Clinical trial NCT03660930
Conditions: Advanced Soft Tissue Sarcoma Locally Advanced Soft Tissue Sarcoma Metastatic Soft Tissue Sarcoma
Sponsor: University of Washington
Start date: 2019-04-01; Completion date: 2024-07-31
Enrollment: 19 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase I/II trial studies the side effects and best dose of nab-sirolimus and how well it works when given together with pazopanib hydrochloride in treating participants with nonadipocytic soft tissue sarcomas that has spread to other places in the body (advanced). Nab-sirolimus and pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description:
OUTLINE: This is a phase I, dose-escalation study of nanoparticle albumin-bound rapamycin followed by a phase II study.

Participants receive nab-sirolimus intravenously (IV) on days 1 and 8 or day 1 only and pazopanib hydrochloride orally (PO) daily on days 1-21. Cycles repeat every 21 days until unequivocal clinical disease progression, unacceptable toxicity, or until in the opinion of the investigator the patient is no longer benefiting from therapy, or at the patient's discretion.

After completion of study treatment, participants are followed up at 30 days, then every 12 weeks.

Arms: arm 1: Participants receive nab-sirolimus intravenously (IV) on days 1 and 8 or day 1 only and pazopanib hydrochloride orally (PO) daily on days 1-21. Cycles repeat every 21 days until unequivocal clinical disease progression, unacceptable toxicity, or until in the opinion of the investigator the patient is no longer benefiting from therapy, or at the patient's discretion.
Interventions: intervention 1: Sirolimus Albumin-bound Nanoparticles intervention 2: Pazopanib hydrochloride
Intervention descriptions: intervention 1: Given IV intervention 2: Given PO

Protocol documents:
Prot_SAP_001.pdf: 
Oﬃcial Title: 
A phase 1/2 study of ABI-009 (nap-rapamycin) with pazopanib 
(VOTRIENT®) in paƟents with advanced nonadipocyƟc soŌ-Ɵssue 
sarcomas 
NCT Number: 
NCT03660930 
Document Type: 
Study Protocol and StaƟsƟcal Analysis Plan 
Date of the Document 
October 25, 2022 
 


Nab-Sirolimus/Pazopanib 
Protocol: CC10015      
University of Washington 
Confidential and Proprietary 
1 
Final Protocol v5.0: July 28, 2022 
A phase 1/2 study of nab-Sirolimus with pazopanib (VOTRIENT®) in patients 
with advanced nonadipocytic soft-tissue sarcomas 
Investigational Product 
nab-Sirolimus 
Protocol Number 
10015  
Study Phase: 
1/2  
IND Number: 
139,306 
Sponsor Name / Address: 
Lee Cranmer, MD, PhD 
Seattle, WA, USA 
Sponsor-Investigator: 
Lee Cranmer, MD 
University of Washington  
825 Eastlake Avenue E., LG-350 
Seattle, WA, USA 98109 
Collaborator and Funding Source: 
Aadi Bioscience, Inc 
1343 Luna Vista Dr 
Pacific Palisades, CA 90272 
Statistics: 
Ted A. Gooley, Ph.D. 
Fred Hutchinson Cancer Center 
1100 Fairview Avenue N., M2-B230 
Seattle, WA, 98109 
Protocol Versions 
Date 
Original v1.0: 
April 13, 2018 
Amendment 1, Version 2.0 
May 14, 2018 
Amendment 2, Version 3.0 
January 30, 2020 
Amendment 3, Version 4.0 
May 26, 2021 
Amendment 4, Version 5.0 
July 28, 2022 
IRO REC'D SEPT 23 2022
FHCRC IRB Approval  
10/25/2022 
Document Released Date


Nab-Sirolimus/Pazopanib 
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CONFIDENTIAL 
This protocol is provided to you as an Investigator, potential Investigator, or 
consultant for review by you, your staff, and ethics committee/institutional review 
board.  The information contained in this document is regarded as confidential and, 
except to the extent necessary to obtain informed consent, may not be disclosed to 
another party unless such disclosure is required by law or regulations.  Persons to 
whom the information is disclosed must be informed that the information is 
confidential and may not be further disclosed by them. 
 
SPONSOR-INVESTIGATOR SIGNATURE PAGE 
 
 
 
 
 
Signature of Sponsor-Investigator 
 
dd/mm/yyyy 
Lee D. Cranmer, MD, PhD 
Printed Name of Sponsor-Investigator 
Institution Name:  University of Washington  
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Aadi Bioscience representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies. 
 
 
 
 
 
 
        
 
 
 
 
 
 
 
 
 


Nab-Sirolimus/Pazopanib 
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PROTOCOL SYNOPSIS 
 
INVESTIGATIONAL 
PRODUCT 
Nab-Sirolimus, ABI-009, sirolimus protein-bound nanoparticles for 
injectable suspension (albumin bound), nab-rapamycin, nanoparticle 
albumin-bound rapamycin 
FDA APPROVED 
STUDY AGENT 
Pazopanib (VOTRIENT®), is a kinase inhibitor indicated for the treatment 
of subjects with 1) advanced renal cell carcinoma, and 2) advanced soft 
tissue sarcoma (STS) who have received prior chemotherapy 
INDICATION 
Previously treated subjects with advanced (metastatic or locally 
advanced) nonadipocytic STS, for which surgery is not an option 
TITLE 
A phase 1/2 study of nab-Sirolimus (ABI-009, nab-rapamycin) with 
pazopanib (VOTRIENT®) in subjects with advanced nonadipocytic soft-
tissue sarcomas 
PROTOCOL 
NUMBER 
CC10015 
PHASE OF 
DEVELOPMENT 
1/2 
STUDY 
OBJECTIVES 
Objectives in Phase 1 
Primary 
• 
To identify the recommended phase 2 dose (RP2D) of nab-
Sirolimus given intravenously (IV) plus continuous daily oral 
pazopanib, for subjects with nonadipocytic STS 
Secondary 
• 
To evaluate the safety profile of the nab-Sirolimus plus pazopanib 
combination therapy in advanced nonadipocytic STS 
Objectives in Phase 2 
Primary 
• To evaluate the efficacy of the combination of nab-Sirolimus and 
pazopanib at the RP2D 
Secondary 
• 
To evaluate the safety profile and to further evaluate the efficacy 
of 
nab-Sirolimus 
plus 
pazopanib 
combination 
therapy 
 


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Exploratory 
• To study the correlation of clinical outcomes with Next Generation 
Sequencing and Immunohistochemical analyses of tumor 
biomarkers, including baseline secreted protein acidic and rich in 
cysteine (SPARC) expression. 
• To assess baseline tumoral immune parameters, including PD-1, 
PD-L1, mutational burden, and infiltrating lymphocytes, in 
correlation with clinical outcomes. 
STUDY 
ENDPOINTS 
Endpoints in Phase 1 
Primary Endpoint  
• Dose-limiting-toxicities (DLTs), used to estimate the maximum-
tolerated dose (MTD) of nab-Sirolimus in combination with 
pazopanib, where the MTD is defined as the highest dose where 
≤1 of 6 (or 0 of 3) subjects experience a DLT, thus a target DLT rate 
of roughly 17%. 
Secondary Endpoint 
• Adverse Events profile (based on National Cancer Institute [NCI] 
Common Terminology Criteria for Adverse Events [CTCAE] v5.0) of 
all subjects and each dose cohort 
Endpoints in Phase 2 – data both from Phase 1 and 2  
Primary Endpoint  
• Progression-free survival (PFS) rate at 3 months, based on 
Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 
Secondary Endpoint 
• Adverse Events profile (based on NCI CTCAE v5.0) 
• Median PFS, PFS rate at 6 months, based on RECIST v1.1 
• Median overall survival (OS), OS at 12 months 
• Objective response rate (ORR) based on Response Evaluation 
Criteria in Solid Tumors (RECIST) v1.1 
• Disease control rate (DCR), defined as complete response (CR) 
plus partial response (PR) plus stable disease (SD) ≥18 weeks, 
based on RECIST v1.1 
• Duration of response  
 
Exploratory endpoints 


Nab-Sirolimus/Pazopanib 
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• Optional pre-treatment tumor tissue collection (fresh or archival) 
for biomarker analysis: 
1. Correlation of genetic profiling and tissue biomarker 
analysis with clinical benefit 
2. Correlation of baseline secreted protein acidic and rich in 
cysteine (SPARC) expression with clinical benefit 
3. Correlation of baseline immune parameters with clinical 
benefit 
STUDY DESIGN 
This is an open label, dose-finding, single-arm, prospective phase 1/2 
study to identify the RP2D of nab-Sirolimus given IV on either Day 1 and 
Day 8 (qw2/3), or Day 1 only of a 21-day cycle (qw1/3), plus daily oral 
pazopanib in subjects with advanced nonadipocytic STS.  
The study will be conducted in compliance with International Conference 
on Harmonization (ICH) Good Clinical Practices (GCPs). 
Dose-finding Phase 1 Portion of the Study:   
Dose levels of nab-Sirolimus will be tested in cohorts of 3 subjects each 
using the 3+3 dose-finding design. A summary of dose levels and cohorts 
are provided in Table 1 and Table 2. 
Phase 2 Portion of the Study:  
This will be conducted using Simon’s two-stage design. Subjects enrolled 
in the phase 1 study at the RP2D cohort will be included for response and 
safety evaluation in phase 2. 
STUDY DRUG 
ADMINISTRATION 
Subjects will receive nab-Sirolimus by IV infusion over a minimum of 30 
(+10) minutes at 100, 75, 60, 45, 30, 20, or 15 mg/m2 either Days 1 and 8 
in a 21-day cycle  or on Day 1 only in a 21-day cycle. 
Pazopanib will be given per standard of care guidelines, daily. Pazopanib 
dosing may be initiated at 400, or 800 mg once daily by mouth, without 
food (at least 1 hour before or 2 hours after a meal). Pazopanib starting 
dose must remain consistent within a dose-finding cohort. 
Subjects will continue therapy until unequivocal clinical disease 
progression, unacceptable toxicity, until in the opinion of the investigator 
the subject is no longer benefiting from therapy, or at the subject’s 
discretion. 
 


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Protocol: CC10015                                                    
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TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ...................................................................................................................... 3 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................................ 11 
1. 
INTRODUCTION .......................................................................................................... 15 
1.1. 
Soft Tissue Sarcomas ................................................................................................. 15 
1.2. 
Nab-Sirolimus Background ........................................................................................ 16 
1.2.1. 
Rapamycin and Rapalogs ........................................................................................... 16 
1.2.2. 
Nab-Sirolimus (ABI-009, nab-Rapamycin) ................................................................. 17 
1.2.3. 
Preclinical Studies with nab-Sirolimus ....................................................................... 17 
1.2.4. 
Clinical Studies with nab-Sirolimus ............................................................................ 19 
1.3. 
Pazopanib in Soft Tissue Sarcoma ............................................................................. 20 
1.4. 
Rationale for Combination of nab-Sirolimus with Pazopanib for 
Nonadipocytic Soft Tissue Sarcoma ........................................................................... 20 
1.5. 
Rationale for Starting Dose Selection and Schedule of nab-Sirolimus and 
Pazopanib................................................................................................................... 21 
2. 
STUDY OBJECTIVES AND ENDPOINTS ........................................................................ 23 
2.1. 
Objectives .................................................................................................................. 23 
2.2. 
Endpoints ................................................................................................................... 23 
2.3. 
Study Design .............................................................................................................. 24 
2.4. 
Study Duration, End of Study, End of Treatment, End of Treatment Visit, 
Follow-up Period ........................................................................................................ 26 
3. 
STUDY POPULATION .................................................................................................. 28 
3.1. 
Number of Subjects ................................................................................................... 28 
3.2. 
Inclusion Criteria ........................................................................................................ 28 
3.3. 
Exclusion Criteria ....................................................................................................... 29 
4. 
TABLE OF EVENTS ...................................................................................................... 31 
5. 
PROCEDURES ............................................................................................................. 36 
5.1. 
Screening Evaluations ................................................................................................ 36 
5.2. 
Treatment Period ....................................................................................................... 37 
5.2.1. 
Day 1 Assessment ...................................................................................................... 37 
5.2.2. 
Day 8 Assessment ...................................................................................................... 38 
5.2.3. 
Day 15 Assessment .................................................................................................... 38 


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5.2.4. 
Response Assessment ................................................................................................ 39 
5.3. 
End of Treatment Visit Assessment ........................................................................... 39 
5.4. 
30-Day Follow Up Visit ............................................................................................... 40 
5.5. 
Rapamycin Trough levels ........................................................................................... 40 
5.6. 
Follow-up Period for Survival and Initiation of Anticancer Therapy ......................... 41 
6. 
DESCRIPTION OF STUDY TREATMENTS ..................................................................... 42 
6.1. 
Nab-Sirolimus............................................................................................................. 42 
6.1.1. 
Nab-Sirolimus/Pazopanib Dosage, Administration, and Schedule ............................ 42 
6.1.2. 
Nab-Sirolimus Dose Modification and Stopping Rules .............................................. 43 
6.1.3. 
Nab-Sirolimus Hepatotoxicity Stopping Rules ........................................................... 48 
6.1.3.1. 
Criteria for Permanent Discontinuation of nab-Sirolimus Due to Potential 
Hepatotoxicity............................................................................................................ 48 
6.1.3.2. 
Criteria for Conditional Withholding of nab-Sirolimus Due to Potential 
Hepatotoxicity............................................................................................................ 48 
6.2. 
Pazopanib................................................................................................................... 49 
6.2.1. 
Dose Levels for Pazopanib ......................................................................................... 49 
6.2.2. 
Pazopanib Dose Modification and Stopping Rules .................................................... 49 
6.3. 
Dosing Schedules (D1 vs D1/D8) ................................................................................ 54 
6.4. 
Dose Limiting Toxicity ................................................................................................ 54 
6.5. 
Dose Modification Algorithms for Adverse Events Possibly Related to nab-
Sirolimus and Pazopanib ............................................................................................ 55 
6.6. 
Overdose .................................................................................................................... 58 
6.6.1. 
Nab-Sirolimus............................................................................................................. 58 
6.6.2. 
Pazopanib................................................................................................................... 58 
7. 
STUDY DRUG MANAGEMENT .................................................................................... 59 
7.1. 
Description of Study Drugs ........................................................................................ 59 
7.1.1. 
Nab-Sirolimus Packaging, Labeling, and Storage ....................................................... 59 
7.2. 
Nab-Sirolimus and Pazopanib Accountability, Disposal, and Compliance ................ 59 
7.2.1. 
Nab-Sirolimus............................................................................................................. 59 
7.2.2. 
Pazopanib................................................................................................................... 59 
7.3. 
Nab-Sirolimus Reconstitution and Use ...................................................................... 60 
7.4. 
Receipt and Return of nab-Sirolimus ......................................................................... 60 


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8. 
CONCOMITANT MEDICATIONS AND PROCEDURES ................................................... 61 
8.1. 
Permitted Medications and Procedures .................................................................... 61 
8.2. 
Prohibited Medications and Procedures ................................................................... 61 
9. 
STATISTICAL CONSIDERATIONS ................................................................................. 63 
9.1. 
Study Endpoints ......................................................................................................... 63 
9.2. 
Safety Analysis ........................................................................................................... 63 
9.3. 
Efficacy Analysis ......................................................................................................... 64 
9.4. 
Exploratory Analysis................................................................................................... 64 
9.5. 
Sample Size Considerations ....................................................................................... 64 
9.6. 
Primary Analysis ......................................................................................................... 65 
10. 
MONITORING, RECORDING, AND REPORTING OF ADVERSE EVENTS ....................... 66 
10.1. 
Toxicities of Nab-Sirolimus ........................................................................................ 66 
10.2. 
Toxicities of Pazopanib .............................................................................................. 66 
10.3. 
Evaluation of Adverse Events .................................................................................... 66 
10.4. 
Serious Adverse Events .............................................................................................. 66 
10.4.1. 
Definition of Serious Adverse Events ........................................................................ 66 
10.4.2. 
Reporting Procedures for Serious Adverse Events .................................................... 67 
10.5. 
Pregnancy and Breastfeeding Reporting ................................................................... 67 
11. 
WITHDRAWAL FROM TREATMENT, PROCEDURES, AND STUDY ............................... 69 
11.1. 
Discontinuation from Investigational Product .......................................................... 69 
11.2. 
Discontinuation from the Study ................................................................................ 69 
11.3. 
Decision to Withdraw or Terminate Subject’s Participation Prior to Study 
Completion ................................................................................................................ 69 
12. 
REGULATORY OBLIGATIONS ...................................................................................... 70 
12.1. 
Informed Consent ...................................................................................................... 70 
12.2. 
Institutional Review Board/Independent Ethics Committee .................................... 70 
12.3. 
Subject Confidentiality ............................................................................................... 70 
12.4. 
Protocol Amendments ............................................................................................... 71 
12.5. 
Termination of the Study ........................................................................................... 71 
13. 
DATA HANDLING AND RECORDKEEPING ................................................................... 72 
13.1. 
Data/Documents ........................................................................................................ 72 


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13.2. 
Data Management ..................................................................................................... 72 
13.3. 
Responsibilities for Data Collection ........................................................................... 72 
13.4. 
Sample Storage and Destruction ............................................................................... 72 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE......................................................... 74 
14.1. 
Study Monitoring ....................................................................................................... 74 
14.2. 
Audits and Inspections ............................................................................................... 74 
15. 
PUBLICATIONS ........................................................................................................... 75 
16. 
REFERENCES ............................................................................................................... 76 
17. 
APPENDIX 1 - WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION ................................................................................ 80 
17.1. 
Definitions .................................................................................................................. 80 
17.1.1. 
Woman of Childbearing Potential (WOCBP) ............................................................. 80 
17.2. 
Contraception Guidance for Females of Childbearing Potential ............................... 80 
17.3. 
Contraception Guidance for Males of Childbearing Potential .................................. 82 
 
List of Tables 
Table 1. Day 1 and Day 8 Dosing Levels (Closed/Completed Cohorts) ......................................... 24 
Table 2 - Day 1 Only Dosing Levels (Amendment 3, Version 4.0 and Later Only) ........................ 25 
Table 3 - Summary of DLT (Combined Cohorts 0, -1, -2) .............................................................. 25 
Table 4. Schedule of Assessments (Day 1 and Day 8 Dosing – Subjects enrolled under 
Amendment 2, v3.0 or earlier) .................................................................................. 32 
Table 5. Schedule of Assessments (Day 1 Only Dosing – Subjects Enrolled under 
Amendment 3, v 4.0 or later, or Subjects who swap to a D1 only dosing 
schedule) .................................................................................................................... 34 
Table 6. Analyte Listing ................................................................................................................. 39 
Table 7 - Day 1 and Day 8 Dosing Levels (Closed – Enrolled under Am2, v3.0 or earlier) ............ 42 
Table 8 - Day 1 Only Dosing Levels ............................................................................................... 42 
Table 9. Dose Modification Algorithms for Adverse Events Possibly Related to ABI-009 
(See also Table 10 and Table 11) ............................................................................... 45 
Table 10. Dose Modification Algorithms for Adverse Events Possibly Related to 
Pazopanib (See also Table 9 and Table 11) ............................................................... 51 
Table 11 - Dose Modification Algorithms for Overlapping Adverse Events Possibly 
Related to nab-Sirolimus and Pazopanib (See also Table 9 and Table 10) ................ 55 


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LIST OF FIGURES 
Figure 1: 
Antitumor Activity of ABI-009 in Tumor Xenografts ................................................. 18 
 


Nab-Sirolimus/Pazopanib 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
adverse event 
ALP 
alkaline phosphatase  
ALT 
alanine transaminase (SGPT) 
ANC 
absolute neutrophil count 
AST 
aspartate transaminase (SGOT) 
AUC 
area under the time-concentration curve 
BSA 
body surface area 
Cmax 
maximum plasma drug concentration 
Cmin 
minimum plasma drug concentration 
CBC 
complete blood count 
CI 
confidence interval 
CNS 
central nervous system 
CR 
complete response 
CT 
computed tomography 
DLT 
dose-limiting toxicity 
DMC 
data monitoring committee 
DNA 
deoxyribonucleic acid 
DCR 
DOR 
disease control rate 
duration of response 
ECOG PS 
Eastern Cooperative Oncology Group performance status 
CRF 
electronic case report form 
EOS 
end of study 
EOT 
end of treatment 
GCP 
Good Clinical Practice 
G-CSF 
granulocyte-colony stimulating factor 
ICH 
International Conference on Harmonisation  
IEC 
Independent Ethics Committee 
IHC 
Immunohistochemistry 
IND 
investigational new drug  
IP 
investigational product 


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IRB 
Institutional Review Board 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
mL 
milliliter 
MRI 
magnetic resonance imaging 
MTD 
maximum-tolerated dose 
mTOR 
mammalian target of rapamycin 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
ORR 
overall response rate 
OS 
overall survival 
PD 
progressive disease 
PFS 
Progression-free survival 
PK 
pharmacokinetics 
PR 
partial response 
PTEN 
protein tyrosine phosphatase 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
serious adverse event 
SD 
stable disease 
SGOT 
serum glutamic oxaloacetic transaminase (AST) 
SGPT 
serum glutamic pyruvic transaminase (ALT) 
TBL 
total bilirubin level 
ULN 
upper limit of normal 
 
 


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Abbreviation or Term 
Definition/Explanation 
Study Day 1 
First day that protocol-specified IP is administered to the subject. 
End of Treatment 
The date of the last dose of ABI-009 or pazopanib, whichever is later 
for an individual subject. 
End of Treatment Visit 
For a subject is when safety assessments and procedures are 
performed after the last treatment, which should occur within 1 
week (±3 days) after the last dose of ABI-009 or pazopanib, 
whichever is later.  
30 Day Follow-Up Visit 
For a subject is when safety assessments and procedures are 
performed after the End of Treatment visit. The 30-Day Follow-Up 
visit should occur 30 days (+/- 7 days) after the last dose of ABI-009 
or pazopanib, whichever is later. 
End of Study 
 
Either the date of the last visit of the last subject to complete the 
study, or the date of receipt of the last data point from the last 
subject that is required for primary, secondary, and/or exploratory 
analysis, as pre-specified in the protocol.  
Follow-up Period 
 
The on-study time period after the 30-Day Follow-Up Visit. All 
subjects that discontinue study drug and have not withdrawn full 
consent to participate in the study will continue in the follow-up 
phase for survival and initiation of new anticancer therapy. Follow 
up will continue approximately every 12 weeks (±3 weeks) from the 
30-Day Follow-Up Visit, or more frequently as needed, until death, 
withdrawal of consent, or the study closes, whichever is the earliest. 
This evaluation may be made by record review and/or telephone 
contact. 
Primary Analysis 
 
For this study will occur after all subjects have either completed the 
study or completed 12 months of treatment. Subjects who are still 
active at the time of the primary analysis may continue on study until 
disease progression or medication intolerance is observed. 
Efficacy Analysis 
Dataset  
 
All enrolled subjects with measurable tumor per RECIST v1.1 at 
baseline who received at least 2 doses of ABI-009 and had a follow-
up CT / MRI (modified treated population). 


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Full Analysis Set 
All enrolled subjects who receive at least 1 dose of ABI-009 (treated 
population). 
Per-protocol 
Analysis 
Set 
All enrolled subjects who do not have any prospectively defined 
protocol violations.  
Progression-free 
survival 
The time from the first dose date to the first observation of a disease 
progression or death due to any cause.   
Overall survival 
The time from the first dose date to the date of death due to any 
cause. 
Overall response rate 
 
The proportion of subjects who achieve a confirmed partial response 
or complete response per RECIST v1.1. Response rates based on a 
local radiologic assessment. 
Duration of response 
The time from when criteria of response are first met until the first 
observation of disease progression per RECIST v1.1 or death due to 
any cause, whichever comes first.  
 
 


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1. 
INTRODUCTION 
1.1. 
Soft Tissue Sarcomas 
Soft tissue sarcoma (STS) is a relatively rare and histologically diverse neoplasm of mesenchymal 
origin, occurring with an incidence of about 1% of all adult cancers, and includes >70 histologic 
subtypes.1-3  For localized resectable disease, surgical resection is the standard of care, and for 
unresectable sarcomas, radiation therapy is offered. However, recurrence rate is high (~50%) and 
treatment options for metastatic/relapsed STS are limited to anthracycline-based chemotherapy 
(i.e., doxorubicin), administered alone or in combination with alkylating agents (ifosfamide 
and/or dacarbazine).4-6 However, drug resistance and toxicities often limit beneﬁts of 
chemotherapy used to treat metastatic sarcomas. 
Recently, in 2015, 2 therapeutics were approved by the United States Food and Drug 
Administration (US FDA) for STS, pazopanib (Votrient®, Novartis Pharma) and trabectedin 
(Yondelis®, Janssen Biotech, Inc.). Pazopanib is a multiple tyrosine kinase inhibitor (TKI), which 
hinders growth factor-mediated signal transduction pathways involved in tumor angiogenesis, 
and was approved for nonadipocytic STSs refractory to chemotherapy.7-9 Trabectedin, a natural 
alkaloid which interferes with gene transcription and DNA repair, was approved for liposarcoma 
and leiomyosarcoma.10,11 Although the new therapeutic options offer improvement of the course 
of disease in specific subtypes of STSs, the prognosis of advanced disease has remained uniformly 
poor, with an estimated median survival of only 8 to 13 months,12-14 and more efficacious 
therapeutics options are needed. 
1.1.1 mTOR Inhibition in Soft Tissue Sarcoma 
Aberrant signaling of the mammalian target of rapamycin (mTOR) pathway is common in 
sarcomas and other malignancies. A multicenter, open-label, single-arm, phase 2 trial with oral 
ridaforolimus, an mTOR inhibitor, showed evidence of activity in sarcomas.15 A total of 212 
heavily pretreated subjects were treated in 4 separate histologic cohorts of STS; 61 subjects 
(28.8%) achieved disease control rate (DCR, defined as subjects who achieved complete response 
(CR) or partial response (PR) or stable disease (SD) for ≥16 weeks). Median progression-free 
survival (PFS) was 15.3 weeks; median overall survival (OS) was 40 weeks, which compared 
favorably to historical metrics. The conﬁrmed overall response rate (ORR) was 1.9%, with 4 
subjects achieving conﬁrmed PR (2 with osteosarcoma, 1 with spindle cell sarcoma, and 1 with 
undifferentiated pleomorphic sarcoma [formerly malignant ﬁbrous histiocytoma]). Related 
adverse events (AEs) were generally mild or moderate and consisted primarily of stomatitis, 
mucosal inﬂammation, mouth ulceration, rash, and fatigue, all typical of the rapalogs. 
Based on promising results from phase 2, a large randomized placebo-controlled phase 3 trial (N 
= 711) evaluated ridaforolimus to assess disease control in advanced sarcomas after benefit from 
prior chemotherapy.16 Subjects with metastatic soft tissue or bone sarcomas who achieved 
objective response or SD with prior chemotherapy were randomly assigned to receive 
ridaforolimus 40 mg or placebo once per day for 5 days every week. Ridaforolimus treatment led 
to a modest, although signiﬁcant, improvement in PFS per independent review compared with 
placebo (hazard ratio [HR], 0.72; P < 0.001; median PFS, 17.7 v 14.6 weeks). Ridaforolimus 
induced a mean 1.3% decrease in target lesion size vs a 10.3% increase with placebo (P < 0.001). 


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Protocol: CC10015                                                    
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Median OS with ridaforolimus was modest: 90.6 weeks versus 85.3 weeks with placebo (HR, 0.93; 
P = 0.46). Adverse events were more common with ridaforolimus than with placebo and were as 
expected with mTOR inhibition, including stomatitis, infections, fatigue, thrombocytopenia, 
noninfectious pneumonitis, hyperglycemia, and rash. Grade 3 AEs were 64% vs 26% for 
ridaforolimus vs placebo, respectively. While there was no associated survival benefit, the trial 
provided proof of principle that mTOR inhibition could demonstrate clinical activity in STS. 
Other mTOR inhibitors, including sirolimus and everolimus, have also been tested in clinical trials 
for advanced STS as single-agents or as part of a combination regimen, producing modest 
improvement. While rapamycin and analogs (rapalogs) are promising therapeutics for the 
treatment of sarcomas, they have low water solubility (hydrophobic), limiting their 
bioavailability. Oral agents, such as rapamycin, everolimus, or ridaforolimus are primarily 
eliminated via hepatic clearance, which result in negligible drug levels in most organs, limiting 
their therapeutic potential. Temsirolimus, a prodrug of rapamycin requiring conversion by 
CYP3A, has higher water solubility than the oral agents but still require solvents (polysorbate 80, 
polyethylene glycol, and dehydrated alcohol) for the injectable formulation. Solvents reduce drug 
efficacy due to micellar sequestration and thus, improved formulations are needed that are both 
solvent-free and allow high bioavailability in order to unleash the full potential of mTOR 
inhibitors. 
A novel mTOR inhibitor ABI-009 (albumin-bound rapamycin nanoparticles, nab-rapamycin) is 
solvent-free and has relatively high bioavailability, and is a promising new therapeutic for 
sarcoma. 
1.2. 
Nab-Sirolimus Background 
1.2.1. 
Rapamycin and Rapalogs 
Rapamycin is a protein kinase inhibitor that is approved for immunosuppression in renal 
transplant subjects and is under investigation as a cancer treatment. Rapamycin inhibits mTOR, 
a regulatory protein kinase in cancer that recognizes high stress levels, including depleted 
nutrient levels and states of hypoxia.17 mTOR is a serine/threonine-specific protein kinase, 
downstream of the phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B) pathway, and a 
key regulator of cell survival, proliferation, and metabolism. Additionally, mTOR is involved in 
regulating angiogenesis by controlling endothelial and smooth muscle cell proliferation via the 
hypoxia-inducible factor-1α and vascular endothelial growth factor (VEGF).18 Consistent with its 
role in cell proliferation, the mTOR pathway is frequently overactivated in a number of human 
malignancies, and is thus considered to be an attractive target for anti-cancer therapy. 
Rapamycin and its analogs (rapalogs) function as allosteric inhibitors of mTORC1. Rapalogs are 
currently used in the treatment of advanced renal cell carcinoma and other tumors.19 
Although rapamycin (sirolimus) is an efficacious mTOR inhibitor, it has poor solubility, low oral 
bioavailability, and produce dose-limiting toxicities (DLTs), including mucositis and stomatitis.17,20 
Marketed rapamycin analogs are temsirolimus and everolimus. Temsirolimus, a prodrug of 
rapamycin, is approved for the treatment of kidney cancer. Everolimus is approved for pediatric 
and adult subjects with subependymal giant cell astrocytoma, for advanced hormone receptor-
positive, HER2-negative breast cancer in combination with exemestane, progressive 


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neuroendocrine tumors of pancreatic origin (PNETs), subependymal giant cell astrocytoma 
(SEGA) associated with tuberous sclerosis and advanced renal cell carcinoma after failure of 
treatment with sunitinib or sorafenib.21-25 
Oral rapamycin and currently available rapalogs induce common side effects including 
hypertension, maculopapular rash (75%), mucositis (50%), asthenia (40%), nausea (43%), 
thrombocytopenia, metabolic abnormalities and more rarely pneumonitis (8%, 3% grade 3) 
sometimes fatal.26-28 The most frequently occurring grade 3 or 4 AEs were hyperglycemia (17%), 
hypophosphatemia (13%), anemia (9%), and hypertriglyceridemia (6%).29 These side effects lead 
to the discontinuation of the treatment in 60% of subjects in some studies. 
1.2.2. 
Nab-Sirolimus (ABI-009, nab-Rapamycin) 
The novel nanoparticle albumin-bound rapamycin (nab-Sirolimus, nab-rapamycin, ABI-009) is 
freely dispersible in saline and is suitable for intravenous (IV) administration, and has produced 
both a favorable safety profile and evidence of efficacy in subjects with metastatic solid tumors.30 
Nanoparticle albumin-bound or nab® technology (Abraxis Bioscience, a wholly-owned subsidiary 
of Celgene Corporation) when applied to hydrophobic molecules, such as paclitaxel (nab-
paclitaxel; Abraxane®), has led to improved drug delivery, safety, and efficacy in various solid 
tumors compared with the conventional paclitaxel formulation.31 This suggests that the nab 
formulation of rapamycin may also produce similar advantages over the standard rapamycin. 
The nab technology may enhance tumor penetration and accumulation via the albumin receptor-
mediated (gp60) endothelial transcytosis. Albumin is highly soluble, has long plasma half-life, 
broad binding affinity, and accumulates in tumors, making it an ideal candidate for drug 
delivery.32,33 Albumin circulating in the bloodstream can interact with gp60 to initiate caveolae-
mediated transcytosis to reach tumor cells.34,35 Indeed, nab-paclitaxel transcytosis across the 
epithelial monolayer was dependent on caveolae formation.36 In accordance with these 
observations, at equal doses, nab-paclitaxel showed greater selectivity to tumors compared with 
solvent-based paclitaxel, which is likely attributed to the biologically active ingredient albumin 
and lack of solvent.36 
Additionally, a study previously published by our group examined the prognostic implications of 
expression of the Serum Protein Acidic and Rich in Cysteine (SPARC) in sarcomas.37 We found that 
elevated SPARC expression, found in about 50% of a random selection of cases, was associated 
with a particularly adverse prognosis, as compared to those with low expression. SPARC has been 
hypothesized as a potential receptor of nanoparticle-albumin encapsulated drug preparations, 
making nab-Sirolimus a promising targeted mTOR for the treatment of STSs.  
1.2.3. 
Preclinical Studies with nab-Sirolimus 
Preclinical primary pharmacology studies in vivo demonstrated significant antitumor activity of 
nab-Sirolimus as a single agent administered intravenously at 40 mg/kg, 3 times weekly for 4 
weeks, across different tumor xenograft models in nude mice (see Figure 1 below), including 
breast, colorectal, multiple myeloma, and pancreatic cancer.38-42 This dose level correlates to 
approximately 360 mg/m2/week in human. These findings are consistent with published 
information on rapamycin as an mTOR inhibitor and the role of mTOR in tumor growth.43 In 


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addition, recent preclinical study has demonstrated that combination of nab-Sirolimus with the 
Akt inhibitor perifosine induced synergistic antitumor activity and prolonged survival compared 
with either agent alone in multiple myeloma.41 
Figure 1: 
Antitumor Activity of nab-Sirolimus in Tumor Xenografts 
 
Preclinical pharmacokinetic (PK) studies in rats showed that IV nab-Sirolimus exhibited linear PK 
with respect to dose and large volume of distribution (Vz), due to efficient tissue extraction of 
rapamycin from the central blood compartment.40 Shortly after dosing, tissue rapamycin level 
was 3-5 folds higher than that of blood, indicating efficient extraction. The terminal half-life of 
nab-Sirolimus was long in rats, ranging from 13.4 - 25.8 hours and resulted in significant blood 
level at 48 hours (~10 ng/mL) and 120 hours (>1 ng/ml). Consistent with rapamycin literature,44 
excretion of ABI-009 was primarily through the fecal route (68.57 - 69.99%) with minimum 
contribution from the renal route (7.73 - 8.84%). 
The safety and toxicity of nab-Sirolimus were evaluated in a series of preclinical studies. In a 
Good Laboratory Practice (GLP) repeat-dose toxicity study in male and female rats, nab-
Sirolimus administered IV was well tolerated at doses up to 90 mg/kg (equivalent to 540 mg/m2 


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human dose) when delivered every 4 days for 3 cycles. Nonclinical toxicology studies of nab-
Sirolimus showed no new or unexpected toxicity compared to what is already known for 
rapamycin and other rapalogs.45-47  Refer to the Investigator's Brochure for details on preclinical 
studies. 
1.2.4. 
Clinical Studies with nab-Sirolimus 
In a phase 1 dose-finding, tolerability, and PK study conducted at MD Anderson Cancer Center 
(Protocol CA401, NCT00635284), nab-Sirolimus was well tolerated with evidence of responses 
and SD in various solid tumors including renal cell carcinoma and bladder cancer, both of which 
typically express mTOR.30 Twenty-six subjects were treated with 45, 56.25, 100, 125, or 150 
mg/m2 nab-Sirolimus per week for 3 weeks, followed by a week of rest (28-day cycle, q3/4w). 
ABI-009 was administered IV. The maximum tolerated dose (MTD) was established at 100 mg/m2. 
Nineteen subjects were evaluable for efficacy. One subject in the 45 mg/m2 (95 mg actual 
rapamycin dose) cohort diagnosed with adenocarcinoma of the kidney and with bone and 
intrathoracic metastases had a confirmed PR. The target lesion of this subject was reduced by 
35.1% and the duration of response (DOR) lasted 183 days. Two (11%) subjects (at doses 45 and 
125 mg/m2, with actual rapamycin doses of 88 mg and 193 mg, respectively) had an overall tumor 
evaluation of SD (confirmed): 1 subject with mesothelioma had SD for 365 days and 1 subject 
with a neuroendocrine tumor in the left axillary node had SD for 238 days.  
In the phase 1 study described above, for all cohorts and all grades, 25 of 26 (96%) subjects 
experienced at least 1 treatment-related AE (TRAE). The most common nonhematological TRAEs 
were mucosal inflammation (10 subjects, 38%), fatigue (7 subjects, 27%), rash (6 subjects, 23%), 
diarrhea (6 subjects, 23%), and nausea (5 subjects, 19%). Specifically, at the MTD of 100 mg/m2, 
all 7 subjects experienced at least 1 TRAE of any grades, and the most common AEs were 
thrombocytopenia, mucositis and fatigue (5 subjects, 71% each). A total of 7 subjects (27%) in 
the CA401 study had treatment-related infections, including candidiasis, oral candidiasis, 
cellulitis, folliculitis, and urinary tract infection. All these events were grade 1 or 2. Four (15%) 
subjects experienced at least 1 treatment-related serious AE (SAE), including cardiac arrhythmia 
(grade 2), failure to thrive (grade 3), and mood alteration (grade 3) both in the 125 mg/m2 cohort, 
vomiting (grade 3) in the 45 mg/m2 cohort, and dyspnea (grade 3) in the 100 mg/m2 cohort. 
The most common hematologic TRAEs, for all cohorts and grades, were thrombocytopenia (58%), 
followed by hypokalemia (23%), anemia and hypophosphatemia (19% each), and neutropenia 
(15%). Most of these events were grade 1/2, and only 1 grade 4 hematologic event occurred 
(thrombocytopenia in the 150 mg/m2 arm). At the MTD, the only hematologic AE was a grade 3 
anemia. In this clinical study, 16 of 26 subjects (62%) had treatment-related AEs (TRAEs) requiring 
a week dose delay.  
Currently, there are several ongoing trials investigating the safety and efficacy of single-agent 
nab-Sirolimus in various disease areas, including a basket trial in subjects with pathogenic 
inactivating TSC1 or TSC2 alterations (NCT05103358). The particularly safe toxicity profile of nab-
Sirolimus allows this mTOR inhibitor to be combinable with other therapeutics and a trial in 
subjects with advanced STS is complete and evaluating the combination of nab-Sirolimus and 
nivolumab (NCT03190174). Refer to the Investigator's Brochure for details on clinical studies. 


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Protocol: CC10015                                                    
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1.3. 
Pazopanib in Soft Tissue Sarcoma 
Angiogenesis has been explored as a potential target for the treatment of STS.48 A variety of 
multi-targeted TKIs with prominent anti-angiogenic activity (aa-TKI’s) have been studied, 
including pazopanib, with evidence of clinically significant activity.   
Pazopanib was initially approved for the treatment of advanced renal carcinoma and more 
recently, based on a phase 3 randomized trial, as salvage therapy in subjects with advanced, 
nonadipocytic STS.8 In that registrational placebo-controlled, randomized phase 3 study, 
pazopanib demonstrated improved PFS vs placebo in pretreated subjects (median 4.6 vs 1.6 
months; HR=0.31; P < 0.0001).8 Overall survival was not significantly improved and the ORR was 
relatively low (6% pazopanib vs 0% placebo). The most common AEs were fatigue (65% vs 49%), 
diarrhea (58% vs 16%), nausea (54% vs 28%), weight loss (48% vs 20%), and hypertension (41% 
vs 7%) in the pazopanib vs placebo arms, respectively. Although approved for management of 
STS, the activity of pazopanib monotherapy is admittedly modest, with considerable toxicity 
profile.  
A meta-analysis showed evidence that aa-TKIs, including pazopanib, demonstrated improved 
median PFS and ORR vs placebo for the treatment of sarcomas; however, there was no difference 
in the median PFS, median OS, and ORR of pazopanib vs other aa-TKIs.49 Similar to the 
registrational phase 3 study, the meta-analysis also failed to show improvement in median OS 
for aa-TKIs compared with placebo.  
The identification of sarcoma subtypes with particular sensitivity to aa-TKI, along with 
appropriate combination therapies to increase the overall activity in STSs remains an unmet 
need.  
1.4. 
Rationale for Combination of nab-Sirolimus with Pazopanib for Nonadipocytic Soft 
Tissue Sarcoma 
The feasibility to combine an mTOR inhibitor (everolimus) with an aa-TKI (vandetanib) had been 
demonstrated in a phase 1 study in subjects with bone and STSs (N = 21).50 Median PFS and OS 
were 4.5 and 13.9 months, respectively. Two subjects (9.5%) had a CR. These results favorable 
compared with the results from the meta-analysis, in which aa-TKIs produced 3.2 and 11.8 
months of median PFS and OS, respectively, and 5% ORR.49 These results provided proof-of-
concept for the potential to improve efficacy outcomes for subjects with STS with the 
combination of an aa-TKI and an mTOR inhibitor. 
Based on the promising results from the phase 1 study with everolimus combined with 
vandetanib,50 the acceptable toxicity profile of single agent nab-Sirolimus along with evidence of 
antitumor activity in various solid tumors,30 it is plausible that nab-Sirolimus with an aa-TKI may 
potentially offer clinical benefits for subjects with STS. Based on a phase 3 study, PALETTE,8 
pazopanib is now a standard of care for subjects with advanced nonadipocytic STS. Here, we 
propose a phase 1/2 assessment of the safety and antitumor activity of the combination of nab-
Sirolimus with pazopanib for subjects with advanced nonadipocytic STSs.  Given non-overlapping 
toxicity profiles, we hypothesize that combining the 2 drugs will be feasible.   


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1.5. 
Rationale for Starting Dose Selection and Schedule of nab-Sirolimus and Pazopanib 
The established MTD of single-agent nab-Sirolimus for subjects with advanced solid tumors is 
100mg/m2. In the initial cohorts of nab-Sirolimus with pazopanib, the planned starting dose of 
60 mg/m2 ABI-009 [given IV weekly for 2 weeks with a week of rest (q2/3w)] gave a 40% safety 
margin over the established MTD of 100 mg/m2 for subjects with advanced solid tumors 
adipocytic. This dose, assuming a BSA of 1.7, is 102 mg/week (or 68 mg/week on average in a 3-
week cycle), which is within or above the therapeutic range for rapalogs:   
• Rapamune (oral rapamycin) dosing used chronically for transplant subjects is similar to 
the proposed starting dose of nab-Sirolimus.46 Rapamune is dosed at 2-5 mg/day, which 
is 14-35 mg/week. Safety profiles of everolimus and Rapamune are similar. Everolimus 
dosing levels47 are similar to Rapamune dosing, with both being in the same range as 
the planned starting dose of ABI-009. 
• Using the PK data from the phase 1 study30, linear modeling of rapamycin blood 
concentration predicts that 1 week after 10 and 20 mg/m2 nab-Sirolimus IV 
administration, therapeutic trough rapamycin levels are still maintained (7.11 and 14.22 
ng/mL, respectively, Aadi data on file). Thus, potential dose reduction from the starting 
dose of 60 mg/m2 should still result in therapeutic levels. 
• Nab-Sirolimus has shown similar safety profile to other rapalogs, even at a higher dose 
of 100 mg/m2, with no new or unexpected toxicity had been observed. In particular, 
mucositis/stomatitis that were observed with other mTOR inhibitors has not been dose-
limiting with nab-Sirolimus. 
The q2/3w schedule allowed 2 additional drug holidays in 6 months than the q3/4w schedule 
studied in the first-in-human study for nab-Sirolimus (CA401, NCT00635284), allowing more 
time for recovery from potential AEs and is more convenient for subjects. 
A recommended phase 2 dose (RP2D) could not be established in the initial dosing cohorts in 
this present study, after treating 13 subjects. DLTs were observed in all dose cohorts, with the 
most prominent DLT being thrombocytopenia. Despite DLT, subjects have been able to tolerate 
therapy after dose adjustment (dose reductions and delays): only 3 of the first 13 subjects 
enrolled discontinued therapy due to adverse events. Two patients experienced grade 3 and 4 
thrombocytopenia after a single dose of nab-Sirolimus and missed Cycle 1 Day 8, subsequently 
recovered from the event, and were able to resume therapy. Additionally, 10/13 (77%) patients 
experienced myelosuppression during the first cycle, 6 of them had a delay of the next planned 
cycle, D1. Together missed Day 8 doses and dose delays of Day 1 occurred in nearly all patients 
(12/13, 92%) at some point during the treatment course, resulting in 3-week gap between 
dosing, which allowed resolution of AEs and continuous therapy.  These results lead to the 
conclusion that administration of the combination may be feasible but require optimization of 
the q2/3w schedule; and therefore, a new cohort set will explore a q1/3w schedule, i.e. nab-
Sirolimus dosing on Day 1 of a 3-week cycle.    
Assessment of clinical activity of this combination in STS is a secondary objective.  Two of the 13 
subjects enrolled in the initial phase I assessment experienced objective partial responses, in 


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spite of the dose modifications described above. The objective evidence of clinical activity 
further justifies continued efforts to identify a RP2D. 
For further dose-finding studies, nab-Sirolimus will be administered at a starting dose of 30 
mg/m2 every three weeks.  Dose escalation will be in steps, either down to 20 or 15 mg/m2, or 
incrementally increasing to 45, 60, 75 and 100 mg/m2 administered on day 1 of a 21-day cycle.  
This dose range, assuming a BSA of 1.7, yields dose intensity in the range of 8.5-56 mg/wk.  While 
lower than expected in the initially planned dosing schema with q2/3w dosing, this range of dose 
intensity closely approximates that anticipated with rapalogs. In this study, pazopanib will be 
given as standard of care. The starting dose was 800 mg orally once daily without food (at least 
1 hr. before or 2 hrs. after a meal), and is reduced to 400 mg orally once daily.52  In our initial 
experience combining nab-Sirolimus with pazopanib, thrombocytopenia emerged as an apparent 
dose limiting toxicity when pazopanib was administered the daily dose of 800 mg recommended 
by the package insert.52  Thrombocytopenia can be observed with both agents.  We noted with 
several subject that dose reductions of pazopanib to either 400 or 600 mg daily allowed 
administration of nab-Sirolimus.  Of the 2 doses, 400 mg of pazopanib daily appeared to be 
consistently compatible with nab-Sirolimus, whereas subjects receiving 600 mg daily have 
required additional dose reductions to 400 mg daily.  In our further investigation of this 
combination, we propose continuing our investigations at a dose of 400 mg of pazopanib daily. 
Selection of 400 mg of pazopanib as the starting dose for investigation is reasonable.  The 
package insert for pazopanib recommends that “initial dose reduction should be 400 mg, and 
additional dose decrease, or increase should be in 200 mg steps based on individual tolerability.” 
In addition, a subgroup analysis of subjects from the original pazopanib registration trial for soft-
tissue sarcomas has recently been published.53  Dose reductions and dose interruptions were 
reported in 32% (77/240) and 42% (101/240) of those available for analysis.  Thus, changes to 
planned study treatment were frequent due to toxicity from pazopanib. Critically, neither dose 
reductions nor dose interruptions of pazopanib were associated with inferior progression free 
survival in the Intent-to-Treat population.  Specifically, the authors addressed dosing at 400 and 
600 mg daily.  Within the study population, those receiving “…a daily dose between 400 and 600 
mg had higher…[median Progression-Free Survival] then subjects receiving a daily dose between 
600 and 800 mg or a daily dose of less than 400 mg….”53.  While the longer progression-free 
survival among those receiving lower doses of pazopanib likely reflects some element of selection 
bias, the key point is that the lower doses were not associated with worsened progression-free 
survival, the primary endpoint of the study.  Thus, it is reasonable to use a starting dose of 400 
mg of pazopanib as we continue to investigate the combination with nab-Sirolimus. 
 
 
 


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2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Objectives  
Objectives in Phase 1 
Primary 
• To identify the recommended phase 2 dose (RP2D) of nab-Sirolimus given IV plus daily 
oral pazopanib, for subjects with nonadipocytic STS 
Secondary 
• To evaluate the safety profile of the nab-Sirolimus plus pazopanib combination therapy 
in advanced nonadipocytic STS 
Objectives in Phase 2 
Primary 
• To evaluate the efficacy of the combination of ABI-009 and pazopanib at the RP2D. 
Secondary 
• To evaluate the safety profile and to further evaluate the efficacy of nab-Sirolimus plus 
pazopanib combination therapy 
Exploratory 
• To study the correlation of clinical outcomes with Next Generation Sequencing and 
Immunohistochemical analyses of tumor biomarkers, including baseline secreted protein 
acidic and rich in cysteine (SPARC) expression. 
• To assess baseline tumoral immune parameters, including PD-1, PD-L1, mutational 
burden, and infiltrating lymphocytes, in correlation with clinical outcomes. 
2.2. 
Endpoints 
Endpoints in Phase 1 
Primary Endpoint 
• Dose-limiting-toxicities, as defined in Section 6.4 
Secondary Endpoints 
• Adverse Events profile (based on National Cancer Institute [NCI] Common Terminology 
Criteria for Adverse Events [CTCAE] v5.0) of all subjects and each dose cohort 
Endpoints in Phase 2 – Data from both phase 1 and 2 
Primary Endpoint 
• Progression-free survival rate at 3 months, based on Response Evaluation Criteria in 
Solid Tumors (RECIST) v1.1 
 
Secondary Endpoint 
• Adverse Events profile (based on NCI CTCAE v5.0) 


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• Median PFS, PFS rate at 6 months, based on RECIST v1.1 
• Median OS, OS at 12 months 
• Objective response rate based on RECIST v1.1 
• Disease control rate, defined as CR plus PR plus SD ≥18 weeks, based on RECIST v1.1 
• Duration of response  
Exploratory endpoints 
• Optional pre-treatment tumor tissue collection (fresh or archival) for biomarker analysis: 
o Correlation of genetic profiling and tissue biomarker analysis with clinical benefit 
o Correlation of baseline SPARC expression with clinical benefit 
o Correlation of baseline immune parameters with clinical benefit 
2.3. 
Study Design 
This is an open label, dose-finding, single-arm, prospective phase 1/2 study to identify the RP2D 
of nab-Sirolimus given IV on either Day 1 and Day 8, or Day 1 only of a 21-day cycle (q2/3w), plus 
daily oral pazopanib in subjects with advanced nonadipocytic STS. The target DLT rate is ≤20%. 
The study will be conducted in compliance with International Conference on Harmonisation (ICH) 
Good Clinical Practices (GCPs). 
Dose-finding Phase 1 Portion of the Study:   
Dose levels of nab-Sirolimus will be tested in cohorts of 3 subjects each using the 3+3 dose-finding 
design. Potential doses of nab-Sirolimus are contained below in Table 1 and Table 2. All cohorts 
in Table 1 are considered completed. As of this amendment, new enrollments will follow the 
cohort schedule in Table 2. 
Table 1. Day 1 and Day 8 Dosing Levels (Closed/Completed Cohorts) 
Dose 
Levels 
(Day 1 and Day 
8 Dosing) 
Protocol 
Version 
Added 
Planned Starting Dose 
of ABI-009 in mg/m2 
Planned Starting Dose of 
Pazopanib in mg 
-2  
1.0 
30 
800 
-1  
1.0 
45 
800 
0  
1.0 
60 
800 
1 
1.0 
75 
800 
2 
1.0 
100 
800 
0B 
3.0 
60 
400 
1B 
3.0 
75 
400 
2B 
3.0 
100 
400 
-1B 
3.0 
45 
400 
-2B 
3.0 
30 
400 


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Table 2 - Day 1 Only Dosing Levels (Amendment 3, Version 4.0 and Later Only) 
Dose Levels  
(Day 1 Only Dosing) 
Planned Starting Dose 
of ABI-009 in mg/m2 
Planned Starting Dose of 
Pazopanib in mg 
-2C 
15 
400 
-1C 
20 
400 
0C 
30 
400 
1C 
45 
400 
2C 
60 
400 
3C 
75 
400 
4C 
100 
400 
 
After enrollment of the first 3 dose cohorts (0, -1, and -2) an RP2D had not yet been identified. 
DLTs were observed in all three of these enrolled cohorts. A total of 16 subjects were consented 
resulting in 13 enrollments and 3 screen failures. DLTs were observed at all dose levels. A 
summary of DLTs observed in Cohorts 0, -1, and -2 are provided below in Table 3. Of the 13 
subjects enrolled, 11 subjects had nab-Sirolimus and/or pazopanib dose reduced, and three 
subjects discontinued due to toxicity. 
Table 3 - Summary of DLT (Combined Cohorts 0, -1, -2) 
Dose Limiting Toxicity 
Occurrences 
Platelet Count Decrease 
8 
WBC/Neutrophil Count Decrease 
3 
Lipase Increase 
2 
Proteinuria  
1 
Urinary Tract Infection 
1 
Mucositis, Oral 
1 
Alanine Aminotransferase Increase 
1 
Starting dose of pazopanib must remain consistent within each cohort but may be adjusted 
during treatment as needed due to toxicity. Protocol Amendment 3 added the option for 
additional cohorts, and modified the dosing schedule from Day 1/8 to Day 1 only of a 21-day cycle 
as summarized in Table 1 and Table 2. The starting dose  began at 30 mg/m2 of nab-Sirolimus on 
Day 1 and pazopanib at 400 mg daily (Cohort 0C). Starting with Amendment 3, the dose finding 
portion of the study was re-initiated, enrolling 3 subjects at 30 mg/m2 of nab-Sirolimus and 400 
mg of pazopanib with Day 1 dosing only. Cohort 0C and subsequent cohorts  followed the same 
dose-finding and DLT rules outlined below. 
The dose levels of nab-Sirolimus will be tested in cohorts of 3 subjects each using the 3+3 dose-
finding design. The starting doses for each cohort and potential escalation or de-escalation are 


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summarized in Table 1 and Table 2. If no DLT is observed during the first 2 cycles at the starting 
dose in the first 3 subjects, the next dose cohort would enroll subjects at the next highest dose 
level. If no DLT is observed at the first 3 subjects at the higher dose level, the next dose cohort 
would continue to escalate to the next highest dose level, up to a maximum of 100 mg/m2. If 1 
DLT is observed any dose cohorts in the first 3 subjects, then the cohort will expand, and an 
additional 3 subjects will be enrolled at that dose level. The first three subjects in a given cohort 
must complete the DLT window prior to expanding to include the additional 3 subjects. If ≤1 of 6 
subjects experience a DLT at the starting dose or higher, enrollment would continue to the next 
higher dose level. 
If ≥2 subjects experience a DLT at dose level higher than the starting dose, enrollment will be 
discontinued for that dose cohort and the previous dose level would be declared the MTD. If ≥2 
subjects experience a DLT at the starting dose of a given cohort, further enrollment at that dose 
level will be discontinued and nab-Sirolimus will be reduced to the next planned dose level, to a 
lower limit dose level of 15 mg/m2. The MTD of nab-Sirolimus combined with pazopanib is the 
highest nab-Sirolimus dose level at which ≤1 of 6 (or 0 out of 3) subjects experienced a DLT, thus 
a target DLT rate of roughly 17%. RP2D is identified based of the totality of safety and efficacy 
data. 
Phase 2 Portion of the Study:  
This will be conducted using a Simon’s two-stage design. Subjects enrolled in the phase 1 study 
at the RP2D cohort will be included for response and safety evaluation in phase 2. 
2.4. 
Study Duration, End of Study, End of Treatment, End of Treatment Visit, Follow-up 
Period 
The study is expected to take approximately 36 months from first subject enrolled to last subject 
follow-up, including approximately 30 months of enrollment period, an estimated 6 months of 
treatment (or until treatment is no longer tolerated).   
End of Treatment (EOT) for a subject is defined as the date of the last dose of nab-Sirolimus or 
pazopanib, whichever is later. Single agent continuation of nab-Sirolimus is permitted. If a subject 
must discontinue nab-Sirolimus treatment, they will be discontinued from the study. End of 
Treatment Visit for a subject is when safety assessments and procedures are performed after the 
last treatment of nab-Sirolimus or pazopanib, whichever is later (+/- 3 days).   
The 30-Day Follow-Up Visit for a subject is defined as the date when safety assessments and 
procedures are performed after the End of Treatment visit. The 30-Day Follow-Up visit should 
occur 30 days (+/- 7 days) after the last dose of nab-Sirolimus or pazopanib, whichever is later. 
The End of Study (EOS) defined as either the date of the last visit of the last subject to complete 
the study, or the date of receipt of the last data point from the last subject that is required for 
primary, secondary, and/or exploratory analysis, as pre-specified in the protocol.  
Follow-up period is the on-study time period after the 30-Day Follow-Up Visit. All subjects that 
discontinue study drug and have not withdrawn full consent to participate in the study will 
continue in the follow-up phase for survival and initiation of new anticancer therapy. Follow up 
will continue approximately every 12 weeks from the 30-Day Follow-Up Visit (±3 weeks), until 


Nab-Sirolimus/Pazopanib 
Protocol: CC10015                                                    
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death, withdrawal of consent, or the study closes, whichever is the earliest. This evaluation may 
be made by record review and/or telephone contact. 


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Protocol: CC10015                                                    
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3. 
STUDY POPULATION 
3.1. 
Number of Subjects 
Phase 1: up to 49 subjects to identify the MTD, but the MTD may be reached with as few as 22 
subjects. Subjects who discontinue from the study prior to completing the DLT assessment 
window for reasons other than toxicity will be replaced at the same dose level. 
Phase 2: In the first stage, at least 23 subjects would be enrolled, including the 3-6 subjects from 
phase 1 at the RP2D. If at least 11 were progression-free at the 3 months evaluation, then 
additional subjects would be enrolled to a total of 39 subjects in the Phase 2.  
3.2. 
Inclusion Criteria 
A subject will be eligible for inclusion in this study only if all the following criteria are met 
during screening: 
1. Subjects, ≥18 years old, must have a histologically confirmed diagnosis of 
nonadipocytic STS that is either metastatic or locally advanced and for which 
curative therapy is not available, surgery is not a recommended option, and 
pazopanib treatment is indicated. 
2. Subjects must have one or more measurable target lesions by RECIST v1.1, assessed 
via CT scan or MRI. 
3. Clinical or radiological progression or failure due to toxicity on at least 1 prior 
regimen of systemic treatment for advanced disease. Subjects may not have 
received more than 4 prior lines of systemic therapy (no more than 2 prior therapies 
may be combination cytotoxic therapies). Neo-adjuvant/adjuvant/maintenance 
treatments are not included for this criterion. 
4. Last dose of prior therapy must have been completed a minimum of 14 days prior to 
start of protocol therapy. All ongoing toxicities related to prior therapy must be 
resolved or grade 1 (except alopecia). 
a. NOTE: Toxicities from prior therapy that have resolved with sequalae (e.g. 
hypothyroidism) and are asymptomatic or well-controlled are not 
exclusionary. 
5. Subjects must have adequate organ function and blood chemistry and blood count 
parameters: 
a. Total bilirubin ≤ upper limit of normal (ULN) mg/dL (Subjects with known 
Gilbert’s Syndrome and a Total Bilirubin ≤ 3 mg/dl are permitted to enroll to 
Phase 2/expansion phase only with sponsor-investigator approval) 
b. AST ≤2.5 x ULN and ALT ≤2.5x ULN 
c. Serum creatinine ≤1.5 x ULN (If serum creatinine is >1.5 mg/dL, calculated 
creatinine clearance >50 mL/min using the Cockcroft-Gault formula may be 
included) 
d. Absolute neutrophil count (ANC) ≥1.5 × 109/L; 
e. Platelet count ≥100,000/mm3 (100 × 109/L); 
f. Hemoglobin ≥9 g/dL 
g. Serum triglyceride ≤300 mg/dL; serum cholesterol ≤350 mg/dL. 


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Protocol: CC10015                                                    
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Final Protocol v5.0: July 28, 2022 
6. Baseline cardiac left ventricular ejection fraction (LVEF) within institutional limits of 
normal (by echocardiogram or MUGA study).  
7. Baseline electrocardiogram with QTc <480 millisecond (Bazett’s). 
8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 
9. Male or non-pregnant and non-breast feeding female: 
a. Females of child-bearing potential must agree to use highly effective 
contraception without interruption from initiation of therapy and while on 
study medication and have a negative serum pregnancy test (β -hCG) result 
at screening and agree to ongoing pregnancy testing during the course of the 
study, and at the end of study treatment. A highly effective method of 
contraception is defined as one that results in a low failure rate (that is, <1% 
per year), when used consistently and correctly, such as implants, 
injectables, combined oral contraceptives, some intrauterine contraceptive 
devices, sexual abstinence, or a vasectomized partner (Appendix 1).  
b. Male subjects must practice abstinence or agree to use a condom during 
sexual contact with a pregnant female or a female of childbearing potential 
while participating in the study (Appendix 1). 
10. Life expectancy of >3 months, as determined by the investigator. 
11. Ability to understand and sign informed consent. 
12. Willingness and ability to comply with scheduled visits, laboratory tests, and other 
study procedures. 
 
3.3. 
Exclusion Criteria  
A subject will not be eligible for inclusion in this study if any of the following criteria apply during 
screening: 
1. Soft tissue sarcomas with biology or defined treatments for which pazopanib is not 
indicated, including adipocytic STS, gastrointestinal stromal tumors (GIST), or Kaposi's 
sarcoma. 
2. Previously received an mTOR inhibitor or angiogenesis inhibitor. 
3. Known active uncontrolled or symptomatic central nervous system (CNS) metastases. A 
subject with controlled and asymptomatic CNS metastases may participate in this study. 
As such, the subject must have completed any prior treatment for CNS metastases ≥28 
days (including radiotherapy and/or surgery) prior to start of treatment in this study and 
should not be receiving chronic corticosteroid therapy for the CNS metastases. 
4. Subjects with hemoptysis, central nervous system hemorrhage, or gastrointestinal 
hemorrhage within the last 6 months prior to treatment are excluded due to pazopanib-
associated risk of bleeding. 
5. Subjects with severe hepatic impairment and active gastrointestinal bleeding. 


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Final Protocol v5.0: July 28, 2022 
6. Uncontrolled serious medical or psychiatric illness.  
7. Subjects with a currently active second malignancy other than non-melanoma skin 
cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, or other 
adequately treated carcinoma-in-situ are ineligible. Subjects are not considered to have 
a currently active malignancy if they have completed therapy and are free of disease for 
≥1 year). 
8. Recent infection requiring systemic anti-infective treatment that was completed ≤14 days 
prior to enrollment (with the exception of uncomplicated urinary tract infection or upper 
respiratory tract infection). 
9. No clinically significant gastrointestinal abnormalities including malabsorption syndrome, 
major resection of the stomach or small bowel that could affect the absorption of study 
drug, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other 
gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, 
gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning 
study treatment. 
10. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy. 
11. Subjects with unstable coronary artery disease, myocardial infarction, or an arterial 
thromboembolic event during preceding 6 months. 
12. Subjects with history of interstitial lung disease and/or pneumonitis, or pulmonary 
hypertension. 
13. Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the 
first dose of nab-Sirolimus. Additionally, use of any known CYP3A4 substrates with narrow 
therapeutic 
window 
(such 
as 
fentanyl, 
alfentanil, 
astemizole, 
cisapride, 
dihydroergotamine, pimozide, quinidine, terfenadine) within the 14 days prior to 
receiving the first dose of nab-Sirolimus.  
14. Active Hepatitis B or Hepatitis C infection.  
15. Systemic immunosuppression, including HIV positive status with or without AIDS. 
16. Subjects with history of intestinal perforations, fistula, hemorrhages and/or hemoptysis 
≤ 6 months prior to first study treatment 
17. Subjects with hypercholesterolemia receiving ongoing treatment with simvastatin. 
18. Subjects who have had major surgery within 28 days of planned initiation of protocol 
therapy, or subjects who have/have had wound dehiscence, or other open wounds 
(including diabetic or infectious wounds) with active wound complications. 
19. Subjects with prior history of severe hypersensitivity (Grade 3 or higher) to any known 
drug excipients, including anaphylaxis to human serum albumin. 
20. Subjects with uncontrolled hypertension, defined as an average SBP ≥140 mmHg or an 
average DBP ≥90 mmHg despite best supportive care measures.  


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4. 
TABLE OF EVENTS 
The schedule of assessments in Table 4 and Table 5 outline the specific time points for study 
assessments. 
 


Nab-Sirolimus/Pazopanib 
Protocol: CC10015                                                    
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Final Protocol v5.0: July 28, 2022 
Table 4. Schedule of Assessments (Day 1 and Day 8 Dosing – Subjects enrolled under Amendment 2, v3.0 or earlier) 
 Assessments a 
Baseline 
Screening b 
Treatment Phase 
21-day (3-week) Cycles Days 
End of Treatment 
(EOT) Visit d 
30 Day 
Follow-Up 
Visit  
(+/-7 days) 
Follow-up Q12W after last visit 
till study closes or withdrawal of 
consent – via phone call 
1 
8 
15 c 
Informed Consent 
x 
 
 
 
 
Medical History/Demographics 
x 
 
 
 
 
I/E Criteria 
x 
 
 
 
 
 
 
HIV, HBV sAg, HBV cAb, HCV Ab 
x 
 
 
 
 
Urinalysis 
x 
x 
 
 
x 
 
 
TSH, T3, T4 e 
x 
 
 
 
 
 
 
Optional Biomarker f 
x 
 
 
 
 
 
 
Pregnancy Test g 
x 
 
 
 
x 
x 
LVEF (echocardiogram or 
MUGA) 
x 
 
 
 
 
x 
 
12-lead electrocardiogram h 
x  
x h 
 
 
 
Physical Exam 
x 
x 
x 
x 
x 
x 
Vital Signs, height, and weight i 
x 
x 
x 
x 
x 
x 
 
Prior / Concomitant 
Medications and Procedures 
x 
x 
x 
x 
x 
x 
CBC/Differential 
x 
x 
x 
x 
x 
x 
Chemistry Panel 
x 
x 
x 
x 
x 
x 
 
Lipid Panel h 
x h 
x h 
 
 
 
 
Rapamycin level j 
 
x j 
x j 
x j 
 
 
ECOG performance status 
x 
x 
x 
x 
x 
x 
CT k 
x 
Every 6 weeks for the first year, then every 12 weeks  
 
 
nab-Sirolimus infusion l 
 
x 
x 
 
 
Pazopanib m 
 
Daily 
 
Adverse Event Assessment 
 
Continuous from time of consent to 30 days after last study drug 
 
Survival Assessment 
 
 
x 
 
 


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Final Protocol v5.0: July 28, 2022 
a All visits are allowed to occur in a window of ±3 days unless otherwise specified. 
b Baseline screening visit will be done within 28 days prior to study treatment Day 1. Baseline scans should be completed within 28 days of C1D1, as close to C1D1 as possible.  
c Day 15 visit is only in Cycle 1 and 2. Cycle 3+ does not have a Day 15 visit. 
d End of Treatment-phase (EOT) Visit should be within ±3 days of last study treatment.  
e Thyroid function test to be repeated as needed, based on investigator’s opinion. 
f Subjects who consent for pre-treatment tissue collection for biomarker analysis: either fresh-frozen or formalin-fixed paraffin-embedded (FFPE) tumor blocks or unstained 
slides (min 10). Fresh tissue collection may only be obtained if clinically feasible and without undue risk to the subject. 
g For all female subjects of childbearing potential (see Inclusion 5), a serum pregnancy test will be done at screening. A serum or urine pregnancy test will be repeated within 72 
hours before first treatment if the serum pregnancy test occurred >72 hours before dosing, and at EOT and 30-Day Follow-Up (if applicable). Pregnancy tests conducted after 
screening will be recorded in the source documentation only.  
h Single tracing ECG and lipids evaluations are every even cycle (C2, C4, C6, etc.). Only lipid panel at baseline is required to be fasting lipid. 
i Height is measured only at C1D1. BSA is calculated ONLY on C1D1; to be recalculated only if the weight changes by > 10% in subsequent cycles, at which point the recalculated 
weight will become the new baseline. Vitals signs to include respiration rate, temperature, systolic/diastolic blood pressure, and pulse. Vital signs to be collected Pre-Dose 
(within 15 minutes prior to start of infusion) and Post-Dose (+10 minutes from end of infusion). 
j Rapamycin levels are done locally and for all subjects in Phase 1 at Cycle 1 D8 prior to infusion (within 15 minutes prior to infusion) and on D15 (any time) to assess trough 
levels as well as in Cycle 2, D1 and D8 prior to infusion and on Day 15 (anytime).  
k Baseline scans should be done within 4 weeks of C1D1, preferably as close to first treatment as possible. Every 6 weeks from C1D1 (±1 week) for the first year, then every 12 
weeks (+/- 1 week) until disease progression or last treatment, regardless of missed or out of window doses. End of Treatment Visit CT/MRI should be performed only for those 
subjects that discontinue treatment for a reason other than disease progression. All responses must be confirmed by an additional CT scan after 6 weeks. MRI may be used if CT 
is contra-indicated for a subject. The same mode of imaging at screening must be used consistently throughout the study.  
l Nab-Sirolimus must be administered after all study specific assessments are done in a visit. Pazopanib dosing is daily and oral and may be dosed anytime in relation to ABI-009 
administration. Nursing supervision or documentation of pazopanib dosing on days where nab-Sirolimus is administered is not needed. See Section 6.2 for pazopanib dosing, 
schedule, and administration. Vital signs to be collected Pre-Dose (within 15 minutes prior to start of infusion) and Post-Dose (+10 minutes from end of infusion). There is a 60-
minute observation window post end of infusion for Cycle 1. If a subject completes Cycle 1 with no infusion related reactions, the observation period may be omitted for Cycle 2 
and onwards. If at any time the subject experiences an infusion related reaction, the 60-minute post-dose observation period will be reinstated.  
m Subjects will complete daily drug diary when receiving pazopanib, to be reviewed on Day 1 of each cycle. 
 
 
 
 
 
 
 
 
 


Nab-Sirolimus/Pazopanib 
Protocol: CC10015                                                    
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Final Protocol v5.0: July 28, 2022 
 
Table 5. Schedule of Assessments (Day 1 Only Dosing – Subjects Enrolled under Amendment 3, v 4.0 or later, or Subjects who swap to a D1 only 
dosing schedule) 
 Assessments a 
Baseline 
Screening b 
Treatment Phase 
21-day (3-week) Cycles Days 
End of Treatment 
(EOT) Visit d 
30 Day 
Follow-Up 
Visit  
(+/-7 days) 
Follow-up Q12W after last visit 
till study closes or withdrawal of 
consent – via phone call 
1 
8 
15 c 
Informed Consent 
x 
 
 
 
 
Medical History/Demographics 
x 
 
 
 
 
I/E Criteria 
x 
 
 
 
 
HIV, HBV sAg, HBV cAb, HCV Ab 
x 
 
 
 
 
 
 
Urinalysis 
x 
x 
 
 
x 
 
 
TSH, T3, T4 e 
x 
 
 
 
 
 
 
Optional Biomarker f 
x 
 
 
 
 
 
 
Pregnancy Test g 
x 
 
 
 
x 
x 
 
LVEF (echocardiogram or 
MUGA) 
x 
 
 
 
 
x 
 
12-lead electrocardiogram h 
x  
x h 
 
 
 
Physical Exam 
x 
x 
X 
x 
x 
x 
Vital Signs, height, and weight i 
x 
x 
X 
x 
x 
x 
Prior / Concomitant 
Medications and Procedures 
x 
x 
X 
x 
x 
x 
CBC/Differential 
x 
x 
X 
x 
x 
x 
Chemistry Panel 
x 
x 
X 
x 
x 
x 
 
Lipid Panel h 
x h 
x h 
 
 
 
 
Rapamycin level j 
 
x j 
x j 
x j 
 
 
ECOG performance status 
x 
x 
X 
x 
x 
x 
CT k 
x 
Every 6 weeks for the first year, then every 12 weeks  
 
 
Nab-Sirolimus infusion l 
 
x 
 
 
 
Pazopanib m 
 
Daily 
 
Adverse Event Assessment 
 
Continuous from time of consent to 30 days after last study drug 
 
Survival Assessment 
 
 
x 


Nab-Sirolimus/Pazopanib 
Protocol: CC10015                                                    
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Final Protocol v5.0: July 28, 2022 
 
 
a All visits are allowed to occur in a window of ±3 days unless otherwise specified. 
b Baseline screening visit will be done within 28 days prior to study treatment Day 1. Baseline scans should be completed within 28 days of C1D1, as close to C1D1 as possible.  
c Day 15 visit is only in Cycle 1 and 2. Cycle 3+ does not have a Day 15 visit. 
d End of Treatment-phase (EOT) Visit should be within ±3 days of last study treatment.  
e Thyroid function test to be repeated as needed, based on investigator’s opinion. 
f Subjects who consent for pre-treatment tissue collection for biomarker analysis: either fresh-frozen or formalin-fixed paraffin-embedded (FFPE) tumor blocks or unstained 
slides (min 10). Fresh tissue collection may only be obtained if clinically feasible and without undue risk to the subject. 
g For all female subjects of childbearing potential (see Inclusion 5), a serum pregnancy test will be done at screening. A serum or urine pregnancy test will be repeated within 72 
hours before first treatment if the serum pregnancy test occurred >72 hours before dosing, and at EOT and 30-Day Follow-Up (if applicable). Pregnancy tests conducted after 
screening will be recorded in the source documentation only.  
h Single tracing ECG and lipids evaluations are every even cycle (C2, C4, C6, etc.). Only lipid panel at baseline is required to be fasting lipid. 
i Height is measured only at C1D1. BSA is calculated ONLY on C1D1; to be recalculated only if the weight changes by > 10% in subsequent cycles, at which point the recalculated 
weight will become the new baseline. Vitals signs to include respiration rate, temperature, systolic/diastolic blood pressure, and pulse. Vital signs to be collected Pre-Dose 
(within 15 minutes prior to start of infusion) and Post-Dose (+10 minutes from end of infusion). 
j Rapamycin levels are done locally and for all subjects in Phase 1 at Cycle 1 Day 1 Post-Dose (within +10 minutes from end of infusion), Cycle 1 Day 1 – 24-hour Post-Dose 
(optional, +/- 2 hours),), Cycle 1 Day 8 and Day 15 anytime, as well as in Cycle 2 Day 1 Pre-Dose (within 15 minutes prior to infusion) and on Cycle 2 Day 8 and Day 15 (anytime).  
k Baseline scans should be done within 4 weeks of C1D1, preferably as close to first treatment as possible. Every 6 weeks from C1D1 (±1 week) for the first year, then every 12 
weeks (+/- 1 week) until disease progression or last treatment, regardless of missed or out of window doses. End of Treatment Visit CT/MRI should be performed only for those 
subjects that discontinue treatment for a reason other than disease progression. All responses must be confirmed by an additional CT scan after 6 weeks. MRI may be used if CT 
is contra-indicated for a subject. The same mode of imaging at screening must be used consistently throughout the study.  
l Nab-Sirolimus must be administered after all study specific assessments are done in a visit. Pazopanib dosing is daily and oral and may be dosed anytime in relation to ABI-009 
administration. Nursing supervision or documentation of pazopanib dosing on days where nab-Sirolimus is administered is not needed. See Section 6.2 for pazopanib dosing, 
schedule, and administration. Vital signs to be collected Pre-Dose (within 15 minutes prior to start of infusion) and Post-Dose (+10 minutes from end of infusion). There is a 60-
minute observation window post end of infusion for Cycle 1. If a subject completes Cycle 1 with no infusion related reactions, the observation period may be omitted for Cycle 2 
and onwards. If at any time the subject experiences an infusion related reaction, the 60-minute post-dose observation period will be reinstated.  
m Subjects will complete daily drug diary when receiving pazopanib, to be reviewed on Day 1 of each cycle


Nab-Sirolimus/Pazopanib 
Protocol: CC10015                                                    
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Final Protocol v5.0: July 28, 2022 
5. 
PROCEDURES 
5.1. 
Screening Evaluations 
This study will be conducted at the University of Washington, Seattle, USA; other centers may be 
considered to join. Each subject who enters into the screening period for the study receives a 
unique subject identification number before any study-related procedures are performed. The 
subject identification number will be assigned. This number will be used to identify the subject 
throughout the clinical study and must be used on all study documentation related to that 
subject.  
The subject identification number must remain constant throughout the entire clinical study; it 
must not be changed after initial assignment, including if a subject is rescreened.  
Before subjects may be entered into the study, the Sponsor-Investigator requires a copy of the 
written IRB/IEC approval of the protocol, informed consent form, and all other subject 
information and/or recruitment material, if applicable. A signed and dated Institutional Review 
Board (IRB) approved informed consent form (latest approved version) must be obtained from 
each subject prior to performing any study-specific procedures. All subjects must personally sign 
and date the consent form before commencement of study-specific procedures.  
Screening evaluations will be performed for all subjects to determine study eligibility.  These 
evaluations must be obtained ≤28 days prior to enrollment. Baseline imaging should be obtained 
as close to initiation of protocol therapy as possible. Any questions regarding subject eligibility 
should be directed to the Sponsor-Investigator for approval. 
The following procedures are to be completed during the screening period, after signed informed 
consent has been obtained, designated in the Schedule of Assessments found in Table 4 and 
Table 5. 
• Demographics (if allowed by local regulations, date of birth, sex, race, and ethnicity) 
• Physical examination (including medical/cancer history, ECOG performance status 
assessment, weight)  
• Prior/concomitant medications and procedures evaluation to include all medications 
taken ≤28 days prior to date of informed consent  
• Vital signs (temperature, sys/dias blood pressure, respiration rate, and pulse) 
• ECG   
• Left ventricular ejection fraction (LVEF, by echocardiogram or MUGA) 
• Local Laboratory Assessments: chemistry, complete blood count (CBC with 
differential, platelet count, urinalysis, pregnancy test (women of child-bearing 
potential, includes tubal ligations), thyroid panel (TSH, T3, T4), HIV, hepatitis B surface 
antigen, hepatitis B core antibody (HBV cAb), hepatitis C antibody, lipids 
• CT or MRI, must be done within 28 days of C1D1, but preferably should be done as 
close to the day of enrollment as possible 


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Final Protocol v5.0: July 28, 2022 
• Optional: Subjects who consent for pre-treatment tissue collection for biomarker 
analysis shall provide either fresh-frozen or formalin-fixed paraffin-embedded (FFPE) 
tumor blocks or unstained slides (min 10). Fresh tissue collection may only be 
obtained if clinically feasible and without undue risk to the subject. 
A subject is considered enrolled when the investigator decides that the subject has met all 
eligibility criteria and an enrollment packet has been completed. The investigator is to document 
this decision and date, in the subject’s medical record and in/on the electronic case report form 
(eCRF). 
5.2. 
Treatment Period 
A subject is considered enrolled on study day 1 when the IP, nab-Sirolimus, is first administered. 
Nab-Sirolimus is to be administered after all other protocol-specified pre-dose assessments have 
been performed during each visit that it is required. Subjects will continue therapy until disease 
progression, unacceptable AEs, or withdrawal of consent. 
5.2.1. 
Day 1 Assessment 
The following assessments will be performed on Day 1 of each cycle, unless otherwise specified: 
• Physical examination  
• Weight assessment 
• Height assessment (only in C1) 
• Concomitant medication and procedures evaluation  
• Vital signs (temperature, sys/dias blood pressure, respiration rate, and pulse) 
• ECOG performance status 
• CBC with differential  
• Clinical chemistry panel  
• ECG and lipid panel (every even visit, i.e. C2, C4, etc.) 
• Urinalysis 
• Adverse Event assessment 
• Rapamycin levels (only in Phase 1, C1 and C2) 
• 60-minute observation window post end of infusion for Cycle 1. If a subject 
completes Cycle 1 with no infusion related reactions, the observation period may be 
omitted for Cycle 2 and onwards. If at any time the subject experiences an infusion 
related reaction, the 60-minute post-dose observation period will be reinstated. 
All Day 1 evaluations for Cycle 1 may be omitted if screening evaluations are performed within 
72 hours of Cycle 1 Day 1. All Day 1 laboratory assessments and physical examination for Cycle 
2+ may be performed up to 72 hours prior to planned treatment. 


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Final Protocol v5.0: July 28, 2022 
5.2.2. 
Day 8 Assessment 
The following assessments will be performed on Day 8 of each cycle, unless otherwise specified: 
• Physical examination 
• Weight assessment 
• Vital signs (temperature, sys/dias blood pressure, respiration rate, and pulse) 
• Concomitant medication and procedures evaluation 
• CBC with differential 
• Clinical chemistry panel  
• Adverse Event assessment 
• Rapamycin levels (only in Phase 1, C1 and C2) 
For subjects receiving treatment on Day 8, all Day 8 laboratory assessments and physical 
examination may be performed up to 72 hours prior to planned treatment. 
5.2.3. 
Day 15 Assessment 
The following assessments will be performed on Day 15 of Cycle 1 and 2 only.  
• Physical examination 
• Weight assessment 
• Vital signs (temperature, sys/dias blood pressure, respiration rate, and pulse) 
• Concomitant medication and procedures evaluation 
• CBC with differential  
• Clinical chemistry panel  
• Adverse Event assessment 
• Rapamycin levels (only Phase 1) 


Nab-Sirolimus/Pazopanib 
Protocol: CC10015                                                    
University of Washington 
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Final Protocol v5.0: July 28, 2022 
Table 6. Analyte Listing 
Chemistry 
Hematology 
 
Urinalysis 
Other Labs 
Sodium 
WBC 
 
Specific gravity 
Pregnancy test 
Potassium 
RBC 
 
pH 
HIV 
Bicarbonate 
Hemoglobin 
 
Blood 
HBV sAg 
Chloride 
Hematocrit 
 
Protein 
HBV cAb 
Total protein 
MCV 
 
Glucose 
HCV Ab 
Albumin 
MCH 
 
Ketones 
Total Cholesterol  
Calcium 
MCHC 
 
Microscopic 
HDL 
Magnesium 
RDW 
 
 
LDL 
Phosphorus 
Platelets 
 
 
Triglyceride 
Glucose 
Differential: 
 
 
TSH, T3, T4 
BUN 
-Neutrophils 
 
 
Rapamycin 
Creatinine 
-Lymphocytes 
 
 
 
Total bilirubin 
-Monocytes 
 
 
 
Alkaline phosphatase 
-Eosinophils 
 
 
 
AST (SGOT) 
-Basophils 
 
 
 
ALT (SGPT) 
 
 
 
 
Amylase 
 
 
 
 
Lipase 
 
 
 
 
5.2.4. 
Response Assessment  
Tumor response will be assessed by CT or MRI scan of the chest, abdomen, and pelvis (CAP) per 
institutional guidelines; image preparation and evaluation will follow the specifications provided 
in the RECIST version 1.1. The same modality (CT or MRI) must be used at screening and 
throughout the study.  
CT/MRI scans to be performed at the following frequency: 
• ≤4 weeks prior to C1D1 (as close to C1D1 as possible) (screening) 
• Followed by every 6 weeks from C1D1 (± 1 week) for the first year; then every 12 
weeks (± 1 week) until disease progression or unacceptable toxicity. End of Treatment 
Visit CT/MRI should be performed only for those subjects that discontinue treatment 
for a reason other than disease progression. 
An unscheduled scan for suspected disease progression may be performed at any time. However, 
adherence to the planned imaging schedule is critical regardless of dose delays or unscheduled 
or missed assessments. Determination of disease progression for clinical management of 
subjects on study will be assessed at the local site. If an initial observation of objective response 
(CR or PR) is made, a confirmation scan should be done at 6 weeks after initial observation.  
5.3. 
End of Treatment Visit Assessment 
The EOT Visit is a safety follow-up visit that is to be performed after the last dose of nab-Sirolimus 
or pazopanib, whichever is later (±3 days). All efforts should be made to conduct this visit. If it is 


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not possible to conduct the EOT Visit, documentation of efforts to complete the visit should be 
provided. 
The following procedures will be completed at the EOT Visit as designated in the Schedule of 
Assessments in Table 4 and Table 5. 
• Physical examination (including ECOG Performance Status assessment, weight)  
• Vital signs (e.g., blood pressure, pulse, respiration rate, temperature) 
• Concomitant medication and procedures evaluation  
• Adverse Event assessment 
• Laboratory assessments: chemistry, CBC with differential, platelet count, pregnancy 
test (women of child-bearing potential, includes tubal ligations), urinalysis 
• Imaging Assessment: CT/MRI is to be performed at the end of study visit only for those 
subjects that discontinue treatment for a reason other than disease progression per 
RECIST v1.1  
5.4. 
30-Day Follow Up Visit 
Active subject participation is complete after the 30-Day Follow-Up Visit. The 30-Day Follow-Up 
Visit is a safety follow-up visit that is to be performed 30 days after the last dose of protocol 
therapy (±7 days). All efforts should be made to conduct this visit. If it is not possible to conduct 
the 30-Day Follow-Up Visit, documentation of efforts to complete the visit should be provided. 
The following procedures will be completed at the 30-Day Follow-Up Visit as designated in the 
Schedule of Assessments in Table 4 and Table 5. 
• Physical examination (including ECOG Performance Status assessment, weight)  
• Vital signs (e.g., blood pressure, pulse, respiration rate, temperature) 
• Concomitant medication and procedures evaluation 
• Adverse Event assessment 
• Laboratory assessments: chemistry, CBC with differential, platelet count, pregnancy 
test (women of child-bearing potential, includes tubal ligations) 
• Left ventricular ejection fraction (LVEF, by echocardiogram or MUGA) 
 
5.5. 
Rapamycin Trough levels 
Assays for rapamycin will be performed on subjects in the dose-finding (phase 1) portion of the 
study, who received nab-Sirolimus during C1 and C2, to determine trough levels, assessed via 
local lab. The rapamycin sampling schedule is outlined below, based on dosing schedule. 
• Q2/3W Dosing: 
• 
Cycle 1: 


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 C1D8: Prior to treatment (within 15 minutes pre-infusion)  
 C1D15: Day 15 collection any time 
• 
Cycle 2: 
 C2D1: prior to treatment (within 15 minutes pre-infusion) 
 C2D8: prior to treatment (within 15 minutes pre-infusion) 
 C2D15: Day 15 collection any time 
• Q1/3W Dosing: 
• 
Cycle 1:  
 C1D1: End of infusion (within +10 minutes of EOI) and Optional 24-hour 
post dose (Day 2, +/- 2 hours),  
 C1D8: Day 8 collection any time 
 C1D15: Day 15 collection any time 
• 
Cycle 2: 
 C2D1: prior to treatment (within 15 minutes pre-infusion) 
 C2D8: Day 8 collection any time 
 C2D15: Day 15 collection any time 
 
5.6. 
Follow-up Period for Survival and Initiation of Anticancer Therapy  
Post-treatment survival time and any subsequent anticancer therapy information status will be 
monitored approximately every 12 weeks (±3 weeks) from 30-Day Follow Up Visit or more 
frequently as needed, until death, withdrawal of consent, or the study closes, whichever is 
earliest.  This evaluation may be by record review and/or telephone contact.  


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6. 
DESCRIPTION OF STUDY TREATMENTS  
6.1. 
Nab-Sirolimus 
6.1.1. 
Nab-Sirolimus/Pazopanib Dosage, Administration, and Schedule 
Treatment with nab-Sirolimus combined with pazopanib will continue until disease progression, 
unacceptable toxicity, or withdrawal of consent. A physician must be available at the time of 
administration of IP on dosing days that correspond to study visits. Supportive care per the 
institution’s normal standard of care including concomitant medications can be provided at the 
investigator’s discretion.  
Table 7 - Day 1 and Day 8 Dosing Levels (Closed – Enrolled under Am2, v3.0 or earlier) 
Dose Levels (Day 
1 and Day 8 
Dosing) 
Planned Starting Dose 
of 
nab-Sirolimus 
in 
mg/m2 
Planned Starting Dose of 
Pazopanib in mg 
-2 
30 
800 
-1 
45 
800 
0 
60 
800 
1 
75 
800 
2 
100 
800 
0B 
60 
400 
1B 
75 
400 
2B 
100 
400 
-1B 
45 
400 
-2B 
30 
400 
 
Table 8 - Day 1 Only Dosing Levels 
Dose Levels (Day 
1 Only Dosing) 
Planned Starting Dose 
of 
nab-Sirolimus 
in 
mg/m2 
Planned Starting Dose of 
Pazopanib in mg 
-2C 
15 
400 
-1C 
20 
400 
0C 
30 
400 
1C 
45 
400 
2C 
60 
400 
3C 
75 
400 
4C 
100 
400 


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6.1.2. 
Nab-Sirolimus Dose Modification and Stopping Rules 
If treatment cannot be administered on the planned visit date, nab-Sirolimus may be 
administered ±3 days from the scheduled date. Prior to nab-Sirolimus administration, subjects 
must meet the following hematological requirements for dosing on every dosing day: 
• ANC ≥1.5 x 109/L 
• Platelet count ≥100 x 109/L 
• Hemoglobin ≥9.0 g/dL 
The treatment may be held (delayed) up to 21 days due to toxicity. Treatment may also be 
interrupted for situations other than treatment-related AEs such as medical/surgical events or 
logistical reasons not related to study therapy. Participants should be placed back on study 
therapy within 21 days of the scheduled interruption, unless otherwise discussed with the 
Sponsor-Investigator. The reason for interruption should be documented in the subject’s study 
record. 
If the dose held or missed was to be Day 1 of the next cycle, the next cycle will not be 
considered to start until the day the first dose is actually administered to the subject. 
If the subject is dosing on a q2/3w schedule, if the dose held or missed was to be Day 8, that 
week becomes the week of rest. Next dose becomes Day 1 of a new cycle. The cycle with the 
missed Day 8 dose would become 14 days long versus the normal 21-day cycle. If the cycle with 
the missed Day 8 dose is Cycle 1 or Cycle 2, the Day 15 visit would also be omitted. If the 
subject is dosing on a q1/3w schedule, a cycle is not considered to have begun until the subject 
receives the Day 1 dose. If the subject misses a Day 8 or Day 15 visit, the cycle continues 
without interruption and the visits are recorded as missed. The following cycle is considered to 
have begun when the subject receives their next dose. 
In the event of clinically significant AE in any part of the study, treatment may be held, and 
supportive therapy administered as clinically indicated. If the toxicity or event is not grade 3/4 
and resolves to baseline or grade 1 in less than or equal to 21 days of stopping therapy, then 
treatment may be restarted.  
Dose reduction of nab-Sirolimus to the next lower dose level should be considered as clinically 
indicated for subjects who are receiving nab-Sirolimus at above the lowest dose level. In phase 
1, once a dose has been reduced, it may not be increased to the previous level. In phase 2, if an 
AE resolves to grade 1 or baseline at the reduced dose level, and no additional toxicities are seen 
during the following cycle of study treatment at the reduced dose, the dose may be re-escalated 
to the previous dose level.  
The maximum delay between a missed scheduled dose and the next one (whichever dose was 
missed) should not be longer than 21 days. If a dose delay over 21 days is required, Sponsor-
Investigator Approval is required, otherwise the subject should be discontinued. If Sponsor-
Investigator approval is granted, a secondary approval is required to restart study treatment after 
≥21 days of interruption. If the toxicity does not resolve to at least grade 1 in less than 21 days, 
withdrawal from the treatment with the IP is recommended. However, if the investigator and 


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Sponsor-Investigator agree that further treatment would benefit the subject, treatment can 
continue with at least 1 dose level dose reduction. Adjustments to the dosing schedule may be 
made, at investigator discretion, according to Section 6.3.


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Table 9. Dose Modification Algorithms for Adverse Events Possibly Related to ABI-009 (See also Table 10 and Table 11) 
 
System/Organ 
Adverse Event 
CTCAE 
Grade 
v5.0 
Dose modification Algorithm 
Mucosa a 
Stomatitis, mucosal 
inflammation 
Grade 2 or 
3 
Hold ABI-009 until resolution to grade 1 or baseline and restart at the same dose for 1st 
occurrence; for subsequent occurrences, drug will be restarted at a reduced dose; provide 
supportive care as clinically indicated.  
Grade 4 
Permanently discontinue ABI-009. 
Skin and 
Subcutaneous 
Tissue Disorders 
Skin rash 
Grade 2 
Tolerable: Continue ABI 009 at full dose, monitor as clinically indicated. 
Intolerable: Hold ABI-009 until resolution to grade 1 or baseline and restart at the same dose 
for 1st occurrence; for subsequent occurrences, drug will be restarted at a reduced dose; 
provide supportive care as clinically indicated.  
Grade ≥3 
Hold ABI-009 until resolution to grade 1 or baseline; for subsequent events, drug will be 
restarted at a reduced dose; provide supportive care as clinically indicated.  
Gastrointestinal 
Disorders 
Diarrhea despite 
optimal medication 
Grade 2 
Hold ABI-009 until resolution to grade 1 or baseline and restart at the same dose for 1st 
occurrences; for 2nd and subsequent events, drug will be restarted at a reduced dose; provide 
supportive care as clinically indicated.  
Grade ≥3 
Hold ABI-009 until resolution to grade 1 or baseline; for subsequent events, drug will be 
restarted at a reduced dose; provide supportive care as clinically indicated.  
Metabolic 
disorders 
Hyperlipemia 
(cholesterol, 
triglycerides) 
Grade 3 
If this is persistent for 2 months, reduce by 1 dose level at start of next cycle. 
Grade 4 
If this is persistent for 1 month, reduce by 1 dose level at start of next cycle. 
Hyperglycemia 
 
 


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Grade ≥3 
Hold ABI-009 until grade 2 or less, restart 1 dose level lower.  
Hypokalemia 
Grade 2 
Withhold treatment until Grade ≤1,  restart at the same dose level. If recurs, restart 1 dose level 
lower. 
Grade ≥3 
Withhold treatment until Grade ≤1, restart at 1 dose level lower. If recurs, permanently 
discontinue ABI-009. 
Respiratory 
events 
Pneumonitis, 
bronchiolitis 
obliterans, and/or 
organizing 
pneumonia, 
Interstitial Lung 
Disease 
Grade 2  
Hold ABI-009 immediately for up to 3 weeks until resolved to ≤ grade 1, then reduce by 1 dose 
level. If it is still a Grade 2 after 3 weeks, discontinue treatment. If grade 2 recurs after resuming 
ABI-009 at a reduced dose level, discontinue treatment. 
For noninfectious pneumonitis, if cough is troublesome, prescribe corticosteroids. 
Grade ≥3 
Permanently discontinue ABI-009. 
For grade 3 noninfectious pneumonitis, prescribe corticosteroids if infection is ruled out. Hold 
ABI-009 until recovery to ≤ grade 1; may restart within 3 weeks at reduced dose level if 
evidence of clinical benefit. Subjects will be withdrawn from the study if they fail to recover to ≤ 
grade 1 within 3 weeks. 
For grade 4 noninfectious pneumonitis, discontinue ABI-009. 
Infections and 
infestations 
Infections 
Grade 3 
Withhold treatment until resolved, then restart at 1 dose level lower. If recurs, permanently 
discontinue ABI-009. 
Grade 4 
Withhold treatment until resolved. Restart at 1 dose level lower,. If recurs, or permanently 
discontinue ABI-009. 
General 
Disorders 
Hemorrhage 
Grade 2 or 
3 
Withhold treatment until Grade ≤1, then resume at 1 dose level lower.  If recurs, permanently 
discontinue ABI-009. 


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Grade 4 
Permanently discontinue ABI-009. 
Other Adverse 
Reactions 
Other Adverse 
Reactions 
Grade 3 
Withhold treatment until Grade ≤1, then restart at the same dose level. If recurs, restart at 1 
dose level lower. 
Grade 4 
Permanently discontinue ABI-009. 
a Subjects who develop or at risk for stomatitis, a steroid mouthwash (10 mL dexamethasone 0.1 mg/mL oral solution four times daily) could be considered. 


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6.1.3. 
Nab-Sirolimus Hepatotoxicity Stopping Rules  
Subjects with abnormal hepatic laboratory values (i.e., ALP, AST, ALT, total bilirubin TBL) and/or 
international normalized ratio (INR) and/or signs/symptoms of hepatitis may meet the criteria 
for withholding or permanent discontinuation of nab-Sirolimus as specified in the Guidance for 
Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation, July 2009. 
6.1.3.1. 
Criteria for Permanent Discontinuation of nab-Sirolimus Due to Potential 
Hepatotoxicity 
Nab-Sirolimus should be discontinued permanently and the subject should be followed for 
possible drug-induced liver injury (DILI), if ALL of the criteria below are met:  
• Total bilirubin >2 x ULN or INR >1.5 x ULN 
• AND increased AST or ALT from the relevant baseline ≥3 x ULN  
• AND no other cause for the combination of the above laboratory abnormalities is 
immediately apparent; important alternative causes for elevated AST/ALT and/or 
total bilirubin values include, but are not limited to: 
− Hepatobiliary tract disease 
− Viral hepatitis (e.g., Hepatitis A/B/C/D/E, Epstein-Barr Virus, Cytomegalovirus, 
Herpes Simplex Virus, Varicella, Toxoplasmosis, and Parvovirus) 
− Right sided heart failure, hypotension or any cause of hypoxia to the liver causing 
ischemia.   
− Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and 
dietary supplements, plants and mushrooms   
− Heritable disorders causing impaired glucuronidation (e.g., Gilbert’s Syndrome, 
Crigler-Najjar syndrome) and drugs that inhibit bilirubin glucuronidation 
(e.g., indinavir, atazanavir) 
− Alpha-one antitrypsin deficiency 
− Alcoholic hepatitis 
− Autoimmune hepatitis  
− Wilson’s disease and hemochromatosis 
− Nonalcoholic Fatty Liver Disease including Steatohepatitis (NASH)  
− Non-hepatic causes (e.g., rhabdomyolysis, hemolysis) 
6.1.3.2. 
Criteria for Conditional Withholding of nab-Sirolimus Due to Potential 
Hepatotoxicity 
For subjects who do not meet the criteria for permanent discontinuation of ABI-009 and have no 
underlying liver disease, and eligibility criteria requiring normal transaminases and TBL at 
baseline or subjects with underlying liver disease and baseline abnormal transaminases, the 
following rules are recommended for withholding of nab-Sirolimus: 


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• Elevation of either AST or ALT according to the following schedule: 
AST or ALT elevation  
>8 x ULN at any time 
>5 x ULN but <8 x ULN for ≥2 weeks 
>5 x ULN but <8 x ULN and unable to adhere to 
enhanced monitoring schedule 
≥3 x ULN with clinical signs or symptoms that are 
consistent with hepatitis (such as right upper 
quadrant pain/tenderness, fever, nausea, vomiting, 
jaundice).   
• OR: Total bilirubin >3 x ULN at any time 
• OR: Alk Phos >8 x ULN at any time 
Nab-Sirolimus should be withheld pending investigation into alternative causes of DILI. Re-
challenge may be considered if an alternative cause for impaired liver tests (ALT, AST, and ALP) 
and/or elevated TBL is discovered and the laboratory abnormalities resolve to normal or baseline. 
6.2. 
Pazopanib 
6.2.1. 
Dose Levels for Pazopanib 
Pazopanib starting dose may be at either 400 or 800 mg daily. Pazopanib decrease should be in 
200-mg steps,52 for pazopanib-related AEs that require dose reductions (Section 6.2.2). 
Pazopanib dosing may not be reduced below 200 mg daily. Subjects requiring a dose reduction 
below 200 mg daily should discontinue pazopanib therapy. Pazopanib dosing may not be 
increased above 800 mg daily. Dose modification algorithms for specific toxicities are detailed 
below in Section 6.2.2. For all other Grade 3 or 4 non-hematologic toxicities (except alopecia, 
nausea, or vomiting) that are at least in part attributable to the study drug, the dose should be 
held until the toxicity resolves to ≤ Grade 1. Treatment should then be resumed at a reduction 
of one dose level. For recurrent grade 3 or 4 toxicity, the study drug should again be held until 
the toxicity resolves to ≤ Grade 1 and then reintroduced at another dose level reduction. If the 
toxicity has abated with reduction of the dose and dose re-escalation is considered safe by the 
investigator, the study drug dose can then be increased step-wise back to the pre-event dose 
(in 200 mg increments, after monitoring for 14 days at each dose level to ensure that toxicity 
did not recur or worsen). 
Pazopanib is absorbed orally, with median time to achieve peak concentrations of 2 to 4 hours 
after the dose. If a dose is missed, it should not be taken if it is less than 12 hours until next dose. 
For pazopanib dose reduction and stopping rules, please refer to Table 10 and Table 11. 
6.2.2. 
Pazopanib Dose Modification and Stopping Rules 
Pazopanib is dosed continuously. Modifications to pazopanib dosing should follow the table 
below. Additional dose reductions may be made outside of the defined parameters below, at 


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investigator discretion. Dose levels may not be re-escalated outside of the defined guidelines. 
All dose reductions or re-escalations must be made in 200 mg increments, unless otherwise 
specified.


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Table 10. Dose Modification Algorithms for Adverse Events Possibly Related to Pazopanib (See also Table 9 and Table 11) 
System/Organ 
Adverse Event 
CTCAE Grade 
v5.0 
Dose modification Algorithm 
Skin/Mucosa 
Palmar-plantar 
Erythrodysesthesia 
Syndrome 
Grade 2 
Hold pazopanib until resolved to ≤ grade 1, then resume with one dose level reduced. If 
recurrent, consider further dose reduction or discontinuation. 
Grade 3 
Permanently discontinue pazopanib. 
Lab 
Abnormalities 
Proteinuria 
UPC Ratio ≥ 2.0 
and < 3.0 or 
urine protein ≥ 
2.0 g/24 hours 
and < 3.0 
Hold pazopanib until proteinuria resolves to UPC < 2.0 or urine protein < 2.0 g/24 hours, then 
resume pazopanib at current dose level. 
For UPC Ratio ≥ 
3.0 and < 4.0 or 
urine protein ≥ 
3.0 g/24 hours 
and < 4.0 
Hold pazopanib until proteinuria resolves to UPC < 2.0 or urine protein <2.0 g/24 hours. Once 
resolved, resume pazopanib with one dose level reduced. 
For UPC Ratio ≥ 
4.0 or 
Nephrotic 
Syndrome 
Discontinue pazopanib. 
Hyperthyroidism / 
Hypothyroidism 
Grade 3 or 
Grade 4 
Discontinue pazopanib. 
Elevated 
Creatinine 
Grade 2 
Delay pazopanib until toxicity resolves to Grade 1 or better, then resume pazopanib with one 
dose level reduction. 
Grade 3-4 
Discontinue pazopanib. 
 
 


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Cardiac Toxicity 
Hypertension 
Grade 3 (Systolic ≥ 160, 
Diastolic ≥ 100) 
Hold pazopanib until grade ≤ 2, then resume pazopanib at 1 
dose level reduction. 
HOWEVER, if the subject requires hospitalization for 
management of symptomatic systolic BP > 180 or diastolic 
BP > 110, permanently discontinue pazopanib. 
Grade 4 
Permanently discontinue pazopanib. 
Venous Thrombosis 
Grade 2-3, requiring 
anticoagulation 
Delay pazopanib. 
If the planned duration of full dose anticoagulation is ≤ 2 
weeks, omit pazopanib until anticoagulation is completed, 
then resume pazopanib at same dose. If the planned 
duration of full dose anticoagulation is > 2 weeks, 
pazopanib may be restarted at same dose during 
anticoagulation if all of the following are met: 
- The subject must have an in-range INR (usually between 2 
and 3) on a stable dose of warfarin or be on a stable dose of 
LMWH prior to restarting pazopanib. 
- The subject must not have any pathological condition that 
carries a high risk of bleeding. 
- The subject must not have had any hemorrhagic events 
while on study. 
Grade 4 
Permanently discontinue pazopanib. 
Recurrent / Worsening 
Thrombosis 
If venous thromboembolic events worsen or reoccur after 
resumption of pazopanib, permanently discontinue 
pazopanib. 
Arterial Thromboembolic 
Events 
Any Grade 
Discontinue pazopanib. 
 
ECG QTc Interval Prolonged 
(Bazett’s) 
Grade 3 
Delay pazopanib until ≤ grade 1, then resume pazopanib 
with one dose level reduction. 


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Grade 4 
Discontinue pazopanib. 
Other 
CNS or Pulmonary 
Hemorrhage 
Grade 2 or Greater 
Permanently discontinue pazopanib. 
Non-CNS, Non-Pulmonary 
bleeding 
Grade 2  
Delay pazopanib until ≤ grade 1, then resume with one dose 
level reduction. 
Grade 3 or 4 
Permanently discontinue pazopanib. 
Fistula, perforations, bowel 
obstruction, or wound 
dehiscence 
Any Grade 
For any grade perforation of any organ, GI leak, or any 
fistula, discontinue pazopanib. 
For any grade bowel obstruction requiring medical 
intervention, delay pazopanib until obstruction resolves 
completely, and then resume pazopanib at the previous 
dose. For obstruction requiring surgery delay pazopanib 
until full recovery from surgery, then resume pazopanib at 
the previous dose. 
For wound dehiscence requiring medical or surgical 
intervention discontinue pazopanib. 
Hemolytic Uremic Syndrome / 
Thrombotic Thrombocytopenic 
Purpura 
Any Grade 
For any grade of hemolytic uremic syndrome (thrombotic 
microangiopathy) or thrombotic thrombocytopenic 
purpura, discontinue pazopanib. 
Other Non-Hematologic Grade 
3 or 4 Toxicity 
Grade 3 or 4 
For other grade 3 or 4 non-hematologic toxicity not 
described above, (excluding nausea, vomiting, and diarrhea; 
unless refractory to anti-emetics and/or antidiarrheals) and 
considered at least possibly related to treatment, delay 
pazopanib treatment until toxicity improves to ≤ grade 1, 
then resume treatment with one dose level reduction. 


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6.3. 
Dosing Schedules (D1 vs D1/D8) 
Nab-Sirolimus may be dosed on either Day 1 or Day 1/Day 8 of a 21-day cycle, based on which 
cohort a subject is assigned to. Subjects initially assigned to Day 1/Day 8 dosing may switch to a 
Day 1 only dosing schedule at investigator discretion, after completion of at least two full cycles 
of treatment.  
Subjects initially enrolled on a Day 1 only schedule may not switch the dosing schedule. Once a 
subject has switched a dosing schedule, this change is considered permanent and they may not 
switch back.  
6.4. 
Dose Limiting Toxicity 
Dose-limiting toxicities will be assessed in the first 2 cycles (2, 3-week cycles).  
A DLT is defined as any Grade 3 or greater AE, at least possibly related to either or both nab-
Sirolimus and pazopanib. Only toxicities with a clearly identified and documented alternative 
explanation may be deemed non-DLT. Dose-limiting toxicities include any death not clearly due 
to underlying disease or extraneous causes, or persistent intolerable nonhematologic AE of any 
grade that requires dose reduction or permanent discontinuation of the study-drug, in the 
opinion of the investigator. 
The following adverse events may be excluded from being considered a DLT:  
• Grade 3 nausea/vomiting or diarrhea for less than 72 hours, with adequate antiemetic 
and other supportive care;  
• Grade 3 fatigue for less than 1 week;  
• Grade 3 or higher electrolyte abnormality that lasts up to 72 hours, is not clinically 
complicated, and resolves spontaneously or responds to conventional medical 
interventions. 
• Lab abnormalities that have no clinical sequelae (e.g. febrile neutropenia from low ANC, 
bleeding from thrombocytopenia, etc.) and resolve to grade 1 or better within 7 days will 
not be considered a DLT. 
Nab-Sirolimus dose modification guidelines are outlined in Table 9 and Table 11 for clinically 
significant toxicities that are deemed related to nab-Sirolimus. 


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6.5. 
Dose Modification Algorithms for Adverse Events Possibly Related to nab-Sirolimus and Pazopanib 
Table 11 - Dose Modification Algorithms for Overlapping Adverse Events Possibly Related to nab-Sirolimus and Pazopanib (See also 
Table 9 and Table 10) 
System/Organ 
Adverse Event 
CTCAE Grade v5.0 
Dose Modification Algorithm 
Hematologic 
toxicity 
Thrombocytopenia, 
Anemia 
Grade 2 
Nab-Sirolimus: 
Nab-Sirolimus can be administered if meeting the following hematological requirements:  
platelets >100 × 109/L  and hemoglobin ≥8 g/dL. 
Pazopanib: 
No changes to pazopanib dosing. 
Grade 3-4 
nab-Sirolimus:  
Hold nab-Sirolimus immediately for the remainder of that cycle.  Repeat blood collection 
within 3 days.  Nab-Sirolimus can resume once meeting following requirements:  platelet 
count >100 × 109/L  and hemoglobin ≥8 g/dL. For 2nd and subsequent events, drug will be 
restarted at a reduced dose; G-CSF may be given as deemed indicated. 
Pazopanib:  
Delay pazopanib until platelets ≤ grade 1, resume pazopanib with one dose level reduction. 
Neutropenia, Febrile 
or Afebrile 
Grade 3 
nab-Sirolimus: 
Hold nab-Sirolimus.  Repeat blood collection within 3 days.  Nab-Sirolimus can resume 
once meeting following requirements: absolute ANC ≥1.5×109/L. For 2nd and subsequent 
events, drug will be restarted at a reduced dose; G-CSF may be given as deemed indicated. 
Pazopanib: 
Delay pazopanib until ≤ grade 2, and then resume pazopanib at the current dose level. 
Grade 4 
Nab-Sirolimus: 
Hold nab-Sirolimus.  Repeat blood collection within 3 days.  Nab-Sirolimus can resume 
once meeting following requirements: absolute ANC ≥1.5×109/L. For 2nd and subsequent 
events, drug will be restarted at a reduced dose; G-CSF may be given as deemed indicated. 
Pazopanib: 
Delay pazopanib until ≤ grade 2, then resume pazopanib with one dose level reduction. 


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Hepatic 
Toxicity 
Hepatic Failure 
Grade 3 
Nab-Sirolimus: 
See Section 6.1.3.1and 6.1.3.2.  
Subjects with ALT/AST > 3 x ULN, or Total Bilirubin > 3 x ULN, or Alk Phos > 8 x ULN are 
recommended for withholding of nab-Sirolimus. 
Pazopanib: 
Discontinue pazopanib. 
ALT, AST, or 
Bilirubin Elevation 
Grade 2 
Nab-Sirolimus: 
See Section 6.1.3.1 and 6.1.3.2.  
Subjects with ALT/AST > 3 x ULN, or Total Bilirubin > 3 x ULN, or Alk Phos > 8 x ULN are 
recommended for withholding of nab-Sirolimus. 
Pazopanib: 
Continue pazopanib, but monitor weekly until ALT, AST, and bilirubin return to ≤ grade 1. 
Grade 3-4 
Nab-Sirolimus: 
See Section 6.1.3.1and 6.1.3.2.  
Subjects with ALT/AST > 3 x ULN, or Total Bilirubin > 3 x ULN, or Alk Phos > 8 x ULN are 
recommended for withholding of nab-Sirolimus. 
Pazopanib: 
Delay pazopanib until improved to ≤ grade 1. Restart treatment with one dose level 
reduction of pazopanib. 
ALT/AST and 
Bilirubin (Grade 2 or 
greater ALT/AST 
elevation with 
concurrent Grade 2 
or greater bilirubin 
elevation) 
Grade 2+ 
 
Nab-Sirolimus: 
Discontinue nab-Sirolimus. 
Pazopanib: 
Discontinue pazopanib. 
 
Other Adverse 
Reactions 
Other Adverse 
Reactions 
Grade 3 
Withhold treatment until Grade ≤1, then restart at the same dose level. If recurs, restart at 
1 dose level lower. 


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Grade 4 
Permanently discontinue nab-Sirolimus. 


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6.6. 
Overdose  
6.6.1. 
Nab-Sirolimus 
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of nab-
Sirolimus or pazopanib assigned to a given subject, regardless of any associated AEs or sequelae. 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency.  
On an infusion rate basis, an overdose is defined as any rate faster than the protocol-specified 
rate of 30 minutes (+10 minutes) for each infusion. 
6.6.2. 
Pazopanib 
No MTD was reached in the dose escalation study of pazopanib administered as a single agent 
at repeated doses of up to 2000 mg/day (Study VEG10003). Systemic exposure to pazopanib at 
steady-state appeared to plateau at doses greater than 800 mg once daily. Increases in the daily 
pazopanib dose above 800 mg in the fasted state resulted in a small or no increase in mean 
systemic exposure to pazopanib. 
 
 
 


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7. 
STUDY DRUG MANAGEMENT  
7.1. 
Description of Study Drugs  
7.1.1. 
Nab-Sirolimus Packaging, Labeling, and Storage 
Nab-Sirolimus will be supplied Aadi Bioscience in single-use vials as lyophilized product. Each 
single-use 50-mL vial will contain 100 mg rapamycin and approximately 800 mg of human 
albumin as a stabilizer. Each vial will be labeled according to country-specific regulatory 
requirements for labeling of IPs.  
Unopened vials of nab-Sirolimus should be stored in a refrigerator (2°-8°C; 36°-46°F) in original 
cartons to protect from light. Reconstituted nab-Sirolimus may be stored for up to 4 hours at 2-
8°C (36°- 46°F), followed by 4 hours at room temperature (<25°C) in the IV bag. Both unopened 
vials of nab-Sirolimus and reconstituted nab-Sirolimus should be stored in an area free of 
environmental extremes and must be accessible only to study personnel. 
Temperature records for nab-Sirolimus must be made available to Aadi Bioscience or Sponsor-
Investigator approved monitoring teams for verification of proper study drug storage. 
7.2. 
Nab-Sirolimus and Pazopanib Accountability, Disposal, and Compliance 
7.2.1. 
Nab-Sirolimus 
For nab-Sirolimus, only completely unused study drug vials should be retained by the site until a 
representative from Aadi Bioscience or Sponsor-Investigator approved study monitor has 
completed an inventory. Partially used and completely used vials should be destroyed according 
to the site’s guidelines, and their disposition should be recorded on the Investigational Drug 
Accountability Record Form. 
For nab-Sirolimus the Sponsor-Investigator, or designee, shall record the dispensing of study drug 
to subjects and any remaining study drug after dosing in a study drug accountability record. The 
study drug record will be made available to monitoring personnel for the purpose of accounting 
for the study drug supply. Inspections of the study drug supply for inventory purposes and 
assurance of proper storage will be conducted as necessary. Any significant discrepancy will be 
recorded and reported to the Sponsor-Investigator and Aadi Bioscience or their designee and a 
plan for resolution will be documented. 
Accurate recording of all nab-Sirolimus administration will be made in the appropriate section of 
the subject’s CRF and source documents. The Sponsor-Investigator or designee is responsible for 
accounting for all study-specific IP either administered or in their custody during the course of 
the study. 
7.2.2. 
Pazopanib 
Pazopanib is managed as a prescribed medication and administered as standard of care, 
according to institutional practices. 
Accurate recording of all pazopanib administration will be made in the appropriate section of 
the subject’s CRF and source documents. Subjects will complete a daily drug diary recording 
time of self-administration of pazopanib dosing. This diary will be reviewed at Day 1 of each 
cycle. Pharmacy accountability and dispensation records will not be maintained for pazopanib.  


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7.3. 
Nab-Sirolimus Reconstitution and Use 
It is not a requirement to use filter needles in the preparation, or in-line filters during the 
administration of nab-Sirolimus. In any event, filters of pore size less than 15 microns (15 µm) 
must not be used. 
Nab-Sirolimus will be reconstituted by appropriate study personnel following the Pharmacy 
Manual and administered to the subject at the study site. The investigator or qualified designee 
will calculate the BSA of the subject in order to determine the total amount of nab-Sirolimus to 
be administered. 
7.4. 
Receipt and Return of nab-Sirolimus 
The process for handling the receipt and return of the study drug supplies are described in the 
Pharmacy Manual. 
 
 


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8. 
CONCOMITANT MEDICATIONS AND PROCEDURES 
All concomitant treatments, including blood and blood products, must be reported on the CRF. 
Throughout the study, investigators may prescribe any concomitant medications or treatments 
deemed necessary to provide adequate supportive care except for those listed in Section 8.2. 
Concomitant therapies are to be collected from 28 days prior to signing of informed consent 
through the 30-Day Follow Up Visit. Therapy name including indication, dose, frequency, route, 
start date and stop date will be recorded on each subject’s CRF(s). 
8.1. 
Permitted Medications and Procedures 
The investigator must be informed as soon as possible about any medication taken from the time 
of screening until the end of the clinical phase of the study (final study visit). Any concomitant 
medication(s), including herbal preparations, taken during the study will be recorded in the CRF. 
The minimum requirement is that drug name, dose, and the dates of administration are to be 
recorded. Additionally, a complete list of all prior cancer therapies will be recorded in the CRF. 
Subjects should receive full supportive care during the study, including transfusions of blood and 
blood products, and treatment with antibiotics, anti-emetics, anti-diarrheas, and analgesics, and 
other care as deemed appropriate, in accordance with their institutional guidelines. WBC growth 
factors may be administered at the discretion of the investigator, consistent with institutional 
guidelines. 
Extreme precaution must be taken with contraceptives (either combined or progesterone only), 
as it is not known if there is the potential of inhibition/induction of enzymes that affect the 
metabolism of estrogens and/or progestins.  
8.2. 
Prohibited Medications and Procedures 
The use of certain medications and illicit drugs within 5 half-lives or 28 days, whichever is shorter, 
prior to the first dose of study drug and for the duration of the study will not be allowed. If a 
prohibited medication is required for single use (such as for a procedure) while study drug is held, 
the Sponsor-Investigator can approve such use. 
The following medications or non-drug therapies are prohibited: 
• Other anti-cancer therapy while on treatment in this study. 
• Antiretroviral drugs (subjects with known HIV are ineligible for study participation). 
• Herbal remedies (e.g., St. John’s wort) unless approval is granted by the Sponsor-
Investigator. 
• Rapamycin is metabolized primarily by CYP3A4. Drugs that are strong inhibitors or 
inducers of CYP3A4 may only be used under special circumstances (e.g., as a single use 
for a procedure) while treatment with study drug is interrupted. The list may be modified 
based on emerging data.  
• Use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, 
alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfanide) 


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within the 14 days prior to receiving the first dose of ABI-009.  Other medications may be 
allowed with approval of the Sponsor-Investigator. 
• Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the 
first dose of ABI-009.  


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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Study Endpoints 
Endpoints in Phase 1 
Primary Endpoint 
• DLT, as defined in Section 6.4. 
Secondary Endpoint 
• Adverse Events profile (based on NCI CTCAE v5.0) of all subjects and each dose cohort 
Endpoints in Phase 2 – Data from both phase 1 and 2 
Primary Endpoint 
• Progression-free survival (PFS) rate at 3 months, based on Response Evaluation Criteria 
in Solid Tumors (RECIST) v1.1 
Secondary Endpoints 
• Adverse Events profile (based on NCI CTCAE v5.0) 
• Median PFS, PFS rate at 6 months, based on RECIST v1.1 
• Median OS, OS at 12 months 
• Objective response rate (ORR) based on RECIST v1.1 
• Disease control rate, defined as CR plus PR plus SD ≥18 weeks, based on RECIST v1.1 
• Duration of response  
Exploratory endpoints 
• Correlation of baseline immune parameters with clinical benefit 
• Correlation of genetic profiling and optional tissue biomarker analysis with clinical benefit 
• Correlation of baseline SPARC expression with clinical benefit 
9.2. 
Safety Analysis 
The safety analysis set includes all treated subjects. 
Safety and tolerability will be monitored through continuous reporting of treatment emergent 
and TRAEs, AEs of special interest, laboratory abnormalities, and incidence of subjects 
experiencing dose modifications, dose delay/dose not given, dose interruptions, and/or 
premature discontinuation of IP due to an AE. All AEs will be recorded by the investigator from 
the time the subject signs informed consent until 30 days after the last dose of protocol therapy. 
Adverse events will be graded by NCI CTCAE v5.0. 
Physical examination, vital signs, laboratory assessments (e.g., serum chemistry, hematology), 
and ECOG performance status will be monitored and reviewed per institutional standards. All 
SAEs (regardless of relationship to IP) will be followed until resolution. Local laboratory analysis 
will be performed as per study schedule. 


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9.3. 
Efficacy Analysis  
Subjects will be evaluated for ORR, DCR, or progressive disease (PD) by CT imaging. Contrast 
enhanced MRI can also be used if CT is contra-indicated, as long as the same modality is used 
throughout the study. Baseline scan results can be accepted from outside institutions but must 
be done within 4 weeks of starting therapy and must include (as clinically indicated), chest 
abdominal, and pelvic CT or MRI. The first response assessment by CT or MRI scans documenting 
target lesions will be done 6 weeks after C1D1 and should be repeated every 6 weeks for the first 
year, then every 12 weeks thereafter until the end of treatment. If an initial observation of 
objective response (CR or PR) is made, a confirmation scan should be done at 6 weeks after initial 
observation. Scans should continue on schedule regardless of delays in nab-Sirolimus dosing.  
The efficacy endpoints of ORR (CR + PR), DCR (CR, PR, and SD ≥18 weeks), and PFS will be 
determined by a local radiologic assessment using RECIST v1.1. After the 30-Day Follow Up Visit, 
subjects will be followed for survival every 12 weeks (±3 weeks), or more frequently as needed, 
until death, withdrawal of consent, or the study closes, whichever is the earliest. 
The number and percentage of subjects achieving response ORR, DCR, or progressed will be 
summarized.   
Median PFS and OS will be summarized using Kaplan-Meier (KM) analysis. Analysis of other 
efficacy endpoints, PFS rate at 3 and 6 months, and OS rate at 12 months will be assessed via 
descriptive statistics, for the number of subjects is expected to be small. 
Response duration usually will be measured from the time of initial response until documented 
tumor progression. 
9.4. 
Exploratory Analysis 
Presence/level of expression of immune parameters, gene profiling, and SPARC will be analyzed 
and their relationship to clinical responsiveness will be explored. 
9.5. 
Sample Size Considerations 
Phase 1: Up to 49 subjects to identify the MTD, but the MTD may be reach with as few as 22 
subjects. Subjects who discontinue from the study prior to completing the DLT assessment 
window for reasons other than toxicity will be replaced at the same dose level. 
Phase 2: For sample size determination, we assume the following: 
1. For aa-TKI/pazopanib monotherapy in nonadipocytic STS, the baseline anticipated PFS 
rate at 3 months is approximately 50%49.   
2. An increase by the combination therapy of the PFS rate at 3 months to 70% would be 
considered clinically meaningful. 
3. This is an exploratory phase 1/2 study. Thus, type I (false positive) errors are less 
worrisome than type II (false negative). We therefore set alpha=0.1 for rejection of null 
hypothesis. Beta is set at 0.1 (90% power), again, to minimize type II errors. 
4. We are using a Simon’s two-stage study design for the phase 2 efficacy evaluation. 


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In the first stage, at least 23 subjects would be enrolled, including the 3-6 subjects from phase 1 
at the RP2D. If at least 11 were progression-free at the 3 months evaluation, then additional 
subjects would be enrolled to a total of 39 subjects in Phase 2. If at least 23 were progression-
free at 3 months, then this would provide preliminary data to indicate that the combination was 
active and worthy of further evaluation in this clinical setting. 
Subjects who fail to become evaluable for the secondary endpoint with a follow-up CT/MRI will 
be replaced. 
To assess the primary endpoint, we elected to use a Simon’s minimax design52. This was selected 
to be most conservative in evaluable subjects needed to answer the primary hypothesis. In this 
case, a total of 39 evaluable subjects will be required in the phase II component of the study, if it 
extends through both stages.   
This type of design has greater statistical power than a single-arm design. For example, a single 
arm trial enrolling the same number of subjects (n=39) would only have a statistical power of 
82%, versus 90% for the proposed design. Alternatively, it would require 50 evaluable subjects in 
a single-arm design to achieve the desired 90% power. 
 
9.6. 
Primary Analysis 
Primary analysis for this study will occur after all subjects have either completed the study or 
completed 12 months of treatment. Subjects who are still active at the time of the primary 
analysis may continue on study until disease progression or medication intolerance is observed. 


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10. 
MONITORING, RECORDING, AND REPORTING OF ADVERSE EVENTS  
10.1. 
Toxicities of Nab-Sirolimus 
Nab-Sirolimus is a formulation of rapamycin. No unexpected toxicities not already known for 
rapamycin (Rapamune®) or the rapamycin prodrug, temsirolimus (Torisel®), were identified in the 
nonclinical toxicity studies, or observed in the phase 1 studies for nab-Sirolimus. 
More details on the known precautions, warnings, and AEs of rapamycin and rapalogs are found 
in the Rapamune® and Torisel® Package Inserts.45,46 
10.2. 
Toxicities of Pazopanib 
Per the Prescribing information, the most common AEs in subjects with advanced STS (greater 
than or equal to 20%) are fatigue, diarrhea, nausea, decreased weight, hypertension, decreased 
appetite, hair color changes, vomiting, tumor pain, dysgeusia, headache, musculoskeletal pain, 
myalgia, gastrointestinal pain, and dyspnea.52 
10.3. 
Evaluation of Adverse Events  
The investigator must assign the following AE attributes: 
• AE diagnosis or syndrome(s), if known (if not known, signs or symptoms) 
• Dates of onset and resolution (if resolved) 
• Severity [and/or toxicity per protocol] 
• Assessment of relatedness to the IP 
• Assessment of relatedness to protocol-required procedures  
• Action taken 
The AE toxicity grading scale used will be the NCI CTCAE Version 5.0.  
10.4. 
Serious Adverse Events 
10.4.1. 
Definition of Serious Adverse Events 
An SAE is defined as an AE that meets at least 1 of the following serious criteria: 
• fatal 
• life-threatening (places the subject at immediate risk of death) 
• requires in-patient hospitalization or prolongation of existing hospitalization 
• results in persistent or significant disability/incapacity 
• congenital anomaly/birth defect 
• other medically important serious event 
An AE would meet the criterion of “requires hospitalization”, if the event necessitated an in-
patient admission to a health care facility (e.g., overnight stay).   


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If an investigator considers an event to be clinically important, but it does not meet any of the 
serious criteria, the event could be classified as an SAE under the criterion of “other medically 
important serious event”.  Examples of such events could include allergic bronchospasm, 
convulsions, blood dyscrasias, drug-induced liver injury, or events that necessitate an emergency 
room visit, outpatient surgery, or urgent intervention. 
Since the criteria for the CTCAE grading scale differs from the regulatory criteria for SAEs, if AEs 
correspond to grade 4 “life threatening” CTCAE grading scale criteria (e.g., laboratory 
abnormality reported as grade 4 without manifestation of life-threatening status), it will be left 
to the investigator’s judgment to also report these abnormalities as SAEs. For any AE that applies 
to this situation, comprehensive documentation of the event’s severity status must be recorded 
in the subject’s medical record.   
10.4.2. 
Reporting Procedures for Serious Adverse Events 
All SAEs that are drug-related and unexpected must be reported by the Sponsor-Investigator to 
their IRB in writing, and to the FDA within 15 days as required by law. 
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the CRF.  All SAEs must be reported to Aadi 
Bioscience Drug Safety within 24 hours of the Sponsor-Investigator’s knowledge of the event by 
facsimile, or other appropriate method, using the SAE Report Form, or approved equivalent form. 
This instruction pertains to initial SAE reports as well as any follow-up reports. 
The Sponsor-Investigator or treating investigator is required to ensure that the data on these 
forms is accurate and consistent. This requirement applies to all SAEs (regardless of relationship 
to IP) that occur during the study (from the time of signing of the informed consent form to 30 
days after the last dose of IP), and those made known to the investigator at any time thereafter 
that are suspected of being related to IP.   
The SAE report should provide a detailed description of the SAE and include a concise summary 
of hospital records and other relevant documents. If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Aadi Bioscience 
Drug Safety as soon as these become available. Any follow-up data will be detailed in a 
subsequent SAE Report Form, or approved equivalent form, and sent to Aadi Bioscience Drug 
Safety.  
Where required by local legislation, the Sponsor-Investigator is responsible for informing the 
IRB/EC of the SAE and providing them with all relevant initial and follow-up information about 
the event. The Sponsor-Investigator must keep copies of all SAE information on file including 
correspondence with Aadi Bioscience and the IRB/EC. 
10.5. 
Pregnancy and Breastfeeding Reporting 
If a pregnancy occurs in a female subject, or female partner of a male subject, while the subject 
is taking protocol-required therapies, report the pregnancy to Aadi Bioscience as specified below. 
In addition to reporting any pregnancies occurring during the study, investigators should monitor 
for pregnancies that occur up to 3 months after the last dose of protocol-required therapies.  


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The investigator will follow the female subject until completion of the pregnancy, and must notify 
Aadi Bioscience Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form, 
if the female subject consents to allow the study team to follow the pregnancy to completion or 
termination.  
If a lactation case occurs while the female subject is taking protocol-required therapies, report 
the lactation case to Aadi Bioscience as specified below. In addition to reporting a lactation case 
during the study, investigators should monitor for lactation cases that occur up to 1 week after 
the last dose of protocol-required therapies. 


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11. 
WITHDRAWAL FROM TREATMENT, PROCEDURES, AND STUDY 
11.1. 
Discontinuation from Investigational Product 
The following events are considered sufficient reasons for discontinuing a subject from the IP: 
• AE(s) (that are intolerable) 
• Disease progression 
• Physician decision 
• Withdrawal of consent (from treatment only) 
• Death 
• Lost to follow up 
• Protocol violation 
• Other (to be specified on the CRF) 
The reason for treatment discontinuation should be recorded in the CRF and in the source 
documents. 
11.2. 
Discontinuation from the Study 
The following events are considered sufficient reasons for discontinuing a subject from the study: 
• Withdrawal of consent 
• Death 
• Lost to follow up 
• Protocol violation 
• Other (to be specified on the CRF) 
The reason for study discontinuation should be recorded in the CRF and in the source documents. 
At the time of withdrawal, it should be determined whether the subject is withdrawing from 
treatment alone, or from treatment and collection of further data (e.g., survival). Every effort 
should be made to collect survival data after subject withdraws from treatment.  
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to his or her future medical care by the physician or at the institution. 
11.3. 
Decision to Withdraw or Terminate Subject’s Participation Prior to Study 
Completion 
The Sponsor-Investigator can decide to withdraw a subject(s) from Investigational Product 
and/or other protocol-required therapies, protocol procedures, or the study as a whole at any 
time prior to study completion.    
Subjects may be eligible for continued treatment with Aadi Bioscience’s Investigational Product 
and/or other protocol-required therapies by a separate protocol or as provided for by the local 
country’s regulatory mechanism. 


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12. 
REGULATORY OBLIGATIONS 
12.1. 
Informed Consent 
The Informed Consent Document must be reviewed and approved by the Sponsor-Investigator, 
Aadi Biosciences, and the IRB prior to use. Updates to the informed consent document are to be 
communicated to Aadi Bioscience prior to submitting for IRB review and approval. For research 
participants who do not speak and/or read English, a short-form consent should be used. The 
short form is used to document that the elements of informed consent were orally presented to 
the research participant by a qualified interpreter. Both the short form and a written summary, 
which may also be the IRB-approved English-language informed consent document, must be 
submitted filed in the subject chart. 
Before a subject’s participation in the clinical study, the investigator is responsible for obtaining 
written informed consent from the subject after adequate explanation of the aims, methods, 
anticipated benefits, and potential hazards of the study and before any protocol-specific 
screening procedures or the IP is administered.  
The acquisition of informed consent is to be documented in the subject’s medical records, and 
the informed consent form to be signed and personally dated by the subject and by the person 
who conducted the informed consent discussion. The original signed informed consent form is 
to be retained in accordance with institutional policy, and a copy of the signed consent form is to 
be provided to the subject. 
If a potential subject is illiterate or visually impaired, the investigator must provide an impartial 
witness to read the informed consent form to the subject and must allow for questions. 
Thereafter, both the subject and the witness must sign the informed consent form, per 
institutional policy, to attest that informed consent was freely given and understood.   
12.2. 
Institutional Review Board/Independent Ethics Committee  
A copy of the protocol, informed consent form, other written subject information, and any 
proposed advertising material must be submitted to the IRB for written approval. A copy of the 
written approval of the protocol and informed consent form must be received by Aadi Bioscience 
before recruitment of subjects into the study and shipment of Aadi Bioscience IP. 
The Sponsor-Investigator must submit and, where necessary, obtain approval from the IRB for all 
subsequent protocol amendments and changes to the informed consent document.  The 
Sponsor-Investigator is to notify the IRB of reportable deviations from the protocol or SAEs 
occurring at the site and other AE reports received from Aadi Bioscience, in accordance with local 
procedures. 
The Sponsor-Investigator is responsible for obtaining annual IRB approval [IRBs only]/renewal 
[IRBs and IECs] throughout the duration of the study. Copies of the Sponsor-Investigator’s reports 
and the IRB continuance of approval must be sent to Aadi Bioscience. 
12.3. 
Subject Confidentiality 
The Sponsor-Investigator must ensure that the subject’s confidentiality is maintained for 
documents submitted to Aadi Bioscience. 


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• Subjects are to be identified by a unique subject identification number. 
• Where permitted, date of birth is to be documented and formatted in accordance 
with local laws and regulations. 
• On the CRF demographics page, in addition to the unique subject identification 
number, include the age at time of enrollment. 
• For SAEs reported to Aadi Bioscience, subjects are to be identified by their unique 
subject identification number, initials (for faxed reports, in accordance with local laws 
and regulations), and date of birth (in accordance with local laws and regulations). 
• Documents that are not submitted to Aadi Bioscience (e.g., signed informed consent 
forms) are to be kept in confidence by the investigator, except as described below. 
In compliance with Federal regulations/ICH GCP Guidelines, it is required that the Sponsor-
Investigator and institution permit authorized representatives of the company, of the regulatory 
agency(s), and the IRB direct access to review the subject’s original medical records for 
verification of study-related procedures and data. Direct access includes examining, analyzing, 
verifying, and reproducing any records and reports that are important to the evaluation of the 
study. The investigator is obligated to inform and obtain the consent of the subject to permit 
such individuals to have access to his/her study-related records, including personal information. 
12.4. 
Protocol Amendments   
If Sponsor-Investigator amends the protocol, agreement from Aadi Bioscience must be obtained. 
The IRB must be informed of all amendments and give approval. The Sponsor-Investigator must 
send a copy of the approval letter from the IRB to Aadi Bioscience. 
12.5. 
Termination of the Study 
Both Aadi Bioscience and the Sponsor-Investigator reserve the right to terminate the Sponsor-
Investigator’s participation in the study according to the study contract. The Sponsor-
Investigator is to notify the IRB in writing of the study’s completion or early termination and send 
a copy of the notification to Aadi Bioscience. 
 


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13. 
DATA HANDLING AND RECORDKEEPING 
13.1. 
Data/Documents 
The Sponsor-Investigator must ensure that the records and documents pertaining to the conduct 
of the study and the distribution of the investigational product are complete, accurate, filed, and 
retained. Examples of source documents include: hospital records; clinic and office charts; 
laboratory notes; memoranda; checklists; dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy; and the laboratories, as 
well as copies of CRFs or CD-ROM. 
13.2. 
Data Management 
Data will be collected via CRF and entered into the clinical database. These data will be 
electronically verified through use of programmed edit checks specified by the clinical team. 
Discrepancies in the data will be brought to the attention of the clinical team, and investigational 
site personnel, if necessary. Resolutions to these issues will be reflected in the database. An audit 
trail within the system will track all changes made to the data. 
13.3. 
Responsibilities for Data Collection 
The Sponsor-Investigator is responsible for complying with the requirements for all assessments 
and data collection (including subjects not receiving protocol-required therapies) as stipulated in 
the protocol for each subject in the study. For subjects who withdraw prior to completion of all 
protocol-required visits and are unable or unwilling to continue the Schedule of Assessments (in 
Table 3, the investigator can search publicly available records (where permitted) to ascertain 
survival status.  
This ensures that the data set(s) produced as an outcome of the study is/are as comprehensive 
as possible. 
13.4. 
Sample Storage and Destruction 
Any blood or tumor sample collected can be analyzed for any of the tests outlined in the protocol 
and for any tests necessary to minimize risks to study subjects. This includes testing to ensure 
analytical methods produce reliable and valid data throughout the course of the study. This can 
also include, but is not limited to, investigation of unexpected results, incurred sample reanalysis, 
and analyses for method transfer and comparability.  
All samples and associated results will be no less than single coded prior to being shipped from 
the site for analysis, or storage. Tracking of samples will be independent of the subject’s 
identification number for the study. Results are stored in a secure database to ensure 
confidentiality.   
Results from this analysis are to be documented and maintained but are not necessarily reported 
as part of this study.  
The records should be retained by the Sponsor-Investigator according to ICH, local regulations, 
or as specified in the Clinical Trial Agreement, whichever is longer; but at a minimum, all study 
documentation must be retained for 2 years after the last marketing application approval in an 


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ICH region or after at least 2 years have elapsed since formal discontinuation of clinical 
development of nab-Sirolimus. 
Since the evaluations are not expected to benefit the subject directly or to alter the treatment 
course, the results of other exploratory studies are not placed in the subject’s medical record and 
are not to be made available to the subject, members of the family, the personal physician, or 
other third parties, except as specified in the informed consent. 
The subject retains the right to request that the sample material be destroyed by contacting the 
Sponsor-Investigator.  Following the request from the subject, the Sponsor-Investigator is to 
provide the sponsor with the required study and subject number so that any remaining blood or 
tumor samples and any other components from the cells can be located and destroyed. Samples 
will be destroyed once all protocol-defined procedures are completed.   
The Sponsor-Investigator is the exclusive owner of any data, discoveries, or derivative materials 
from the sample materials and is responsible for the destruction of the sample(s) at the request 
of the subject, at the end of the storage period, or as appropriate (e.g., the scientific rationale for 
experimentation with a certain sample type no longer justifies keeping the sample). The subject 
has no commercial rights to such product and has no commercial rights to the data, information, 
discoveries, or derivative materials gained or produced from the sample.  


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14. 
QUALITY CONTROL AND QUALITY ASSURANCE 
14.1. 
Study Monitoring 
Institutional support of trial monitoring will be in accordance with the FHCC/University of 
Washington Cancer Consortium Institutional Data and Safety Monitoring Plan. Under the 
provisions of this plan, FHCC Clinical Research Support (CRS) coordinates data and compliance 
monitoring conducted by consultants, contract research organizations, or FHCC employees 
unaffiliated with the conduct of the study. Independent monitoring visits occur at specified 
intervals determined by the assessed risk level of the study and the findings of previous visits per 
the institutional DSMP.  
In addition, protocols are reviewed at least annually and as needed by the Consortium Data and 
Safety Monitoring Committee (DSMC), FHCC Scientific Review Committee (SRC) and the 
FHCC/University of Washington Cancer Consortium Institutional Review Board (IRB). The review 
committees evaluate accrual, adverse events, stopping rules, and adherence to the applicable 
data and safety monitoring plan for studies actively enrolling or treating subjects. The IRB reviews 
the study progress and safety information to assess continued acceptability of the risk-benefit 
ratio for human subjects. Approval of committees as applicable is necessary to continue the 
study.  
The trial will comply with the standard guidelines set forth by these regulatory committees and 
other institutional, state and federal guidelines. 
 
14.2. 
Audits and Inspections 
In accordance with ICH GCP and the sponsor’s audit plans, this study may be selected for audit 
by representatives from Aadi Bioscience’s Inspection of site facilities (e.g., pharmacy, protocol-
required therapy storage areas, laboratories) and review of study-related records will occur to 
evaluate the study conduct and compliance with the protocol, ICH GCP, and applicable regulatory 
requirements. 


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15. 
PUBLICATIONS 
The results of this study may be published in a medical publication, journal, or may be used for 
teaching purposes.  Additionally, this study and its results may be submitted for inclusion in all 
appropriate health authority study registries, as well as publication on health authority study 
registry websites, as required by local health authority regulations. Selection of first authorship 
will be based on several considerations, including, but not limited to study participation, 
contribution to the protocol development, and analysis and input into the manuscript, related 
abstracts, and presentations in a study. 


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16. 
REFERENCES 
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2. Clark MA, Fisher C, Judson I, Thomas JM. Soft-tissue sarcomas in adults. N Engl J Med 
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3. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017;67:7-30. 
4. Judson I, Verweij J, Gelderblom H, et al. Doxorubicin alone versus intensified doxorubicin 
plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a 
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5. Wagner MJ, Amodu LI, Duh MS, et al. A retrospective chart review of drug treatment 
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6. Ratan R, Patel SR. Chemotherapy for soft tissue sarcoma. Cancer 2016;122:2952-60. 
7. Gotink KJ, Verheul HM. Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism 
of action? Angiogenesis 2010;13:1-14. 
8. van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma 
(PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2012;379:1879-
86. 
9. Coens C, van der Graaf WT, Blay JY, et al. Health-related quality-of-life results from PALETTE: 
A randomized, double-blind, phase 3 trial of pazopanib versus placebo in patients with soft 
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Organization for research and treatment of cancer soft tissue and bone sarcoma group global 
network study (EORTC 62072). Cancer 2015;121:2933-41. 
10. D'Incalci M, Galmarini CM. A review of trabectedin (ET-743): a unique mechanism of action. 
Molecular cancer therapeutics 2010;9:2157-63. 
11. Demetri GD, von Mehren M, Jones RL, et al. Efficacy and Safety of Trabectedin or 
Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional 
Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. Journal of clinical 
oncology : official journal of the American Society of Clinical Oncology 2016;34:786-93. 
12. Mocellin S, Rossi CR, Brandes A, Nitti D. Adult soft tissue sarcomas: conventional therapies 
and molecularly targeted approaches. Cancer treatment reviews 2006;32:9-27. 
13. Sharma S, Takyar S, Manson SC, Powell S, Penel N. Efficacy and safety of pharmacological 
interventions in second- or later-line treatment of patients with advanced soft tissue sarcoma: a 
systematic review. BMC Cancer 2013;13:385. 
14. Petek BJ, Loggers ET, Pollack SM, Jones RL. Trabectedin in soft tissue sarcomas. Marine 
drugs 2015;13:974-83. 
15. Chawla SP, Staddon AP, Baker LH, et al. Phase II study of the mammalian target of 
rapamycin inhibitor ridaforolimus in patients with advanced bone and soft tissue sarcomas. 
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 
2012;30:78-84. 
16. Demetri GD, Chawla SP, Ray-Coquard I, et al. Results of an international randomized phase 
III trial of the mammalian target of rapamycin inhibitor ridaforolimus versus placebo to control 


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metastatic sarcomas in patients after benefit from prior chemotherapy. Journal of clinical 
oncology : official journal of the American Society of Clinical Oncology 2013;31:2485-92. 
17. Yuan R, Kay A, Berg WJ, Lebwohl D. Targeting tumorigenesis: development and use of mTOR 
inhibitors in cancer therapy. J Hematol Oncol 2009;2:45. 
18. Corradetti MN, Guan KL. Upstream of the mammalian target of rapamycin: do all roads pass 
through mTOR? Oncogene 2006;25:6347-60. 
19. Dowling RJ, Topisirovic I, Fonseca BD, Sonenberg N. Dissecting the role of mTOR: lessons 
from mTOR inhibitors. Biochimica et biophysica acta 2010;1804:433-9. 
20. O'Donnell A, Faivre S, Burris HA, 3rd, et al. Phase I pharmacokinetic and pharmacodynamic 
study of the oral mammalian target of rapamycin inhibitor everolimus in patients with 
advanced solid tumors. Journal of clinical oncology : official journal of the American Society of 
Clinical Oncology 2008;26:1588-95. 
21. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-
positive advanced breast cancer. N Engl J Med 2012;366:520-9. 
22. Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N 
Engl J Med 2011;364:514-23. 
23. Hanna SC, Heathcote SA, Kim WY. mTOR pathway in renal cell carcinoma. Expert Rev 
Anticancer Ther 2008;8:283-92. 
24. Molina AM, Feldman DR, Voss MH, et al. Phase 1 trial of everolimus plus sunitinib in 
patients with metastatic renal cell carcinoma. Cancer 2011;118:1868-76. 
25. Thompson LA, Kim M, Wenger SD, O'Bryant CL. Everolimus: a new treatment option for 
advanced pancreatic neuroendocrine tumors. Ann Pharmacother 2012;46:1212-9. 
26. Albiges L, Chamming's F, Duclos B, et al. Incidence and management of mTOR inhibitor-
associated pneumonitis in patients with metastatic renal cell carcinoma. Ann Oncol 
2012;23:1943-53. 
27. de Oliveira MA, Martins EMF, Wang Q, et al. Clinical presentation and management of 
mTOR inhibitor-associated stomatitis. Oral Oncol 2011;47:998-1003. 
28. Qi WX, Huang YJ, Yao Y, Shen Z, Min DL. Incidence and risk of treatment-related mortality 
with mTOR inhibitors everolimus and temsirolimus in cancer patients: a meta-analysis. PloS one 
2013;8:e65166. 
29. Zhou H, Luo Y, Huang S. Updates of mTOR inhibitors. Anti-cancer agents in medicinal 
chemistry 2010;10:571-81. 
30. Gonzalez-Angulo AM, Meric-Bernstam F, Chawla S, et al. Weekly nab-Rapamycin in patients 
with advanced nonhematologic malignancies: final results of a phase I trial. Clinical cancer 
research : an official journal of the American Association for Cancer Research 2013;19:5474-84. 
31. Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin-bound 
paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast 
cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 
2005;23:7794-803. 
32. Kratz F. Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J 
Control Release 2008;132:171-83. 
33. Kremer P, Hartung G, Bauder-Wust U, et al. Efficacy and tolerability of an aminopterin-
albumin conjugate in tumor-bearing rats. Anticancer Drugs 2002;13:615-23. 


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34. Schnitzer JE. gp60 is an albumin-binding glycoprotein expressed by continuous endothelium 
involved in albumin transcytosis. Am J Physiol 1992;262:H246-54. 
35. Schnitzer JE, Oh P, Jacobson BS, Dvorak AM. Caveolae from luminal plasmalemma of rat 
lung endothelium: microdomains enriched in caveolin, Ca(2+)-ATPase, and inositol 
trisphosphate receptor. Proc Natl Acad Sci U S A 1995;92:1759-63. 
36. Desai N, Trieu V, Yao Z, et al. Increased antitumor activity, intratumor paclitaxel 
concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, 
ABI-007, compared with cremophor-based paclitaxel. Clinical cancer research : an official 
journal of the American Association for Cancer Research 2006;12:1317-24. 
37. Morgan S.S. NRB, Cranmer L.D. Serum protein acidic and rich in cysteine (SPARC) as a 
prognostic marker in soft tissue sarcomas. Clinical Sarcoma Research 2014;4. 
38. Kennecke H, Rahman M, Yip S, Woods R, Schaeffer D, Tai I. Effect of nab-rapamycin versus 
rapamycin in colorectal cancer cell lines and associations with KRAS and PI3K mutations.  
Proceedings of the 47th American Society of Clinical Oncology (ASCO) Annual Meeting; 2011 
June 3-7; Chicago, IL,: J Clin Oncol p. abstr e13532. 
39. Trieu V, Ran S, Volk L, Stutzman A, D'Cruz O, Desai N. CNS safety, antitumor activity, and 
antiangiogenic activity of nab-rapamycin (ABI-009).  Proceedings of the 100th American 
Association for Cancer Research Annual Meeting (AACR); 2009 Apr 18-22; Denver CO: AACR. p. 
abstr 136. 
40. De T, Trieu V, Yim Z, et al. Nanoparticle albumin-bound (nab) rapamycin as an anticancer 
agent.  Proceedings of the 98th American Association for Cancer Research Annual Meeting 
(AACR); 2007 Apr 14-18; Los Angeles CA: AACR. p. abstr 4719. 
41. Cirstea D, Hideshima T, Rodig S, et al. Dual inhibition of akt/mammalian target of rapamycin 
pathway by nanoparticle albumin-bound-rapamycin and perifosine induces antitumor activity in 
multiple myeloma. Molecular cancer therapeutics 2010;9:963-75. 
42. Desai N, D'Cruz O, Trieu V. Potent antitumor effects of nab-rapamycin (ABI-009) in 
combination with kinase inhibitors erlotinib and perifosine.  Proceedings of the 100th American 
Association for Cancer Research Annual Meeting (AACR); 2009 Apr 18-22; Denver CO: AACR. p. 
abstr 4576. 
43. Fasolo A, Sessa C. Targeting mTOR pathways in human malignancies. Curr Pharm Des 
2012;18:2766-77. 
44. Sehgal SN. Sirolimus: its discovery, biological properties, and mechanism of action. 
Transplant Proc 2003;35:7S-14S. 
45. Pfizer. Prescribing Information: TORISEL Kit (temsirolimus) injection, for intravenous 
infusion only2011. 
46. Pfizer. Rapamune Prescribing Information. 2011. 
47. Novartis. Everolimus (Afinitor) Prescribing Information. 2017. 
48. Cranmer LD, Loggers ET, Pollack SM. Pazopanib in the management of advanced soft tissue 
sarcomas. Ther Clin Risk Manag 2016;12:941-55. 
49. Cranmer LD LE, Pollack SM. A systematic review and meta-analysis comparing pazopanib 
with other small molecule, anti-angiogenic, tyrosine kinase inhibitors in the treatment of 
advanced sarcomas.  Connective Tissue Oncology Society. Lisbon, Portugal2016. 


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50. Conley AP RV, Somaiah N,. Safety, toxicity and activity of multi-kinaseVEGFR vandetanib 
combined with mTOR inhibitor everolimus in advanced sarcomas cohort of a phase I study.  
Connective Tissue Oncology Society. Lisbon, Portugal2016. 
51. Cranmer LD, Moore R, Duffy S, Wagner M, Loggers ET, Pollack S. A PHASE 1/2 STUDY OF ABI-
009 (NAB-SIROLIMUS) WITH PAZOPANIB IN PATIENTS WITH ADVANCED NONADIPOCYTIC SOFT 
TISSUE SARCOMAS.  Connective Tissue Oncology Society. Virtual Conference2020. 
52. Novartis. Pazopanib (Votrient) Prescribing Information. 2017. 
53. Cesne AL, Bauer S, Demetri GD, et al. Safety and efficacy of Pazopanib in advanced soft 
tissue sarcoma: PALETTE (EORTC 62072) subgroup analyses. BMC Cancer 2019;19:794. 
 


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17. 
APPENDIX 1 - WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS 
AND METHODS OF CONTRACEPTION 
17.1. 
Definitions 
17.1.1. 
Woman of Childbearing Potential (WOCBP) 
 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. 
 
Women in the following categories are not considered WOCBP 
 
• Premenarchal 
• Premenopausal female with 1 of the following: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
Note: Documentation can come from the site personnel’s review of the 
participant’s medical records, medical examination, or medical history interview. 
• Postmenopausal female 
o A postmenopausal state is defined as 12 months of amenorrhea in a woman over 
age 45 years in the absence of other biological or physiological causes.  
17.2. 
Contraception Guidance for Females of Childbearing Potential 
 
One of the highly effective methods of contraception listed below is required during study 
duration and until the end of relevant systemic exposure, defined as 3 months after last 
treatment. Local laws and regulations may require use of alternative and/or additional 
contraception methods. 
 
Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of < 1% per year when used consistently and correctly.a 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation 
o oral 
o intravaginal 
o transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation 
o oral 
o injectable 
 
Highly Effective Methods That are User Independent 
• Implantable progestogen-only hormonal contraception associated with inhibition of 


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Ovulation  
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
• Vasectomized partner 
• Sexual abstinence Sexual abstinence is considered a highly effective method only if 
defined as refraining from heterosexual intercourse during the entire period of risk 
associated with the study treatment. The reliability of sexual abstinence needs to be 
evaluated in related to the duration of the study and the preferred and usual lifestyle of 
the participant. 
o It is not necessary to use any other method of contraception when complete 
abstinence is elected. 
• WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests as specified in study calendar. 
• Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participants chooses to forego complete abstinence. 
 
a Typical use failure rates may differ from those when used consistently and correctly. Use 
should be consistent with local regulations regarding the use of contraceptive methods for 
participants participating in clinical studies. 
 
Less Than Highly Effective Contraceptive Methods That are User Dependent 
 
Failure rate of > 1% per year when used consistently and correctly. 
• Male or female condom with or without spermicide. Male and female condoms cannot 
be used simultaneously. 
• Diaphragm with spermicide 
• Cervical cap with spermicide 
• Vaginal sponge with spermicide 
• Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action 
 
Unacceptable Methods of Contraception 
• Periodic abstinence (calendar, symptothermal, post-ovulation methods) 
• Withdrawal (coitus interruptus) 
• Spermicide only 
• Lactation amenorrhea method (LAM) 
 
 
 
 


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17.3. 
Contraception Guidance for Males of Childbearing Potential 
 
Male participants with female partners of childbearing potential are eligible to participate if 
they agree to the following during the treatment and until the end of relevant systemic 
exposure. 
 
• Inform any and all partner(s) of their participation in a clinical drug study and the need 
to comply with contraception instructions as directed by the investigator. 
 
• Male participants are required to use a condom for study duration and until the end of 
relevant systemic exposure defined as 3 months after last systemic dose. 
 
• Female partners of males participating in the study to consider use of effective methods 
of contraception until the end of relevant systemic exposure, defined as 3 months after 
last systemic dose. 
 
• Male participants with a pregnant or breastfeeding partner must agree to remain 
abstinent from penile vaginal intercourse or use a male condom during each episode of 
penile penetration during the treatment and until 3 months after last systemic dose. 
 
• Refrain from donating sperm for the duration of the study treatment and for 3 months 
after last systemic dose. 
 
• Male participants may experience testicular side effects, such as reduced sperm 
production rates, reduced sperm concentrations, decreased epidydimal weights, 
atrophy and degeneration of the testes with aspermia (no sperm production), 
hypospermia (low or reduced sperm production), and cellular changes in the epididymis 
(a tube within the testes that transports sperm).  
 
 

ICF_000.pdf: 
 
 
Official Title: 
A phase 1/2 study of ABI-009 (nab-rapamycin) with 
pazopanib (VOTRIENT®) in patients with advanced 
nonadipocytic soft-tissue sarcomas  
NCT Number: 
NCT03660930 
Document Type:  
Informed Consent Form 
Date of the 
Document: 
December 9, 2021 
 
 


 
 
 
 
 
Main Consent 
Version 8.0 04 Nov 2021 
 
 
 
 
 
Page 1 of 24 
University of Washington 
RESEARCH SUBJECT INFORMATION AND CONSENT FORM 
 
 
TITLE: 
A phase 1/2 study of ABI-009 (nab-rapamycin) with pazopanib 
(VOTRIENT®) in patients with advanced nonadipocytic soft-
tissue sarcomas 
 
PROTOCOL NO.: 
Protocol No.: CC10015 
 
FUNDING SOURCE: 
Aadi Bioscience, Inc.  
 
INVESTIGATOR: 
Lee Cranmer, MD, PhD  
 
825 Eastlake Avenue E. 
 
Seattle, Washington 98109 
 
United States 
 
SITE(S): 
University of Washington 
 
1959 NE Pacific Street 
  
Seattle, Washington 98195 
 
United States 
 
 
Seattle Cancer Care Alliance 
 
825 Eastlake Avenue East 
  
Seattle, Washington 98109 
 
United States 
 
STUDY-RELATED 
PHONE NUMBER(S): 
Lee Cranmer, MD, PhD 
 
206-606-7439 
 
 
Roxanne Moore 
206-606-6425 (Office Hours) 
romoore@seattlecca.org 
 
Oncology Fellow On-Call 
206-598-6190 (24 hours) 
 
 
Emergency (24-hour) phone: Call the Seattle Cancer Care Alliance at 206-606-7400 Monday 
through Friday from 9 am to 5 pm. At all other times call the paging operator at the University of 
Washington Medical Center at 206-598-6190 and ask the operator to page the oncology fellow 
on call. 
 
 
 
IRO received 12/06/21
FHCRC IRB Approval  
DEC 09 2021 
Document Released Date


 
 
 
 
 
Main Consent 
Version 8.0 04 Nov 2021 
 
 
 
 
 
Page 2 of 24 
RESEARCHER’S STATEMENT 
 
We are asking you to be in a drug research study. You have been asked to take part in this study 
because you have been diagnosed with an advanced nonadipocytic soft-tissue sarcoma that has 
not been cured. The purpose of this consent form is to give you the information you will need to 
help you decide if you want to be in the study. Please read the form carefully. You may ask 
questions about the purpose of the research, what we would ask you to do, the possible risks and 
benefits, your rights as a volunteer, and anything else about the research or this form that is not 
clear. The research team will discuss the requirements for participating in this study. When we 
have answered all your questions, you can decide if you want to be in the study or not. This 
process is called “informed consent.” We will give you a signed and dated copy of this form for 
your records. 
 
This consent form may contain words that you do not understand. Please ask the researcher or 
the study staff to explain any words or information that you do not clearly understand. You may 
take home an unsigned copy of this consent form to think about or discuss with family or friends 
before making your decision. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 
 
PURPOSE OF THE STUDY 
 
The purpose of this study is to determine whether ABI-009 (study drug) in combination with an 
FDA approved standard of care agent, Votrient®, also known as pazopanib, will make your 
cancer smaller and slow the spread of your cancer. You may receive lower doses than the 
standard of care or the standard of care may be delayed due to unexpected toxicities of the 
combination.  
 
ABI-009, human albumin-bound rapamycin, is an experimental drug used to treat patients with 
advanced nonadipocytic soft-tissue sarcoma in this study. Rapamycin and similar types of drugs 
have been used in many other tumors, including advanced renal cell carcinoma. The human 
albumin component of ABI-009 may allow rapamycin to reach cancer cells more effectively. 
 
ABI-009 has not been approved by the U.S. Food and Drug Administration (FDA) for the treatment 
of advanced nonadipocytic soft-tissue sarcoma. The information from this study might help us 
identify if ABI-009 in combination with pazopanib is a safe and effective treatment for this 
disease.   
 
Pazopanib has been approved by the FDA for treatment of soft tissue sarcoma. It is also 
approved for the treatment of kidney cancer. The study drug is a cancer medicine that targets 
blood vessel growth. It may stop the growth of your soft tissue sarcoma by blocking blood flow 
to the tumor and blocking some of the enzymes needed for tumor cell growth. 
This consent form gives you detailed information about this research study. If you wish to 
participate in the study, you will be asked to sign and date the informed consent form, and you 
will be given a complete copy of this informed consent form to keep. 
FHCRC IRB Approval  
DEC 09 2021 
Document Released Date


 
 
 
 
 
Main Consent 
Version 8.0 04 Nov 2021 
 
 
 
 
 
Page 3 of 24 
WHY ARE WE DOING THIS STUDY? 
 
We are doing this study to examine the antitumor activity of ABI-009 (also called nab-
rapamycin) with pazopanib in subjects with advanced nonadipocytic soft-tissue sarcomas. This 
combination is investigational, which means it has not been approved for use by the FDA. This 
study is made up of two parts. Phase 1 and Phase 2.  
 
The first part of the study, the Phase 1 portion, is the dose-escalation Phase. The objective of this 
Phase is to determine how much ABI-009 can be given safely. Subjects will be treated at 
different doses of ABI-009 in combination with pazopanib. This is done to determine the 
maximum tolerated dose of ABI-009. There will be different dosing groups of ABI-009, 
receiving a dose level that is predetermined for each group. Subjects that join in the beginning of 
the study may receive a lower or higher dose than subjects who join at a later date. Based on the 
presence of effects (either good or bad), the dose level can be escalated (raised) or de-escalated 
(reduced) accordingly. Your study doctor will watch carefully for any side effects.  
 
Once the recommended dose is determined in the Phase 1 portion, the Phase 2 portion of the 
study will begin. In this part, additional subjects will be enrolled and assigned to the 
recommended dose level determined in Phase 1, described above. The objective for the Phase 2 
portion is to evaluate the effects (good or bad) of ABI-009 in combination with pazopanib in 
treating subjects with advanced nonadipocytic soft-tissue sarcomas. 
 
PROCEDURES 
 
What is involved in the study? 
 
Before you can receive study treatment, the doctor will perform tests to find out whether you can 
participate in the study. 
 
In this study, you will receive ABI-009 given through a vein (intravenous) either once weekly on 
days 1 and 8 of a 21-day cycle, or day 1 only of a 21-day cycle, depending on when you entered 
the study, in addition to daily pazopanib tablets.  
 
If you were initially enrolled to a day 1 and day 8 dosing, you may switch to a day 1 only dosing 
schedule at the study doctor’s discretion, after you complete at least two full cycles of treatment. 
If you do switch a dosing schedule, this change is permanent and you may not switch back. If 
you are initially enrolled on a day 1 only schedule, you may not switch the dosing schedule. 
 
Pazopanib is given in 200 mg oral tablets, so if you are taking a total dose of 400 mg, you would 
have 2 tablets, for 600 mg you would have 3 tablets, and for 800 mg you would have 4 tablets. 
Your study team will let you know what dose of pazopanib you will be taking. 
 
You will be required to record when you take pazopanib each day in a medication diary. The 
medication diary should be returned to your treating physician, along with any leftover pills that 
you did not take. 
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Screening Evaluations 
Screening evaluations will be performed for all subjects to determine study eligibility. These 
evaluations must be obtained within 28 days prior to enrollment. Your baseline imaging 
assessments may be completed on a separate date than the rest of your screening evaluations, in 
order to have them be as close to initiation of protocol therapy as possible. 
The following procedures are to be completed during the screening period: 
• Demographics (including date of birth, sex, race, and ethnicity) 
• Physical examination including medical/cancer history, weight, and assessment of 
your general well-being (called an ECOG score)  
• Prior and concomitant medications and procedures evaluation to include: all 
medications taken within 28 days prior to the date of informed consent 
• Vital signs (temperature, systolic/diastolic blood pressure, respiration rate, and pulse) 
• Electrocardiogram (ECG), a test that measures the electrical activity of your heart  
• Left ventricular ejection fraction (LVEF, by echocardiogram or multigated 
acquisition [MUGA] scan) to measure how well your heart pumps with every 
heartbeat 
• Urinalysis 
• Local Laboratory Assessments including a chemistry panel, complete blood count 
(CBC) with differential, pregnancy test (people who are able to bear children), HIV, 
hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, lipids, and 
thyroid function tests 
• Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan to measure 
the amount of disease in your body 
Treatment Period 
A subject is considered enrolled on study day 1 when the investigational product, ABI-009, is 
first administered. ABI-009 is to be administered after all other protocol-specified pre-dose 
assessments have been performed during each visit that it is required.  
Day 1 Assessment 
The following assessments will be performed on Day 1 of each cycle, unless otherwise specified: 
• Physical examination as per standard of care including assessment of your general 
well-being (called an ECOG score) 
• Height and weight assessment (height to be collected only for Cycle 1 Day 1) 
• Concomitant medication and procedures evaluation  
• Vital signs (temperature, blood pressure, respiration rate, and pulse) 
• Laboratory assessments including a CBC with differential and chemistry panel 
• ECG and lipid panel (every even visit: Cycle 2, Cycle 4, etc.) 
• Urinalysis 
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• Adverse event assessment 
• Rapamycin levels test (only in Phase 1 at Cycle 1 and 2) 
• Observation period of 60 minutes on dosing days for Cycle 1. If there are no infusion 
related reactions in Cycle 1, the observation period may be omitted moving forward. 
If at any time an infusion-related adverse event occurs, the observation period will be 
reinstated.  
All Day 1 evaluations for Cycle 1 may be omitted if screening evaluations are performed within 
72 hours of Cycle 1 Day 1. All Day 1 laboratory assessments and physical examination for Cycle 
2+ may be performed up to 72 hours prior to planned treatment. 
Day 8 Assessment 
The following assessments will be performed on Day 8 of each cycle, unless otherwise specified: 
• Physical examination including assessment of your general well-being (called an 
ECOG score) 
• Weight assessment 
• Vital signs (temperature, blood pressure, respiration rate, and pulse) 
• Concomitant medication and procedures evaluation 
• Laboratory assessments including a CBC with differential and chemistry panel 
• Adverse event assessment 
• Rapamycin levels test (only in Phase 1 at Cycle 1 and Cycle 2) 
All Day 8 laboratory assessments and physical examination may be performed up to 72 hours 
prior to planned treatment. 
Day 15 Assessment 
The following assessments will be performed on Day 15 of Cycle 1 and 2 only.  
• Physical examination including assessment of your general well-being (called an 
ECOG score) 
• Weight assessment 
• Vital signs (temperature, blood pressure, respiration rate, and pulse) 
• Concomitant medication and procedures evaluation 
• Laboratory assessments including a CBC with differential and chemistry panel 
• Adverse event assessment 
• Rapamycin levels (only Phase 1, Cycle 1 and Cycle 2)  
Response Assessment  
CT or MRI scans will be completed at the below time points: 
• Within 4 weeks prior to Cycle 1 Day 1 (as close to Cycle 1 Day 1 as possible - 
screening) 
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• Every 6 weeks from Cycle 1 Day 1 for the first year. Then every 12 weeks until 
disease progression or unacceptable toxicity. End of Treatment Visit CT/MRI should 
be performed only for those subjects that discontinue treatment for a reason other 
than disease progression. 
End of Treatment (EOT) Visit Assessment 
The following procedures will be completed at the EOT Visit: 
• Physical examination including assessment of your general well-being (called an ECOG 
score) 
• Weight assessment 
• Vital signs (temperature, blood pressure, respiration rate, and pulse) 
• Concomitant medication and procedures evaluation 
• Adverse event assessment 
• Urinalysis 
• Laboratory assessments including a CBC with differential, chemistry panel, pregnancy 
test (for people who are able to bear children) 
• Imaging Assessment: CT or MRI is to be performed at the end of study visit only for 
those subjects that discontinue treatment for a reason other than disease progression  
30 Day Follow-Up Visit 
This visit will be completed 30 days after your last dose of ABI-009 or pazopanib, whichever is 
later. We will perform the following procedures at the follow-up visit: 
• Physical examination including assessment of your general well-being (called an ECOG 
score) 
• Weight assessment 
• Vital signs (temperature, blood pressure, respiration rate, temperature) 
• Concomitant medication and procedures evaluation 
• Adverse Event assessment 
• Laboratory assessments including a CBC with differential, chemistry panel, and 
pregnancy test (for people who are able to bear children) 
• Left ventricular ejection fraction (LVEF, by echocardiogram or MUGA scan) 
Rapamycin Trough levels 
Assays for rapamycin will be performed on subjects in the dose-finding (Phase 1) portion of the 
study, who received ABI-009 during Cycle 1 and Cycle 2, to determine trough levels, assessed 
via local lab. The rapamycin sampling schedule is outlined below, based on dosing schedule: 
Day 1 and Day 8 ABI-009 Dosing: 
• Cycle 1 
• 
Cycle 1 Day 8: Prior to treatment (within 15 minutes before your infusion)  
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• 
Cycle 1 Day 15: Anytime  
• Cycle 2 
• 
Cycle 2 Day 1: Prior to treatment (within 15 minutes before your infusion) 
• 
Cycle 2 Day 8: Prior to treatment (within 15 minutes before your infusion) 
• 
Cycle 2 Day 15: Anytime 
 
Day 1 ABI-009 Dosing: 
• Cycle 1 
o Cycle 1 Day 1: End of infusion (within +10 minutes) and Optional 24-hour post 
dose (Day 2, +/- 2 hours) 
o Cycle 1 Day 8: Anytime 
o Cycle 1 Day 15: Anytime 
• Cycle 2 
o Cycle 2 Day 1: Prior to treatment (within 15 minutes before your infusion) 
o Cycle 2 Day 8: Anytime 
o Cycle 2 Day 15: Anytime 
Follow-up Period for Survival and Initiation of Anticancer Therapy  
Post-treatment survival time and any subsequent anticancer therapy information status will be 
monitored approximately every 12 weeks (±3 weeks) from the 30-Day Follow-Up visit or more 
frequently as needed, until death, withdrawal of consent, or the study closes, whichever is 
earliest. This evaluation may be by record review or telephone contact. 
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Schedule of Assessments – Day 1 and Day 8 Dosing 
 Assessments  
Baseline 
Screening 
Treatment Phase 
21-day (3-week) Cycles Days 
End of 
Treatment (EOT) 
Visit 
30 Day Follow-Up 
Visit 
Follow-up every 12 
weeks after the 30-Day 
Follow-Up Visit till 
study closes or 
withdrawal of consent  
1 
8 
15 
Informed Consent 
x 
 
 
 
 
Medical History/Demographics 
x 
 
 
 
 
 
 
HIV and Hepatitis Screening 
x 
 
 
 
 
 
 
Urinalysis 
x 
x 
 
 
x 
 
 
Thyroid Function Tests 
x 
 
 
 
 
 
 
Optional Biomarker 
x 
 
 
 
 
 
 
Pregnancy Test  
x 
 
 
 
x 
x 
 
Cardiac Assessment (Echo or 
MUGA) 
x 
 
 
 
 
x 
 
12-lead electrocardiogram  
x 
x 
 
 
 
 
 
Physical Exam (including vital 
signs, height [C1D1], and 
weight) 
x 
x 
x 
x 
x 
 
x 
Blood Chemistry and CBC 
x 
x 
x 
x 
x 
x 
Lipid Panel  
x 
x 
 
 
 
 
 
Rapamycin Level Collection 
 
x 
x 
x 
 
 
ECOG Performance Status 
x 
x 
x 
x 
x 
x 
 
CT/MRI Disease Assessment  
x 
Every 6 weeks for the first year, then every 12 weeks  
ABI-009 infusion  
 
x 
x 
 
 
 
Pazopanib  
 
Daily 
Adverse Event Assessment and 
Concomitant Medication 
Review 
Continuous from the signing of the informed consent to 30 days after last study drug 
Long-Term Follow Up 
 
x 
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Schedule of Assessments – Day 1 Dosing 
 Assessments  
Baseline 
Screening 
Treatment Phase 
21-day (3-week) Cycles Days 
End of 
Treatment (EOT) 
Visit 
30 Day Follow-Up 
Visit 
Follow-up every 12 
weeks after the 30-Day 
Follow-Up Visit till 
study closes or 
withdrawal of consent  
1 
8 
15 
Informed Consent 
x 
 
 
 
 
 
 
Medical History/Demographics 
x 
 
 
 
 
HIV and Hepatitis Screening 
x 
 
 
 
 
 
 
Urinalysis 
x 
x 
 
 
x 
 
 
Thyroid Function Tests 
x 
 
 
 
 
 
 
Optional Biomarker 
x 
 
 
 
 
 
 
Pregnancy Test  
x 
 
 
 
x 
x 
Cardiac Assessment (Echo or 
MUGA) 
x 
 
 
 
 
x 
 
12-lead electrocardiogram  
x 
x 
 
 
 
Physical Exam (including vital 
signs, height [C1D1], and 
weight) 
x 
x 
x 
x 
x 
 
x 
 
Blood Chemistry and CBC 
x 
x 
x 
x 
x 
x 
Lipid Panel  
x 
x 
 
 
 
 
Rapamycin Level Collection 
 
x 
x 
x 
 
 
ECOG Performance Status 
x 
x 
x 
x 
x 
x 
 
CT/MRI Disease Assessment  
x 
Every 6 weeks for the first year, then every 12 weeks  
ABI-009 infusion  
 
x 
 
 
Pazopanib  
 
Daily 
 
 
Adverse Event Assessment and 
Concomitant Medication 
Review 
Continuous from the signing of the informed consent to 30 days after last study drug 
Long-Term Follow Up 
 
x 
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How many subjects will take part in the study? 
 
Up to 82 subjects will be entered in this study. 
 
How long will you be in the study? 
 
You may be in the study for as long as your cancer responds to the study treatment, until you 
experience an unacceptable side effect, you no longer wish to participate, or your study doctor 
feels that it is in your best interest to stop your participation. You may stop participating at any 
time without penalty or loss of benefits. However, if you decide to stop participating in the study, 
we encourage you to talk to your study doctor and your regular doctor first. 
 
RISKS, STRESSES, AND DISCOMFORTS 
 
There may be risks to you if you are in this study. You may have side effects while you are in the 
study. You will be carefully and regularly monitored by the study doctor for any problems. There 
may be risks or side effects of the study drug that are unknown at this time. You should tell the 
study doctor/staff about anything that is bothering you or any side effect you have, even if you 
do not think they are related to the study drug.  
 
ABI-009 Risks  
 
The following is a list of the most medically significant or most common side effects reported in 
previous or ongoing studies and considered to be related to ABI-009. In some cases, side effects 
can be serious, long-lasting, or permanent. Some side effects may go away soon after you stop 
the study treatment and some may take time to resolve. The study doctor may alter the dosage 
regimen of ABI-009 or give you medicines to help lessen the side effects. This is not a complete 
list of all side effects that may occur. For more information about risks and side effects, please 
ask the study doctor.  
 
Very common (>10% or more chance that this will happen, based on a previous study with 
ABI-009): 
• Low blood platelets (thrombocytopenia, can increase risks of bleeding) 
• Low blood hemoglobin (anemia, which can cause fatigue and may require blood 
transfusion)  
• Low white blood cell count (neutropenia, can increase risk of infection) 
• Low potassium levels (hypokalemia) 
• Elevated lipid levels (hypertriglyceridemia) 
• Elevated cholesterol (hypercholesterolemia)  
• Elevated blood glucose (hyperglycemia)  
• Diarrhea 
• Nausea 
• Vomiting 
• Inflammation of the mucus membrane (mucosal inflammation) 
• Fatigue  
• Decreased liver function (elevated aspartate aminotransferase [AST] levels) 
• Decreased liver function (elevated alanine transaminase [ALT] levels) 
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• Weight decrease 
• Rash 
• Dermatitis (eczema, skin inflammation) 
• Headache 
• Infection (including candidiasis [yeast], cellulitis [skin], folliculitis [hair follicles], 
urinary tract) 
• Decreased appetite (anorexia) 
 
Common (between a 1% to less than 10% chance that this will happen): 
• Edema (swelling) 
• Constipation 
• Altered sense of taste (dysgeusia) 
• Low blood phosphate levels (hypophosphatemia) 
• Increased amylase levels (may indicate damage to the pancreas) 
• Increased lipase levels (may indicate damage to the pancreas) 
• Low magnesium levels (hypomagnesemia) 
• Decreased liver function 
• Elevated creatinine levels, which may be related to kidney damage 
• Elevated potassium levels (hyperkalemia) 
• Protein in the urine (proteinuria) 
• Low lymphocyte count 
• Acid reflux 
• Nasal congestion 
• Abdominal cramping 
• Cough 
• Labored breathing (dyspnea) 
• Fast heart rate (tachycardia) 
• Lung tissue inflammation (pneumonitis) 
• Insomnia (trouble sleeping) 
• Nose bleeds (epistaxis) 
• Dry mouth 
• Hair loss (alopecia) 
• Nail disorder 
• Muscle pain (myalgia)  
• High blood pressure (hypertension) 
• Fever 
• Acute kidney injury 
• Failure to thrive 
• Inflammation of the stomach and colon (including enteritis, ileitis, colitis) 
• Weakness, numbness, or tingling in hand and feet (neuropathy) 
• Dizziness (vertigo) 
• Unbalanced feeling (ataxia) 
• Chest pain (non-cardiac) 
• Confusion 
• Speaking disorder that affects a person’s ability to communicate (dysphasia) 
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• Change in voice (dysphonia) 
• Damage or disease that affects the brain (encephalopathy) 
• Frequent urination 
• Feeling of discomfort (malaise) 
• Nervousness 
• Sore throat 
• Toothache 
 
Uncommon (between a 0.1 to less than 1% chance that this will happen):  
• Alkaline phosphate elevation (liver enzyme) 
• Decreased levels of red blood cells, white blood cells and platelets (pancytopenia)  
• Alkalosis (an imbalance of pH in the blood) 
• Decrease of blood albumin (a protein in the blood) 
• Neutrophil count increase 
• Double vision (diplopia) 
• Decrease in a type of white blood cell (leukopenia) 
• Inflammation of the esophagus (esophagitis) 
• Inflammation of the stomach (gastritis) 
• Hemorrhoids 
• Rectum bleeding 
• Swelling in the scrotum (hydrocele) 
• Swelling around the eyes (orbital edema) 
• Jittery 
• Limb discomfort 
• Swelling caused by inflammation, commonly with tumors (neoplasm swelling) 
• Tingling or prickling sensation (paresthesia) 
• Pink eye 
• A certain type of rash caused by small blood vessels leaking (purpura)  
• Discharge from nose (rhinorrhea) 
• Scar pain 
• Sinus drainage 
• Skin disorder 
• Skin lesion 
• Sore skin 
• Non-cancerous mass of tissue on the tongue (benign tongue neoplasm) 
• Vitamin D deficiency 
• Weakness 
• Underactive thyroid (hypothyroidism) 
• Dehydration 
• Low sodium levels (hyponatremia)  
• Infusion site pain 
• Thirst 
• Suicidal ideas 
• Transient chest pain (acute coronary syndrome) 
• Painful or difficult urination (dysuria) 
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In at least one case, a subject receiving ABI-009 developed kidney failure requiring lifelong 
dialysis. This might have been due to treatment with ABI-009, but this is not clear as other 
possible causes also existed in that subject.  
 
ABI-009 contains human serum albumin. Human serum albumin presents a small risk of allergic 
or anaphylactic type reactions. Severe allergic reactions can be life threatening. Tell your doctor if 
you have ever had a reaction to human serum albumin. 
 
Human serum albumin is a derivative of human blood. Based on effective donor screening and 
product manufacturing processes, it carries an extremely remote risk for transmission of viral 
diseases and variant Creutzfeldt-Jakob disease (vCJD). There is a theoretical risk for 
transmission of Creutzfeldt-Jakob disease (CJD), but if that risk exists, the risk of transmission 
would also be considered extremely remote. No cases of transmission of viral diseases, CJD, or 
vCJD have ever been identified for licensed albumin. 
 
Long term use of Sirolimus, also known as rapamycin, is potentially associated with testicular 
toxicities, pulmonary toxicities (pneumonitis), and increased risk for cancer. 
 
Pazopanib Risks  
 
Studies in animals indicate that pazopanib may slow or stop bone growth. There is a possibility 
that pazopanib may affect bone growth in children, adolescents and young adults who are still 
growing. 
 
Very common, in 100 people receiving pazopanib, more than 20 and up to 100 may have: 
• Diarrhea  
• Nausea  
• Vomiting 
• Tiredness (fatigue) 
• Bruising, bleeding 
• Infection, especially when white blood cell count is low 
• Loss of appetite 
• Change in hair color 
• High blood pressure which may cause blurred vision 
• Tumor pain 
• Musculoskeletal pain 
• Changes in taste 
• Weight loss 
• Dizziness, headache 
• Gastrointestinal pain 
• Shortness of breath 
• Decreased platelet count 
• Decrease in white blood cells (leukocytes, neutrophils, and lymphocytes) which may 
lead to greater risk of infection 
• Elevated liver enzymes 
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• Increased blood sugar 
• Increased bilirubin levels 
• Decrease in electrolyte levels in the blood (magnesium, sodium, phosphorus) 
• Anemia which may require blood transfusion 
 
Common, in 100 people receiving pazopanib, from 4 to 20 may have: 
• Abnormal heartbeat 
• Decreased blood sugar 
• Pain 
• Constipation, heartburn 
• Sore in the mouth which may cause difficulty swallowing 
• Swelling of arms, legs 
• Fever 
• Dehydration 
• Cough 
• Internal bleeding which may cause coughing up blood, black tarry stool, blood in 
vomit, or blood in urine 
• Bleeding from multiple sites including the nose or vagina 
• Hair loss, rash, skin changes 
• Redness, pain, or peeling of palms and soles 
 
Rare and Serious, in 100 people receiving pazopanib, 3 or fewer may have: 
• Anemia 
• Blood clot which may cause confusion, paralysis, swelling, pain, or shortness of 
breath 
• Heart failure, heart attack which may cause shortness of breath, swelling of ankles, 
and tiredness 
• Bleeding of the eye which may cause blurred vision with a chance of blindness 
• A tear or hole in internal organs that may require surgery 
• Liver damage which may cause yellowing of eyes and skin, swelling 
• Liver failure 
• Change in heart function 
• Bleeding in the brain 
• Brain damage which may cause headache, seizure, blindness (also known as 
Reversible Posterior Leukoencephalopathy Syndrome) 
• Kidney damage which may require dialysis 
• Damage to the lungs which may cause shortness of breath 
• Collapsed lung (pneumothorax) where air may get trapped in the space between your 
lung and chest wall. This may cause you to have shortness of breath, pain, and may 
require emergency evaluation and treatment. 
 
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Side effects from testing: 
 
Taking blood: may cause bruising at the place where the needle goes into the skin. Fainting, and 
in rare cases, infection may occur. If you have a central venous catheter, the blood sample may 
be taken from there instead of having a needle inserted into a separate vein. 
 
Electrocardiogram (ECG): patches may cause a skin reaction such as redness or itching. You 
may also experience localized skin discomforts and/or hair loss associated with the placement of 
ECG patches. 
 
Tumor biopsy: There are small risks associated with percutaneous (needle puncture) biopsies, 
these risks include bruising (scarring is usually minimal), infection and hematoma (pooling of 
blood trapped in the biopsy area). These risks are small, and even when one or more 
complications do occur they usually resolve within a brief period of time with the proper medical 
attention. 
 
Echocardiogram (Echo): Echocardiograms are very safe. The gel may feel cold when it is first 
places. Some people with sensitive skin can develop a rash from the gel. 
 
Radiation Risks 
 
There are some risks from the CT scans used to watch your tumor status and health. These scans 
will expose you to radiation. A MUGA (multigated acquisition scan) takes images of the beating 
heart to see how well your heart is pumping blood. A small amount of radioactive material will 
be injected into your vein and bind to your red blood cells. If you live in the US, you receive 
about 3 millisieverts of radiation each year. It comes from space and the earth around you. This 
is called “background radiation.” A “millisievert” (mSv) is a unit used to measure radiation dose. 
The radiation dose to your whole body from each of your scans will be about as follows: 
 
• 
CT scan of the chest: 7 mSv 
• 
CT scan of the abdomen: 8 mSv 
• 
CT scan of the pelvis: 6 mSv 
• 
CT biopsy: 5 mSv 
• 
MUGA scan: 8 mSv 
 
The usual lifetime risk of getting cancer is 42%. For every 10 mSv you receive, your risk will 
increase 0.1%. If you have more procedures that expose you to radiation, your risk will go up. 
You may need to have other x-rays or scans for your care. Your doctors will explain the risks of 
the other x-rays or scans. 
 
Reproductive risks 
 
Taking ABI-009 in combination with pazopanib may involve unknown risks to an embryo fetus 
(unborn baby) or nursing infant. Therefore, you could not join this study if you are pregnant, if 
you are planning to become pregnant, or if you are breast-feeding.  
 
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If you join this study, you would have to use an effective method of birth control from the time 
this form is signed until at least 3 months after the last dose of ABI-009 in combination with 
pazopanib. If you are already using a method of birth control, you will need to check with the 
study doctor or a member of the study staff to make sure it is acceptable.  
 
If you became pregnant after joining this study, you will need to notify the study doctor 
immediately. You would no longer be able to participate in this study. If this happens, you would 
receive counseling and follow up throughout the pregnancy and for about 6 months after the 
child is born.  
 
The effects of fathering a child are also unknown. Men who join this study must also agree to use 
one or more forms of effective and acceptable birth control from the time this form is signed 
until at least 3 months after the last dose of ABI-009 in combination with pazopanib. 
 
NEW FINDINGS 
 
During the study we may learn new information you need to know. For example, some 
information may affect your health or well-being. Other information may make you change your 
mind about being in this study. If we learn these kinds of information, we will tell you. 
 
BENEFITS 
 
You may or may not receive any benefit from being in this study. It is possible that you may get 
better, stay the same, or get worse. If you take part in this study, other people with soft tissue 
sarcoma may be helped. 
 
You may receive information from physical examinations, laboratory tests, or other testing that 
is done in this study but these tests may not have any impact on your health. 
 
Information obtained from this study will benefit the sponsor and funding source of the study 
and may benefit patients in the future.  
 
COSTS 
 
The funding source of this study, Aadi Bioscience Inc., will provide the ABI-009 study drug to 
you free of charge. Pazopanib will not be provided by Aadi and will be billed to you or your 
insurance as a standard of care medication. Study related medical examinations and laboratory 
tests that are not part of your routine care for your condition will be provided at no charge. 
Administration of IV drug is considered standard of care and will be billed to your insurance. 
You may have to pay for some expenses related to this study, such as transportation to the study 
site, parking, meals, etc. Aadi pays the study doctor to conduct the study and covers the cost of 
study-related tests and procedures. 
 
You or your insurance company will be billed in the usual manner for examinations, testing, and 
treatments that are considered routine and required for the management of your cancer. Some 
examples of standard procedures include routine laboratory blood tests, x-rays, CT scans, 
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surgeries, blood transfusions, physicians’ charges, IV drug administration, and routine medical 
care. 
 
Ask your study doctor to discuss the costs that will or will not be covered by Aadi. This 
discussion should include the costs of treating side effects. Examples of medications you could 
possibly require in addition to the study medications include antibiotics or other medications to 
manage side effects of treatment. Otherwise, you might have unexpected expenses from being in 
this study. Your health insurance company might not pay for these charges because you are in a 
research study. You are responsible for charges your insurance company does not pay. 
 
If you are on a Medicare Advantage Plan, please check with your plan regarding coverage as you 
may be responsible for certain costs. 
 
PAYMENT FOR PARTICIPATION 
 
You will not be paid for being in the study or for the use of your samples or any information 
obtained from your samples or medical information. Taking part in this study does not make you 
an employee of the sponsor or Aadi. You will not be compensated if a commercial 
pharmaceutical or diagnostic product(s) is developed through the use of your samples or medical 
information collected during this study.  
 
ALTERNATIVE TREATMENT 
 
Instead of taking part in this study, you may choose to receive standard treatment with other 
drugs or therapies that may be used to treat advanced cancers. Some of these include 
chemotherapy, radiation therapy, hormonal therapy, experimental therapy, or surgery. You could 
also participate in another research study or choose no treatment at all. The risks and benefits of 
these other treatments will be explained to you by your doctor. The study doctor will answer any 
questions you have about these other treatments. 
 
If you decide that you don’t want any more active treatment, one of your options is called 
“comfort care.” Comfort care includes pain medication and other support. It aims to maintain 
your comfort and dignity rather than cure disease. Usually this care can be provided at home. If 
you think you might prefer comfort care, please discuss this with your family, friends and your 
doctor. 
 
VOLUNTARY PARTICIPATION AND WITHDRAWAL 
 
Taking part in this study is voluntary. You do not have to be in this research study. You can 
agree to be in the study now and change your mind later. Your decision will not affect your 
regular care or the benefits to which you are otherwise entitled. 
 
You can decide to stop at any time. Tell your study doctor if you are thinking about stopping or 
decide to stop. Your study doctor will tell you how to stop safely. 
 
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It is important to tell your study doctor if you are thinking about leaving the study. This is so you 
and your study doctor can discuss what follow-up care, testing, and other treatments could be 
most helpful for you. 
 
If you want to stop participating in the study and you withdraw after you have started, the study 
staff and the study doctor will stop collecting your health information. Although they will stop 
collecting new information about you, they will need to use the information they have already 
collected to evaluate the study results. If you start the study and then withdraw, you will not be 
able to continue to participate in the study or receive any treatment as part of the study. This is 
because the study staff and/or the study doctor would not be able to collect the information 
needed to evaluate the study drug. 
 
The study team or the funding source may take you off this study at any time without your 
consent. There are other reasons that you may be removed from the study including: 
 
• Your study doctor believes it is in your best interest, 
• You need treatment that is not allowed in the study, 
• You do not follow the study requirements, 
• If the study is stopped by the funding source for any reason, 
• You do not consent to continue in the study after being told of changes in the research 
that may affect you or, 
• For any other reason. 
 
If the study doctor or funding source ends your participation, or you decide not to continue, you 
will be asked to return to the study doctor or study site to have the final clinical evaluations and 
laboratory tests done. 
 
CONFIDENTIALITY AND PRIVACY OF STUDY INFORMATION 
 
If you join this study, some people or organizations might need to look at your medical records 
and research records for quality assurance or data analysis. They include:  
• Researchers involved with this study 
• Institutional Review Boards (IRB), including the Fred Hutchinson Cancer Research 
Center IRB. An IRB is a group that reviews the study to protect the rights and welfare of 
research participants  
• Fred Hutchinson Cancer Research Center, University of Washington, Seattle Children’s, 
and Seattle Cancer Care Alliance 
• Office for Human Research Protections, Food and Drug Administration, and other 
regulatory agencies as required  
• National Cancer Institute 
• US National Institutes of Health 
• Aadi Bioscience, Inc., the funding source for this study, and their agents 
 
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We will do our best to keep personal information confidential. But we cannot guarantee total 
confidentiality. Personal information may be given out if required by law. For example, 
workplace safety rules may require health workers to contact you about lab tests. Or a court may 
order study information to be disclosed. Such cases are rare. 
 
We will not use personal information in any reports about this study, such as journal articles or 
presentations at scientific meetings. 
 
If you join this study, information about your participation would be made part of your permanent 
medical record. This information would include a copy of this consent form. If an insurance 
company or employer or anyone else were authorized to see your medical record, they would see a 
copy of this consent form. 
How is my genetic information protected? 
 
A federal law called the Genetic Information Nondiscrimination Act (GINA) helps protect 
genetic information about people who join research studies.  
 
GINA restricts access to genetic information so that it cannot be used for health insurance 
coverage decisions. GINA prevent health insurance companies or group health plans from:  
 
• 
Asking for genetic information obtained in research studies, or 
• 
Using genetic information when making decisions regarding your eligibility or 
premiums  
GINA does not help or protect against genetic discrimination by companies that sell life, 
disability or long-term care insurance. 
 
COMPENSATION FOR INJURY 
 
For a life-threatening problem, call 911 right away or seek help immediately. Contact your study 
doctor when the medical emergency is over or as soon as you can.   
 
For all other medical problems or illness related to this research, immediately contact Dr. Lee 
Cranmer (206-606-7439). They will treat you or refer you for treatment. Aadi Biosciences, Inc. 
will pay for medical expenses relating to your care and treatment of any side effect, adverse 
reaction, illness or injury resulting from participation in this study provided that the study has 
been conducted properly. There are no funds to pay you for loss of a job, or other costs to you or 
your family. State or national law may give you rights to seek payment for some of these 
expenses. You do not waive any right to seek payment by signing this consent form. 
 
You or your insurer will be billed for treatment of problems or complications that result from 
your condition or from standard clinical care. 
 
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YOUR RESPONSIBILITIES 
 
If you join this study, you would have some responsibilities:  
• Follow the schedule of study visits and procedures.  
• Take study medications as directed.  
• Prevent pregnancy.  
• Tell us about side effects.  
 
FOR MORE INFORMATION 
 
If you have questions or concerns about this study, you could talk to your doctor anytime. Other 
people you could talk to are listed below. 
 
If you have questions about: 
 
Call: 
This study (including complaints 
and requests for information) 
 
206-606-7439 Dr. Lee Cranmer 
206-606-6425 Roxanne Moore, Assistant Director 
If you get sick or hurt in this 
study 
 
206-606-7439 Dr. Lee Cranmer 
206-598-6190 UW operator and ask to page the oncology 
fellow on call. 
Your rights as a research 
participant 
 
206-667-5900 or email irodirector@fredhutch.org 
(Director of Institutional Review Office, Fred 
Hutchinson Cancer Research Center) 
206-543-0098 (Human Subjects Division, University of 
Washington) 
Your bills and health insurance 
coverage 
 
The financial services department at Seattle Cancer Care 
Alliance at 206-606-6226 
 
Emergency number (24 hours): 206-598-6190 
 
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You may call the National Cancer Institute (NCI) Cancer Information Service at 1-800-422-6237 
or TTY 1-800-332-8615. For NCI’s general information about cancer, go to 
http://cancer.gov/cancerinfo/. This website provides general information on cancer types, 
treatments, and coping with cancer.   
 
You may also visit one of the websites listed below: 
For NCI’s clinical trials information, go to: http://cancer.gov/clinicaltrials/. This website 
provides general information on what clinical trials are and allows searching for specific 
clinical trials. 
 
A description of this clinical trial will be available on http://www.clinicaltrials.gov/ as  
required by U.S. law. This website will not include information that can identify you. At  
most, the website will include a summary of the results. You can search this website at  
any time.  
 
When visiting either of these websites, use the search terms “sarcoma, pazopanib, ABI-
009” to locate information on this trial. 
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Biosamples 
There is an optional pre-treatment tissue collection for biomarker analysis; either archival tissue 
or a fresh biopsy sample can be used. If you do not have left over tissue from a previous surgery 
or biopsy, you may agree to undergo a fresh tumor biopsy if it is clinically feasible and there is 
no undue risk to you. The risks and side effects for a fine needle aspiration or biopsy are: 
 
Likely (21-100 subjects out of 100) and Not Serious 
• Inflammation (redness and swelling) of the area of the biopsy 
• Pain 
• Bruising 
• Bleeding at the site of puncture 
 
Less Likely (Approximately 5-20 subjects out of 100) and Not Serious 
• Faintness 
 
Rare but Serious (Less than 5 subjects out of 100) 
• Infection at the biopsy site 
 
These tests will not tell if your disease is inherited and will not involve members of your family. 
The samples will be analyzed for the purposes of the study. They will be stored in a secure 
storage facility so that we can re-test them or conduct additional analyses on them in order to 
follow up the safety of the study medication or to better understand the course of the disease or 
the disease’s response to the study medication. The results of these tests may help us improve the 
diagnosis and the treatment of the disease in the future. 
 
All the samples will be processed without your name, ID number, or any other information 
which allows your identification. They will be labeled with a code. Only authorized people will 
have access to the list of names which links your name to the code. Only authorized members of 
the study doctor’s staff or Aadi’s personnel or third parties, which assist Aadi with the conduct 
of the study (e.g., laboratories), will have access to the samples. 
 
The samples will be destroyed 20 years after completion of the study or earlier if required by 
law. If you leave the study or after your participation has been stopped for any other reason you 
may ask for all samples that were collected from you to be destroyed or sent back to you. If you 
decide to withdraw your consent, you can request that all left-over identifiable samples be 
destroyed to prevent future testing. If you make this decision, you must notify the study doctor in 
writing. Data collected from analyses already completed cannot be withdrawn. 
 
Please read the sentence below and think about your choice. After reading the sentence, check 
either “Yes” or “No” box and initial next to your choice. If you have any questions, please 
contact your study doctor. 
 
My remaining tumor tissue from a previous surgery or biopsy, or tissue from a fresh 
tumor biopsy may be stored and used for analysis.  
 
 YES ___________ 
 
 
 NO _____________ 
 Initials 
 
 
 
 
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SUBJECT’S STATEMENT 
 
I have read the information in this consent form (or it has been read to me). All my questions 
about the study and my part in it have been answered. I freely consent to take part in this 
research study. If I sign this form I will not lose any of the legal rights that I would otherwise 
have as a subject in a research study. 
 
CONSENT SIGNATURE: 
 
 
_______________________________________ 
Subject Name (printed):  
 
 
________________________________________ 
__________________ 
Signature of Subject (18 years and older) 
Date 
 
 
RESEARCHER’S STATEMENT 
 
I confirm that the research study was thoroughly explained to the subject. I reviewed the consent 
form with the subject and answered the subject’s questions. The subject appeared to have 
understood the information and was able to answer the following questions correctly: 
 
1. What is the purpose of this study? 
2. If you decide to be in the study, what will you be asked to do? 
3. What is the possible benefit of participating in this study? 
4. What are the possible risks of participating in this study?  
5. If you decide not to participate in this study, what options do you have? 
6. Will participating in this study cost you anything? If so, what will you have to pay for? 
7. Do you have to be in this study? 
8. If you decide to be in the study, can you leave the study when you want to? 
 
 
________________________________________ 
 
Printed Name of Person Conducting the 
 
Informed Consent Discussion 
 
 
________________________________________ 
__________________ 
Signature of Person Conducting the 
Date 
Informed Consent Discussion 
 
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WITNESS OR INTERPRETER 
If you served as an interpreter or witness during the consent process, sign below to indicate you 
attest to the accuracy of the presentation to the participant and the apparent understanding of the 
research by the participant. 
 
 
 
 
 
 
 
 
Printed Name 
 
Signature 
 
Date 
 
 
Copies to: Researcher’s file 
 
Subject 
 
Subject’s medical record (if applicable) 
 
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