearon DT. The Carcinoma-Associated Fibroblast Expressing Fibroblast Activation Protein and 
Escape from Immune Surveillance Cancer Immunol Res 2014; 2:187-193. 
Feig C, Jones JO, Kraman M, et al. Targeting CXCL12 from FAP-expressing carcinoma 
associated fibroblasts synergizes with anti–PD-L1 immunotherapy in pancreatic cancer. PNAS 
2013;110: 20212-20217 
Finke J, Ko J Rini B, Rayman P, Ireland J, Cohen P. MDSC as a mechanism of tumor escape 
from sunitinib mediated anti-angiogenic therapy. Int Immunopharmacol 2011; 11: 856-61. 
Houk BE, Bello CL, Poland B, Rosen LS, Demetri GD, Motzer RJ: Relationship between 
exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer. 
INLYTA® (axitinib) tablets for oral administration. US FDA prescribing information. August 
2014. 
Kioi M, Vogel H, Schultz G, et al. Inhibition of vasculogenesis, but not angiogenesis, prevents 
the recurrence of glioblastoma after irradiation in mice. J Clin Invest. 2010; 120:694–705. 

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Maréchal R, Demetter P, Nagy N, et al. High expression of CXCR4 may predict poor survival in 
resected pancreatic adenocarcinoma. Br J Cancer 2009;100: 1444-1451. 
Motzer RJ, Escudier B, Bukowski R, et al. Prognostic factors for survival in 1059 patients 
treated with sunitinib for metastatic renal cell carcinoma. Br J Cancer 2013; 108:2470-
247. 
Moyle G, DeJesus E, Marta Boffito M, et al. Proof of Activity with AMD11070, an Orally 
Bioavailable Inhibitor of CXCR4-Tropic HIV Type 1. Clin Infect Dis. 2009; 48:798–805 
Nagaraj S, Gupta K, Pisarev V, Kinarsky L, Sherman S, Kang L, Herber DL, Schneck J, 
Gabrilovich DI. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in 
cancer. Nat Med 2007; 13: 828-35 
NCI CTCAE v4.03, 14 June 2010 available at (accessed 6 April 2015): 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. 
Nishino M, Giobbie-Hurder A, et al. Developing a common language for tumor response to 
immunotherapy: immune-related response criteria using unidimensional measurements. Clin 
Cancer Res. 2013; 19:3936-43 
Nyunt MM, Becker S, MacFarland RT, et al. Pharmacokinetic Effect of AMD070, an Oral 
CXCR4 Antagonist, on CYP3A4 and CYP2D6 Substrates Midazolam and Dextromethorphan in 
Healthy Volunteers. J Acquir Immune Defic Syndr. 2008; 47:559-565. 
Panka DJ, Liu Q, Geissler AK, Mier JW. HDM2 antagonism delays the development of sunitinib 
resistance in RCC xenografts: Effects of MI-319 on sunitinib-induced p53 activation, SDF-1 
induction, and tumor infiltration by CD11b+/Gr-1+ myeloid suppressor cells. Mol Cancer 2013; 
12: 17. 
Parameswaran R, Yu M, Groffen J, Heisterkamp N. Combination of drug therapy in acute 
lymphoblastic leukemia with a CXCR4 antagonist. Leukemia 2011; 8:1314-23 
Righi E, Kashiwagi S, Yuan J, et al. CXCL12/CXCR4 Blockade Induces Multimodal Antitumor 
Effects That Prolong Survival in an Immunocompetent Mouse Model of Ovarian Cancer. Cancer 
Res 2011; 71:5522-5534. 
Rini BI, Cohen DP, Lu DR, et al. Hypertension as a biomarker of efficacy in patients with 
metastatic renal cell carcinoma treated with sunitinib. J Natl Canc Inst 2011a;103(9):763-773. 
Rini BI, Schiller JH, Fruehauf JP, et al, Diastolic blood pressure as a biomarker of axitinib 
efficacy in solid tumors. Clin Cancer Res 2011b;17(11)3841-9. 
Sekiya R, Kajiyamo H, Sakai K, et al. Expression of CXCR4 indicates poor prognosis in patients 
with clear cell carcinoma of the ovary. Human Pathology. 2012; 43:904-910. 

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Seymour, L., Bogaerts, J., Perrone, A. et al, iRECIST: guidelines for response criteria for use in 
trials testing immunotherapeutics.  Lancet Oncol. 2017;18:e143-e152 
Shojaei F, Wu X, Malik AK, Zhong C, Baldwin ME, Schanz S, Fuh G, Gerber HP, Ferrara N. 
Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nature 
Biotech 2007; 25: 911-20. 
Staller P, Sulitkova J, Lisztwan J, et al. Chemokine receptor CXCR4 downregulated by von 
Hippel–Lindau tumour suppressor pVHL. Nature 2003; 425:307-311. 
Stone ND, Dunaway SB, Flexner C, et al. Multiple-Dose Escalation Study of the Safety, 
Pharmacokinetics, and Biologic Activity of Oral AMD070, a Selective CXCR4 Receptor 
Inhibitor, in Human Subjects. Antimicrob Agents Chemother. 2007;51(7):2351–2358. 
Tarhini AA, Edington H, Butterfield LH, et al. Immune Monitoring of the Circulation and the 
Tumor Microenvironment in Patients with Regionally Advanced Melanoma Receiving 
Neoadjuvant Ipilimumab. PLoS One 2014;9(2): e87705. 
Turner KJ, Moore JW, Jones A, et al. Expression of Hypoxia-inducible Factors in Human Renal 
Cancer: Relationship to Angiogenesis and to the von Hippel-Lindau Gene Mutation. Cancer Res. 
2002; 62:2957-2961. 
United States Department of Health and Human Services, Food and Drug Adminstration. 
Guidance for Industry: Cancer Drug and Biological Products — Clinical Data in Marketing 
Applications, 2001. Available at: 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/u 
cm071323.pdf. Accessed:  15 December 2016. 
Wang X, Zhang L, Goldberg SN, et al. High dose intermittent sorafenib shows improved 
efficacy over conventional continuous dose in renal cell carcinoma. J Translat Med. 2011; 
9:220- 227. 
WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human 
Subjects, 19 October 2013. Available at (accessed 6 April 2015) https://www.wma.net/policies-
post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-
subjects 
Wolchok J, Hoos A, et al. Guidelines for the evaluation of immune therapy activity in solid 
tumors: immune-related response criteria. Clinical Cancer Research 2009;15: 7412-7420. 
Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, McDermott D, 
Quiceno D, Youmans A, O’Neill A, Mier J, Ochoa AC. Arginase-producing myeloid suppressor 
cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res 2005; 65: 
3044-8. 

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18. 
APPENDICES 
 
18.1. 
Revision History and Sponsor Signature 
The revision history is summarized in Table 18-1. Significant revisions made in each protocol 
version are provided in a separate Summary of Changes document. 
 
Table 18-1: 
Protocol Revision History 
Ver. 
No. 
Date 
Comment 
1.0 
7 Apr 2015 
Initial release – submitted with IND 
2.0 
24 June 2015 
Revised based on FDA Comments 
3.0 
9 Sep 2015 
Technical corrections, including RECIST 1.1 
4.0 
3 Mar 2016 
Updated safety experience; technical corrections 
5.0 
20 Jun 2016 
Changed dose regimen from BID to QD, added clinical PK 
data supporting QD dosing, and updated sample size 
justification section. 
6.0 
01 Feb 2017 
Change Part B study design 
6.1 
23 Feb 2017 
South Korea specific amendment only.  Fixed errors in Table 1-1 
(schedule of events) and 1-2 (blood volumes table).  Fixed typos 
in Section 7.4.1.3 & Section 10.4.3 
6.2 
08 March 2017 
South Korea specific amendment only.  Updated table on page 23 
6.3 
02 Nov 2017 
South Korea specific amendment only.  Updated information 
around using iRECIST criteria, modification of exclusion 
criterion #14, removal of unnecessary laboratory tests, and minor 
administrative changes 
6.4 
15 February 
2018 
South Korea specific amendment only.  Updated schedule of 
procedures & correction to blood volume in table 1-2 
7.0 
08 June 2018 
US specific amendment only. Updated information around using 
iRECIST criteria, modification of exclusion criterion #14, 
removal of unnecessary laboratory tests, and minor 
administrative changes. Updated study’s planned analysis. 
 
 
 

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This protocol Version 7.0 has been prepared and approved by the Sponsor. 
 
 
 
 
X4 Pharmaceuticals, Inc.  
 
Signature and Date 
 
 
 
June 08, 2018

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18.2.
Potential CYP-Related Drug-Drug Interactions 
Strong CYP3A 
inhibitor1 
Strong CYP3A 
inducer1
Moderate 
CYP3A 
inhibitor2
Moderate 
CYP3A 
inducer2
CYP2D6 sensitive 
substrate1
CYP2D6 
moderate 
sensitive 
substrate2
boceprevir, 
clarithromycin, 
cobicistat, 
conivaptan, 
danoprevir and 
ritonavir, 
diltiazem, 
elvitegravir and 
ritonavir, 
grapefruit juice, 
idelalisib, 
indinavir, 
itraconazole, 
ketoconazole, 
lopinavir and 
ritonavir, 
mibefradil, 
nefazodone, 
nelfinavir, 
paritaprevir and 
ritonavir, 
ombitasvir and/or 
dasabuvir, 
posaconazole, 
saquinavir, 
telaprevir, 
telithromycin, 
tipranavir and 
ritonavir, 
troleandomycin, 
voriconazole 
carbamazepine, 
enzalutamide, 
mitotane, 
phenytoin, 
rifampin, 
St. John’s wort 
amprenavir, 
aprepitant, 
atazanavir, 
cimetidine, 
ciprofloxacin, 
clotrimazole, 
crizotinib, 
cyclosporine, 
darunavir and 
ritonavir, 
dronedarone, 
erythromycin, 
fluconazole, 
fluvoxamine, 
fosamprenavir, 
imatinib, 
tofisopam, 
verapamil 
bosentan, 
efavirenz, 
etravirine, 
modafinil, 
nafcillin 
atomoxetine, 
desipramine, 
dextromethorphan, 
eliglustat, nebivolol, 
nortriptyline, 
perphenazine, 
pimozide, 
thioridazine, 
tolterodine, 
venlafaxine 
amitriptyline, 
encainide, 
imipramine, 
metoprolol, 
propafenone, 
propranolol, 
tramadol, 
trimipramine 
1 
Prohibited. 
2 
Use with Medical Monitor approval only. 
Note: This list of drugs may not be a complete list, consultation with the Medical Monitor is requested for any concerns about 
concomitant medication use. 
Sources: 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm