Clinical trial NCT03670030
Conditions: Neuroendocrine Tumors
Sponsor: Robert Ramirez
Start date: 2018-11-05; Completion date: 2021-02-26
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to determine whether ABI-009 will make advanced, malignant neuroendocrine tumor(s) of the lung, gastrointestinal tract and/or pancreas that cannot be removed by surgery smaller and slow the spread of your cancer in patients who have progressed or been intolerant to everolimus. All eligible participants will receive ABI-009, the study drug.

Detailed description:
ABI-009, human albumin-bound rapamycin, is an experimental drug. "Experimental" means that the drug has not been approved by the Food and Drug Administration (FDA).

Rapamycin, the active part of the drug, inhibits a biological pathway (mTOR) that certain cancers use to grow. Rapamycin and similar types of drugs have been used in many other tumors, including advanced renal cell carcinoma. A standard mTOR inhibitor used in neuroendocrine tumors is everolimus. The human albumin component of ABI-009 may allow rapamycin to reach cancer cells more effectively.

ABI-009 has not been approved for the treatment of advanced, malignant neuroendocrine tumors of the lung, gastrointestinal tract and/or pancreas. The information from this study might help us identify if ABI-009 is safe and effective in this disease.

Arms: arm 1: In this study, you will receive ABI-009 given through a vein (intravenous) once weekly for 2 weeks (on days 1 and 8) followed by a week of rest in a 21-day cycle.
Interventions: intervention 1: ABI-009
Intervention descriptions: intervention 1: rapamycin protein-bound nanoparticles for injectable suspension (albumin bound)

Protocol documents:
ICF_001.pdf: 
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OCHSNER CLINIC FOUNDATION
RESEARCH INFORMED CONSENT
A pilot phase 2 study of albumin-bound sirolimus nanoparticles, ABI-009, in 
patients with metastatic, unresectable, low or intermediate grade neuroendocrine 
tumors of the lung or gastroenteropancreatic system
Principal Investigator: Robert Ramirez, DO
Contact Information: Ochsner Clinic Foundation
    1514 Jefferson Highway
    New Orleans, LA 70121
    504-842-3910
Alternate Study Contact: Marc Matrana, MD
           504-842-3910 or 1-800-956-6247
Sponsor’s Protocol # NET-001
Sponsor name: Robert Ramirez, DO funded by Aadi Bioscience, Inc.
You have been invited to participate in a research study. The doctors and staff at 
Ochsner study the nature of disease and attempt to improve methods of diagnosis and 
treatment.  This is called clinical research.  Understanding this study’s risks and benefits 
will allow you to make an informed judgment about whether to be part of it.  This 
process is called informed consent.
This consent form may contain words that you do not understand.  Please ask the study 
doctor 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.
Participating in a research study is not the same as getting regular medical care.  The 
purpose of regular medical care is to improve your health.  The purpose of a research 
study is to gather information.  Being in this study does not replace your regular medical 
care.
PURPOSE
You are being asked to take part in this study because you have been diagnosed with 
an advanced, malignant neuroendocrine tumor of the lung, gastrointestinal tract and/or 
pancreas that cannot be removed by surgery.
The purpose of this study is to determine whether ABI-009 (study drug) will make your 
cancer smaller and slow the spread of your cancer. 
ABI-009, human albumin-bound sirolimus, is an experimental drug. “Experimental” 
means that the drug has not been approved by the Food and Drug Administration 
(FDA).
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Sirolimus, the active part of the drug, prevents a biological pathway that is out of control 
in neuroendocrine cancer cells. Sirolimus 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 sirolimus to reach cancer cells more effectively.
ABI-009 has not been approved for the treatment of advanced, malignant 
neuroendocrine tumors of the lung, gastrointestinal tract and/or pancreas.  There are no 
drugs currently approved for this.  The information from this study might help us identify 
if ABI-009 is safe and effective in this disease.
LENGTH OF STUDY AND NUMBER OF PARTICIPANTS
You will remain on study drug until your disease gets worse or you or your doctor 
decide that the treatment is not right for you. After your last dose of study drug, you will 
be followed by phone every 3 months until you start a new treatment, withdraw consent, 
or the study closes.  This study will only take place at Ochsner and will enroll 10 
subjects. 
PROCEDURE
Before you can receive study drug, 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) once weekly 
for 2 weeks (on days 1 and 8) followed by a week of rest in a 21-day cycle.
If you are found to be eligible by your study doctor, you will receive therapy within 
28 days. You will be given this study drug until your disease progresses or depending 
on how well you tolerate the therapy. After you are finished receiving the study drug, 
you will be followed by phone calls every 3 months, or more frequently if needed, to see 
how you are doing, and to collect information on any new anti-cancer treatment you 
may be taking. Your study doctor or staff will tell you when and where you will go for 
treatment, tests, exams, and procedures.
The study doctor or his/her staff will perform the following procedures during the study:
Screening (≤ 28 days prior to the first dose of study drug)

Demographics (date of birth, sex, race, and ethnicity) 

Medical/cancer history, record medications you are taking, and record 
procedures you have had

Physical examination, performance status assessment

Vital signs (e.g., blood pressure, pulse, respiration rate, temperature, height, 
weight)

Blood Tests: chemistry, complete blood count (CBC), differential, platelet 
count, pregnancy test for women of childbearing potential, fasting lipids and 
cholesterol

CT scans (or MRI, if CT is not possible) 

Adverse events
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Day 1 of every cycle (unless otherwise stated)

Physical examination 

Vital signs (e.g., blood pressure, pulse, respiration rate, temperature, weight)

Record medications you are taking and procedures you have had

Blood samples including complete blood count (CBC), differential, and clinical 
chemistry panel

Blood sample for fasting lipids and cholesterol (every even cycle)

Blood sample for sirolimus levels which show the amount of study drug in your 
body (cycle 2 only)

ECOG performance status – an assessment your doctor makes about your 
disease to help them treat your cancer

Adverse events assessment
Day 8 of every cycle (unless otherwise stated)

Physical evaluation

Vital signs (e.g., blood pressure, pulse, respiration rate, temperature, weight)

Record medications you are taking and procedures you have had

Blood samples including complete blood count (CBC), differential, and clinical 
chemistry panel 

Blood sample for sirolimus levels which show the amount of study drug in your 
body (cycle 1 and cycle 2 only)

Adverse event assessment
Day 15 of cycle 1 and cycle 2 (these may be performed as needed on Day 15 of 
other cycles after cycle 1 and cycle 2)

Physical evaluation

Vital signs (e.g., blood pressure, pulse, respiration rate, temperature, weight)

Record medications you are taking and procedures you have had

Blood samples including complete blood count (CBC), differential, and clinical 
chemistry panel 

Blood sample for sirolimus levels which show the amount of study drug in your 
body (cycle 1 and cycle 2 only)

Adverse event assessment
End of Treatment Visit
The EOT Visit is a safety follow-up visit that is to be performed within 1 month after the 
last dose of ABI-009.

Physical evaluation including performance status assessment

Vital signs (e.g., blood pressure, pulse, respiration rate, temperature, weight)
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
Record medications you are taking and procedures you have had

Urine pregnancy test for women of childbearing potential

Blood samples including complete blood count (CBC), differential, and clinical 
chemistry panel 
Response Assessment
Tumor response will be assessed by CT (or MRI, if CT is not possible) scan of the chest, 
abdomen, and pelvis. 
CT or MRI scans to be performed at the following frequency:

screening

followed by every 9 weeks after the first dose of study drug for the first year; 
then every 12 weeks until disease progression or unacceptable toxicity. End of 
Treatment Visit CT (or 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. 
Follow-up Period
Post-treatment survival time will be recorded about every 12 weeks (±3 weeks) from the 
end of treatment visit or more frequently as needed. This information will be recorded until 
death, withdrawal of consent, new anticancer therapy, or when the study closes, 
whichever is earliest.  This evaluation may be by medical record review and/or telephone 
contact. 
RISKS
Risks from ABI-009, the Study Drug 
You may have side effects while you are in the study, but you will be carefully checked 
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 effects you have, even if you do not think they are 
related to the study drug. 
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 or long-lasting. Some side effects go away 
soon after you stop the study drug/therapy, 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.  
Based on ABI-009 Investigator Brochure v7.0, the most common to uncommon side 
effects as follows:
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Very common (>10% or more chance that this will happen, based on a previous study 
with ABI-009):

low blood platelets (thrombocytopenia)

low blood hemoglobin (anemia) 

low white blood cell count (neutropenia)

low potassium levels (hypokalemia)

elevated lipid levels (hypertriglyceridemia)

elevated cholesterol (hypercholesterolemia)

elevated blood glucose (hyperglycemia)

diarrhea

nausea

vomiting

constipation

inflammation of the mucus membrane (mucosal inflammation)

fatigue 

decreased liver function (elevated AST)

weight decrease

rash

dermatitis

headache

infection (including candidiasis, cellulitis, folliculitis, urinary tract)

decreased appetite (anorexia)

altered sense of taste (dysgeusia)

edema
Common (between a 1% to less than 10% chance that this will happen):

low blood phosphate levels (hypophosphatemia)

increased amylase

increased lipase

low magnesium levels (hypomagnesemia)

decreased liver function (elevated ALT)

elevated creatinine levels

low lymphocyte count 

cough

labored breathing (dyspnea)

pneumonitis

insomnia

epistaxis

dry mouth

hair loss (alopecia)

nail disorder

muscle pain (myalgia)
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
hypertension

fever 

acute kidney injury

failure to thrive

enteritis (including ileitis, colitis) 

weakness, numbness, or tingling in hand and feet (neuropathy)

vertigo (dizziness)
Uncommon (between a 0.1 to less than 1% chance that this will happen): 

elevated potassium levels (hyperkalemia)

low sodium levels (hyponatremia)

low blood albumin levels

pancytopenia

alkalosis

hypothyroidism

dehydration

odynophagia

lip blister

infusion site pain

thirst

suicidal ideas

disorientations

fast heart rate (tachycardia)

transient chest pain (acute coronary syndrome)
ABI-009 contains human serum albumin. Human serum albumin presents a small risk of 
allergic or anaphylactic type reactions. 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 
actually 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.
Sirolimus, also known as rapamycin, is known to be associated with the following 
potential risks after long term use: 

testicular toxicities 

pulmonary toxicities (pneumonitis)

increased risk for cancer
Risks from the Study Procedures 
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Risk with Intravenous (IV) Drug Administration:  Temporary irritation and bruising 
may occur at the infusion site.  There may also be discomfort, pain, or bruising from the 
needle puncture.  In rare cases, an infection may also occur at the site of the needle 
stick.
Blood draws: Needle sticks carry some risks such as fainting, bleeding, bruising, 
discomfort, dizziness, infection and/or pain at the puncture site.
CT and MRI Scans: As part of this study, you will have CT and MRI scans. CT scans 
involve exposure to radiation. Some people may be worried about the amount of 
radiation they receive during a CT scan. The amount of radiation from this entire study 
is well below the levels that are thought to result in a significant risk of harmful effects. 
Radiation exposure from a CT scan can be higher than from a regular x-ray. 
Some people experience mild itching or hives. Signs of a more serious allergic reaction 
include shortness of breath and swelling of the throat or other parts of the body, 
abdominal pain, or vomiting. You should tell the technologist immediately if you 
experience any of these symptoms, so you can be treated immediately. You may 
experience discomfort related to lying still in an enclosed space for a prolonged period 
of time while the CT scan or MRI is being taken.
General / Unforeseeable
There may be side effects and discomforts that are not yet known. You should tell your 
study doctor about any side effects you experience even if you think they are not 
related.
Louisiana law requires us to set forth the known risks of a medical treatment, including 
the risks, if any, of death, brain damage, quadriplegia (paralysis in all arms and legs), 
paraplegia (paralysis of both legs), the loss or loss of function of any organ or limb, and 
disfiguring scars, which might be associated with a necessary procedure.  Any clinical 
study carries with it risks of which we may be unaware at this time, including those listed 
in this paragraph. 
Reproductive Risks
No studies of ABI-009 have been conducted in pregnancy. It is not known if ABI-009 
passes into milk during breast feeding
Females:  If you decide to take part in this study, and are able to have children, you 
must agree to use medical doctor-approved contraception plus a barrier contraceptive 
throughout the study, and for 3 months after your last dose of study treatment. In 
addition, if you have had your tubes tied (tubal ligation) you must also agree to use a 
second form of birth control. If you become pregnant while receiving study treatment 
you must tell the study doctor right away. If this happens, your participation in this study 
treatment will be discontinued.  If you become pregnant within 3 months after taking 
your last dose of study drug you must tell the study doctor right away. The study doctor 
will follow you and your pregnancy to birth.  
Males: If you are a man, you will not be able to donate sperm for the length of the trial 
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and for 3 months following treatment. If you have a partner able to have children, you 
must agree to use a medical doctor-approved form of contraception plus a barrier 
contraceptive throughout the study and should avoid fathering a child for 3 months after 
your last dose of study treatment. In addition, if you have had a vasectomy you must 
also agree to use a second form of birth control. If your partner becomes pregnant 
during the study or within 3 months after you took your last dose of study treatment, you 
must tell the study doctor right away. Your study doctor and the sponsor will ask your 
partner to allow them to collect information about her pregnancy and the health of the 
baby in a separate consent form.
If you or your partner becomes pregnant while participating in this study, you MUST 
contact your study doctor immediately.
Radiation Risks
Although you will undergo some tests involving ionizing radiation in this protocol, they 
are the same you would undergo if you were not in this study, and at the same 
frequency.  Therefore, this study does not involve any additional radiation risk for you.
POTENTIAL BENEFITS
You may not receive direct personal or health benefit from taking part in this study.  
However, the information gained from your participation in this study may be used to 
help others in the future. 
COSTS  
Although the Sponsor may pay for certain study-related items and services, any other 
tests, procedures, or medications that may be necessary for the treatment of your 
medical condition will be billed to your insurance in the normal way.  You may be 
responsible for co-payments or deductibles.  These costs are not covered by this 
research study.  If you have any questions about treatment for which you may be 
responsible for paying, please discuss this with your physician or study staff.
PAYMENT FOR PARTICIPATION AND/OR REIMBURSEMENT OF EXPENSES
You will not be paid or offered any other compensation for participating in this study.
Ochsner Clinic Foundation is being funded by Aadi Bioscience, Inc. to conduct this 
research. 
ALTERNATIVE METHODS/TREATMENTS
You do not have to join this study. If you do not join, your care at Ochsner will not be 
affected.
STUDY RELATED QUESTIONS AND COMPENSATION FOR INJURY
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If you have any questions concerning your participation in this study or if at any time you 
feel you have experienced a research-related injury, contact the study doctor or their 
alternate contact listed on the front page of this consent form.
If you believe you are injured as a direct result of your participation in this study, you 
should seek appropriate medical attention and immediately contact your study doctor at 
the number provided above. Medical treatment and/or hospitalization, if necessary for 
such injuries, is available. This medical treatment and/or hospitalization is not free of 
charge.  You, your insurance company or the Sponsor may be billed for the care you 
receive for the injury.  We will try to get these costs paid for you, but you may be 
responsible for some or all of them. You may be responsible for all co-payments and 
deductibles required under your insurance.  If injuries occur that are the result of a 
medication, device, procedure or test required for this study that is not part of your usual 
medical care, the Sponsor will reimburse the standard charges for the treatment of 
these injuries.
By signing this consent form you have not given up any legal rights.
QUESTIONS ABOUT YOUR RIGHTS
If you have questions about your rights as a research subject, you may contact:
Ochsner Clinic Foundation Institutional Review Board
1514 Jefferson Highway
New Orleans, LA 70121
Telephone:  1-504-842-3535
Email: IRB@ochsner.org
The Institutional Review Board (IRB) is a group of people who perform independent 
review of research for human subject protection. You may contact the IRB to discuss 
any problems, concerns or questions you have about research. The IRB can assist you 
in obtaining information about research and encourages input from research subjects.
VOLUNTARY PARTICIPATION
Participation in this study is voluntary.  You may decide not to participate in this study or 
you may withdraw from this study at any time without penalty or loss of benefits to which 
you are otherwise entitled at this site.  If you leave the study before the final regularly 
scheduled visit, you may be asked by the study doctor to make a final visit for some end 
of study procedures.
Your participation in this study will be entered in your electronic medical record here at 
Ochsner.  You should tell your study doctor about all of your past and present health 
conditions and allergies of which you are aware, and all drugs and medications which 
you are presently using.
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EMPLOYEES IN RESEARCH
If you are an employee of Ochsner Clinic Foundation (OCF), you are not required to 
participate in this research study to maintain employment nor will your employment 
status or performance evaluations be negatively affected in any way if you decide not to 
be a research subject. Should you decide to enroll yourself or your child in this study, 
you may withdraw your (or your child’s) participation at any time, and this decision will 
not affect your employment or performance evaluations.
NEW FINDINGS
During the study you will be told about any important new information that may change 
your mind about staying in the study.
STUDY WITHDRAWAL
Your participation in this study may be stopped at any time by the study doctor or the 
sponsor without your consent because:

You do not meet study criteria

the study doctor thinks it necessary for your health or safety;

you have not followed study instructions;

the sponsor has stopped the study; or

administrative reasons require your withdrawal.
UNEXPECTED FINDINGS
When your data/images are collected and studied, there is the chance of finding 
something unexpected. There may be benefits to learning such results (such as early 
detection and treatment of a medical condition), but there are risks as well (such as 
feeling worried about a finding for which no treatment is available or appropriate).
In this study, you will be told of any unexpected findings that may be discovered. The 
results from the data/images we collect in this research study are the same quality as 
what you would receive as part of your health care. The data/images will be reviewed by 
a physician who normally reads such results. You will be given this information so that 
you may discuss it with your primary care physician. However, if you believe you are 
having symptoms that may require care prior to receiving any information from this 
study, you should contact your primary care physician.
CONFIDENTIALITY
Your identity and your personal records will be kept confidential and, to the extent 
permitted by the applicable laws and/or regulations, will not be made publicly available. 
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Confidentiality will be maintained during and after your participation in this study.
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.
The results of this research may also be published in scientific journals or presented at 
medical meetings, but your identity will not be disclosed.
HIPAA AUTHORIZATION TO RELEASE INFORMATION FOR RESEARCH 
Under federal law (the “Privacy Rule”), your Protected Health Information (PHI) that is 
created or obtained during this clinical research study cannot be “used” to conduct the 
research or “disclosed” (given to anyone) for research purposes without your 
permission. This permission is called an “Authorization”. Therefore, you may not take 
part in this study unless you agree to this authorization. 
Before you agree to take part in the study, we want to tell you:

How study information may identify you

Who may use or share your protected health information

Why your protected health information will be used or shared

Your rights concerning use and/or sharing of your protected health information
How may study information identify me?
Study information may identify you in the following ways:

Name, address, telephone number

Other details about you including your past medical records
Medical information that identifies you and relates to your participation will be created, and 
may be used and/or shared, including information obtained from:

Study visits and phone calls

Physical examinations, blood and urine tests, x-rays, and other procedures or tests

Your response to any study treatments you receive

Any other information that you may release to us, including information about your 
health history.
Who may use or share my protected health information?
The Investigator (study doctor) and research staff may give protected health information 
to others during and after the study, including:

The study sponsor, including any people or companies working for or with the 
sponsor or owned by the sponsor.

Doctors and healthcare professionals taking part in the study

Government agencies in the United States and in other countries

Ochsner Clinic Foundation
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
Third party vendors as authorized by Ochsner Clinic Foundation
Why will this study information be used and/or shared?

To carry out the research study

To analyze and evaluate the results of the study

To conduct internal research compliance reviews

To comply with governmental reporting requirements

To obtain marketing approval for new products
What are my rights regarding my health information?

You have the right to review and copy your health information.  However, as a 
participant in this research study, you would not be allowed to look at or copy your 
information until after the research is completed.

You may withdraw or revoke (cancel) your permission to use and disclose your 
health information at any time. However, unless you revoke your permission by 
sending written notice to the study doctor, this authorization (permission) will not 
expire (end) until it is no longer required by the Sponsor. 
When you withdraw your permission, no new health information that might identify you 
will be gathered after that date.  Information that has already been gathered may still be 
used and given to others.  This would be done if it were necessary for the research to be 
reliable. If you withdraw your permission, you will not be able to continue being in 
this study. 
Are there possible limitations on the protection of my health information?

If your health information is given to the parties listed above and/or to others who 
are not required to comply with federal privacy laws, your information may no 
longer be protected, and there is a risk that your information will be released to 
others without your permission.

Your personal information may be disclosed if required by law.  

Your records for this study may be sent by facsimile transmission (FAX) or over 
the Internet. It is possible that your records could be sent to the wrong person.
How long is my information kept?
Ochsner Clinic Foundation policy requires that all files related to a research study are 
stored for ten (10) years after the research study has been closed at the Ochsner site.
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Do not sign this consent form unless you have had a chance to ask questions 
and have received satisfactory answers to all of your questions.
If you agree to participate in this study, you will receive a signed and dated copy 
of this consent form for your records.
CONSENT
I have been informed about this study’s purpose, procedures, possible benefits and 
risks, and the use and disclosure of my health care information from this research.  All my 
questions about the study and my participation in it have been answered.  I freely 
consent to participate in this research study.  I authorize the use and disclosure of my 
health information to the parties listed in the authorization section of this consent for the 
purposes described above. By signing this consent form I have not waived any of the 
legal rights that I otherwise would have as a subject in a research study.
CONSENT SIGNATURE
______________________________________________________________________
Subject Signature
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IRB # 2018.162
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Sponsor’s Version: 16APR2018
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------------------------------------ Use the following only if applicable -----------------------------
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If this consent and authorization document is read to the subject because the subject is 
unable to read the document, an impartial witness (a person, who is independent of the 
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informed consent process if the subject cannot read, and who reads the informed 
consent and any other written information supplied to the subject) must be present for 
the consent and sign the following statement: 
I attest that the information in this consent and authorization was explained to and 
understood by the subject. I also attest that the subject agreed to participate in this 
research study.  
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Prot_SAP_002.pdf: 
ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
Confidential and Proprietary 
1 
Final Protocol v3.0  
A pilot phase 2 study of albumin-bound sirolimus nanoparticles, ABI-009, in 
patients with metastatic, unresectable, low or intermediate grade 
neuroendocrine tumors of the lung or gastroenteropancreatic system 
 
 
Investigational Product: 
 ABI-009 
Protocol Number: 
 NET-001 
Study Phase: 
 Pilot Phase 2 
Sponsor Name / Address: 
 
 
 Ochsner Clinic Foundation 
1514 Jefferson Highway 
New Orleans, LA 70121 
Principal Investigator: 
 Robert Ramirez, DO, FACP  
Medical Oncologist 
Collaborator: 
 Aadi Bioscience, Inc 
1343 Luna Vista Dr 
Pacific Palisades, CA 90272 
 
Protocol Versions 
 Date 
Amendment v3.0: 
Amendment v2.0: 
Original v1.0: 
 November 13, 2019 
June 15, 2018 
April 19, 2018 
 
CONFIDENTIAL 
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. 
  
 
 
 
 


ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
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PROTOCOL SYNOPSIS 
 
INVESTIGATIONAL 
PRODUCT 
ABI-009, sirolimus protein-bound nanoparticles for injectable suspension 
(albumin bound), sirolimus (formerly nab-rapamycin), nanoparticle albumin-
bound rapamycin 
TITLE 
A pilot phase 2 study of albumin-bound sirolimus nanoparticles, ABI-009, in 
patients with metastatic, unresectable, low or intermediate grade 
neuroendocrine tumors of the lung or gastroenteropancreatic system 
PROTOCOL 
NUMBER 
NET-001 
PHASE  
Pilot Phase 2 
STUDY OBJECTIVES Objectives  
• The primary objective of this pilot phase 2 study is to evaluate the 
preliminary efficacy of ABI-009 in patients with grade 1 and 2 
neuroendocrine tumors (NETs) of the gastroenteropancreatic system or 
lung, as measured by disease control rate (DCR) at 6 months 
• The secondary objective is to evaluate the safety and toxicity profile of ABI-
009 and the overall response rate (ORR) 
STUDY ENDPOINTS Endpoints  
Primary Endpoint  
• Disease control rate at 6 months, assessed by investigator using 
Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 
Secondary endpoint 
• Safety 
• Overall response rate (ORR) 
STUDY DESIGN 
and DOSE-
FINDING RULES 
This study is a prospective, single arm, single institution pilot phase 2 study to 
evaluate 
the 
efficacy 
and 
safety 
ABI-009 
in 
patients 
with 
gastroenteropancreatic NET (GEPNETs) or NET of the lung and prior exposure 
to everolimus. 
ABI-009 will be given weekly for 2 weeks followed by a week of rest (qw2/3) in 
a 21-day cycle (on D1 and 8).  
The study will be conducted in compliance with International Conference on 
Harmonisation (ICH) Good Clinical Practices (GCPs). 
NUMBER OF 
PATIENTS 
Up to 10 evaluable patients will be enrolled. 
INCLUSION 
CRITERIA 
A patient will be eligible for inclusion in this study only if all of the following 
criteria are met at screening: 


ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
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1. Unresectable or metastatic patients with typical or atypical carcinoid 
tumors of the lung or low or intermediate grade GEPNETS. 
2. Patients must have measurable disease per RECIST 1.1. 
3. Patients must have progressed on everolimus or been intolerant to 
everolimus as defined as discontinued for any adverse reactions other than 
allergic reaction.  
4. Patients, ≥18 years old, must have Eastern Cooperative Oncology Group 
(ECOG) Performance Status 0 or 1. 
5. Concurrent use of somatostatin analogs (SSAs) is allowed if currently used 
for symptom control. 
6. Adequate liver function: 
a. Total bilirubin ≤1.5 x upper limit of normal (ULN) mg/dL 
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤2.5 x ULN (<5 x ULN if the patient has liver metastases). 
7. Adequate renal function: 
a. Serum creatinine ≤2 x ULN or creatinine clearance >50 ml/min 
(Cockcroft-Gault). 
8. Adequate biological parameters: 
a. Absolute neutrophil count (ANC) ≥1.5 × 109/L 
b. Platelet count ≥100,000/mm3 (100 × 109/L) 
c. Hemoglobin ≥8 g/dL (transfusions are allowed if clinically indicated) 
9. Fasting serum triglyceride ≤300 mg/dL; fasting serum cholesterol ≤350 
mg/dL. 
10. Male or non-pregnant and non-breast feeding female: 
• Females of child-bearing potential must agree to use effective 
contraception without interruption from 28 days prior to starting IP 
throughout 3 months after last dose of IP 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 after the end of 
study treatment. A second form of birth control is required even if she 
has had a tubal ligation. 
• Male patients 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 and throughout 3 months 
after last dose of IP. A second form of birth control is required even if 
he has undergone a successful vasectomy. 
11. 
Life expectancy of >3 months, as determined by the investigator. 
12. Ability to understand and sign informed consent. 
13. Willingness and ability to comply with scheduled visits, laboratory tests, 
and other study procedures. 


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Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
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EXCLUSION 
CRITERIA 
A patient will not be eligible for inclusion in this study if any of the following 
criteria apply: 
1. Patients currently undergoing anti-cancer therapy for neuroendocrine 
tumors (other than SSAs for symptoms). 
2. History of allergic reactions to compounds of similar chemical or biologic 
composition to ABI-009. 
3. Known active uncontrolled or symptomatic central nervous system (CNS) 
metastases. A patient with controlled and asymptomatic CNS metastases 
may participate in this study. As such, the patient 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. Active gastrointestinal bleeding. 
5. Uncontrolled serious medical or psychiatric illness.  
6. Patients with a "currently active" second malignancy other than non-
melanoma skin cancers, carcinoma in situ of the cervix, resected incidental 
prostate cancer (staged pT2 with Gleason Score ≤ 6 and postoperative PSA 
<0.5 ng/mL), or other adequately treated carcinoma-in-situ are ineligible. 
Patients are not considered to have a "currently active" malignancy if they 
have completed therapy and are free of disease for ≥1 year). 
7. 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). 
8. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate 
therapy. 
9. Unstable coronary artery disease or myocardial infarction during preceding 
6 months. 
10. Patients with history of interstitial lung disease and/or pneumonitis, or 
pulmonary hypertension. 
11. Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to 
receiving the first dose of ABI-009. Additionally, use of any known CYP3A4 
substrates with narrow therapeutic window (such as fentanyl, alfentanil, 
astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfanide) 
within the 14 days prior to receiving the first dose of ABI-009.  
12. Known Human Immunodeficiency Virus (HIV). 
13. Known active Hepatitis B or Hepatitis C. 
DURATION OF 
TREATMENT AND 
STUDY 
PARTICIPATION  
The study is expected to take approximately 24 months from first patient 
enrolled to last patient follow-up. The study will take 12 months to enroll all 
subjects and an estimated 12 months of treatment per subject or until 
treatment is no longer tolerated.   
End of Treatment (EOT) for a patient is defined as the date of the last dose of 
ABI-009. End of Treatment Visit for a patient is when safety assessments and 


ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
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procedures are performed after the last treatment, which must occur within 1 
month after the last dose of ABI-009.   
The End of Study (EOS) defined as either the date of the last visit of the last 
patient to complete the study, or the date of receipt of the last data point from 
the last patient that is required for primary, secondary, and/or exploratory 
analysis, as pre-specified in the protocol.  
Follow-up period begins after the EOT Visit. All patients that discontinue study 
drug and have not withdrawn full consent to participate in the study will 
continue in the follow-up phase for survival or initiation of new anticancer 
therapy. Follow up will continue approximately every 12 weeks (±3 weeks), 
until death, withdrawal of consent, start of new anticancer therapy, or the 
study closes, whichever is the earliest. This evaluation may be made by record 
review and/or telephone contact. 
STUDY DRUG 
ADMINISTRATION 
Patients will receive 75 mg/m2 ABI-009 weekly for 2 weeks followed by a week 
of rest (qw2/3, 21-day cycle) by IV infusion over 30 minutes.  
Patients will continue on therapy until disease progression, unacceptable 
toxicity, until in the opinion of the investigator the patient is no longer 
benefiting from therapy, or at the patient’s discretion.  
KEY EFFICACY 
ASSESSMENTS 
Efficacy will be assessed every 9 weeks by investigators using CT scans (or MRI 
if CT is contraindicated) and RECIST v1.1.   
Descriptive statistics and cox proportional hazards will be used in this analysis.  
Matching patients based on demographics and other cofounders such as 
disease primary site, site of metastatic disease and Ki-67 proliferative index as 
indicated on the original pathology report will be utilized to try to create a 
comparison group to identify possible differences.   
KEY SAFETY 
ASSESSMENTS 
Safety and tolerability will be monitored through continuous reporting of 
treatment-emergent and treatment-related adverse events (AEs), AEs of 
special interest, laboratory abnormalities, and incidence of patients 
experiencing dose modifications, dose delay/dose not given, dose 
interruptions, and/or premature discontinuation of ABI-009 due to an AE. All 
AEs will be recorded by the investigator from the time the patient signs 
informed consent until 28 days after the last dose of IP. Adverse events will be 
graded by National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE) v5.0. 
Physical examination, vital signs, laboratory assessments (eg, serum chemistry, 
hematology), and ECOG performance status will be monitored. All serious AEs 
(regardless of relationship to ABI-009) will be followed until resolution. Local 
laboratory analysis will be performed as per study schedule. 


ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
 
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TABLE OF CONTENTSPROTOCOL SYNOPSIS .................................................................................... 2 
1. 
INTRODUCTION .......................................................................................................... 14 
1.1. 
Neuroendocrine Tumors of the Gastroenteropancreatic System or Lung ............... 14 
1.2. 
Treatment Options in Neuroendocrine Tumors ........................................................ 14 
1.2.1. 
mTOR Inhibition in Neuroendocrine Tumors ............................................................ 14 
1.3. 
ABI-009 Background .................................................................................................. 15 
1.3.1. 
Sirolimus and Rapalogs .............................................................................................. 15 
1.3.2. 
ABI-009 (sirolimus, formerly nab-Rapamycin) .......................................................... 16 
1.3.3. 
Preclinical Studies with ABI-009 ................................................................................ 16 
1.3.4. 
Clinical Studies with ABI-009 ..................................................................................... 18 
1.4. 
Rationale for Investigating ABI-009 in Neuroendocrine Tumors of the 
Gastroenteropancreatic System or Lung ................................................................... 19 
1.5. 
Rationale for the Schedule of Administration for ABI-009 ........................................ 19 
2. 
STUDY OBJECTIVES AND ENDPOINTS ........................................................................ 20 
2.1. 
Objectives .................................................................................................................. 20 
2.2. 
Endpoints ................................................................................................................... 20 
2.3. 
Study Design .............................................................................................................. 20 
2.4. 
Study Duration, End of Study, End of Treatment, End of Treatment Visit, 
Follow-up Period ........................................................................................................ 20 
3. 
STUDY POPULATION .................................................................................................. 21 
3.1. 
Number of Patients .................................................................................................... 21 
3.2. 
Inclusion Criteria ........................................................................................................ 21 
3.3. 
Exclusion Criteria ....................................................................................................... 22 
4. 
TABLE OF EVENTS ...................................................................................................... 23 
5. 
PROCEDURES ............................................................................................................. 26 
5.1. 
Screening Evaluations ................................................................................................ 26 
5.2. 
Treatment Period ....................................................................................................... 26 
5.2.1. 
Day 1 Assessment ...................................................................................................... 27 
5.2.2. 
Day 8 Assessment ...................................................................................................... 27 
5.2.3. 
Day 15 Assessment .................................................................................................... 27 
5.2.4. 
Response Assessment ................................................................................................ 28 


ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
 
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5.3. 
End of Treatment Visit Assessment ........................................................................... 28 
5.4. 
Sirolimus Trough Levels ............................................................................................. 29 
5.5. 
Follow-up Period for Survival and Initiation of Anticancer Therapy ......................... 29 
6. 
DESCRIPTION OF STUDY TREATMENTS ..................................................................... 30 
6.1. 
ABI-009 Dosage, Administration, and Schedule ........................................................ 30 
6.2. 
ABI-009 Dose Modification and Stopping Rules ........................................................ 30 
6.3. 
Hepatotoxicity Stopping Rules ................................................................................... 34 
6.3.1. 
Criteria for Permanent Discontinuation of ABI-009 Due to Potential 
Hepatotoxicity............................................................................................................ 34 
6.3.2. 
Criteria for Conditional Withholding of ABI-009 Due to Potential 
Hepatotoxicity............................................................................................................ 34 
6.3.3. 
Overdose .................................................................................................................... 35 
7. 
STUDY DRUG MANAGEMENT .................................................................................... 36 
7.1. 
Description of Study Drugs ........................................................................................ 36 
7.1.1. 
ABI-009 Packaging, Labeling, and Storage ................................................................. 36 
7.2. 
ABI-009 Accountability, Disposal, and Compliance ................................................... 36 
7.3. 
ABI-009 Reconstitution and Use ................................................................................ 36 
7.4. 
Receipt and Return of ABI-009 .................................................................................. 36 
8. 
CONCOMITANT MEDICATIONS AND PROCEDURES ................................................... 37 
8.1. 
Permitted Medications and Procedures .................................................................... 37 
8.2. 
Prohibited Medications and Procedures ................................................................... 37 
9. 
STATISTICAL CONSIDERATIONS ................................................................................. 39 
9.1. 
Study Endpoints ......................................................................................................... 39 
9.2. 
Safety Analysis ........................................................................................................... 39 
9.3. 
Efficacy Analysis ......................................................................................................... 39 
9.4. 
Sample Size Considerations ....................................................................................... 39 
9.5. 
Primary Analysis ......................................................................................................... 39 
10. 
MONITORING, RECORDING AND REPORTING OF ADVERSE EVENTS ........................ 40 
10.1. 
Toxicities of ABI-009 .................................................................................................. 40 
10.2. 
Evaluation of Adverse Events .................................................................................... 40 
10.3. 
Serious Adverse Events .............................................................................................. 40 
10.3.1. 
Definition of Serious Adverse Events ........................................................................ 40 


ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
 
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10.3.2. 
Reporting Procedures for Serious Adverse Events .................................................... 41 
10.4. 
Pregnancy and Breast-feeding Reporting .................................................................. 41 
11. 
WITHDRAWAL FROM TREATMENT, PROCEDURES, AND STUDY ............................... 42 
11.1. 
Discontinuation from Investigational Product .......................................................... 42 
11.2. 
Discontinuation from the Study ................................................................................ 42 
11.3. 
Investigator or Sponsor Decision to Withdraw or Terminate Patient’s 
Participation Prior to Study Completion .................................................................... 42 
12. 
REGULATORY OBLIGATIONS ...................................................................................... 43 
12.1. 
Informed Consent ...................................................................................................... 43 
12.2. 
Institutional Review Board ........................................................................................ 43 
12.3. 
Patient Confidentiality ............................................................................................... 43 
12.4. 
Protocol Amendments ............................................................................................... 44 
12.5. 
Termination of the Study ........................................................................................... 44 
13. 
DATA HANDLING AND RECORDKEEPING ................................................................... 45 
13.1. 
Data/Documents ........................................................................................................ 45 
13.2. 
Data Management ..................................................................................................... 45 
13.3. 
Investigator Responsibilities for Data Collection ....................................................... 45 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE......................................................... 46 
14.1. 
Study Monitoring, Audits and Inspections ................................................................ 46 
15. 
PUBLICATIONS ........................................................................................................... 47 
16. 
REFERENCES ............................................................................................................... 48 
LIST OF TABLES 
Table 1. Schedule of Assessments ................................................................................................ 24 
Table 2. Analyte Listing ................................................................................................................. 28 
Table 3:  
Dose Level Reduction Guidelines .............................................................................. 31 
Table 4. Dose Modification Algorithms for Adverse Events Possibly Related to ABI-009 ............ 32 
 
LIST OF FIGURES 
Figure 1: Antitumor Activity of ABI-009 in Colon and Pancreatic Cancer Tumor 
Xenografts .................................................................................................................. 16 
Figure 2: ABI-009 Administered IV Compared with Equal Weekly Dosing of Oral 
Sirolimus and Oral Everolimus ................................................................................... 17 
 


ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
 
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ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
 
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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 
CEA 
CI 
carcinoembryonic antigen 
confidence interval 
CNS 
central nervous system 
CR 
complete response 
CT 
computed tomography 
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 
Imunohistochemistry 
IND 
investigational new drug  


ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
 
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IP 
investigational product 
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 sirolimus 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
ORR 
overall response rate 
OS 
overall survival 
PD 
progressive disease 
PF rate 
PFS 
Progression-free rate 
Progression-free survival 
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 
 
 


ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
 
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Term 
Definition/Explanation 
Study Day 1 
First day that protocol-specified IP is administered to the patient. 
End of Treatment 
The date of the last dose of ABI-009 for an individual patient. 
End of Treatment Visit 
For a patient 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.  
Follow-up Period 
 
The time period after the End of Treatment Visit. All patients 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), 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. 
End of Study 
 
Either the date of the last visit of the last patient to complete the 
study, or the date of receipt of the last data point from the last 
patient that is required for primary, secondary, and/or exploratory 
analysis, as pre-specified in the protocol.  
Primary Analysis 
 
For this study will occur after all patients have either completed the 
study or completed 12 months of treatment. Patients 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 patients with measurable tumor per RECIST v1.1 at 
baseline who received at least 1 dose of ABI-009 and had a follow-up 
CT / PET (or MRI) (modified treated population). 
Safety Analysis Set 
All enrolled patients who receive at least 1 dose of ABI-009 (treated 
population). 
Per-protocol 
Analysis 
Set 
All enrolled patients who do not have any prospectively defined 
protocol violations.  
Disease control rate at 
6 months 
Disease control rate at 6 months is the proportion of patients who 
have partial or complete response or stable disease at 6 months. 
Overall response rate 
 
The proportion of patients who achieve a confirmed partial response 
or complete response per RECIST 1.1. Response rates based on a 
local radiologic assessment. 


ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
 
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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.  
Progression-free 
survival 
The time from the first dose date to the first observation of a disease 
progression, assessed radiologically, or death due to any cause.   
Overall survival 
The time from the first dose date to the date of death due to any 
cause. 
 
 


ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
 
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1. 
INTRODUCTION 
1.1. 
Neuroendocrine Tumors of the Gastroenteropancreatic System or Lung 
Neuroendocrine tumors (NETs) are a group of rare and heterogeneous malignancies, most 
commonly arise from neuroendocrine cells of the gastrointestinal tract (particularly pancreas and 
small bowel), followed by lung, liver, and thymus (Yao 2008). While most NETs are more indolent 
than other epithelial malignancies, poorly differentiated NETs can become aggressive and 
resistant to therapy.  In a population analysis from SEER registry, the median survival for high-
grade (3 and 4) NETs with localized, regional, and distant disease were 34, 14, and 5 months, 
respectively (Yao, Hassan 2008). The 10-year survival rate for any grade NETs is approximately 
46% (Hallet 2015). 
Because of their rarity and heterogeneity, nonspecific presentation symptoms, unique indolent 
biology, and lack of awareness, diagnosis can be delayed up to 7 years. The incidence of NETs has 
been increasing in recent years, doubling between 1994 and 2009, in part due to improved 
detection and greater clinician and patient awareness (Hallet, Law 2015).  
1.2. 
Treatment Options in Neuroendocrine Tumors 
When possible, surgery for is performed with the intent to cure or remove as much tumor as 
possible (debulking). Somatostatin analogues (SSAs) are highly effective for controlling the 
symptoms of hormone release by carcinoid and pancreatic NETs (pNETs), but their anti-tumor 
efficacy is modest. Interferon has utility in NETs, especially in combination with SSA. Combination 
chemotherapy using temozolomide and capecitabine has shown efficacy in various NETs 
(Strosberg 2011). Recently the FDA has approved radionuclide therapy with Lu-177 in patients 
with gastroenteropancreatic neuroendocrine tumors (GEPNETs) based off a study comparing 
high dose SSA to Lu-177 which indicated impressive PFS with Lu-177 compared to the SSA 
(Strosberg 2017). 
The management of NETs is still challenging, and effective and safe therapeutic options are 
needed for the treatment of these tumors. Targeted therapies, such as sunitinib and everolimus 
produced promising efficacy in clinical trials.  Subsequently, both therapeutics were approved by 
the United States (US) Food and Drug Administration (FDA); sunitinib is approved for pNETs and 
everolimus is approved for NETs of gastrointestinal (GI) or lung origin (Novartis-Gleevec 2017, 
Novartis 2017). 
1.2.1. 
mTOR Inhibition in Neuroendocrine Tumors 
Preclinical evidence has shown that the PI3K/AKT/mTOR signaling pathway plays a central role in 
the pathogenesis and progression of NETs (Manfredi 2015, Chan 2017). In accordance with 
preclinical evidence, clinical studies with everolimus (RADIANT 1-4 trials) demonstrated its safety 
and efficacy, which was a major advance in the treatment for NETs. The tolerability profile of 
everolimus has been consistent across clinical studies. The most adverse events (AEs) have been 
mild or moderate in severity, with grade 3/4 anemia and hyperglycemia occurring about 5% of 
patients.  
The RADIANT trials (Pusceddu 2017) 


ABI-009 
Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
 
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RADIANT 1 was a phase 2 open label trial in patients with metastatic pNET, who have progressed 
on chemotherapy. Patients received either everolimus 10 mg alone or everolimus + octreotide. 
The combination arm had a 7-month longer median progression-free survival (PFS, 9.7 vs 16.7 
months). RADIANT 3 was a subsequent phase 3 trial in patients with advanced low or 
intermediate grade pNET receiving everolimus 10 mg alone or placebo. In this study, the median 
PFS was 11 vs 4.6 months, respectively, HR 0.35 [95% CI 0.27-0.45], p< 0.001.  
RADIANT 2 was a phase 2 study in patients with NETs and carcinoid syndrome, receiving either 
everolimus 10 mg + octreotide or placebo + octreotide. The median PFS was 16.4 vs 11.3, 
respectively, HR 0.77 [95% CI 0.059-1.00], p=0.026. RADIANT 4 was a subsequent phase 3 trial in 
patients with pulmonary or gastrointestinal NETs, with low grade well-differentiated disease, 
receiving everolimus 10 mg alone or placebo. Similar to RADIANT 3, in RADIANT 4 median PFS 
was nearly 3x longer in the combination arm (11 vs 3.9 months, HR 0.48 [95% CI 0.35-0.67], 
p<0.00001). Tumor shrinkage occurred in 64% vs 26%, in the everolimus versus placebo groups 
respectively (Pusceddu, Verzoni 2017). 
While the optimal treatment sequence and patient population for mTOR inhibitors are still to be 
investigated, given the RADIANT trial results, everolimus might be a particularly suitable for 1st-
line treatment for patients with grade 2 pNET and rapidly evolving disease and high disease 
burden, given the antiproliferative efficacy and tolerability profile of everolimus. On the other 
hand, in patients with G1 pNET with low tumor burden and indolent disease, everolimus may be 
more useful as a second-line therapy, after treatments with SSAs (Pusceddu, Verzoni 2017). 
1.3. 
ABI-009 Background 
1.3.1. 
Sirolimus and Rapalogs 
Sirolimus (rapamycin) is a protein kinase inhibitor that is approved for immunosuppression in 
renal transplant patients and is under investigation for various cancer treatment. Sirolimus 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 (Dowling 2010). 
Although sirolimus is an efficacious mTOR inhibitor, it has poor solubility, low oral bioavailability, 
and produces DLTs, including mucositis and stomatitis (O'Donnell 2008, Yuan 2009). Marketed 
sirolimus analogs are temsirolimus and everolimus. Temsirolimus, a prodrug of sirolimus 
requiring conversion to sirolimus in vivo, is approved for the treatment of kidney cancer. 
Everolimus is approved for pediatric and adult patients with subependymal giant cell 
astrocytoma, advanced hormone receptor-positive HER2-negative breast cancer in combination 
with exemestane, progressive NET of pancreatic or lung origin, subependymal giant cell 
astrocytoma (SEGA) associated with tuberous sclerosis, and advanced renal cell carcinoma after 
failure of treatment with sunitinib or sorafenib (Hanna 2008, Molina 2011, Yao 2011, Baselga 
2012, Thompson 2012). 
Oral sirolimus 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 (de Oliveira 2011, Albiges 2012, Qi 2013). The most frequently occurring grade 


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Protocol: NET-001                                                                                 Ochsner Clinic Foundation 
 
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3 or 4 adverse events (AEs) were hyperglycemia (17%), hypophosphatemia (13%), anemia (9%), 
and hypertriglyceridemia (6%) (Zhou 2010). 
A novel mTOR inhibitor, ABI-009 (albumin-bound sirolimus nanoparticles, nab-rapamycin), is a 
solvent-free, intravenous (IV) form of sirolimus and has relatively high bioavailability. Dose-
limiting toxicities (DLT) including mucositis/stomatitis that were observed with other mTOR 
inhibitors were not dose-limiting with ABI-009 (Gonzalez-Angulo 2013). The particularly safe 
toxicity profile of ABI-009 offers a promising new therapeutic for NETs. 
1.3.2. 
ABI-009 (sirolimus, formerly nab-Rapamycin) 
The novel nanoparticle albumin-bound sirolimus (formerly nab-rapamycin, ABI-009) is freely 
dispersible in saline and is suitable for IV administration, and has produced both a favorable 
safety profile and evidence of efficacy in patients with metastatic solid tumors (Gonzalez-Angulo, 
Meric-Bernstam 2013). 
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 vs conventional paclitaxel formulation (Gradishar 2005). This suggests that the nab form 
of sirolimus may also produce similar advantages over the standard sirolimus. 
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 
(Kremer 2002, Kratz 2008). Albumin circulating in the bloodstream can interact with gp60 to 
initiate caveolae-mediated transcytosis to reach tumor cells (Schnitzer 1992, Schnitzer 1995). 
Indeed, nab-paclitaxel transcytosis across the epithelial monolayer was dependent on caveolae 
formation (Desai 2006). 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 (Desai, Trieu 2006). 
1.3.3. 
Preclinical Studies with ABI-009 
Preclinical primary pharmacology studies in vivo demonstrated significant antitumor activity of 
ABI-009 as a single agent administered IV at 40 mg/kg, 3 times weekly for 4 weeks, across 
different tumor xenograft models in nude mice (see Figure 1A and B, below), including colorectal 
and pancreatic cancer (De 2007, Desai 2009, Trieu 2009, Cirstea 2010, Kennecke 2011). This dose 
level correlates to approximately 120 mg/m2 in human. These findings are consistent with 
published information on sirolimus as an mTOR inhibitor and the role of mTOR in tumor growth 
(Fasolo 2012). 
Figure 1: Antitumor Activity of ABI-009 in Colon and Pancreatic Cancer Tumor Xenografts 
 
 
 
 
 
 
B
A


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A recent preclinical study demonstrated significantly greater antitumor activity and prolonged 
survival with ABI-009 administered IV compared with equal weekly dosing of oral sirolimus and 
oral everolimus (Aadi internal data, Figure 2). In athymic mice bearing UMUC3 human bladder 
cancer xenografts, ABI-009 was administered IV at 7.5 mg/kg, 2x weekly (total weekly dose: 15 
mg/kg), whereas sirolimus and everolimus were administered PO at 3 mg/kg/day, 5 days per 
week to achieve the same weekly total dose. The tumor growth inhibition (TGI) was 69.6% with 
ABI-009, significantly greater than oral sirolimus (TGI 24.3%; P < 0.00001 vs ABI-009, ANOVA) and 
oral everolimus (TGI 36.2%; P = 0.0023 vs ABI-009, ANOVA). The median OS was also significantly 
longer with ABI-009 (not reached) compared with oral sirolimus (21 days; P < 0.05, log rank test) 
and oral everolimus (19 days; P < 0.05, log rank test). Results from this preclinical study clearly 
demonstrate superior therapeutic efficacy of ABI-009 to oral mTOR inhibitors in this setting. 
Figure 2: ABI-009 Administered IV Compared with Equal Weekly Dosing of Oral Sirolimus and 
Oral Everolimus  
 
Preclinical pharmacokinetic (PK) studies in rats showed that IV ABI-009 exhibited linear PK with 
respect to dose and large volume of distribution (Vz), due to efficient tissue extraction of 
sirolimus from the central blood compartment (De, Trieu 2007). Shortly after dosing, tissue 
sirolimus level was 3-5 folds higher than that of blood, indicating efficient extraction. The 
terminal half-life of ABI-009 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 


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sirolimus literature (Sehgal 2003), 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 ABI-009 were evaluated in a series of preclinical studies. In a Good 
Laboratory Practice (GLP) repeat-dose toxicity study in male and female rats, ABI-009 
administered IV was well tolerated at doses up to 90 mg/kg (equivalent to 540 mg/m2 human 
dose) when delivered every 4 days for 3 cycles. Nonclinical toxicology studies of ABI-009 showed 
no new or unexpected toxicity compared to what is already known for sirolimus and other 
rapalogs (Pfizer 2011, Pfizer 2011, Novartis 2017). 
1.3.4. 
Clinical Studies with ABI-009 
In a phase 1 dose-finding, tolerability, and PK study conducted at MD Anderson Cancer Center 
(Protocol CA401, NCT00635284), ABI-009 was well tolerated with evidence of responses and 
stable disease (SD) in various solid tumors including renal cell carcinoma, bladder cancer, and 
colorectal cancer, all of which typically overexpress mTOR (Gonzalez-Angulo, Meric-Bernstam 
2013). Twenty-six patients were treated with 45, 56.25, 100, 125, or 150 mg/m2 ABI-009 per week 
for 3 weeks, followed by a week of rest (28-day cycle, qw3/4). ABI-009 was administered IV. The 
maximum-tolerated dose (MTD) was established at 100 mg/m2. 
Nineteen patients were evaluable for efficacy. One patient in the 45 mg/m2 (95 mg actual 
sirolimus dose) cohort, diagnosed with adenocarcinoma of the kidney and with bone and 
intrathoracic metastases, had a confirmed partial response (PR). The target lesion of this patient 
was reduced by 35.1% and the duration of response lasted 183 days. Two (11%) patients (at doses 
45 and 125 mg/m2, with actual sirolimus doses of 88 mg and 193 mg, respectively) had an overall 
tumor evaluation of SD (confirmed): 1 patient with mesothelioma had SD for 365 days and 1 
patient with a NET 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%) patients 
experienced at least 1 AE. The most common AEs were mucosal inflammation (10 patients, 38%), 
fatigue (7 patients, 27%), rash (6 patients, 23%), diarrhea (6 patients, 23%), and nausea (5 
patients, 19%). Most of these AEs were grade 1/2 events, with only 3 grade 3 nonhematologic 
AEs (2 elevated AST and 1 dyspnea). Specifically, at the MTD of 100 mg/m2, all 7 patients 
experienced at least 1 AE of any grades, and the most common AEs were mucositis and fatigue 
(5 patients, 71% each). Four (15%) patients experienced at least 1 treatment-related serious AE 
(SAE), including arrhythmia (grade 2) 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 AEs, for all cohorts and grades, were thrombocytopenia (58%), 
followed by hypokalemia (23%), and anemia and hypophosphatemia (19% each), and 
neutropenia and hypertriglyceridemia (15% each). 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 patients (62%) had 
treatment-related adverse events (TRAEs) requiring a week dose delay.  
Currently, there are several ongoing trials investigating the safety and efficacy of single-agent 
ABI-009 in various disease areas, including a trial in patients with malignant perivascular 
epithelioid tumors (PEComas), a rare type of soft-tissue tumors (NCT02494570). The particularly 


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safe toxicity profile of ABI-009 allows this mTOR inhibitor to be combinable with other 
therapeutics and a trial in patients with advanced STS is currently evaluating the combination of 
ABI-009 and nivolumab (NCT03190174). 
1.4. 
Rationale for Investigating ABI-009 in Neuroendocrine Tumors of the 
Gastroenteropancreatic System or Lung  
Based on results from the phase 1 study with single agent ABI-009 (Section 1.3.4, NCT00635284), 
the safety profile, evidence of antitumor activity and SD in various solid tumors, particularly in 
the patients with pNET and mesothelioma, as well as the tumor xenograft study demonstrating 
improved therapeutic potential of ABI-009 vs oral sirolimus or everolimus, we propose this pilot 
phase 2 study of ABI-009 for patients with GEPNET or NET of the lung. Particularly, the preclinical 
data showing improved tumor growth inhibition and survival with ABI-009 vs everolimus, dose 
for dose (Figure 2) and the potentially enhanced tumor penetration of the therapeutic by the 
nab-technology (described in 1.3.2.), ABI-009 may result in disease control even after everolimus 
failure. The goal of this phase 2 pilot study is to demonstrate that ABI-009 is safe and produce 
promising efficacy to warrant a full phase 2 study in patients who progressed on or failed 
everolimus treatment.  
1.5. 
Rationale for the Schedule of Administration for ABI-009 
A slightly different schedule, 2 of 3 weekly administration, has been selected in the present study 
than was studied in the first-in-human (FIH) phase 1 study (NCT00635284).  Additionally, to 
improve safety, the original starting dose was reduced from 100 mg/m2 (MTD) to 75 mg/m2 , with 
the option to escalate to the MTD after completing 2 cycles of continuous treatment at their 
originally assigned dose level and upon meeting the criteria as follows: 
• No observation of Grade > 2 adverse event(s) considered related to study treatment  
• Meet the hematological requirements as outlined in section 6.2 
• Ongoing clinical benefit: Patients must have no clinical signs or symptoms of progressive 
disease  
• No clinically significant safety or tolerability concern in the opinion of the investigator   
The rationale for the modification to the dose and schedule of administration of a dose of 100 
mg/m2 (MTD) is to further improve the tolerance of ABI-009. In the FIH phase 1 study, 19.4% of 
doses were missed at doses ≤100 mg/m2. Most of the missing doses (83%) occurred at day 15, 
corresponding to the 3rd administration within a cycle. Thus, the present study will examine 100 
mg/m2 ABI-009 given weekly for 2 weeks followed by a week off. This change in schedule will not 
substantially impact the total drug received by the patients. In a period of 6 months (24 weeks) 
of treatment, the 2/3 schedule will allow 16 administrations, while the 3/4 schedule will allow 18 
administrations.   


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2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Objectives  
• The primary objective of this pilot phase 2 study is to evaluate the preliminary efficacy of 
ABI-009 in patients with grade 1 and 2 neuroendocrine tumors (NETs) of the 
gastroenteropancreatic system or lung, as measured by disease control rate (DCR) at 6 
months 
• The secondary objectives are to evaluate the safety and toxicity profile of ABI-009 as well 
as the Overall Response Rate (ORR) 
2.2. 
Endpoints 
Primary Endpoint 
• Disease control rate at 6 months, assessed by investigator using Response Evaluation 
Criteria in Solid Tumors (RECIST) v1.1 
Secondary Endpoints 
• Safety and toxicity 
• ORR: partial or complete response per RECIST v1.1 
2.3. 
Study Design 
This study is a prospective pilot phase 2, single arm, single center, open-label, evaluate the 
efficacy and safety ABI-009 in patients with gastroenteropancreatic NET (GEPNETs) or NET of the 
lung and prior exposure to everolimus. ABI-009 at 75 mg/m2 will be given IV weekly for 2 weeks 
followed by a week of rest (qw2/3) in a 21-day cycle (on D1 and 8).  
The study will be conducted in compliance with International Conference on Harmonisation (ICH) 
Good Clinical Practices (GCPs). 
2.4. 
Study Duration, End of Study, End of Treatment, End of Treatment Visit, Follow-up 
Period 
The study is expected to take approximately 24 months from first patient enrolled to last patient 
follow-u.p The study will take approximately  12 months to enroll all patients and an estimated 
12 months of treatment per patient, or until treatment is no longer tolerated.   
End of Treatment (EOT) for a patient is defined as the date of the last dose of ABI-009. End of 
Treatment Visit for a patient is when safety assessments and procedures are performed after the 
last treatment, which must occur within 1 month after the last dose of ABI-009.   
The End of Study (EOS) defined as either the date of the last visit of the last patient to complete 
the study, or the date of receipt of the last data point from the last patient that is required for 
primary, secondary, and/or exploratory analysis, as pre-specified in the protocol.  
The follow-up period begins after the EOT Visit. All patients that discontinue study drug and have 
not withdrawn full consent to participate in the study will continue in the follow-up phase for 
survival or initiation of new anticancer therapy. Follow up will continue approximately every 12 
weeks (±3 weeks), until death, withdrawal of consent, start of new anticancer therapy, or the 
study closes, whichever is the earliest. This evaluation may be made by record review and/or 
telephone contact. 


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3. 
STUDY POPULATION 
3.1. 
Number of Patients 
The sample size for pilot phase 2 will be up to 10 evaluable patients. 
3.2. 
Inclusion Criteria  
A patient will be eligible for inclusion in this study only if all of the following criteria are met 
during screening: 
1. Unresectable or metastatic patients with typical or atypical carcinoid tumors of the 
lung or low or intermediate grade GEPNETS. 
2. Patients must have measurable disease per RECIST 1.1. 
3. Patients must have progressed on everolimus or been intolerant to everolimus as 
defined as discontinued for any adverse reactions other than allergic reaction.  
4. Patients, ≥18 years old, must have Eastern Cooperative Oncology Group (ECOG) 
Performance Status 0 or 1. 
5. Concurrent use of somatostatin analogs (SSAs) is allowed if currently used for 
symptom control. 
6. Adequate liver function: 
a. Total bilirubin ≤1.5 x upper limit of normal (ULN) mg/dL 
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN 
(<5 x ULN if the patient has liver metastases). 
7. Adequate renal function: 
a. Serum creatinine ≤2 x ULN or creatinine clearance >50 ml/min (Cockcroft-Gault). 
8. Adequate biological parameters: 
a. Absolute neutrophil count (ANC) ≥1.5 × 109/L 
b. Platelet count ≥100,000/mm3 (100 × 109/L) 
c. Hemoglobin ≥8 g/dL. 
9. Fasting serum triglyceride ≤300 mg/dL; fasting serum cholesterol ≤350 mg/dL. 
10. Male or non-pregnant and non-breast feeding female: 
• 
Females of child-bearing potential must agree to use effective contraception 
without interruption from 28 days prior to starting IP throughout 3 months after 
last dose of IP 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 after the end of study treatment. A second form of birth control is required 
even if she has had a tubal ligation. 
• 
Male patients 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 and throughout 3 months after last dose of IP. A second 
form of birth control is required even if he has undergone a successful vasectomy. 
11. Life expectancy of >3 months, as determined by the investigator. 
12. Ability to understand and sign informed consent. 
13. Willingness and ability to comply with scheduled visits, laboratory tests, and other 
study procedures. 


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3.3. 
Exclusion Criteria  
A patient will not be eligible for inclusion in this study if any of the following criteria apply during 
screening: 
1. Patients currently undergoing anti-cancer therapy for neuroendocrine tumors (other than 
SSAs for symptoms). 
2. History of allergic reactions to compounds of similar chemical or biologic composition to 
ABI-009. 
3. Known active uncontrolled or symptomatic central nervous system (CNS) metastases. A 
patient with controlled and asymptomatic CNS metastases may participate in this study. 
As such, the patient 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. Active gastrointestinal bleeding. 
5. Uncontrolled serious medical or psychiatric illness.  
6. Patients with a "currently active" second malignancy other than non-melanoma skin 
cancers, carcinoma in situ of the cervix, resected incidental prostate cancer (staged pT2 
with Gleason Score ≤6 and postoperative PSA <0.5 ng/mL), or other adequately treated 
carcinoma-in-situ are ineligible. Patients are not considered to have a "currently active" 
malignancy if they have completed therapy and are free of disease for ≥1 year). 
7. 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). 
8. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy. 
9. Unstable coronary artery disease or myocardial infarction during preceding 6 months. 
10. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary 
hypertension. 
11. Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the 
first dose of ABI-009. Additionally, use of any known CYP3A4 substrates with narrow 
therapeutic 
window 
(such 
as 
fentanyl, 
alfentanil, 
astemizole, 
cisapride, 
dihydroergotamine, pimozide, quinidine, terfanide) within the 14 days prior to receiving 
the first dose of ABI-009.  
12. Known Human Immunodeficiency Virus (HIV). 
13. Known active Hepatitis B or Hepatitis C. 


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4. 
TABLE OF EVENTS 
The schedule of assessments in Table 1 outlines the specific time points for study assessments. 
 


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Table 1. Schedule of Assessments 
  
Assessments a 
Baseline 
Screening 
b 
Treatment Phase 21-day (3-week) Cycles 
Days 
End of Treatment (EOT) Visit d 
Follow-up d  
 
1  
8 
15c 
Informed Consent 
x 
 
 
 
Demographics / Medical History e 
x 
 
 
 
 
 
I/E Criteria 
x 
 
 
 
 
 
Pregnancy Test f 
x 
 
 
 
x 
Physical Exam 
x 
x 
x 
x 
x 
Vital Signs, Height, and Weight g 
x 
x 
x 
x 
x 
Prior / Concomitant Medications 
and Procedures 
x 
x 
x 
x 
x 
CBC/Differential 
x 
x 
x 
x 
x 
 
Chemistry Panel 
x 
x 
x 
x 
x 
 
Fasting Lipids and Fasting 
Cholesterol 
x 
Even Cycles 
 
 
 
Sirolimus level h 
 
C2, C3 and C4 
C1, C2, C3 
and C4 
C1, C2, C3 
ad C4 
 
ECOG Performance Status 
x 
x 
 
 
x 
CT i 
x 
Every 9 weeks from 1st dose during the 1st year, then every 12 weeks until disease progressions or last 
treatment 
ABI-009 Infusion j 
 
x 
x 
 
Adverse Event Assessment 
Continuous from the signing of the informed consent to 28 days after last study treatment 
Survival 
 
 
 
 
 
x 
 
 
 
 
 
a All visits are allowed to occur in a window of ±3 days unless otherwise specified.  


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b Baseline screening visit will be done within 28 days prior to study treatment Day 1.  
c Day 15 evaluations are required only during Cycles 1 and 2 to obtain additional safety and laboratory evaluations, then, based on investigator discretion, 
patients may opt to take ‘visit holidays’ on D15.  
d End of Treatment-phase (EOT) Visit should be within 1 month of last study treatment. Follow up will be every 12 weeks, after EOT or last visit till study closes 
or withdrawal of consent, via phone call. 
e Collect reports of tumor molecular profiling, if available. 
f For all female patients of childbearing potential, a serum pregnancy test will be done at screening. A 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. Pregnancy tests conducted after screening will be recorded in 
the source documentation only.  
g Height is measured only at screening. BSA will be capped at 2 m2 for dose calculation. 
h Sirolimus levels are done locally and for all patients to determine trough levels: C1 D8 prior to dosing and on the D15 visit, and in C2 through C4 D1 and 8 prior 
to dosing and on D15 visit.  
i Baseline imaging should be done as close to C1 D1 as possible, then every 9 weeks (±1 week) from first treatment during the 1st year, and every 12 weeks 
thereafter through disease progressions, regardless of missed or out of window doses. If a patient discontinued treatment other than disease progression, scan 
should be done at EOT visit. MRI is allowed, if CT is contra-indicated for a patient. The same mode of imaging at screening must be used consistently throughout 
the study. If functional imagining, including GA68 PET/CT were done as SOC, they may be collected if they were conducted within 60 days prior to enrollment 
and/or 60 days after last treatment. 
j ABI-009 must be administered after all study specific assessments are done in a visit. 


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5. 
PROCEDURES 
5.1. 
Screening Evaluations 
This study will be conducted at 1 US center. Each patient who enters into the screening period 
for the study receives a unique patient identification number before any study-related 
procedures are performed. This number will be used to identify the patient throughout the 
clinical study and must be used on all study documentation related to that patient.  
The patient identification number must remain constant throughout the entire clinical study; it 
must not be changed after initial assignment, including if a patient is rescreened.  
Before patients may be entered into the study, the study funder requires a copy of the sites’ 
written IRB approval of the protocol, informed consent form, and all other patient 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 patient 
prior to performing any study-specific procedures. All patients must personally sign and date the 
consent form before commencement of study-specific procedures. Adverse events are to be 
collected for a patient once they have signed the informed consent.  
Screening evaluations will be performed for all patients to determine study eligibility. These 
evaluations must be obtained ≤28 days prior to enrollment. Any questions regarding patient 
eligibility should be directed to the investigator or designees 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, Table 1. 
• Demographics (date of birth, sex, race, and ethnicity)  
• Medical /cancer history, prior/concomitant medications and procedures evaluation: 
all medications taken ≤28 days prior to screening  
o Collect reports of tumor molecular profiling, if available 
• Physical examination as per standard of care (including physical exam, ECOG 
performance status assessment)  
• Vital signs (blood pressure, pulse, respiration rate, temperature, height, weight) 
• Local Laboratory Assessments: chemistry, complete blood count (CBC), differential, 
platelet count, pregnancy test (women of child-bearing potential, includes tubal 
ligations), fasting cholesterol and fasting lipids 
• CT scans (or MRI, if CT is contraindicated) should be done as close to C1D1 as possible 
• Adverse event assessment 
A patient is considered eligible when the investigator decides that the patient has met all 
eligibility criteria and documents this  in the patient’s medical record.. 
For laboratory assessments, see Table 2 for analyte listing. 
5.2. 
Treatment Period 
A patient is considered enrolled on study Day 1 when ABI-009, is first administered. ABI-009 must 
be administered after all other protocol-specified pre-dosing assessments have been performed. 
Patients will continue therapy until disease progression, unacceptable AE, withdrawal of consent, 
or withdrawal by the investigator.  


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5.2.1. 
Day 1 Assessment 
The following assessments will be performed on Day 1 of each cycle, unless otherwise specified: 
• Physical examination  
• Vital signs, including weight 
• Concomitant medication and procedures evaluation  
• CBC, differential  
• Clinical chemistry panel 
• Fasting lipids and fasting cholesterol (every even cycles) 
• Sirolimus level, C2 through C4 (for trough level) prior to dosing 
• ECOG performance status 
• Adverse events assessment 
Day 1 evaluations for Cycle 1 may be omitted if screening evaluations are performed within 72 
hours of Cycle 1 Day 1. 
5.2.2. 
Day 8 Assessment 
The following assessments will be performed on Day 8 of each cycle, unless otherwise specified: 
• Physical evaluation 
• Vital signs, including weight 
• Concomitant medication and procedures evaluation 
• CBC, differential 
• Clinical chemistry panel  
• Sirolimus level, C1 through C4 (for trough levels) prior to dosing 
• Adverse event assessment 
5.2.3. 
Day 15 Assessment 
The following assessments will be performed on Day 15 in Cycles 1 and 2, there after this visit is 
optional: 
• Physical evaluation 
• Vital signs, including weight 
• Concomitant medication and procedures evaluation 
• CBC, differential  
• Clinical chemistry panel  
• Sirolimus level, C1 through C4 (for trough levels) prior to dosing 
• Adverse event assessment 


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Table 2. Analyte Listing 
Chemistry 
Hematology 
Other Labs 
Sodium 
WBC 
Pregnancy test 
Potassium 
RBC 
Total Cholesterol  
Bicarbonate 
Hemoglobin 
HDL 
Chloride 
Hematocrit 
LDL 
Total protein 
MCV 
Triglyceride 
Albumin 
MCH 
Sirolimus 
Calcium 
MCHC 
 
Magnesium 
RDW 
 
Phosphorus 
Platelets 
 
Glucose 
Differential: 
 
BUN 
-Neutrophils 
 
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, if CT is contra-indicated) 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 or MRI scans to be performed at the following frequency during the study: 
• Screening, preferable as close to C1 D1 as possible 
• followed by every 9 weeks for the first year; then every 12 weeks until disease 
progression. End of Treatment Visit CT (or MRI) should be performed only for those 
patients 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 and clinical management of 
patients on study will be assessed at the local site.  
5.3. 
End of Treatment Visit Assessment 
The EOT Visit is a safety follow-up visit that is to be performed within 1 month after the last dose 
of ABI-009. All efforts should be made to conduct this visit. If it is 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 (Table 1): 
• Physical examination  
• Vital signs, including weight  
• Concomitant medications and procedures evaluations 


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• Pregnancy test (urine test is sufficient) 
• CBC /differential 
• Chemistry panel 
• ECOG performance status 
• Imaging Assessment: CT/PET (or MRI) is to be performed at the EOT visit only for those 
patients that discontinue treatment for a reason other than disease progression per 
RECIST v1.1  
5.4. 
Sirolimus Trough Levels 
Assays for sirolimus will be performed on patients in the dose-finding (phase 1) portion of the 
study, who received ABI-009 during C1 through C4, to determine trough levels, assessed via 
local lab: 
• 
Cycle 1: D8 prior to dosing, and on the D15 visit 
• 
Cycle 2 through Cycle 4: D1 and 8 prior to dosing, and on D15 visit 
5.5. 
Follow-up Period for Survival and Initiation of Anticancer Therapy  
Post-treatment survival time will be monitored approximately every 12 weeks (±3 weeks) from 
EOT 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. 
ABI-009 Dosage, Administration, and Schedule 
Treatment cycles are 21 days in duration and patients are treated until disease progression or 
unacceptable toxicities. Patients will receive ABI-009 75 mg/m2 (IV infusion over 30 minutes, 
+10 min) weekly for 2 weeks followed by a week of rest (2/3 weekly schedule). The schedule 2 
weeks out of a 3-weekly schedule will allow the patient to have 1-week rest, when most of the 
toxicities occur, based on experience in the phase 1 study of ABI-009 (Protocol CA401). The 
starting dose may be escalated from 75 mg/m2 to 100 mg/m2 only after completing 2 cycles of 
continuous treatment at their originally assigned dose level and upon meeting the criteria as 
follows: 
• No observation of Grade > 2 adverse event(s) considered related to study treatment  
• Meet the hematological requirements as outlined in section 6.2 
• Ongoing clinical benefit: Patients must have no clinical signs or symptoms of progressive 
disease  
• No clinically significant safety or tolerability concern in the opinion of the investigator   
Dose reduction levels are allowed from 75 mg/m2: 60, 45, and 30 mg/m2 in incremental order. 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. 
The subject’s weight on Cycle 1 Day 1 will be considered the baseline weight for drug dosing. BSA 
will be calculated at baseline and recalculated if the weight changes by 10%. BSA will be capped 
at 2m2. 
6.2. 
ABI-009 Dose Modification and Stopping Rules 
If, treatment cannot be administered on the planned visit date, ABI-009 may be administered ± 
2 days from the scheduled date. Prior to ABI-009 administration on Day 1 of each cycle, patients 
must meet the following hematological requirements: 
• ANC ≥1.5 x 109/L 
• Platelet count ≥100 x 109/L 
• Hemoglobin ≥8 g/dL (transfusions are allowed if clinically indicated) 
The treatment will be on hold up to 14 days until the patient has fulfilled these criteria. 
Day 1 Dose Missed 
If the dose held or missed was to be given on Day 1 of the next cycle, that next cycle will not be 
considered to start until the day the first dose is actually administered to the patient (ie, D1-D8-
Rest, X-D1-D8-Rest, etc). 
Day 8 Dose Is Missed 
That week becomes the week of rest. Next dose (if counts and chemistries permit) becomes Day 
1 of a new cycle (ie, D1-D8-Rest, D1-X, D1-D8-Rest, etc).   
The maximum delay between a missed scheduled dose and the next one (whichever dose was 
missed) should not be longer than 14 days. When there is evidence of clinical benefit or in the 


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opinion of the principal investigator the patient’s best interest is to continue therapy, treatment 
may be restarted after ≥21 days.  
Doses will be reduced for hematologic and other toxicities, according to criteria below. Dose 
reductions will occur sequentially (60, 45, and 30 mg/m2), there should be no direct reduction 
by 2 dose levels. Dose adjustments are to be made according to the system showing the 
greatest degree of toxicity.  Toxicities will be graded using the National Cancer Institute (NCI) 
Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 
Guidelines for dose modifications and interruptions for management of common toxicities 
associated with the study treatment(s) are provided in this section: 
• General guidelines for clinically significant toxicities related to study treatment 
And 
• Specific guidelines for adverse events of special interest, which are events that have been 
observed with higher frequency or severity. 
In the event of clinically significant AE in any part of the study (Table 4), treatment may be 
withheld, 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 14 days of stopping 
therapy, then treatment may be restarted. Dose reduction of ABI-009 should be considered as 
clinically indicated. 
If the toxicity does not resolve to at least grade 1 in less than 14 days, withdrawal from treatment 
with the IP is recommended. However, if, in the opinion of the investigator, further treatment 
would benefit the patient, treatment can continue with at least 1 dose level dose reduction, per 
Table 3.  
Table 3:  
Dose Level Modification Guidelines 
Dose level 
ABI-009 Dose/Schedule 
+1 (optional dose escalation) 
100 mg/m2 (if criteria in section 6.1 is met) 
0 
Initial Dose: 75mg/m2 
-1 (first dose reduction) 
20% reduction of initial dose of 75 mg/m2: 60 mg/m2 
-2 (second dose reduction) 
25% reduction from 60 mg/m2: 45 mg/m2 
-3 (third dose reduction)  
33% reduction from 45 mg/m2: 30 mg/m2 
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 
increased to the previous dose level. The dose of ABI-009 will not be increased to the previous 
dose level if a second AE requiring dose reduction occurs. 
Any patient meeting the criteria for Hy’s Law case (ie, severe drug-induced liver injury) will be 
considered a Adverse Event. A Hy’s Law case is defined as: AST or ALT values of ≥3 x ULN AND 
with serum total bilirubin level (TBL) of >2 x ULN without signs of cholestasis and with no other 
clear alternative reason to explain the observed liver-related laboratory abnormalities. 


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ABI-009 dose modification guidelines are outlined in Table 3. for clinically significant toxicities 
that are deemed related. The dosing schedule is described in the Schedule of Assessments Table 
1. 
Table 4. Dose Modification Algorithms for Adverse Events Possibly Related to ABI-009 
System/Organ 
Adverse Event 
CTCAE 
Grade 
v5.0 
Dose modification Algorithm 
Mucosa a 
Stomatitis, mucosal 
inflammation 
Grade 2 
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 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. 
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. 


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Metabolic 
disorders 
Hyperlipidemia 
(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 
Grades 1 
and 2 
Start at home 2x/day glucose monitoring; 
initiate medical management. 
Grade 3 
Initiate medical management; If recurrent 
post ABI-009 despite adequate medical 
management, reduce by 1 dose level. 
Grade 4 
Initiate medical management, hold ABI-009 
until grade 2 or less, restart 1 dose level 
lower 
Hematologic 
toxicity 
Thrombocytopenia, 
Neutropenia, Anemia 
Grade 2 
ABI-009 can be administered if the following 
hematological requirements: ANC >1.5 x 
109/L, platelets >100 x 109/L and hemoglobin 
≥8 g/dL. 
Grade ≥3 
Hold ABI-009 immediately for the remainder 
of that cycle.  Repeat blood collection within 
3 days.  ABI-009 can resume once meeting 
following requirements: absolute ANC >1.5 x 
109/L, platelet count > 100 x 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. 
Respiratory 
events 
Pneumonitis, 
bronchiolitis 
obliterans, and/or 
organizing 
pneumonia 
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 remove patient from protocol 
treatment. 
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. Patients 


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will be withdrawn from the study if they fail 
to recover to ≤ grade 1 within 3 weeks. 
For grade 4 noninfectious pneumonitis, 
permanently discontinue ABI-009. 
a Prophylactic approaches to prevent stomatitis such as steroid mouthwash (10 mL dexamethasone 0.1 mg/mL oral 
solution four times daily) could be considered for those who develop or at risk for stomatitis. 
6.3. 
Hepatotoxicity Stopping Rules  
Patients with abnormal hepatic laboratory values (ie, ALP, AST, ALT, total bilirubin TBL) and/or 
signs/symptoms of hepatitis may meet the criteria for withholding or permanent discontinuation 
of ABI-009 as specified in the Guidance for Industry Drug-Induced Liver Injury: Premarketing 
Clinical Evaluation, July 2009. 
6.3.1. 
Criteria for Permanent Discontinuation of ABI-009 Due to Potential Hepatotoxicity 
ABI-009 should be discontinued permanently and the patient should be followed for possible 
drug-induced liver injury (DILI), if ALL of the criteria below are met:  
• TBL >2 x upper limit of normal (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 TBL 
values include, but are not limited to: 
− Hepatobiliary tract disease 
− Viral hepatitis (eg, 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 (eg, Gilbert’s Syndrome, 
Crigler-Najjar syndrome) and drugs that inhibit bilirubin glucuronidation 
(eg, 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 (eg, rhabdomylosis, hemolysis) 
6.3.2. 
Criteria for Conditional Withholding of ABI-009 Due to Potential Hepatotoxicity 
For patients 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 


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baseline or patients with underlying liver disease and baseline abnormal transaminases, the 
following rules are recommended for withholding of ABI-009: 
• Elevation of either AST or ALT according to the following schedule: 
Baseline AST or ALT value 
AST or ALT elevation  
Any 
>8 x ULN at any time 
Any 
>5 x ULN but <8 x ULN for ≥2 weeks 
Any 
>5 x ULN but <8 x ULN and unable to adhere to 
enhanced monitoring schedule 
Any 
≥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: TBL >3 x ULN at any time 
• OR: ALP >8 x ULN at any time 
ABI-009 should be withheld pending investigation into alternative causes of DILI.  Rechallenge 
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. 
6.3.3. 
Overdose  
On a per dose basis, an overdose is defined as 10% over the protocol-specified dose of ABI-009 
assigned to a given patient, 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 for each infusion. 
 
 


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7. 
STUDY DRUG MANAGEMENT  
7.1. 
Description of Study Drugs  
7.1.1. 
ABI-009 Packaging, Labeling, and Storage 
ABI-009 will be supplied to the sponsor in single-use vials as lyophilized product. Each single-use 
50-mL vial will contain 100 mg sirolimus 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 ABI-009 should be stored in a refrigerator (2°-8°C; 36°-46°F) in original cartons 
to protect from light. Reconstituted ABI-009 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 ABI-009 
and reconstituted ABI-009 should be stored in an area free of environmental extremes and must 
be accessible only to study personnel. 
Temperature records for ABI-009 must be made available to Aadi Bioscience or designee for 
verification of proper study drug storage. 
7.2. 
ABI-009 Accountability, Disposal, and Compliance 
For ABI-009, only completely unused study drug vials should be retained by the site until a 
representative from Aadi Bioscience or designee 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 ABI-009, the investigator or designee shall record the dispensing of study drug to patients 
and any remaining study drug after dosing in a study drug accountability record. The study drug 
record will be made available to Aadi Bioscience or designated 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 Aadi Bioscience or their designee and a plan for resolution will be 
documented. 
Accurate recording of all ABI-009 administration will be made in the appropriate section of the 
patient’s CRF and source documents. The investigator or designee is responsible for accounting 
for all study-specific IP either administered or in their custody during the course of the study. 
7.3. 
ABI-009 Reconstitution and Use 
NOTE: It is not a requirement to use filter needles in the preparation, or in-line filters during the 
administration of ABI-009. In any event, filters of pore size less than 15 microns (15 µm) must not 
be used. 
ABI-009 will be reconstituted by appropriate study personnel following the Pharmacy Manual 
and administered to the patient in the study site (see below). The investigator will calculate the 
BSA of the patient in order to determine the total amount of ABI-009 to be administered. The 
BSA will be capped at 2 m2. 
7.4. 
Receipt and Return of ABI-009 
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 the signing of informed consent through the EOT 
Visit. Use of prohibited medications and procedures will be evaluated and documented during 
screening and on study. Therapy name including indication, dose, frequency, route, start date 
and stop date will be recorded on each patient’s CRF(s).  
Concurrent use of somatostatin analogs can be used for symptom control.  Initial dosing as well 
as any dose adjustments will be documented. 
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. 
Patients should receive full supportive care during the study, including transfusions of blood and 
blood products, and treatment with antibiotics, anti-emetics, anti-diarrheals, and analgesics, and 
other care as deemed appropriate, and in accordance with their institutional guidelines. G-CSF 
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. For patients that are able to have children, two 
methods of contraceptives should be used, one of which should be a barrier contraceptive.  
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 investigator can approve such use. 
The following medications or non-drug therapies are prohibited: 
• Other anti-cancer therapy while on treatment in this study (other than somatostatin 
analogs if used for symptom control). 
• Antiretroviral drugs (patients with known HIV are ineligible for study participation). 
• Herbal remedies (eg, St. John’s wort) unless approval is granted by the medical monitor. 
• Sirolimus is metabolized primarily by CYP3A4. Drugs that are strong inhibitors or inducers 
of CYP3A4 may only be used under special circumstances (eg, as a single use for a 
procedure) while treatment with study drug is interrupted. The list may be modified 
based on emerging data.  


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• Use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, 
alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfanide) that 
are contra-indicated in the opinion of the investigator, within the 14 days prior to 
receiving the first dose of ABI-009.   
• 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 
Primary Endpoint:  
• Disease control rate at 6 months, assessed by investigator using Response 
Evaluation Criteria In Solid Tumors (RECIST) v1.1.  
Secondary Endpoints:  
• ORR  
• Safety  
9.2. 
Safety Analysis 
The safety analysis set includes all treated patients. 
Safety and tolerability will be monitored through continuous reporting of treatment-emergent 
and treatment-related AEs, AEs of special interest (Table 4), laboratory abnormalities that are 
clinically significant, and incidence of patients 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 patient signs informed consent until 28 days 
after the last dose of IP. Adverse events will be graded by NCI CTCAE v5.0. Clinically significant 
labs will be determined by the investigator. 
Physical examination, vital signs, laboratory assessments (eg, serum chemistry, hematology), and 
ECOG performance status will be monitored. All SAEs (regardless of relationship to IP) will be 
followed until resolution. Local laboratory analysis will be performed as per study schedule. 
9.3. 
Efficacy Analysis  
The Efficacy Analysis Set includes all enrolled patients with measurable tumor per RECIST v1.1 at 
baseline who received at least 1 dose of ABI-009 and had a follow-up CT (or MRI). 
Efficacy will be assessed by investigators using CT scans and RECIST v1.1.   
The DCR at 6 months is the proportion of patients who achieve complete response (CR) or partial 
response (PR) or stable disease (SD) at 6 months.  
9.4. 
Sample Size Considerations 
In this pilot phase 2 study, up to 10 evaluable patients should be sufficient to provide preliminary 
information for efficacy and safety of ABI-009 in this patient population. 
9.5. 
Primary Analysis 
For this study will occur after all patients have either completed the study or completed at least 
12 months of treatment. Patients 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 ABI-009  
ABI-009 is a formulation of sirolimus. No unexpected toxicities not already known for sirolimus 
(Rapamune®) or the sirolimus prodrug, temsirolimus (Torisel®), were identified in the nonclinical 
toxicity studies, or observed in the phase 1 studies for ABI-009. 
More details on the known precautions, warnings, and AEs of sirolimus and rapalogs are found 
in the Rapamune® and Torisel® Package Inserts (Pfizer 2011, Pfizer 2011). 
10.2. 
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  
• Expectedness  
• Action taken 
The AE toxicity grading scale used will be the NCI CTCAE v5.0. 
10.3. 
Serious Adverse Events 
10.3.1. 
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 patient at immediate risk of death) 
• requires inpatient 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 (eg, overnight stay).   
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 (eg, 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 


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situation, comprehensive documentation of the event’s severity status must be recorded in the 
patient’s medical record.   
10.3.2. 
Reporting Procedures for Serious Adverse Events 
All SAEs that are treatment-related must be reported by the investigator to their IRB in writing, 
and to the FDA within 7 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 or designee within 24 hours of the 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 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 28 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 patient 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 investigator is responsible for informing the IRB of the 
SAE and providing them with all relevant initial and follow-up information about the event. The 
investigator must keep copies of all SAE information on file including correspondence with Aadi 
Bioscience and the IRB. 
10.4. 
Pregnancy and Breast-feeding Reporting 
If a pregnancy occurs in a female patient, or female partner of a male patient, while the patient 
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.  
The investigator will follow the female patient 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 a lactation case occurs while the female patient 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 patient 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 patient 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 patient 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 patient withdraws from treatment.  
Patients 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. 
Investigator or Sponsor Decision to Withdraw or Terminate Patient’s Participation 
Prior to Study Completion 
The investigator and/or sponsor can decide to withdraw a patient(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.    
Patients may be eligible for continued treatment with Aadi Bioscience’s IP 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 
An initial sample informed consent form is provided for the investigator to prepare the informed 
consent document to be used at his or her site. Updates to the template are to be communicated 
formally in writing from the investigator to Aadi Bioscience. The written informed consent 
document is to be prepared in the language(s) of the potential patient population. 
Before a patient’s participation in the clinical study, the investigator is responsible for obtaining 
written informed consent from the patient 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 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 patient. 
If a potential patient is illiterate or visually impaired, the investigator must provide an impartial 
witness to read the informed consent form to the patient and must allow for questions. 
Thereafter, both the patient and the witness must sign the informed consent form to attest that 
informed consent was freely given and understood.   
12.2. 
Institutional Review Board  
A copy of the protocol, proposed informed consent form, other written patient 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 patients into the study and shipment of Aadi Bioscience’s IP. 
The investigator must submit and, where necessary, obtain approval from the IRB for all 
subsequent protocol amendments and changes to the informed consent document. The 
investigator is to notify the IRB of deviations from the protocol or SAEs occurring at the site and 
other AE reports received from Aadi Bioscience, in accordance with local procedures. 
The investigator is responsible for obtaining annual IRB approval /renewal throughout the 
duration of the study. Copies of the investigator’s reports and the IRB continuance of approval 
must be sent to Aadi Bioscience. 
12.3. 
Patient Confidentiality 
The investigator must ensure that the patient’s confidentiality is maintained for documents 
submitted to Aadi Bioscience. 
• Patients are to be identified by a unique patient 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 patient identification 
number, include the age at time of enrollment. 
• For SAEs reported to Aadi Bioscience, patients are to be identified by their unique 
patient identification number, initials (for faxed reports, in accordance with local laws 
and regulations), and date of birth (in accordance with local laws and regulations). 


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• Documents that are not submitted to Aadi Bioscience (eg, 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 investigator 
and institution permit authorized representatives of the company, of the regulatory agency(s), 
and the IRB direct access to review the patient’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 patient to permit such 
individuals to have access to his/her study-related records, including personal information. 
12.4. 
Protocol Amendments   
If investigator amends the protocol, agreement from Aadi Bioscience must be obtained. The IRB 
must be informed of all amendments and give approval. The 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 investigator reserve the right to terminate the investigator’s 
participation in the study according to the study contract. The 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 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. 
Investigator Responsibilities for Data Collection 
The investigator is responsible for complying with the requirements for all assessments and data 
collection (including patients not receiving protocol-required therapies) as stipulated in the 
protocol for each patient in the study. For patients who withdraw prior to completion of all 
protocol-required visits and are unable or unwilling to continue the Schedule of Assessments 
(Table 1), 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. 


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14. 
QUALITY CONTROL AND QUALITY ASSURANCE 
14.1. 
Study Monitoring, Audits and Inspections 
The investigator will permit study-related monitoring, audits, and inspections by the IRB, 
government regulatory bodies, and institution’s compliance and quality assurance groups of all 
study related documents (e.g. source documents, regulatory documents, data collection 
instruments, study data etc.).  The investigator will ensure the capability for inspections of 
applicable study-related facilities (e.g. pharmacy, diagnostic laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable Ochsner compliance and quality assurance 
offices. 


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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. 
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