Conditions: Triple Negative Breast Cancer Breast Neoplasms
Keywords: clinical stage I, II or III TNBC ER positive PR positive HER2 positive
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 16
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate a new investigational cancer vaccine, P10s-PADRE in combination with standard neoadjuvant chemotherapy and surgery in patients with clinical stage I, II or III triple negative breast cancer (TNBC). This study will compare the vaccine plus standard neoadjuvant chemotherapy and surgery to standard neoadjuvant chemotherapy and surgery alone.

Detailed description:
The purpose of this study is to evaluate an investigational agent, P10s-PADRE, a peptide mimotope-based vaccine, in combination with standard neoadjuvant chemotherapy in patients with clinical stage I, II or III estrogen-receptor (ER) negative, progesterone receptor (PR) negative and HER2-negative (= triple negative - TN) breast cancer. P10s-PADRE will be administered with MONTANIDE™ ISA 51 VG as adjuvant. Human breast cancers that express Tumor Associated Carbohydrate Antigens (TACAs) can be immunogenic, and enhancing the anti-TACA antibodies and immune effector function already present may augment the cytotoxic effects of standard therapies.

A randomized two-arm, open-label, multi-center phase I/II trial is designed with the goal being to evaluate the efficacy of combining vaccination of the P10s-PADRE formulation with neoadjuvant chemotherapy. Patients will be randomly assigned in a 2:1 ratio to standard chemotherapy plus P10s-PADRE or to standard chemotherapy alone. Efficacy will be based on the rate of pathologic Complete Response (pCR) observed among TN breast-cancer patients treated with the combination as compared with the group of patients who receive standard chemotherapy alone.

Arms:
arm 1: Subjects randomized to the control arm will receive SoC neoadjuvant chemotherapy starting on week 1. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks. arm 2: Subjects randomized to the chemo+vaccine arm will be immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG a total of three times. The vaccine will be administered on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant chemotherapy on week 4. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks.

Interventions: intervention 1: P10s-PADRE with MONTANIDE™ ISA 51 VG intervention 2: Doxorubicin intervention 3: Cyclophosphamide intervention 4: Paclitaxel
Intervention descriptions: intervention 1: Subjects randomized to the control arm will receive SoC neoadjuvant chemotherapy starting on week 1. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks. intervention 2: Subjects randomized to the chemo+vaccine arm will be immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG a total of three times. The vaccine will be administered on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant chemotherapy on week 4. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks. intervention 3: Subjects randomized to the chemo+vaccine arm will be immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG a total of three times. The vaccine will be administered on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant chemotherapy on week 4. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks. intervention 4: Subjects randomized to the chemo+vaccine arm will be immunized with P10s-PADRE in MONTANIDE™ ISA 51 VG a total of three times. The vaccine will be administered on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant chemotherapy on week 4. Doxorubicin and cyclophosphamide (AC) will be administered concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks.

Protocol document:
ICF_002.pdf: 
 
 
 
 
 
 
 
 
 
 
Official Title: A Combined Phase i/II Efficacy Study of a Carbohydrate Mimotope-based 
Vaccine With MONTANIDE™ ISA 51 VG STERILE Combined With Neoadjuvant 
Chemotherapy in Triple Negative Breast Cancer 
 
“Vaccination of Triple Negative Breast Cancer Patients” 
IRB Number: 206010 
NCT Number: NCT02938442 
 
to be conducted at 
University of Arkansas for Medical Sciences 
Highlands Oncology Group 
 
Sponsor: University of Arkansas for Medical Sciences 
 
Principal Investigator: 
Sindhu Malapati 
4301 West Markham, Slot #724 
Little Rock, AR  72205 
Phone: (501) 686-8530 (during business hours) 
(501) 686-8511 (after business hours) 
 
Main Consent Form  
Version 10 
Dated October 6, 2021 


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CONSENT FORM 
AND INFORMATION ABOUT 
 
 
“Vaccination of Triple Negative Breast Cancer Patients” 
 
 
A Combined Phase I/II Efficacy Study of a Carbohydrate Mimotope-Based Vaccine 
with MONTANIDE™ ISA 51 VG STERILE Combined with Neoadjuvant 
Chemotherapy in Triple Negative Breast Cancer 
 
 
TO BE CONDUCTED AT 
UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES 
 
(Study Doctor: Sindhu Malapati, MD) 
 
 
 
 
 
 
 
SUBJECT NAME 
HOSPITAL ID NUMBER 
 
 
INTRODUCTION 
This is a clinical trial, a type of research study being conducted at the University of Arkansas for 
Medical Sciences (UAMS) and Highlands Oncology Group (HOG). This research is being 
sponsored by UAMS. Your research doctor will explain the clinical trial to you. Clinical trials 
include only people who choose to take part. Please take your time to make your decision about 
taking part. You may discuss your decision with your friends and family. You can also discuss it 
with your health care team. If you have any questions, you can ask your research doctor for more 
information. The vaccine that will be used in this study is not approved by the Food and Drug 
Administration (FDA) for general public use; however, the FDA has allowed it to be used in this 
research study. 
 
You are being asked to take part in this research study because you have triple negative breast 
cancer (breast cancer that is not very responsive to hormonal treatment or treatment targeting 
the HER2/neu protein). 
 
Why is this research being done? 
The purpose of this research is to compare the effect on your cancer of using a new experimental 
breast cancer vaccine (used to stimulate immune cell production) with chemotherapy and surgery 
versus the usual treatment of chemotherapy and surgery. This study will help us learn if the 
vaccine is safe and whether your body responds to the vaccine. We will also see if the vaccine 
helps to improve the effectiveness of the chemotherapy for treating your cancer. There are no 
commercially available breast cancer vaccines at this time. There are other breast cancer vaccine 
trials at other institutions but no other breast cancer vaccine trials are now available in Arkansas. 
 
 


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If you are eligible to participate, you will be randomized, like flipping a coin, into one of the two 
treatment groups in this study. Neither you nor your doctor can choose the group you will be 
assigned. The two treatment groups are described below: 
 
 
Group 1: subjects will receive the standard of care treatment for triple negative breast cancer 
consisting of chemotherapy and surgery. 
 
Group 2: subjects will receive the experimental vaccine in addition to the standard of care 
treatment for triple negative breast cancer consisting of chemotherapy and surgery. 
 
Mimotope P10s-PADRE Vaccine: 
The experimental vaccine is a small protein that is similar to proteins on breast cancer cells. 
Because the vaccine has a different chemical make-up, if the vaccine is successful, it will increase 
your body’s immune response against breast cancer. 
 
MONTANIDE™ ISA 51 VG STERILE: 
MONTANIDE™ ISA 51 VG is an investigational agent (not commercially available to the general 
public) that is mixed with the vaccine to make it stronger. Adding MONTANIDE™ ISA 51 VG to 
the experimental vaccine may stimulate your immune system even more than if the vaccine was 
given by itself. 
 
Throughout the remainder of this document, the combined P10s-PADRE/MONTANIDE™ ISA 51 
VG mixture is referred to simply as “the vaccine.” 
 
How many people will take part in research? 
We will screen up to 120 women in order to enroll up to 102 women, ages 18 and older with 
clinical stage I, II or III triple negative breast cancer from two sites in Arkansas: the University of 
Arkansas for Medical Sciences (UAMS) and Highlands Oncology Group (HOG). It is possible that 
up to 102 women are enrolled at either site but the total combined enrollment for both sites 
combined will not be more than 102. A total of 34 subjects will be enrolled into Group 1 (standard 
of care only) and a total of 68 subjects will be enrolled into Group 2 (standard of care plus 
experimental vaccine). This means you have a one in three chance of being assigned to the usual 
care group, and a two in three chance of being assigned to the usual care plus vaccine group. 
 
What is involved in this research? 
Your participation in this research is voluntary. If you refuse to participate in this research, you 
will not be penalized in any way and you will not lose any benefits to which you are otherwise 
entitled. If you choose to participate in this research, but then change your mind, you can stop 
participating in the research and you will not be penalized or lose any benefits. 
 
Before you begin the research: 
You will need to have the following exams, tests or procedures to find out if you can participate in 
the research study. Most of these exams, tests or procedures are part of regular cancer care and 
will be done even if you do not join the research. If you have had some of them recently, they may 
not need to be repeated. This will be up to your research doctor. 
 
 


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Summary of tests to be done prior to the study: 
Standard medical care for cancer treatments: 
 
Medical history and physical exam 
 
Blood work for blood counts, liver and kidney function and calcium level 
 
Urine pregnancy test if you are able to have children 
 
The total amount of blood that will be taken for standard medical care is one and a half teaspoons. 
 
Summary of tests to be done during the clinical trial: 
If the exams, tests and procedures show that you can be in the research, and you choose to take 
part, then you will need the following tests and procedures at different times throughout the study. 
 
These are standard for patients undergoing cancer treatments: 
 
Blood work for blood counts, liver and kidney function and calcium level 
 
Medical history and physical exams 
 
Notations of side effects 
 
Chemotherapy 
 
You will need the following tests and procedures that are either being tested in this research or 
are being done to see how the research is affecting your body: 
 
Blood work for research 
 
Investigational vaccine (for subjects assigned to Group 2 only) 
 
During this study, you will be asked to provide blood samples for research. For subjects in Group 
1, you will have three blood samples for research. For subjects in Group 2, you will have eight 
blood samples for research. Up to 100mL (approximately seven tablespoons) of blood will be 
collected each time “Blood work for research” is listed in the breakdown of study visits below. 
These samples will be used to determine the effect of the vaccine on your immune system. Any 
leftover samples will be discarded, unless you give us permission to save them for future research. 
 
We would like to collect leftover archival breast tissue samples from tissue collected as part of 
standard biopsy and/or surgery. Your doctor will not take any more tissue during biopsy and/or 
surgery than is needed for your care. These samples will be used to look at and examine the 
tissue and the effect of the vaccine on the tissue. 
 
To examine the effect of the vaccine on your immune system and tissue, we may test your blood 
and tumor samples for immune and tumor cell gene expression (genetic information about how 
cells behave) or methylation (epigenetic information about changes in genes that turn them “on” 
or “off”). 
 
What happens when I am finished taking the vaccine? 
The research lasts for approximately 70 weeks (about one year and three months). You will 
continue your standard treatments and follow-ups for breast cancer after completing the study. 
 
You should avoid becoming pregnant for at least 18 months after participation in the study (see 
additional information about pregnancy risks in the “Reproductive Risks” section). To avoid 
becoming pregnant, you should either abstain from sexual activity or practice a method of birth 
control. Except for surgical removal of the uterus, tubal ligation, and abstinence, birth control 


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methods such as oral contraceptives (birth control pills), barrier method, and IUDs (implanted 
device) are not totally effective in preventing pregnancy. 
 
Breakdown of study visits: 
Group 1 (standard chemotherapy and surgery only) 
The visit breakdowns below will give you a detailed description of everything that will happen 
while participating in this study. 
 
This breakdown includes standard chemotherapy and surgery, which are part of standard care. 
The chemotherapy and surgery are not being tested as part of this study. Your research visits will 
be combined with your regularly scheduled clinic visits. Research blood samples will be collected 
two times during the study. 
 
Screening visit prior to starting chemotherapy 
 
Sign informed consent 
 
Clinic visit for history and physical exam 
 
Body Mass Index (BMI) and the evaluation of weight change before the study 
 
Review of medications you are taking 
 
Routine blood work 
 
Urine pregnancy test for women who are able to have children 
 
Skin test 
 
48-72 hours after Screening visit 
 
Skin test reading 
 
Week 1 
 
Clinic visit for history and physical exam 
 
Administer routine chemotherapy - cyclophosphamide and doxorubicin with pegfilgrastim on 
day two of each AC cycle 
 
Review of side effects 
 
Review of medications you are taking 
 
Routine blood work (not repeated if screening blood work is done within 7 days of Week 1) 
 
Blood work for research 
 
Weeks 3 & 5 
 
Clinic visit for history and physical exam 
 
Administer routine chemotherapy - cyclophosphamide and doxorubicin with pegfilgrastim on 
day two of each AC cycle 
 
Review of side effects 
 
Review of medications you are taking 
 
Routine blood work 
 
Week 7 
 
Clinic visit for history and physical exam 
 
Administer routine chemotherapy - cyclophosphamide and doxorubicin with pegfilgrastim on 
day two of each AC cycle 
 
Review of side effects 
 
Review of medications you are taking 


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 
Routine blood work 
 
Blood work for research 
 
Weeks 9-20 (weekly) 
 
Clinic visit for history and physical exam (week 9, 12, 15, 18 and 20 only) 
 
Administer routine chemotherapy - paclitaxel (may be replaced with docetaxel) 
 
Review of side effects 
 
Review of medications you are taking 
 
Routine blood work 
 
Breast cancer surgery 
It is standard practice for surgery to be performed within 4-8 weeks after completion of 
chemotherapy. 
 
Week 46 & Week 70 
 
Clinic visit for history and physical exam 
 
Review of side effects 
 
Review of medications you are taking 
 
Routine blood work 
 
Blood work for research (Week 46 only) 
 
Group 2 (standard chemotherapy and surgery plus experimental vaccine) 
You will receive subcutaneous (SC) injections, or a shot given under the skin, of the vaccine at 
Weeks 1, 2, and 3 for a total of 3 doses. The shots will be given to you at different places on your 
abdomen. The visit breakdown below will give you a detailed description of everything that will 
happen while participating in this study. 
 
This breakdown includes standard chemotherapy and surgery, which are part of standard care. 
The chemotherapy and surgery are not being tested as part of this study, just your response to 
the vaccine. 
 
Your research visits will be combined with your regularly scheduled clinic visits, with the exception 
of the visits for weeks 2 and 3. These visits are just for research. Research blood samples will be 
collected eight times during the study. 
 
Screening visit prior to starting chemotherapy 
 
Sign informed consent 
 
Clinic visit for history and physical exam 
 
Body Mass Index (BMI) and the evaluation of weight change before the study 
 
Review of medications you are taking 
 
Routine blood work 
 
Urine pregnancy test for women who are able to have children 
 
Skin test 
 
48-72 hours after Screening visit 
 
Skin test reading 
 
 


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Week 1 
 
Clinic visit for history and physical exam 
 
Urine pregnancy test for women who are able to have children 
 
Administer vaccine 
 
Review of side effects 
 
Review of medications you are taking 
 
Blood work for research 
 
Weeks 2 & 3 
 
Administer vaccine 
 
Review of side effects 
 
Review of medications you are taking 
 
Weeks 4 & 6 
 
Clinic visit for history and physical exam 
 
Administer routine chemotherapy - cyclophosphamide and doxorubicin with pegfilgrastim on 
day two of each AC cycle 
 
Review of side effects 
 
Review of medications you are taking 
 
Routine blood work 
 
Week 7 
 
Review of side effects 
 
Review of medications you are taking 
 
Blood work for research 
 
Week 8 
 
Clinic visit for history and physical exam 
 
Administer routine chemotherapy - cyclophosphamide and doxorubicin with pegfilgrastim on 
day two of each AC cycle 
 
Review of side effects 
 
Review of medications you are taking 
 
Routine blood work 
 
Week 10 
 
Clinic visit for history and physical exam 
 
Administer routine chemotherapy - cyclophosphamide and doxorubicin with pegfilgrastim on 
day two of each AC cycle 
 
Review of side effects 
 
Review of medications you are taking 
 
Routine blood work 
 
Blood work for research 
 
Skin test 
 
48-72 hours after Week 7 
 
Skin test reading 
 
 


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Weeks 12-23 
 
Clinic visit for history and physical exam (week 12, 15, 18, 21 and 23 only) 
 
Administer routine chemotherapy - paclitaxel (may be replaced with docetaxel) 
 
Review of side effects 
 
Review of medications you are taking 
 
Routine blood work 
 
Blood work for research (week 15, 18 and 23 only) 
 
Breast cancer surgery 
It is standard practice for surgery to be performed within 4-8 weeks after completion of 
chemotherapy. 
 
Week 46 & Week 70 
 
Clinic visit for history and physical exam 
 
Review of side effects 
 
Review of medications you are taking 
 
Routine blood work 
 
Blood work for research 
 
How long will I be in the research? 
The approximate length of complete study participation will be around 18 months. 
 
If you are in Group 2, you will be treated with the vaccine for 3 doses within 3 weeks. If you have 
significant side effects or problems related to the vaccine, the remaining doses will not be given. 
If you discontinue the vaccine early, your visits will remain the same as listed above including 
collection of blood work for research. 
 
Can I stop being in the research? 
Yes. You can decide to stop at any time. Contact the research doctor if you are thinking about 
stopping or decide to stop. He or she will tell you how to stop safely. It is important to tell the 
research doctor if you are thinking about stopping so any risks from the vaccine can be evaluated 
by your doctor. Another reason to tell your doctor that you are thinking about stopping is to discuss 
what follow up care and testing could be most helpful for you. 
 
The research doctor may stop you from taking part in this study at any time if he/she believes it 
is in your best interest; if you do not follow the study rules; or if the study is stopped. This may 
happen without your consent. 
 
If there is new information from the research concerning side effects or new information about 
alternate treatments, which may benefit you, you will be informed by your research doctor. 
 
If you withdraw from the study, any information collected before you withdraw will be retained in 
the study. If blood samples are collected and you withdraw from the research, we will discard your 
samples. 
 
 


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What side effects or risks can I expect from being in the research? 
You may have side effects while on the research. Everyone taking part in the study will be watched 
carefully for any side effects. However, doctors do not know all the side effects that may happen. 
Side effects may be mild or very serious. Your health care team may give you medicines to help 
lessen side effects. Many side effects go away once you stop taking the vaccine. In some cases, 
side effects can be serious, long lasting, or may never go away. 
 
You should talk to your research doctor about any side effects that you have while taking part in 
the research. In general, the risks and side effects are lower than standard chemotherapy 
treatments and blood draws are similar in the quantity of blood taken and frequency of the tests. 
 
Risks and side effects related to the vaccine: 
Likely 
 
Localized itching, redness, stinging at the site of the injection of the vaccine 
 
A decrease in energy 
 
Temporary swelling, tenderness of the glands (lymph nodes) 
 
Discomfort from needles used for blood work 
 
Less Likely 
 
Flu-like symptoms including muscle ache, joint aches, fever, chills, nausea and diarrhea 
 
Rare but serious 
 
Severe allergic reactions (anaphylaxis) can result in shock and even death 
 
Over activation of your immune system 
 
Guillain-Barre Syndrome: a condition resulting in severe weakness to the point of not being 
able to walk or breathe. In extreme cases, it can require a breathing machine. It can be 
treated and most people recover. 
 
Risks and side effects related to MONTANIDE™ ISA 51 VG: 
 
Redness of the skin, rash, itching 
 
Diarrhea, loss of appetite, nausea, vomiting, abnormal taste 
 
Confusion 
 
Tingling or burning sensation 
 
Shortness of breath, chest pain 
 
High blood pressure, irregular heartbeat, chest pain 
 
Headache, joint pain, bone pain, abdominal pain, muscle pain 
 
Fever 
 
Flu-like syndrome (chills, achiness) 
 
Fatigue 
 
Risks and side effects related to blood collection: 
 
Pain or bruising at the injection site 
 
Rarely – infection 
 
 


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Reproductive Risks 
You should not become pregnant or have a baby while on this study and for 18 months after the 
last dose of the vaccine because the vaccine in this study may affect an unborn baby. Women 
should not breastfeed a baby while on this study. It is important you understand that you need to 
use birth control while on this study. Check with your study doctor about what kind of birth control 
methods to use and how long to use them. It is not known how the vaccine would affect an unborn 
baby. If you or your partner should become pregnant while participating in the study or within 18 
months of study participation, notify your physician. 
 
Other Risks 
 
Identification of previously unknown conditions during collection of medical history, physical 
exam assessment, or blood draw laboratory results. 
 
Possible breach of privacy and confidentiality. Participants will be identified by study 
numbers only on all research documents to minimalize the risk of a privacy and/or 
confidentiality breach. Research records will be stored in a locked area with access to study 
personnel only. 
 
Genetic Testing Risks 
With genetic testing of your tissue, there is a potential risk of loss of confidentiality. Every effort 
will be made to protect your confidential information, but this cannot be guaranteed. The genetic 
information obtained as a result of your participation in this research will not be included in your 
medical record. Information from which you may be personally identified will be maintained in a 
confidential, secure location in the Breast Cancer Vaccine Research Laboratory, accessible only 
by authorized members of the study team, and will not be disclosed to third parties except as 
described in this consent form, with your permission, or as may be required by law. 
 
Genetic testing involves unique risks such as psychological and social risks and the risk of re-
identification. Social risks include being stigmatized, discriminated against, labeled, or having 
difficulty obtaining employment or insurance. Some of your genetic information may be sent to 
other scientific or commercial databases, such as one maintained by the National Institutes of 
Health, for other researchers to use. This information would include a code number instead of 
your name. There is a risk that someone could trace the information back to you. Even without 
your name or other identifiers, your genetic information is unique to you. We believe the chance 
that someone will identify you is very small, because your samples will be coded (without your 
name or identifying information), but the risk may change in the future as people come up with 
new ways of tracing information. The genetic testing will be done for research purposes only, and 
we do not plan to return any results to you or your doctor. 
 
The Genetic Information Nondiscrimination Act (GINA) is a Federal law that will protect you in the 
following ways: 
 
Health insurance companies and group plans may not request genetic information from this 
research; 
 
Health insurance companies and group plans may not use your genetic information when 
making decisions regarding your eligibility or premiums; 
 
Employers with 15 or more employees may not use your genetic information when making 
a decision to hire, promote, or fire you or when setting the terms of your employment. 


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 
GINA does not protect you against genetic discrimination by companies that sell life 
insurance, disability insurance, or long-term care insurance. GINA also does not protect you 
against discrimination based on an already-diagnosed genetic condition or disease. 
 
Are there benefits to taking part in the research? 
Taking part in this research may or may not directly benefit your health. While doctors hope a 
breast cancer vaccine will be more useful against breast cancer as compared to the usual 
treatment, there is no proof of this yet. We do know that the information from this research will 
help doctors learn more about breast cancer treatment. This information could help future breast 
cancer patients. 
 
UAMS cannot and does not guarantee you will benefit if you take part in this study. The research 
drug you receive may even be harmful. You have the right to refuse to participate in this study. 
 
Will I be compensated (paid) to take part in this research? 
You will not receive any form of compensation or payment for your participation in this research 
study. 
 
What if I am injured while participating in this research? 
In the event you are hurt by being in this research, treatment will be available. This treatment may 
include: first aid, emergency treatment, and/or follow-up care. This treatment may be billed to you 
or your insurance company in the normal manner. There is no guarantee that your insurance 
company will agree to cover those charges. Normally, no other form of compensation is available. 
 
If you think you have been hurt by this research or if you have any questions about this medical 
care, let the study investigator know right away by calling Dr. Sindhu Malapati at (501) 686-8530. 
After hours, you may reach Dr. Malapati by digital pager at (501) 405-9707 or the medical 
oncology physician on call at UAMS at (501) 686-8530. 
 
Any suspected side effects must be brought to the attention of your physician immediately. 
 
What other choices do I have if I do not take part in this research? 
Your other choices may include: 
 
Chemotherapy or hormonal therapy as standard treatment or care for your cancer without 
the vaccine. 
 
Taking part in another study. 
 
No treatment 
 
Talk to your doctor about your choices before you decide if you will take part in this research. 
 
 


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Will my medical information be kept private? 
We will do our best to make sure that the personal information in your medical record will be kept 
private. However, we cannot guarantee total privacy. Your personal information may be given out 
if required by law. We may share your de-identified study information with other researchers 
outside of UAMS, and we may publish our findings or present them at scientific meetings. 
However, if information from this study is published, presented at scientific meetings, or shared 
for reanalysis with other researchers, your name and other personal information will not be used. 
Participants will be identified by study numbers only on all research documents. The connection 
with the participants name will be kept by research personnel in a locked facility. The study sites 
shall retain the records and reports for 2 years after a marketing application is approved for the 
drug; or, if an application is not approved for the drug, until 2 years after shipment and delivery of 
the drug for investigational use is discontinued and FDA has been so notified. After such time all 
study records will be destroyed as well as the links between identifiers of the research participants 
and their research study numbers, unless you give us permission to store your study information 
for future research. 
 
Authorized representatives from many organizations are eligible to review your medical records, 
including information that identifies you, as part of their responsibilities to protect human 
participants in research, and to conduct quality assurance, safety and data analysis. These 
organizations include: 
 
Winthrop P. Rockefeller Cancer Institute (WPRCI) 
 
Food and Drug Administration (FDA) 
 
National Cancer Institute (NCI) 
 
Office for Human Research Protections (OHRP) 
 
UAMS Institutional Review Board (IRB) 
 
UAMS Office of Research Compliance (ORC) 
 
UAMS Office of Research Regulatory Affairs (ORRA) 
 
Other institutional oversight offices 
 
Authorized representatives from these agencies may need to review your records and may see 
your name. They are bound by rules of confidentiality not to reveal your identity to others. 
 
In the future, it is possible that we may share your coded (de-identified) genetic testing results 
with other researchers in an public-access national database, so that other investigators can use 
them for research. We would use a code number instead of your name, address, or identifying 
information. This is done to confirm results from studies like ours and to allow for more rapid 
discoveries. There is a risk that someone could trace the information in a central database back 
to you. Even without your name or other identifiers, your genetic information is unique to you. The 
researchers believe the chance that someone will identify you is small, because your samples will 
be coded (without your name or identifying information), but the risk may change in the future as 
people come up with new ways of tracing information. 
 
By law, the study team must release certain information to the appropriate authorities if at any 
time during the study there is concern that abuse has possibly occurred or you disclose a desire 
to harm yourself or others. 
 
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. 
 


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Page 12 of 15 
Are there other things I should know about this trial? 
Dr. Kieber-Emmons, Dr. Karbassi and UAMS have a financial interest in the investigational 
vaccine used in this clinical trial. These financial interests have been reviewed by the UAMS 
Conflicts of Interest Committee. The study will be conducted in accordance with the UAMS conflict 
of interest policies. 
 
What are the costs of taking part in this research? 
The vaccine will be provided free of charge. The research will include tests and procedures that 
are conducted solely for the research study and not as part of routine care for your condition. You 
will not be charged for tests and procedures that are done only for research. You and/or your 
insurance will be billed for your routine care in the usual manner. Your insurance will usually only 
pay for the routine care and they may deny payment making you responsible for payment. 
 
In addition, your physician will discuss with you any additional tests and procedures that may be 
required due to changes of your condition during your research participation, which may or may 
not be routine care. Therefore, there may be additional charges billed to you if these tests are not 
considered as routine care. You have the right to refuse to have any additional tests or procedures 
done. If you feel that you have been billed in error, please contact Dr. Sindhu Malapati, who is 
responsible for conducting this study, at (501) 686-8530. 
 
What are my rights if I take part in this research? 
Taking part in this research is your choice. You may choose either to take part or not to take part 
in the research. If you decide to take part in this study, you may leave the study at any time. No 
matter what decision you make, there will be no penalty to you and you will not lose any of your 
regular benefits. Your relationship with your doctor or with UAMS will not be affected by not 
participating or leaving the research. Leaving the research will not affect your medical care. You 
can still get your medical care from our institution. 
 
We will tell you about new information or changes in the study that may affect your health or your 
willingness to continue in the study. We will tell you of any new findings (good or bad) in the 
research or new alternatives to participation that may cause you to change your mind about 
continuing in the research. If new information is provided to you, your consent may be re-obtained. 
You may also request the results of the research from your research doctor after all the analyses 
are completed. 
 
In the case of injury resulting from this study, you do not lose any of your legal rights to seek 
payment by signing this form. 
 
Who can answer my questions about the research? 
If you have questions during the study about the research, you should contact Dr. Sindhu Malapati 
at (501) 686-8530. For questions about your rights while taking part in this research, or to talk to 
someone independent of the research team, call the UAMS Institutional Review Board (a group 
of people who review the research to protect your rights) at (501) 686-5667. 
 
 


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Genetic Studies 
As described above, as part of this study, your blood and tumor samples may be tested for genetic 
and epigenetic information to examine the effect of the vaccine on your immune system and 
tissue. The samples will be assigned a number instead of your name. The number will be linked 
to your name but the code will be kept by research personnel in a locked facility. Samples will 
either be used immediately or frozen and stored until needed for these tests. You can withdraw 
your cell sample at any time. If at any time you would like to withdraw your stored sample, please 
write to: 
Sindhu Malapati, MD 
University of Arkansas for Medical Sciences 
4301 West Markham Street, Slot 508 
Little Rock, AR 72205 
 
You may agree to participate in this research study, but refuse to allow your samples to be tested 
for the genetic studies mentioned above. Please initial and date below. 
 
 
  
 I AGREE to have my samples tested for genetic studies. 
Initials 
Date 
 
 
 
  
 I DO NOT AGREE to have my samples tested for genetic studies. 
Initials 
Date 
 
 
 
Breast Tissue Samples 
We would like to save any leftover breast tissue collected as part of standard biopsy and/or 
surgery to study the effect of this cancer vaccine on the tissue. Your breast tissue samples will be 
frozen and stored with a number assigned to them instead of your name. The breast tissue 
samples may be stored indefinitely until needed for this cancer vaccine research. The number will 
be linked to your name, which means you can withdraw your tissue samples at any time. If at any 
time you would like to withdraw your stored sample, please write to: 
 
Sindhu Malapati, MD 
University of Arkansas for Medical Sciences 
4301 West Markham Street, Slot 508 
Little Rock, AR 72205 
 
You may agree to participate in this research study, but refuse to allow your tissue samples to be 
stored for this cancer vaccine research. Please initial and date the appropriate line below. 
 
 
 
  
 I AGREE to have my leftover tissue samples saved for this research. 
Initials 
Date 
 
 
 
  
 I DO NOT AGREE to have my leftover tissue samples saved for this research. 
Initials 
Date 
 
 


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Page 14 of 15 
Future Use – Blood Samples 
We would like to save any leftover blood samples for future research studies on cancer vaccines. 
Your blood samples will be frozen and stored with a number assigned to them instead of your 
name. The blood samples may be stored indefinitely until needed for a future research study. The 
number will be linked to your name, which means you can withdraw your blood sample at any 
time. If at any time you would like to withdraw your stored sample, please write to: 
 
Sindhu Malapati, MD 
University of Arkansas for Medical Sciences 
4301 West Markham Street, Slot 508 
Little Rock, AR 72205 
 
You may agree to participate in this research study, but refuse to allow your blood samples to be 
stored for future research. Please initial and date the appropriate line below. 
 
 
 
  
 I AGREE to have my leftover blood samples stored for future research. 
Initials 
Date 
 
 
 
  
 I DO NOT AGREE to have my leftover blood samples stored for future research. 
Initials 
Date 
 
 
 
Future Contact 
You may agree to participate in this research study, but refuse to be contacted for future research. 
Please initial and date the appropriate line below. 
 
 
 
  
 Yes, I agree to be contacted for future research related to this study. 
Initials 
Date 
 
 
 
  
 No, I do not agree to be contacted for future research related to this study. 
Initials 
Date 
 
 


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Signature 
I have been told that I will be given a copy of this form. I have read it or it has been read to 
me. I understand the information and have had my questions answered. I understand my 
participation in this study is voluntary. I agree to take part in this study. 
 
I should avoid becoming pregnant for at least 18 months after participation in the study. To avoid 
becoming pregnant, I should either abstain from sexual relations or practice a method of birth 
control. Except for surgical removal of the uterus, birth control methods such as the use of 
condoms, a diaphragm or cervical cap, birth control pills, IUD, or sperm killing products are not 
totally effective in preventing pregnancy. 
 
 
 
 
 
 
 
 
 
 
Participant Signature 
Date 
Time 
 
 
 
 
 
 
 
 
 
Person Obtaining Consent Signature 
Date 
Time 
 

Prot_SAP_000.pdf: 
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“Vaccination of Triple Negative Breast Cancer Patients” 
 
 
A Combined Phase I/II Efficacy Study of a Carbohydrate Mimotope-Based 
Vaccine with MONTANIDE™ ISA 51 VG STERILE Combined with Neoadjuvant 
Chemotherapy in Triple Negative Breast Cancer 
 
 
Version 11 
06/02/2022 
 
University of Arkansas for Medical Sciences (UAMS) 
Principal Investigator: 
Sindhu Malapati, MD 
 
 
Highlands Oncology Group (HOG) 
Principal Investigator: 
J. Thaddeus Beck, MD 
 
 
Medical Monitor: 
Shi-Ming Tu, MD 
 
 
Biostatisticians: 
Eric Siegel, MS 
Jun Ying, PhD 
 
 
Inventors: 
Thomas Kieber-Emmons, PhD 
Behjatolah Karbassi, PhD 
 
 
Sponsor: 
University of Arkansas for Medical Sciences 
 
IND 14715 
 
NCT Number: NCT02938442 
 


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TABLE of CONTENTS 
 
1. ABBREVIATIONS ........................................................................................................................................ 3 
2. PROTOCOL SUMMARY .............................................................................................................................. 5 
3. BACKGROUND ........................................................................................................................................... 6 
4. STUDY DESIGN ......................................................................................................................................... 12 
5. TRIAL OBJECTIVES ................................................................................................................................... 13 
6. PATIENT POPULATION ............................................................................................................................ 14 
7. INVESTIGATIONAL PRODUCT – P10S-PADRE/ MONTANIDE™ ISA 51 VG STERILE .................................. 15 
8. TREATMENT PLAN ................................................................................................................................... 17 
9. STUDY CALENDARS.................................................................................................................................. 18 
9.1 Study Calendar for Arm 1 (control arm – no vaccine) .................................................................... 19 
9.2 Study Calendar for Arm 2 (chemo+vaccine arm) ............................................................................ 20 
10. VISIT BREAKDOWNS .............................................................................................................................. 21 
10.1 Visit Breakdown for Arm 1 (control arm – no vaccine) ................................................................. 21 
10.2 Visit Breakdown for Arm 2 (chemo+vaccine arm) ........................................................................ 24 
11. RISKS AND TOXICITIES TO BE MONITORED ........................................................................................... 29 
12. SPECIMEN HANDLING ........................................................................................................................... 31 
13. ENDPOINT DEFINITIONS, EVALUATION of IMMUNE RESPONSE, and ENDPOINT-ASSAY METHODS ... 32 
14. STATISTICAL CONSIDERATIONS ............................................................................................................. 37 
15. REGISTRATION GUIDELINES .................................................................................................................. 38 
16. DATA SUBMISSION SCHEDULE .............................................................................................................. 38 
17. ETHICAL AND REGULATORY CONSIDERATIONS .................................................................................... 39 
18. ADVERSE EVENTS .................................................................................................................................. 40 
19. CLINICAL SITE MONITORING ................................................................................................................. 41 
20. DEVIATIONS AND VIOLATIONS.............................................................................................................. 42 
21. BIBLIOGRAPHY ...................................................................................................................................... 43 
 
 


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1. ABBREVIATIONS 
 
AC 
Doxorubicin and Cyclophosphamide Combination Chemotherapy 
ACLS 
Advanced Cardiac Life Support 
ADCC 
Antibody-Dependent Cell-Mediated Cytotoxicity 
AE 
Adverse Event 
AJCC 
American Joint Commission on Cancer 
ALT 
Alanine Aminotransferase Test 
ANOVA 
Analysis of Variance 
AST 
Aspartate Aminotransferase Test 
BMI 
Body Mass Index 
BUN 
Blood Urea Nitrogen 
CBC 
Complete Blood Count 
CTO 
Clinical Trials Office (within the UAMS WPRCI) 
CD 
Cluster of Differentiation 
CDC 
Complement-Dependent Cytotoxicity 
CFR 
Code of Federal Regulations 
Chemistry 
BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium 
CMPs 
Carbohydrate Mimetic Peptides 
cpm 
counts per minute 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTEP 
Cancer Therapy Evaluation Program 
CTL 
Cytotoxic T-Lymphocyte 
CTLA-4 
Cytotoxic T-Lymphocyte-Associated Protein 4 
CY 
Cyclophosphamide 
dL 
Deciliter 
DSMB 
Data Safety Monitoring Board 
DTH 
Delayed-type hypersensitivity 
ECOG score 
Eastern Cooperative Oncology Group performance status 
EDTA 
Ethylenediaminetetraacetic acid 
ELISA 
Enzyme-Linked Immunosorbent Assay 
ELISPOT 
Enzyme-Linked Immunospot Assay 
ER 
Estrogen Receptor 
FBS 
Fetal Bovine Serum 
FDA 
United States Food and Drug Administration 
FITC 
Fluorescein Isothiocyanate 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
HER2 
Human Epidermal Growth Factor Receptor 2 
HLA-DR 
Human Leukocyte Antigen - antigen D Related 
HOG 
Highlands Oncology Group 
HRP 
Horseradish Peroxidase 
ICH 
International Council for Harmonisation 
IFA 
Incomplete Freund's Adjuvant 
IFN-γ 
Interferon Gamma 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 


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IL 
Interleukin 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
IUDs 
Intrauterine Device 
IUL 
Institutional Upper Limit 
LDH 
Lactate Dehydrogenase 
LeY 
Lewis Y antigen 
mAb 
Monoclonal Antibodies 
µg 
Microgram 
mg 
Milligram 
mL 
Milliliter 
mm 
Millimeter 
MDSC 
Myeloid-Derived Suppressor Cells 
NCI 
National Cancer Institute 
NCT 
National Clinical Trial 
NIH 
National Institutes of Health 
NK 
Natural Killer 
OS 
Overall Survival 
P10s-MAP 
10s-Multivalent-Antigen Peptide 
PBMC 
Peripheral Blood Mononuclear Cell 
PD-1 
Programmed Cell Death Protein 
PD-L1 
Programmed Death-Ligand 1 
pCR 
pathological Complete Response 
PE 
Physical Examination 
PHA 
Phytohemagglutinin 
PR 
Progesterone Receptor 
PRMC 
Protocol Review and Monitoring Committee 
RPMI 
Roswell Park Memorial Institute medium 
SAE 
Serious Adverse Event 
SC 
Subcutaneous 
SGOT 
Serum Glutamic-Oxaloacetic Transaminase 
SGPT 
Serum Glutamic-Pyruvic Transaminase 
SI 
Stimulation Index 
SoC 
Standard/Standard of Care 
SOP 
standard operating procedure 
STn 
sialosyl-Tn 
TACA 
Tumor-Associated Carbohydrate Antigen 
TBAPS 
Tissue Biorepository and Procurement Service 
TIL 
Tumor Infiltrating Lymphocytes 
TNBC 
Triple Negative Breast Cancer 
TNFα 
Tumor Necrosis Factor alpha 
Tregs 
Regulatory T cells 
UAMS 
University of Arkansas for Medical Sciences 
UPIRTSO 
Unanticipated Problem Involving Risks to Subjects or Others 
WBC 
White Blood Cell 
WPRCI 
Winthrop P. Rockefeller Cancer Institute 
ypT0/Tis ypN0 absence of residual invasive cancer in the breast and regional lymph nodes 
 
 


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2. PROTOCOL SUMMARY 
 
The purpose of this study is to evaluate an investigational agent, P10s-PADRE, a peptide mimotope-based 
vaccine, in combination with standard (SoC) neoadjuvant chemotherapy in subjects with clinical stage I, II 
or III estrogen-receptor (ER)-negative, progesterone receptor (PR)-negative and human epidermal growth 
factor receptor 2 (HER2)-negative breast cancer (known as triple negative breast cancer (TNBC)). P10s-
PADRE will be administered with MONTANIDE™ ISA 51 VG as adjuvant. Human breast cancers that express 
Tumor-Associated Carbohydrate Antigens (TACAs) can be immunogenic, and enhancing the anti-TACA 
antibodies and immune effector function already present may augment the cytotoxic effects of SoC 
therapies. 
 
This randomized two-arm, open-label, multi-center Phase I/II trial is designed to evaluate the safety and 
efficacy of combining the P10s-PADRE vaccine with neoadjuvant chemotherapy. Subjects will be randomly 
assigned in a 2:1 ratio to SoC chemotherapy plus P10s-PADRE or to SoC chemotherapy alone. Efficacy will 
be based on the rate of pathologic Complete Response (pCR) observed among TNBC subjects treated with 
the combination as compared with the group of subjects who receive SoC chemotherapy alone. 
 
The primary objectives of the study are: 1) to monitor the safety and tolerability of the vaccine when it is 
administered in combination with SoC neoadjuvant chemotherapy; and 2) to determine if the 
chemo+vaccine regimen in TNBC leads to a significantly higher rate of pCR in breast and axillary lymph 
nodes at the time of definitive surgery compared to the corresponding rate expected in the control arm 
as reported by von Minckwitz et al. (1, 2). 
 
The secondary objectives are to determine the short-term and long-term immune responses induced by 
treatment, characterize the functionality of cellular and humoral immune responses and determine the 
delayed-type hypersensitivity (DTH) response to the P10s-PADRE. In addition, it will also attempt to 
evaluate whether the magnitude of the immune response to the vaccine (or the ability to mount an 
immune response) is correlated with important prevaccination clinical characteristics such as ECOG 
(Eastern Cooperative Oncology Group) performance status and the presence of a DTH response at the 
time of enrollment. 
 
This study also has the following correlative objective: to evaluate whether the ability to mount an 
immune response is affected by prevaccination performance status, DTH (delayed-type hypersensitivity) 
at the time of enrollment, BMI (body mass index) at the time of enrollment, and BMI-adjusted weight loss 
during the six months prior to enrollment. The purpose of this objective is to start laying a foundation of 
knowledge that could be used to help future researchers distinguish beforehand between patients who 
are more likely versus less likely to benefit from immunization with P10s-PADRE. 
 
Study Population: We plan to consent up to 120 women in order to enroll up to 102 women, 18 years of 
age or older, from the breast cancer clinics (Medical Oncology and Ladies Oncology Clinics) at the 
Winthrop P. Rockefeller Cancer Institute (WPRCI) at the University of Arkansas for Medical Sciences 
(UAMS) campus and the clinics of the Highlands Oncology Group (HOG) in Northwest Arkansas. A total of 
34 subjects will be enrolled on the control arm (Arm 1) and 68 subjects will be enrolled on the 
chemo+vaccine arm (Arm 2). 
 


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Summary of Inclusion Criteria: Females, 18 years of age or older, with clinical stage I, II or III ER-negative, 
PR-negative, and HER2-negative breast cancer (TNBC) who qualify for SoC neoadjuvant treatment will be 
invited to participate. 
 
Summary of Exclusion Criteria: Females with ER or PR-positive or HER2-positive, inflammatory, or 
metastatic breast cancer; women who are pregnant, breast-feeding, have active autoimmune disease or 
are immunosuppressed or receiving systemic corticosteroids (except from corticosteroids received as 
antiemetics or for hypersensitivity reactions related to chemotherapy) will be excluded from the study. 
 
Investigational product: P10s-PADRE administered with the adjuvant MONTANIDE™ ISA 51 VG STERILE 
 
Study Treatment: P10s-PADRE/MONTANIDE™ ISA 51 VG in combination with SoC neoadjuvant 
chemotherapy versus SoC neoadjuvant chemotherapy alone. 
 
Study Design: This randomized open-label, multi-center Phase I/II efficacy study will have two arms. The 
first or “control” arm (Arm 1) will receive SoC chemotherapy for TNBC. The second or “chemo+vaccine” 
arm (Arm 2) will receive the same SoC chemotherapy as Arm 1 plus P10s-PADRE vaccine. Subjects will be 
randomized at a 2:1 allocation ratio to the chemo+vaccine and control arms, respectively. The total 
sample size in the entire study is 102 subjects (68 vaccinated versus 34 controls) to demonstrate an 
increase of pCR from 40% on the control arm to 65% on the experimental arm. A formal interim analysis 
for both efficacy and futility will be conducted when the 51st study subject has been evaluated for 
response. 
 
To conduct this study, eligible subjects of all races, ages 18 years or older, will be enrolled. Subjects who 
are randomized to the control arm (Arm 1) will receive no immunizations, whereas subjects who are 
randomized to the chemo+vaccine arm (Arm 2) will be immunized by administration of P10s-PADRE 
vaccine on each of 3 separate occasions over a three-week period at a dose level of 500 micrograms (μg) 
per immunization. The vaccine injections will be administered before the initiation of chemotherapy 
based on our Phase I/II study in HR-positive breast cancer, which showed the best immunologic response 
when the vaccine was administered prior to chemotherapy (data unpublished). Blood will be collected 
from each subject once before and 4 times after the first immunization. Follow-up blood samples will also 
be taken approximately 6 and 12 months after immunization to assess durations of the anti-P10s titer and 
anti-breast-cancer cytotoxicity. Safety and tolerability of chemo+vaccine will be evaluated throughout the 
study. The primary efficacy endpoint is pCR and will be used to determine if chemo+vaccine treatment in 
TNBC subjects will improve pCR at time of the definitive surgery to a rate significantly higher than the 
corresponding rate expected in the control arm (1, 2). 
 
3. BACKGROUND 
 
Anticipated anti-cancer impact of carbohydrate-targeted vaccines: The potential impact of vaccines that 
induce responses to tumor-associated carbohydrate antigens (TACAs) is demonstrated by clinical trials 
where subject survival significantly correlates with carbohydrate-reactive IgM levels (3). Such results 
suggest that TACA-targeting vaccines might have a beneficial effect on the course of malignant disease. 
Vaccine-induced anti-TACA antibodies can trigger cancer cell death and augmentation of cellular immune 
response through cross presentation of tumor antigens, leading to shrinkage of metastatic lesions and 
further improving survival. TACA-induced responses could also augment naturally occurring 
carbohydrate-reactive antibodies that trigger apoptosis of tumor cells (4). TACAs are attractive targets 


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because the majority of cell-surface proteins and lipids are glycosylated, and the glycosyl moiety is 
fundamental to the biological functions of these molecules in cancer cells (5, 6). A unique advantage in 
targeting TACAs is that multiple proteins and lipids on the cancer cell can be modified with the same 
carbohydrate structure. Thus, targeting the carbohydrate antigen broadens the spectrum of antigens 
recognized by the immune response, thereby lowering the risk of developing resistant tumors due to the 
loss of any one antigen (7). In addition, antibodies that recognize glycolipids are more apt to mediate 
complement-dependent cytotoxicity (CDC) and therefore, may be more cytotoxic to tumor cells than 
antibodies that recognize protein antigens (8). 
 
Approaches to augment immune responses to TACAs: A variety of approaches are being taken to 
generate responses to TACAs. Because TACAs are T-cell-independent antigens and self-antigens, 
conjugation to immunologic carrier proteins is perceived to be essential to recruit T-cell help in antibody 
generation. Conjugation does not, however, assure an increase in immunogenicity because conjugation 
strategies do not uniformly enhance carbohydrate immunogenicity (9, 10). Furthermore, even with 
conjugation, the lack of induction of cellular immune responses that would amplify TACA-reactive humoral 
responses necessitates constant boosting with vaccine. Representative examples of carbohydrate-based 
conjugate vaccines in clinical development include those directed toward gangliosides (11-14), polysialic 
acid (8), Globo-H (15), LeY (16), and the sialosyl-Tn (STn) antigen (17). 
 
An approach predicted to facilitate cellular responses exploits the molecular mimicry of TACAs by protein 
surrogates, as they are T-cell-dependent antigens. Clinical characterizations of anti-idiotypic antibodies 
that mimic the GD3 ganglioside antigen (18) and GD2 (19) have been described. Carbohydrate mimetic 
peptides (CMPs) are alternatives to anti-idiotypic antibodies. The characterization of CMPs is at present 
limited to preclinical studies. CMPs that induce immune responses cross-reactive with TACAs are also 
referred to as peptide mimotopes. Peptide mimotopes have been described for GD2 (20-22), GD3 (23), 
sialylated Lewis a/x (24) and Lewis Y (LeY) antigens (22, 25). Importantly, in preclinical prophylactic and 
therapeutic vaccination studies, peptide mimotopes were efficacious in eliciting immune responses that 
reduced tumor burden and inhibited metastatic outgrowth (25-27). Thus, peptide mimotopes of TACAs 
represent a new and very promising tool to overcome T-cell independence and to increase the efficiency 
of the immune response to glycan antigens. 
 
Benefits of peptide mimotope immunization: There are several benefits to vaccination strategies that 
employ peptide mimotopes of TACAs. First, peptide mimotopes function as xenoantigens and, 
consequently, provide an advantage to overcome tolerance to carbohydrate self-antigens. Antibodies 
induced by peptide mimotopes are thought to have low affinities for TACA; specific targeting of tumor 
cells is due in part to over-expression of the carbohydrate antigen on tumor cells, which compensates for 
the low affinity of the carbohydrate cross-reactive antibodies (29). In addition, mimotope-induced 
antibodies preferentially recognize the terminal residues of the TACA oligosaccharides, which are often 
structurally distinct from those found on normal cells (30). Thus, potential immunopathology due to 
destruction of normal tissue is minimized (31-32). 
 
Second, peptide mimotopes have the potential to overcome immune deficiencies that suppress vaccine-
induced carbohydrate-directed responses (33). Unlike carbohydrate antigens and carbohydrate-
conjugate vaccines, peptide mimotopes also prime B- and T-cells for subsequent memory of carbohydrate 
antigens, facilitating long-term surveillance through recall of carbohydrate immune responses (7). This 
effect may minimize the need for constant boosting. In addition, they can functionally emulate conserved 


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structures of TACA, inducing antibodies that recognize multiple TACA, and therefore functioning like a 
TACA multivalent vaccine. 
 
Third, peptide mimotopes can be manipulated in ways that TACA cannot. Peptide mimotopes can be 
engineered to induce CD8+ T cells cross-reactive with tumor-associated glycopeptides and/or to induce 
CD4+ T cells that benefit the further expansion of CD8+ T cells and B-cells (7, 25-28). The ability to induce 
a humoral carbohydrate cross-reactive response, a CD4+ T helper response, and a CD8+ cytotoxic T 
lymphocyte (CTL) response with one simple inoculation is a novel approach to vaccination. Therefore, 
peptide mimotopes hold the potential to generate a multifaceted TACA-reactive immune response. 
 
Target carbohydrate antigens expressed on breast cancer cells: Tumors expressing high levels of certain 
types of TACAs exhibit greater metastasis than those expressing low levels of these antigens, and this 
negatively impacts prognosis (34-36). In breast cancer, the LeY, STn, and KH-1 antigens, as well as selected 
gangliosides, glycosphingolipids and Globo-H carbohydrate antigens, are considered prime vaccine 
candidates because of their tissue distribution (37-38). In particular, LeY has long been recognized as a 
potential target for immunotherapy because it is expressed in 70–90% of tumors of epithelial origin (39). 
The abundant gangliosides include GM3, GM2, GM1, and GD2, GD3 and GT3 (40). Antibodies to TACAs 
mediate a variety of effector functions and might lend to cross-presentation of tumor antigens to 
stimulate anti-tumor cellular responses. At present, LeY conjugate vaccines appear to have only a limited 
ability to induce anti-LeY immune responses in humans. Our in vitro studies demonstrate that peptide 
mimotopes of LeY and gangliosides induce serum antibodies in mice that recognize the appropriate 
carbohydrate antigens on human or murine breast cancer cell lines. Our in vivo studies demonstrate that 
the peptide mimotopes induce sustained immunity to these antigens. Collectively, these data provide the 
experimental foundation for evaluating peptide mimotopes as potential cancer vaccines in subjects with 
breast cancer. 
 
Role of Natural Killer (NK) cells in P10s mediated anti-tumor activity: In preclinical studies, we observed 
a role for NK cells in tumor-growth inhibition upon immunization with the P10s-PADRE vaccine. NK cells 
are known to have potent anti-tumor activity and thus play an important role in metastasis clearance. In 
light of the finding of increased NK activation in similar preclinical setting by Kawashima et al. (41), we 
hypothesize that the anti-tumor effect observed in mice immunized with P10s could be due to interactions 
between NK cells and the anti-tumor B cell response that has been boosted by the immunization (41). 
Human subjects immunized with P10s-PADRE in the Phase I safety study of P10s-PADRE displayed 
elevated activation of their NK cells. This finding provides an expectation of benefit upon immunization 
with P10s-PADRE. 
 
Role of B and T cells: Chemotherapy is assumed to be immunosuppressive. However, each drug might 
have differing effects when used in combination with specific immunotherapy. Thus, diverse effects may 
have been achieved depending on the time and the dose of administration. For example, high dose 
doxorubicin and cyclophosphamide (CY), while not beneficial for T-cell response, have been noted to 
enhance the immunogen-specific antibody-forming cells (42). Early reports indicated that low dose CY 
treatment might facilitate adaptive T cell immunity by eliminating “suppressor” T cells. In addition to its 
role on T lymphocytes, CY has been shown to switch cytokine production of tumor-infiltrating 
macrophages from IL-10 to IFN-γ (43) and polarize Th1/Th2 responses (44). Our own studies indicate that 
immunization with a CMP followed by CY treatment can facilitate inhibition of tumor growth (45), 
including P10s-PADRE (data unpublished). The administration of docetaxel to subjects with metastatic 
prostate or breast cancer, as well as that of cisplatin plus vinorelbine to non-small cell lung cancer subjects, 


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appears to significantly increase the ratio between effector T cells and regulatory T cells (Tregs) and to 
reduce the immunosuppressive activity of the latter in the majority of subjects (46). Such studies provide 
the rationale for the selective use of active immunotherapy regimens in combination with specific SoC 
therapies to achieve the most beneficial clinical outcome among carcinoma patients. Developing the time 
and dose schedules therefore may increase the effectiveness of combining chemotherapy and 
immunotherapy. Recently introduced immunotherapies, such as anti-PD-1 or anti-CTLA-4 therapeutic 
antibodies, need the presence of anti-tumor immune cells to be effective. A targeted vaccination strategy 
may activate cellular response synergizing the impact of immune checkpoint-based therapies (47-49). 
 
Potential for benefit with combination therapy: Mechanisms by which chemotherapy enhances vaccine-
induced humoral immunity and vice versa remain largely unknown. It is possible that antibodies can 
sensitize tumor cells for more efficient killing by chemotherapeutics. In a Phase I trial with the P10s-PADRE 
vaccine, we observed that antibodies induced by P10s are cytotoxic to human breast cancer cell lines 
including a Trastuzumab-resistant one (50). TACA expression is part of signaling pathways that confer 
death resistance. Cells resistant to death are those that cause treatment failure and can colonize distant 
organs and vice versa. Admixing serum from P10s-PADRE immunized subject with docetaxel was shown 
to lower the LC50 value for the drug in killing a human tumor cell line. Consequently, immunization with 
P10s-PADRE followed by chemotherapy might augment the chemotherapy. 
 
Summary of results from the Phase I trial with P10s-PADRE: A Phase I dose escalation trial was designed 
to determine a maximum tolerated dose of vaccine plus adjuvant in two cohorts of Stage IV breast cancer 
subjects. The study design was the rule based “traditional” 3+3 design (51), with 3 subjects at each dose 
if no toxicities were observed. This dose-escalation Phase I trial was approved by the UAMS Institutional 
Review Board (IRB) and was carried out from 2011 to 2013. 
 
Female subjects 18 years of age or older, of all races with histologically or cytologically confirmed stage IV 
breast cancer were eligible, and subjects were enrolled after providing written, informed consent. The 
following eligibility criteria were used: The cancer must have been newly diagnosed metastatic or relapsed 
after primary or adjunctive therapy and must not have required a treatment change for 2 months. 
Treatments with anti-estrogen therapy or chemotherapy were allowed. The chemotherapy regimen could 
not contain steroids in the pre or post supportive care medications. Disease staging was done according 
to the American Joint Commission on Cancer (AJCC), sixth edition; no expectation of response to other 
therapies; an Eastern Cooperative Oncology Group performance status of 0–1; no prior therapy within 4 
weeks and adequate organ function (white blood cell count ≥3,000/ mm3, hemoglobin ≥8.0 g/dL, platelets 
≥100,000/mm3 within 2 weeks prior to registration, total bilirubin ≤3.0 mg/dL, aspartate aminotransferase 
≤200 IU/L, alanine aminotransferase ≤200 IU/L, and serum creatinine ≤1.5 mg/dL). Subjects had to be 
immunocompetent as measured by responsiveness to two recall antigens by skin testing. The following 
exclusion criteria were applied: massive ascites; known brain metastasis; pregnancy or lactation; known 
history of HIV infection; clinically serious infection; severe cardiac insufficiency; other active malignancy; 
history of organ allograft; immunodeficiency or history of splenectomy; concurrent treatment with 
steroids or immunosuppressive agents; and unsuitability for the trial based on clinical judgment. 
 
The peptide vaccine was administered in liquid form, emulsified with incomplete Freund's adjuvant (IFA; 
MONTANIDE™ ISA 51 VG, SEPPIC), by subcutaneous (SC) injections on 5 separate occasions during Weeks 
1, 2, 3, 7, and 19. The first cohort began with a 300 μg dose, and then the subsequent cohort received a 
500 μg dose of P10s-PADRE. The peptides and IFA were synthesized according to Good Manufacturing 
Practice (GMP) guidelines. The primary endpoint was the safety of P10s-PADRE vaccination. The 


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secondary endpoints were immunologic responses, clinical outcomes, and determination of the optimal 
dose of peptide for further clinical trials. The trial is registered on NIH’s ClinicalTrials.gov results database 
(number NCT01390064). 
 
Subjects were evaluated for signs of toxicity during and after vaccination. Adverse events (AEs) were 
graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI 
CTCAE) Version 4.0. Toxicities assessed were the laboratory parameters listed in the study calendar, as 
well as any sign or symptom found during the history and physical examination not noted at pre-study or 
on the baseline evaluation. Special attention was paid to signs and symptoms related to injection 
reactions, injection-site reactions or symptoms or laboratory findings indicating autoimmune toxicities. 
 
Sixteen subjects were consented, but only 6 that met the eligibility criteria were enrolled. Six subjects 
consequently received the P10s-PADRE vaccine. P10s vaccination was well-tolerated. All 6 subjects 
displayed a persistent IgG response to P10s after the three initial vaccinations, and induced serum and 
plasma antibodies displayed cross-reactivity to TACA-expressing human breast cancer cell lines. Antibody 
induced by P10s displayed cytotoxic functionality to human breast cancer cell lines, including a 
Trastuzumab-resistant one, which established an expectation of therapeutic benefit (expectation of 
efficacy). In summary, P10s vaccination was well-tolerated with injection site irritation as the only 
repetitive AE, and measurable immune responses and anti-cancer-cell efficacy were noted. This is the first 
study to show that CMP vaccination is safe and can induce functional antibodies that might have 
therapeutic benefit in subjects immunized with P10s. 
 
Definition of BMI-Adjusted Weight-Loss Grade: The BMI-adjusted weight-loss grade is defined by Martin 
et al.(52) using the 5x5 grading matrix that appears as Panel D of Figure 2 of their publication; a table 
showing their grading matrix is rendered below. Subjects who experienced weight loss >2.5% of body 
weight during the 6 months prior to enrollment, and subjects whose weight was stable (weight loss within 
±2.5%) during this time will be assigned a BMI-adjusted weight-loss grade according to the grading matrix. 
Grades will range from 0 to 4 as shown in the grading matrix. The few study subjects who experience 
weight gain ≥2.5% of body weight during the 6 months prior to enrollment fall outside the scope of this 
grading system, and will not be graded by it. They will instead be graded as “gained weight”. 
 
BMI-Adjusted Weight-Loss Grading Matrix (from Fig. 2 of Martin et al. (52)) 
Weight-Loss Grading Matrix1 
BMI ≥28 
BMI 25-28 
BMI 22-25 
BMI 20-22 
BMI <20 
Weight loss2 
within ±2.49% 
GRADE 0 
GRADE 0 
GRADE 1 
GRADE 1 
GRADE 3 
Weight loss 
2.50%-5.99% 
GRADE 1 
GRADE 2 
GRADE 2 
GRADE 2 
GRADE 3 
Weight loss 
6.0%-10.99% 
GRADE 2 
GRADE 3 
GRADE 3 
GRADE 3 
GRADE 4 
Weight loss 
11.0%-14.99% 
GRADE 3 
GRADE 3 
GRADE 3 
GRADE 4 
GRADE 4 
Weight loss 
≥15.0% 
GRADE 3 
GRADE 4 
GRADE 4 
GRADE 4 
GRADE 4 
1. Body-mass index at study entry (“current BMI”). 
2. Weight loss in the 6 months prior to study entry, defined as 100% times (previous weight minus current 
weight) divided by previous weight, where current weight is the body weight at study entry and previous 
weight is the body weight measured within 6 months prior to study entry, or the “usual body weight” if 
body weight was not measured within 6 months prior to study entry; see Martin et al. for details. 


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Martin et al. (52) developed their BMI-adjusted Weight Loss grading system using a training sample of 
8,160 patients and a validation sample of 2,693 patients. Cells in the grading matrix that have the same 
grade correspond to combinations of BMI and weight loss that have similar risk of mortality in multivariate 
Cox regression, such that higher grades of weight loss have increased risk of mortality. The table below 
shows, for each BMI-adjusted weight-loss grade, the aggregated median overall survivals (95% confidence 
limits) and hazard ratios associated with subjects assigned that grade, and illustrates how mortality risk 
increases with increasing grade of weight loss. 
 
Mortality Risk versus BMI-Adjusted Weight-Loss Grade (from Fig. 2 of Martin et al. (52)) 
Risk Measure 
GRADE 0 
GRADE 1 
GRADE 2 
GRADE 3 
GRADE 4 
Median Survival1 
20.9 
14.6 
10.8 
7.6 
4.3 
95% Conf. Limits2 
17.9-23.9 
12.9-16.2 
9.7-11.9 
7.0-8.2 
4.1-4.6 
Hazard Ratio3 
1.0 
1.3 
1.5 
2.0 
3.1 
1. Median OS in months. 
2. 95% Confidence Limits on the median OS in months. 
3. Hazard Ratio of higher grades relative to Grade 0 as the reference grade. 
 
These findings by Martin et al. lead us to hypothesize that BMI-associated weight-loss grade will be 
negatively associated with the ability to mount an immune response to P10s-PADRE in cancer subjects 
vaccinated with this peptide. We will evaluate our hypothesis during the course of meeting this study’s 
correlative objective. 
 
Neoadjuvant treatment in breast cancer: The treatment of breast cancer includes the treatment of local 
disease with surgery, radiation therapy, or both, and the treatment of systematic disease with cytotoxic 
chemotherapy, endocrine therapy, biologic therapy (such as Trastuzumab in HER2 positive disease), or 
combination of these. The need for and selection of various local or systemic therapies are based on 
several prognostic and predictive factors that include tumor histology, clinical and pathologic 
characteristics of the primary tumor, axillary lymph node status, tumor hormone receptor content, tumor 
HER2 status, multi-gene testing, presence or absence of detectable metastatic disease, patient 
comorbidities, patient age, and menopausal status. 
 
Neoadjuvant chemotherapy has become commonly used based on results from randomized trials 
suggesting no difference in relapse-free or overall survival whether chemotherapy is administered before 
or after surgery (53). A major benefit of neoadjuvant chemotherapy is the increase in the rate of breast 
conserving surgery. Tumor response to neoadjuvant chemotherapy has proven to be a good surrogate 
end-point for survival; the achievement of pCR is strongly associated with a favorable long-term survival 
rates (75% to 85% at 10 to 15 years) (53-57). Thus, improving pCR has become a valid strategy in the 
development of new treatment regimens. Specifically, the rate of pCR achieved in ER/PR/HER2-negative 
breast cancer subjects following vaccination with P10s-PADRE administered concurrently with 
neoadjuvant chemotherapy will be compared with the corresponding pCR rate with the control arm. 
 
Definition of Pathological Complete Response: Pathological Complete Response will be defined as “the 
absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast 
specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy 
(i.e., ypT0/Tis ypN0 in the current AJCC staging system).” (58) 
 


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Rationale for using P10s-PADRE in the neoadjuvant setting: The traditional drug development process 
based on large Phase III trials to show statistical incremental benefit from SoC therapy is slow, expensive, 
and inefficient. In contrast, the neoadjuvant trial model provides rapid assessment of short-term drug 
efficacy and triage utilizing pCR as the primary endpoint. Thus, improving pCR has become a valid strategy 
in the development of new treatment regimens. 
 
This issue is perhaps best exemplified in the development of HER2-directed therapies, such as lapatininb 
(NeoALTTO trial) (59), and pertuzumab (NeoSphere trial) (60). Recognizing the importance of neoadjuvant 
trials for drug development, the FDA recently announced the consideration of neoadjuvant randomized 
trials for accelerated drug approval in early breast cancer (61). In line with this approach, in September 
2013 the FDA granted accelerated approval of pertuzumab for neoadjuvant treatment of women with 
early-stage HER2-positive breast cancer. 
 
In our Phase I study, we were able to demonstrate that P10s vaccination was well tolerated, and 
measurable immune responses and anti-cancer-cell efficacy were noted. Our previous data suggest that 
both anti-peptide IgM and IgG titers rose sharply by week 7 (four weeks after the third immunization) of 
the study (when additional boost was administered) in most subjects. IgM titers were short-lived and 
returned to baseline by week 19, whereas IgG titers remained elevated through at least week 21. Based 
on the above data, we expect that three doses of the vaccine will be sufficient to achieve a significant 
immune response. Interim data from our ongoing Phase I/II trial suggest that three weekly vaccinations 
prior to the start of the chemotherapy regimen are enough to elevate an anti-peptide antibody response. 
 
Justification for 500 μg vaccine dose: Whereas medications work via distribution through the 
bloodstream, the immune response generated by vaccination typically occurs at or near the injection site. 
In the Phase I study, we observed an increase in IgG binding to the P10s peptide after immunization as 
measured by ELISA assay. Anti-P10s serum reactivity surged dramatically from week 4 to week 7 of the 
study in most subjects except in subject #6, in whom it was already surging at week 4. The increases at 
week 7 compared to pre-immune ranged from 31 fold (in subject #2) to 256 fold (in subjects #5 and #6), 
and the titers in subsequent weeks showed little change from their week-7 values. The cohort immunized 
with the higher dose of vaccine (500 μg dose) displayed higher normalized endpoint titers. In 
nonparametric repeated-measures analysis, the main effects of dose and week were statistically 
significant (both P values <.0001), but the dose×week interaction was not (P=0.40). While we did not 
observe dose-limiting toxicity in this study, it is difficult to determine the maximum tolerated dose of the 
vaccine because of the potential of forming granulomas due to the nature of the adjuvant. P10s is admixed 
with MONTANIDE™ ISA 51 VG, an adjuvant that is known to form granulomas. 
 
4. STUDY DESIGN 
 
This is a randomized two-arm, open-label, multi-center Phase I/II study designed to evaluate the safety 
and efficacy of combining the P10s-PADRE vaccine with neoadjuvant chemotherapy with the primary goal 
to determine if the pCR rate among TNBC subjects treated with the chemo+vaccine combination is 
significantly higher than the 40% pCR rate expected among TNBC subjects treated with SoC chemotherapy 
only. P10s-PADRE vaccine with MONTANIDE™ ISA 51 VG as adjuvant will be given in combination with 
neoadjuvant chemotherapy in female subjects with clinical stage I, II or III ER/PR/HER2-negative breast 
cancer. 
 


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This Phase I/II safety and efficacy study will randomize subjects to the chemo+vaccine arm (Arm 2) vs. 
control arm (Arm 1) on a 2:1 ratio. The vaccination will start four weeks before chemotherapy treatment. 
The total sample size in the entire study will be 102 subjects: 68 on the chemo+vaccine arm and 34 
subjects on the control arm. A formal interim analysis for both efficacy and futility will be conducted when 
51 subjects (50%) have been evaluated for response. 
 
The secondary objectives are to determine the short-term and long-term immune responses induced by 
the vaccine and determine the delayed-type hypersensitivity (DTH) response to the P10s-PADRE. In 
addition, it will also attempt to evaluate whether the magnitude of the immune response to the vaccine 
(or the ability to mount an immune response) is correlated with important prevaccination clinical 
characteristics such as ECOG (Eastern Cooperative Oncology Group) performance status, BMI at the time 
of enrollment, the BMI-adjusted weight change during the six months prior to enrollment, and the 
presence of a DTH response at the time of enrollment. 
 
5. TRIAL OBJECTIVES 
 
Primary Objectives 
1) Safety/tolerability: 
To continue to monitor the safety and tolerability of the investigational product, P10s-PADRE in 
MONTANIDETM ISA 51 VG, when it is administered in combination with SoC Neoadjuvant 
chemotherapy. Toxicities will be graded according to the NCI CTCAE Version 5.0. All subjects who 
receive at least one inoculation of vaccine therapy will be monitored for the vaccine’s safety and 
tolerability. This safety population will also be used for the summaries and analysis of all safety 
parameters (drug exposure, tables of AEs information, including SAEs, etc.). 
 
2) Demonstration of clinical response: 
Determine if the Chemo+vaccine regimen in TNBC would lead to a significantly higher rate of pCR in 
breast and axillary nodes at time of definitive surgery compared to the pCR rate of 40% expected on 
the control arm (1, 2). 
 
Secondary Objectives 
1) Determine Short-term Immune Responses Induced by Treatment: 
a) Determine the functional humoral response as defined by: 
i. 
P10s-MAP-reactive immunoglobulin-G endpoint titers in serum 
ii. Cytotoxicity of serum and plasma samples against two TACA expressing breast cancer cell 
lines following therapy with either chemo+vaccine or SoC chemotherapy 
b) Determine the activation profile of NK cells before and after therapy with either chemo+vaccine 
or SoC chemotherapy 
c) Determine T-cell subpopulations and evaluate the effects of the assigned therapy on the numbers 
of circulating T and B cells as determined by flow cytometry 
d) Perform functional T-cell immune analysis by performing T-cell proliferation, ELISPOT, cytokine 
release and ADCC assays 
e) Determine expression of biomarkers of efficacy and response on tumor tissues and characterize 
tumor infiltrating lymphocytes and their role in response to therapy 
 
 


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2) Determine Long-term Immune Responses Induced by Treatment: 
a) Determine antibody titers against P10s at approximately 6 and 12 months following the initial 
response evaluation (Week 10) 
b) Measure anti-TACA cell-binding levels at approximately 6 and 12 months following the initial 
response evaluation (Week 10) 
c) Determine the cytotoxic activity against TACA-expressing cell lines at approximately 6 and 12 
months following the initial response evaluation (Week 10) 
d) Evaluate the functionality of T- and NK cells 
 
3) Determine DTH Responses: 
a) Determine the delayed-type hypersensitivity (DTH) response to the immunizing mimotope 
 
Correlative Objectives 
Evaluate the relationship of prevaccination performance status, body mass index (BMI) at the time of 
enrollment, the BMI-adjusted weight change during the six months prior to enrollment and DTH at the 
time of enrollment on the development of P10s-MAP-reactive antibodies. BMI-adjusted weight change 
prior to enrollment will be graded using the grading system of Martin et al. (52). 
 
6. PATIENT POPULATION 
 
Eligibility Criteria: Subjects are eligible for the vaccine study if the following inclusion and exclusion 
criteria are met: 
 
Inclusion Criteria 
1. Females of all races with biopsy-proven clinical stage I, II, or III TNBC (ER-negative, PR-negative and 
HER2-negative) who will undergo SoC neoadjuvant treatment 
2. Age 18 years and older 
3. ECOG Performance Status 0 or 1 
4. White blood cell (WBC) count ≥ 3,000/mm3 within 3 weeks prior to registration 
5. Platelet count ≥ 100,000/mm3 within 3 weeks prior to registration 
6. Bilirubin ≤ 2 x institutional upper limit (IUL) of normal obtained within 3 weeks prior to registration 
7. Serum glutamic-oxaloacetic transaminase (SGOT) or aspartate aminotransferase test (AST) ≤ 2 x IUL 
of normal obtained within 3 weeks prior to registration 
8. Serum glutamic-pyruvic transaminase (SGPT) or alanine aminotransferase test (ALT) ≤ 2 x IUL of 
normal obtained within 3 weeks prior to registration 
9. Serum creatinine ≤ 1.8 mg/dl obtained within 3 weeks prior to registration 
10. Must sign an informed consent document approved by the UAMS IRB 
 
Exclusion Criteria 
1. ER-positive, PR-positive, HER2-positive, inflammatory, metastatic, stage IV or recurrent breast cancer. 
2. Active infection requiring treatment with antibiotics. 
3. Existing diagnosis or history of organic brain syndrome that might preclude participation in the full 
protocol. 
4. Existing diagnosis or history of significant impairment of basal cognitive function that might preclude 
participation in the full protocol. 
 
 


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5. Other current malignancies. Subjects with prior history at any time of any in situ cancer, including 
lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or Clark 
I melanoma in situ or basal or squamous skin cancer are eligible, provided they are disease-free at the 
time of registration. Subjects with other malignancies are eligible if they have been continuously 
disease free for ≥ 5 years prior to the time of registration. 
6. Active autoimmune disorders or conditions of immunosuppression; Existing diagnosis or history of 
autoimmune disorders or conditions of immunosuppression that have been in remission for less than 
6 months. 
7. Treatment with corticosteroids, including oral steroids (i.e. prednisone, dexamethasone [except when 
used as an antiemetic in SoC therapy]), continuous use of topical steroid creams or ointments or any 
steroid-containing inhalers. Subjects who discontinue the use of these classes of medication for at 
least 6 weeks prior to registration are eligible if, in the judgment of the treating physician, the subject 
is not likely to require these classes of drugs during the treatment period. Replacement doses of 
steroids for subjects with adrenal insufficiency are allowed. 
8. Pregnancy or breastfeeding (due to the unknown effects of peptide/mimotope vaccines on a fetus or 
infant). Women of childbearing potential must have a negative urine pregnancy test within 72 hours 
prior to starting week 1 and must be counseled to use an accepted and effective method of 
contraception (including abstinence) while on treatment and for a period of 18 months after 
completing or discontinuing treatment. Accepted methods of contraception include oral 
contraceptives, barrier methods, IUDs, and abstinence. 
9. Any other significant medical or psychiatric conditions, which, in the opinion of the enrolling 
investigator, may interfere with consent or compliance of the treatment regimen. 
10. Enrollment in any other clinical trial using investigational drug products or devices prior to first post-
surgery study lab (Week 46 visit). Concurrent enrollment in observational studies is allowed. 
 
7. INVESTIGATIONAL PRODUCT – P10S-PADRE/ MONTANIDE™ ISA 51 VG STERILE 
 
a. General Description: P10s-PADRE is a short peptide (P10s) coupled to PADRE, a synthetic, non-natural 
peptide that binds with high or intermediate affinity to 15 of 16 of the most common HLA-DR types 
tested to date. Both components contribute to the efficacy of this molecule in stimulating an immune 
response. Because of its binding promiscuity, PADRE should overcome the problems posed by the 
extreme polymorphism of HLA-DR molecules in the human population. Furthermore, the PADRE 
peptide was specifically engineered as an antigen-presenting molecule for use in humans. 
Carbohydrate moieties, such as TACAs, typically do not induce T-cell responses. Thus, P10s, a TACA 
peptide mimotope, was developed. By coupling P10s to PADRE, the likelihood of generating an 
immune response increases, including T-cell "help" in the vaccine construct designed for human use. 
 
MONTANIDE™ ISA 51 VG STERILE is defined as an oil adjuvant containing surfactant based mannide 
monooleate and oil, which is of white mineral oil origin. 
 
b. Vaccine Manufacturing and Formulation: AmbioPharm, Inc. (North Augusta, SC) will synthesize 
Mimotope P10s covalently linked with PADRE as a powder manufactured under GMP conditions in 
facilities registered with the FDA. Once P10s-PADRE has been manufactured by AmbioPharm, the 
powder will be shipped to Bioserv Corporation, Inc. (San Diego, CA) for sterile packaging as a 
lyophilized powder in quantities of 500 µg/vial in appropriately sized glass vials under GMP conditions. 
Advantar Laboratories, Inc. (San Diego, CA) will perform product release and stability testing on the 
P10s-PADRE study drug. The study drug will be stored per label instructions. 


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MONTANIDE™ ISA 51 VG STERILE is supplied by SEPPIC, Inc. (Fairfield, NJ). See Investigator’s Brochure 
for formulation and storage conditions. 
 
c. Vaccine Preparation: The following doses of P10s-PADRE and MONTANIDE™ ISA 51 VG STERILE 
vaccine will be administered to subjects subcutaneously in rotating injection sites in the abdomen. 
Subjects in Arm 2 will receive a total of 2 mL SC injections of the vaccine on each of 3 separate 
occasions according to the Arm 2 study schedule. 
 
 
500 µg P10s-PADRE/ MONTANIDE™ ISA 51 VG STERILE Vaccine Dose preparation: Allow P10s-
PADRE to come to room temperature before reconstitution (15 to 30 min). At the same time, 
remove MONTANIDE™ ISA 51 VG STERILE vial from refrigerator. Reconstitute P10s-PADRE with 
1.1 mL sterile water (final concentration 500 µg/mL). Use 1 mL of the peptide solution and mix 
with an equal amount of MONTANIDE™ ISA 51 VG STERILE to a final volume of 2 mL. Mix as 
instructed by Seppic until emulsification is complete. The pharmacist will prepare the vaccine dose 
following the manufacturer’s instructions. 
 
d. DTH Preparation: 
• 
Candida albicans (pre-vaccination DTH testing only): per insert instructions 
• 
100 µg P10s-PADRE (post-vaccination DTH testing only): The UAMS Research Pharmacist will 
prepare the DTH dose following the manufacturer’s instructions 
 
The UAMS Research Pharmacy will not provide the Candida albicans antigen for sites other than 
UAMS. Ordering and preparing this antigen will be the responsibility of each study site. 
 
e. DTH Administration: The DTH dose will be injected intradermally on the back of the subject by clinic 
staff. 
 
f. Label Information: The vaccine drug supply (both P10s-PADRE and MONTANIDE™ ISA 51 VG STERILE) 
will be labeled with the following statement: “Caution: New Drug – Limited by Federal Law to 
Investigational Use.” 
 
g. Agent Ordering: All study drug supplies (P10s-PADRE vials and MONTANIDE™ ISA 51 VG STERILE vials) 
will be sent to the attention of the UAMS Research Pharmacy staff. The initial drug supply order will 
be placed by principal investigator and both P10s-PADRE vials and MONTANIDE™ ISA 51 VG STERILE 
vials will be shipped directly to Cancer Institute Pharmacy, Room 5132, 4301 W. Markham Street, Slot 
721-11, Little Rock, AR 72205-7199. 
 
The UAMS Research Pharmacy is the primary pharmacy for this study. All drug ordering and shipment 
to other sites are described in the Pharmacy Instructions binder. 
 
h. Agent Accountability: P10s-PADRE and MONTANIDE™ ISA 51 VG STERILE will be stored in the 
Pharmacy under the supervision of the research pharmacist who will be responsible for maintaining 
the supply according to the manufacturer’s specifications, dispensing the drug for administration and 
maintaining all accountability logs. Standard UAMS accountability logs will be used. 
 
 


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8. TREATMENT PLAN 
 
a. On-study Plan: After signing the IRB-approved informed consent form, research participants with 
eligibility confirmed will be registered and assigned a study number by a clinical research associate 
(CRA) or Study Coordinator. 
 
b. Randomization and Treatment Allocation: After the subject has been assigned a study number, the 
study coordinator will use the Clinical Trials Management System to randomize the subject in a 2:1 
allocation ratio to either the chemo+vaccine arm or the chemo only (control) arm, respectively. 
Subjects will receive either SoC neoadjuvant chemotherapy or SoC neoadjuvant chemotherapy and 
500 μg P10s-PADRE admixed with MONTANIDE™ ISA 51 VG via SC injections depending on the study 
arm to which they are randomized. The two arms will be treated according to the following schedules: 
 
1. Arm 1 - Chemotherapy only: Subjects randomized to the control arm will receive SoC neoadjuvant 
chemotherapy starting on week 1. Doxorubicin and cyclophosphamide (AC) will be administered 
concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on 
day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks. 
2. Arm 2 - Chemo+vaccine: Subjects randomized to the chemo+vaccine arm will be immunized with 
P10s-PADRE in MONTANIDE™ ISA 51 VG a total of three times. The vaccine will be administered 
on weeks 1, 2 and 3 prior to chemotherapy. Then, they will start their SoC neoadjuvant 
chemotherapy on week 4. Doxorubicin and cyclophosphamide (AC) will be administered 
concurrently every two weeks for four cycles with pegfilgrastim (or equivalent growth factor) on 
day 2 of each AC cycle, followed by paclitaxel weekly x 12 weeks. 
 
Subjects will be monitored for chemotherapy-related toxicities and, if clinically necessary, 
chemotherapy dosing may be modified according to the Chemotherapy Dose Adjustment. 
 
c. Chemotherapy Dose Adjustment: Any or all of the SoC neoadjuvant chemotherapies may be dose-
reduced, as necessary, according to SoC. If paclitaxel is not tolerated, docetaxel may be used in its 
place. Chemotherapy dosing may be re-escalated to the starting dose at the treating physician’s 
discretion and per SoC. Subjects who require different chemotherapy agents prior to Week 46 will be 
followed for 30 days after the last vaccination (if applicable) and then be withdrawn from the study. 
 
SOC neoadjuvant chemotherapy dosing may be delayed up to +7 days due to AEs (e.g. anemia, 
neutropenia, leukopenia, etc.). For delays longer than 7 days, the Medical Monitor and Sponsor 
should be contacted. 
 
Any delay outside the allotted time window will be a deviation. The remainder of the study visits 
should be adjusted accordingly and documented in a note-to-file. Each initial shift in the study 
calendar would be a deviation due to medical necessity and the following visits would be recalibrated 
without deviation. 
 
Subjects who require dose modifications, treatment delays, or who are unable to resume their SoC 
neoadjuvant chemotherapy (e.g. due to chemotherapy-related toxicities) will remain in the study to 
continue with assessments per the study calendar, including collection of study labs. 
 


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d. Sample Collection and Evaluation of Endpoints: Sera and peripheral blood mononuclear cells 
(PBMCs) will be collected from subjects and immune responses will be assessed according to the Study 
Calendar in Section 9 and as detailed below. Subjects will be evaluated for antibody response to TACAs 
at Week 1 prior to receiving any treatment (chemotherapy or vaccine). 
 
e. Prohibited Medications: Immunosuppressant medications are not allowed, including inhaled and 
topical steroids, except for those subjects on chemotherapy as prescribed to reduce chemo symptoms 
by attending oncologist or for subjects with an adrenal insufficiency. All other medications are 
allowed. 
 
Concurrent enrollment in another clinical trial using drugs or devices may be allowed only after the 
first post-surgery study lab at Week 46. Concurrent enrollment in observational trials is allowed 
throughout the study. 
 
f. Treatment Discontinuation: Vaccination may be discontinued due to dose-limiting toxicity or a 
serious adverse event (SAE) possibly/probably related to the vaccine (below). 
 
Dose Limiting Criteria: This dose of investigational agent was well tolerated when used in our Phase I 
study in breast cancer subjects. However, if a subject does not tolerate the vaccine, judged by having 
any of the dose-limiting criteria below, their vaccination will be discontinued. 
 
• 
Any grade 3 or greater toxicity as per NCI CTCAE v5 toxicity criteria 
• 
Grade 2 or greater autoimmune toxicity, with the exception of vitiligo 
• 
Grade 2 or greater hypersensitivity reactions 
 
Subjects who any of the above dose-limiting toxicities will be treated and referred for additional care 
as indicated with systemic steroids, topical steroids, epinephrine or Benadryl. These subjects will no 
longer receive the vaccine but will continue with assessments per the study calendar, including 
collection of study labs. 
 
Serious Adverse Event (SAE) during treatment: If an SAE that is possibly/probably/definitely related 
to the vaccine is detected during the vaccination process, the vaccination treatment will be 
discontinued. The subject will remain on study to continue to receive SoC therapy, to be assessed per 
the study calendar and followed for both short-term and long-term immunological and clinical 
endpoints. 
 
g. Study Pausing Rules: The study will be stopped if either of the following occurs: 
• 
Death (other than due to disease progression or motor vehicle accident or to other fatal 
events determined to be not related to the vaccine) 
• 
Two Grade 4 toxicity events that are possibly/probably related to the vaccine 
 
9. STUDY CALENDARS 
 
See following pages. 


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9.1 Study Calendar for Arm 1 (control arm – no vaccine) 
Procedures 
Pre-study/ 
Screeninga 
Wk 1b 
(± 2 
days) 
Wk 3 
(± 2 
days) 
Wk 5 
(± 2 
days) 
Wk 7 
(± 2 
days) 
Weekly 
Wk 9-20c 
(± 2 days) 
Surgery 
(4-8 wks 
after chemo) 
Wk 46 
(±4 wks) 
Wk 70 
(±4 wks) 
Informed Consent/Randomizationd 
X 
 
 
 
 
 
 
 
 
BMI and % weight change in the 
6 months preceding enrollment 
X 
 
 
 
 
 
 
 
 
ACe 
 
X 
X 
X 
X 
 
 
 
 
Paclitaxelf 
 
 
 
 
 
X 
 
 
 
AEs 
 
X 
X 
X 
X 
X 
 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
 
X 
X 
History/PEg 
X 
X 
X 
X 
X 
X q 3wk 
 
X 
X 
Vital signsh 
X 
X 
X 
X 
X 
X 
 
X 
X 
CBC with Differential 
X 
X 
X 
X 
X 
X 
 
X 
X 
Total Bilirubin 
X 
X 
X 
X 
X 
X q 3wk 
 
X 
X 
SGOT/AST 
X 
X 
X 
X 
X 
X q 3wk 
 
X 
X 
SGPT/ALT 
X 
X 
X 
X 
X 
X q 3wk 
 
X 
X 
Alkaline Phosphate 
X 
X 
X 
X 
X 
X q 3wk 
 
X 
X 
LDH 
X 
X 
X 
X 
X 
X q 3wk 
 
X 
X 
Chemistryi 
X 
X 
X 
X 
X 
X q 3wk 
 
X 
X 
Urine Pregnancy Test 
X 
 
 
 
 
 
 
 
 
DTH Skin Test/Readingj 
X 
 
 
 
 
 
 
 
 
Study Labk 
 
X 
 
 
X 
 
 
X 
 
Surgeryl 
 
 
 
 
 
 
X 
 
 
 
 
                                                                        
a Pre-study/Screening should be completed within 21 days prior to Week 1. 
b Screening blood tests (CBC, Total Bilirubin, SGOT/AST, SGPT/ALT, Alkaline Phosphate, LDH, Creatinine, Calcium) performed within 7 days of Week 1 visit will not be repeated. 
c CBC, AEs, Concomitant Medications to be completed weekly. History/PE and other blood work should be completed every 3 weeks and at last treatment visit (Weeks 9, 12 15, 18 & 20). 
d Registration will occur after subject eligibility confirmed as described in Section 15. Registration may occur prior to Week 1. 
e SoC doxorubicin and cyclophosphamide (AC) to be administered concurrently every two weeks for four cycles with pegfilgrastim on day 2 of each AC cycle. 
f If paclitaxel is not tolerated, docetaxel may be used in its place. 
g Tumor Assessments will be performed by physical exam according to standard practice. 
h Vital signs to include blood pressure, temperature, pulse and weight as described in the visit breakdown section. Height is only required at pre-study/screening. 
i Chemistry (OP Chem 7) includes blood urea nitrogen (BUN), carbon dioxide, creatinine, calcium, chloride, potassium, sodium. 
j DTH skin tests to one recall antigen will be performed as described in the visit breakdown section. Results will be read 48-72 hrs later. 
k Study lab for Week 1 should be completed prior to the chemotherapy. Blood collection: approximately 50 mL in red vacutainer and approximately 50 mL in purple vacutainer 
l Performed according to standard practice unless they are considered inoperable or if surgery is medically contraindicated. 


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9.2 Study Calendar for Arm 2 (chemo+vaccine arm) 
Procedures 
Pre-study/ 
Screeninga 
Wk 1 
(± 2 
days) 
Wk 2 
(± 2 
days) 
Wk 3 
(± 2 
days) 
Wk 4 
(± 2 
days) 
Wk 6 
(± 2 
days) 
Wk 7 
(± 2 
days) 
Wk 8 
(± 2 
days) 
Wk 10 
(± 2 
days) 
Weekly 
Wk 12-23b 
(± 2 days) 
Surgery 
(4-8 wks 
after chemo) 
Wk 46 
(±4 wks) 
Wk 70 
(±4 wks) 
Informed Consent/Randomizationc 
X 
 
 
 
 
 
 
 
 
 
 
 
 
BMI and % weight change in the 
6 months preceding enrollment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination with Mimotope P10s-
PADRE/MONTANIDE™ ISA 51 VG 
 
Xd 
Xd 
Xd 
 
 
 
 
 
 
 
 
 
ACe 
 
 
 
 
X 
X 
 
X 
X 
 
 
 
 
Paclitaxelf 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
History/PEg 
X 
X 
 
 
X 
X 
 
X 
X 
X q 3wk 
 
X 
X 
Vital signs h 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
CBC with Differential 
X 
 
 
 
X 
X 
 
X 
X 
X 
 
X 
X 
Total Bilirubin 
X 
 
 
 
X 
X 
 
X 
X 
X q 3wk 
 
X 
X 
SGOT/AST 
X 
 
 
 
X 
X 
 
X 
X 
X q 3wk 
 
X 
X 
SGPT/ALT 
X 
 
 
 
X 
X 
 
X 
X 
X q 3wk 
 
X 
X 
Alkaline Phosphate 
X 
 
 
 
X 
X 
 
X 
X 
X q 3wk 
 
X 
X 
LDH 
X 
 
 
 
X 
X 
 
X 
X 
X q 3wk 
 
X 
X 
Chemistryi 
X 
 
 
 
X 
X 
X 
X 
X 
X q 3wk 
 
X 
X 
Urine Pregnancy Test 
X 
Xj 
 
 
 
 
 
 
 
 
 
 
 
DTH Skin Test/Reading 
Xk 
 
 
 
 
 
 
 
Xl 
 
 
 
 
Study Labm 
 
X 
 
 
 
 
X 
 
X 
Wk 15, 18, 23 
 
X 
X 
Surgeryn 
 
 
 
 
 
 
 
 
 
 
X 
 
 
                                                                        
a Pre-study/screening should be completed within 21 days prior to Week 1. 
b CBC, AEs, Concomitant Medications to be completed weekly. History/PE and other blood work should be completed every 3 weeks and at last treatment visit (Weeks 12, 15, 18, 21 & 23). 
c Registration to occur after subject eligibility confirmed as described in Section 15. 
d Post-vaccine administration, the following vital signs will be monitored every 15 minutes (± 5 minutes) for one hour: blood pressure, temperature and pulse. 
e SoC doxorubicin and cyclophosphamide (AC) to be administered concurrently every two weeks for four cycles with pegfilgrastim on day 2 of each AC cycle. 
f If paclitaxel is not tolerated, docetaxel may be used in its place. 
g Tumor assessments will be performed by physical exam according to standard practice. 
h Vital signs to include weight (except Weeks 1, 2 and 3), blood pressure, temperature, pulse and as described in the visit breakdown section. Height is only required at pre-study/screening. 
i Chemistry (OP Chem 7) includes blood urea nitrogen (BUN), carbon dioxide, creatinine, calcium, chloride, potassium, sodium. 
j To be performed prior to vaccine dosing. Week 1 test may be omitted if screening urine pregnancy test is performed within the 72 hours prior to first vaccine dose. 
k DTH skin tests to one recall antigen will be performed as described in the visit breakdown section. Results will be read 48-72 hrs later. 
l DTH skin test to 100 µg P10s-PADRE will be performed as described in the visit breakdown section. Results will be read 48-72 hrs later. 
m Study lab for Week 1 should be completed prior to the vaccine or chemotherapy. Blood collection: approximately 50 mL in red vacutainer and approximately 50 mL in purple vacutainer 
n Performed according to standard practice unless they are considered inoperable or if surgery is medically contraindicated. 


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10. VISIT BREAKDOWNS 
10.1 Visit Breakdown for Arm 1 (control arm – no vaccine) 
 
Pre-study/Screening Visit (within 21 days prior to initiating study treatment) 
• 
Informed Consent 
• 
Complete medical history and physical examination. Vital signs to include height, weight, blood 
pressure, temperature and pulse 
• 
BMI and Assessment of BMI-adjusted weight change during the six months preceding enrollment 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 
o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Urine pregnancy test for women of childbearing potential 
• 
DTH skin test: 
o 
Candida albicans antigen will be administered intradermally as a control antigen on the subject’s 
back, and the resulting induration will be read 48-72 hours later. 
 
48-72 hour after Pre-study/Screening Visit 
• 
DTH skin test reading 
 
Week 1 (± 2 days) 
• 
Complete medical history and physical examination. Vital signs prior to SoC chemotherapy to include 
weight, blood pressure, temperature and pulse. 
• 
SoC cyclophosphamide and doxorubicin with pegfilgrastim on day 2 of each cycle 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following (screening blood tests performed within 7 days of Week 1 visit 
will not be repeated): 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 
o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Study Lab (prior to chemotherapy): 
o 
Serum preparation: Approximately 50 mL of blood will be collected in red tubes for serum 
collection to determine the presence of glycan-reactive antibodies through ELISA, and flow-
cytometry assays and also to determine cytotoxicity effect on breast cancer cells. 
o 
Isolation of plasma and PBMCs and immune-cell characterization: Approximately 50 mL of blood 
will be collected in potassium EDTA tubes to collect plasma and PBMCs, and further assess the 


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peripheral-blood NK-cell activation markers pre- and post-vaccine administration. PBMCs will be 
used to characterize B-cell and T-cell sub-populations in pre and post-vaccination blood samples. 
 
Week 3 (± 2 days) 
• 
Complete medical history and physical examination. Vital signs prior to SoC chemotherapy to include 
weight, blood pressure, temperature and pulse 
• 
SoC cyclophosphamide and doxorubicin with pegfilgrastim on day 2 of each cycle 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 
o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
 
Week 5 (± 2 days) 
• 
Complete medical history and physical examination. Vital signs prior to SoC chemotherapy to include 
weight, blood pressure, temperature and pulse 
• 
SoC cyclophosphamide and doxorubicin with pegfilgrastim on day 2 of each cycle 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 
o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
 
Week 7 (± 2 days) 
• 
Complete medical history and physical examination. Vital signs prior to SoC chemotherapy to include 
weight, blood pressure, temperature and pulse 
• 
SoC cyclophosphamide and doxorubicin with pegfilgrastim on day 2 of each cycle 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 
o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 


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• 
Study Lab: 
o 
Serum preparation: Approximately 50 mL of blood will be collected in red tubes for serum 
collection to determine the presence of glycan-reactive antibodies through ELISA, and flow-
cytometry assays and also to determine cytotoxicity effect on breast cancer cells. 
o 
Isolation of plasma and PBMCs and immune-cell characterization: Approximately 50 mL of blood 
will be collected in potassium EDTA tubes to collect plasma and PBMCs, and further assess the 
peripheral-blood NK-cell activation markers pre- and post-vaccine administration. PBMCs will be 
used to characterize B-cell and T-cell sub-populations in pre and post-vaccination blood samples. 
 
Weeks 9-20 (± 2 days) 
• 
Complete medical history and physical exam (Weeks 9, 12, 15, 18 and 20 only). Vital signs prior to SoC 
chemotherapy to include weight, blood pressure, temperature and pulse. 
• 
Weekly SoC Paclitaxel 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin (Weeks 9, 12, 15, 18 and 20 only) 
o 
SGOT/AST (Weeks 9, 12, 15, 18 and 20 only) 
o 
SGPT/ALT (Weeks 9, 12, 15, 18 and 20 only) 
o 
Alkaline Phosphatase (Weeks 9, 12, 15, 18 and 20 only) 
o 
LDH (Weeks 9, 12, 15, 18 and 20 only) 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) (Weeks 9, 12, 
15, 18 and 20 only) 
 
Breast cancer surgery 
• 
Definitive surgery will be performed according to standard practice at the investigational site within 
4-8 weeks after completion of chemotherapy. All subjects should undergo appropriate surgical 
management unless they are inoperable or if surgery is medically contraindicated. This surgery is SoC. 
 
Week 46 (±4 weeks) 
• 
Complete medical history and physical examination. Vital signs to include weight, blood pressure, 
temperature and pulse 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 
o 
LDH 
• 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
 
 


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• 
Study Lab: 
o 
Serum preparation: Approximately 50 mL of blood will be collected in red tubes for serum 
collection to determine the presence of glycan-reactive antibodies through ELISA, and flow-
cytometry assays and also to determine cytotoxicity effect on breast cancer cells. 
o 
Isolation of plasma and PBMCs and immune-cell characterization: Approximately 50 mL of blood 
will be collected in potassium EDTA tubes to collect plasma and PBMCs, and further assess the 
peripheral-blood NK-cell activation markers pre- and post-vaccine administration. PBMCs will be 
used to characterize B-cell and T-cell sub-populations in pre and post-vaccination blood samples. 
 
Week 70 (±4 weeks) 
• 
Complete medical history and physical examination. Vital signs to include weight, blood pressure, 
temperature and pulse 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 
o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
 
10.2 Visit Breakdown for Arm 2 (chemo+vaccine arm) 
 
Pre-study/Screening Visit (within 21 days prior to initiating study treatment) 
• 
Informed Consent 
• 
Complete medical history and physical examination. Vital signs to include height, weight, blood 
pressure, temperature and pulse 
• 
BMI and Assessment of BMI-adjusted weight change during the six months preceding enrollment 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 
o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Urine pregnancy test for women of childbearing potential 
• 
DTH skin test: 
o 
Candida albicans antigen will be administered intradermally as a control antigen on the subject’s 
back, and the resulting induration will be read 48-72 hours later. 
 
48-72 hour after Pre-study/Screening Visit 
• 
DTH skin test reading 
 


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Week 1 (± 2 days) 
• 
Complete medical history and physical examination. Vital signs prior to vaccine administration to 
include blood pressure, temperature and pulse 
• 
Urine pregnancy test for women of childbearing potential (within 72 hours prior to dosing). Test not 
required if screening pregnancy test is performed within 72 hours prior to first vaccine. 
• 
SC administration of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine 
• 
Post-vaccine administration, the following vital signs will be monitored every 15 minutes (± 5 minutes) 
for one hour: blood pressure, temperature, and pulse 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Study Lab: 
o 
Serum preparation: Approximately 50 mL of blood will be collected in red tubes for serum 
collection to determine the presence of glycan-reactive antibodies through ELISA, and flow-
cytometry assays and also to determine cytotoxicity effect on breast cancer cells 
o 
Isolation of plasma and PBMCs and immune-cell characterization: Approximately 50 mL of blood 
will be collected in potassium EDTA tubes to collect plasma and PBMCs, and further assess the 
peripheral-blood NK-cell activation markers pre- and post-vaccine administration. PBMCs will be 
used to characterize B-cell and T-cell sub-populations in pre and post-vaccination blood samples. 
 
Week 2 (± 2 days) 
• 
Vital signs prior to vaccine administration to include blood pressure, temperature, and pulse 
• 
SC administration of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine 
• 
Post-vaccine administration, the following vital signs will be monitored every 15 minutes (± 5 minutes) 
for one hour: blood pressure, temperature, and pulse 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
 
Week 3 (± 2 days) 
• 
Vital signs prior to vaccine administration to include blood pressure, temperature, and pulse 
• 
SC administration of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine 
• 
Post-vaccine administration, the following vital signs will be monitored every 15 minutes (± 5 minutes) 
for one hour: blood pressure, temperature, and pulse 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
 
Week 4 (± 2 days) 
• 
Complete medical history and physical examination. Vital signs prior to SoC chemotherapy to include 
weight, blood pressure, temperature and pulse 
• 
SoC cyclophosphamide and doxorubicin with pegfilgrastim on day 2 of each cycle 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 


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o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
 
Week 6 (± 2 days) 
• 
Complete medical history and physical examination. Vital signs prior to SoC chemotherapy to include 
weight, blood pressure, temperature and pulse 
• 
SoC cyclophosphamide and doxorubicin with pegfilgrastim on day 2 of each cycle 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 
o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
 
Week 7 (± 2 days) 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Study Lab: 
o 
Serum preparation: Approximately 50 mL of blood will be collected in red tubes for serum 
collection to determine the presence of glycan-reactive antibodies through ELISA, and flow-
cytometry assays and also to determine cytotoxicity effect on breast cancer cells. 
o 
Isolation of plasma and PBMCs and immune-cell characterization: Approximately 50 mL of blood 
will be collected in potassium EDTA tubes to collect plasma and PBMCs, and further assess the 
peripheral-blood NK-cell activation markers pre- and post-vaccine administration. PBMCs will be 
used to characterize B-cell and T-cell sub-populations in pre and post-vaccination blood samples. 
 
Week 8 (± 2 days) 
• 
Complete medical history and physical examination. Vital signs prior to SoC chemotherapy to include 
weight, blood pressure, temperature and pulse 
• 
SoC cyclophosphamide and doxorubicin with pegfilgrastim on day 2 of each cycle 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 
o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
 
 


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Version: 11 
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Week 10 (± 2 days) 
• 
Complete medical history and physical examination. Vital signs prior to SoC chemotherapy to include 
weight, blood pressure, temperature and pulse 
• 
SoC cyclophosphamide and doxorubicin with pegfilgrastim on day 2 of each cycle 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 
o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Study Lab: 
o 
Serum preparation: Approximately 50 mL of blood will be collected in red tubes for serum 
collection to determine the presence of glycan-reactive antibodies through ELISA, and flow-
cytometry assays and also to determine cytotoxicity effect on breast cancer cells. 
o 
Isolation of plasma and PBMCs and immune-cell characterization: Approximately 50 mL of blood 
will be collected in potassium EDTA tubes to collect plasma and PBMCs, and further assess the 
peripheral-blood NK-cell activation markers pre- and post-vaccine administration. PBMCs will be 
used to characterize B-cell and T-cell sub-populations in pre and post-vaccination blood samples. 
• 
DTH skin test: 
o 
100 μg Mimotope P10s-PADRE will be administered intradermally on the subject’s back to 
determine subject’s DTH response to the vaccine, and the resulting induration will be read 48-72 
hours later. 
 
48-72 hour after Week 10 
• 
DTH skin test reading 
 
Week 12-23 (± 2 days) 
• 
Complete medical history and physical exam (Weeks 12, 15, 18, 21 and 23 only). Vital signs prior to 
SoC chemotherapy to include weight, blood pressure, temperature and pulse 
• 
Weekly SoC Paclitaxel 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin (Weeks 12, 15, 18, 21 and 23 only) 
o 
SGOT/AST (Weeks 12, 15, 18, 21 and 23 only) 
o 
SGPT/ALT (Weeks 12, 15, 18, 21 and 23 only) 
o 
Alkaline Phosphatase (Weeks 12, 15, 18, 21 and 23 only) 
o 
LDH (Weeks 12, 15, 18, 21 and 23 only) 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) (Weeks 12, 15, 
18, 21 and 23 only) 
 
 


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• 
Study Lab (Week 15, 18 and 23 only): 
o 
Serum preparation: Approximately 50 mL of blood will be collected in red tubes for serum 
collection to determine the presence of glycan-reactive antibodies through ELISA, and flow-
cytometry assays and also to determine cytotoxicity effect on breast cancer cells. 
o 
Isolation of plasma and PBMCs and immune-cell characterization: Approximately 50 mL of blood 
will be collected in potassium EDTA tubes to collect plasma and PBMCs, and further assess the 
peripheral-blood NK-cell activation markers pre- and post-vaccine administration. PBMCs will be 
used to characterize B-cell and T-cell sub-populations in pre and post-vaccination blood samples. 
 
Breast cancer surgery 
• 
Definitive surgery will be performed according to standard practice at the investigational site within 
4-8 weeks after completion of chemotherapy. All subjects should undergo appropriate surgical 
management unless they are inoperable or if surgery is medically contraindicated. This surgery is SoC. 
 
Week 46 (±4 weeks) 
• 
Complete medical history and physical examination. Vital signs to include weight, blood pressure, 
temperature and pulse 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 
o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Study Lab: 
o 
Serum preparation: Approximately 50 mL of blood will be collected in red tubes for serum 
collection to determine the presence of glycan-reactive antibodies through ELISA, and flow-
cytometry assays and also to determine cytotoxicity effect on breast cancer cells. 
o 
Isolation of plasma and PBMCs and immune-cell characterization: Approximately 50 mL of blood 
will be collected in potassium EDTA tubes to collect plasma and PBMCs, and further assess the 
peripheral-blood NK-cell activation markers pre- and post-vaccine administration. PBMCs will be 
used to characterize B-cell and T-cell sub-populations in pre and post-vaccination blood samples. 
 
Week 70 (±4 weeks) 
• 
Complete medical history and physical examination. Vital signs to include weight, blood pressure, 
temperature and pulse 
• 
AEs: events will be monitored using the NCI CTCAE Version 5.0 
• 
Concomitant medications 
• 
Blood tests to include the following: 
o 
Complete blood count with differential 
o 
Total Bilirubin 
o 
SGOT/AST 
o 
SGPT/ALT 
o 
Alkaline Phosphatase 


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o 
LDH 
o 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Study Lab: 
o 
Serum preparation: Approximately 50 mL of blood will be collected in red tubes for serum 
collection to determine the presence of glycan-reactive antibodies through ELISA, and flow-
cytometry assays and also to determine cytotoxicity effect on breast cancer cells. 
o 
Isolation of plasma and PBMCs and immune-cell characterization: Approximately 50 mL of blood 
will be collected in potassium EDTA tubes to collect plasma and PBMCs, and further assess the 
peripheral-blood NK-cell activation markers pre- and post-vaccine administration. PBMCs will be 
used to characterize B-cell and T-cell sub-populations in pre and post-vaccination blood samples. 
 
11. RISKS AND TOXICITIES TO BE MONITORED 
 
a. Potential Toxicities, Risks and Precautions: 
 
Procedure 
Risks 
Measures to Minimize Risks 
Complete history 
and physical exam, 
including blood 
chemistries 
Identification of previously unknown condition 
Qualified health care provider to evaluate 
potential subject 
Research records are kept in a locked area 
accessible only by study personnel. 
Administration of 
study vaccine -  
Mimotope P10s-
PADRE / 
MONTANIDE™ ISA 
51 VG 
Refer to the Investigator’s Brochures for P10s-
PADRE and MONTANIDE™ ISA 51 VG for a 
comprehensive list of possible adverse reactions. 
Experimental agent may be toxic or harmful. 
Risk of local reactions (i.e. swelling, redness, 
tenderness, itching, extravasations) 
Potential for side effects ranging from hematologic 
toxicities and hypersensitivity reactions to 
anaphylaxis 
Unanticipated or unknown risks 
Dermatology/Skin: local erythema, rash, pruritus 
Gastrointestinal: diarrhea, anorexia, nausea, 
vomiting, abnormal taste 
Hepatic: elevated hepatic enzymes, hypo-
albuminemia with prolonged treatment 
Neurology: confusion, neuropathies 
Pulmonary: dyspnea (due to fluid retention and 
capillary leak syndrome), pleuritis 
Cardiovascular: hypertension, cardiac arrhythmias, 
atrial fibrillation, pericarditis 
Pain: headache, arthralgias, bone pain, abdominal 
pain, chest pain, myalgia 
Fever, flu-like syndrome (chills, rigors, myalgias), 
fatigue, headache, abnormal labs including BUN 
and albumin 
Careful monitoring by clinic visits and 24 
hour, 7 days per week physicians on call 
for unexpected problems 
Only non-pregnant, non-lactating females 
may participate. The use of contraception 
during the study and the use of 
contraception for 18 months post 
completion of the trial are required. 
Frequent laboratory tests including CBC 
with differential, liver function tests, etc. 
Close and frequent monitoring of subjects 
by qualified staff 
Emergency equipment including crash 
carts, ACLS certified staff and rescue 
medications such as Benadryl, 
epinephrine, high dose steroids, etc. will 
be on-site during administration. 
The Medical Monitor will review all serious 
toxicities as they occur. 
The study drug may be discontinued if 
significant AE occurs or if subject chooses 
to discontinue. 
Reporting and monitoring mechanisms are 
in place for AEs, SAEs and unanticipated 
problems. 


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Administration of 
SoC chemotherapy 
Refer to the approved Package Insert or 
Investigator’s Brochure for each chemotherapy 
agent for a comprehensive list of possible adverse 
reactions. 
The following is a list of common known possible 
adverse reactions: infections, neutropenia, 
anemia, febrile neutropenia, hypersensitivity, 
thrombocytopenia, anaphylactic reactions, 
dysgeusia, dyspnea, constipation, anorexia, nail 
disorders, fluid retention, asthenia, pain, nausea, 
diarrhea, vomiting, mucositis, alopecia, skin 
reactions, myalgia, arthralgia, fatigue, neuropathy, 
sensory neuropathy, peripheral neuropathy, 
leukopenia, urinary bladder, myeloproliferative or 
lymphoproliferative malignancies, hemorrhagic 
cystitis, cardiotoxicity. 
Careful monitoring by clinic visits and 24 
hour, 7 days per week physicians on call 
for unexpected problems 
Only non-pregnant, non-lactating females 
may participate. The use of contraception 
during the study and the use of 
contraception for 18 months post 
completion of the trial are required. 
Frequent laboratory tests including CBC 
with differential, liver function tests, etc. 
Close and frequent monitoring of subjects 
by qualified staff 
Emergency equipment including crash 
carts, ACLS certified staff and rescue 
medications such as Benadryl, 
epinephrine, high dose steroids, etc. will 
be on-site during administration. 
The Medical Monitor will review all serious 
toxicities as they occur. 
The study drug may be discontinued if 
significant AE occurs or if subject chooses 
to discontinue. 
Reporting and monitoring mechanisms are 
in place for AEs, SAEs and unanticipated 
problems. 
Collection of blood 
samples 
Pain, bruising at the injection site and rarely 
infection 
Discovery of previously unknown conditions 
Experienced personnel will perform the 
phlebotomies using approved techniques. 
Pressure and dressings will be used to 
minimize pain, bruising and infection. 
Research records are kept in a locked area 
accessible only by study personnel. 
Urine pregnancy 
testing 
Discovery of previously unknown conditions 
Possible breach of confidentiality 
Research records are kept in a locked area 
accessible only by study personnel. 
Subjects will only be identified by study 
numbers on all research documents. 
Serum for 
immunologic 
evaluation 
Discovery of previously unknown conditions 
Research records are kept in a locked area 
accessible only by study personnel. 
Subjects will only be identified by study 
numbers on all research documents. 


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Collection of data 
Possible breach of confidentiality 
Research records are kept in a locked area 
accessible only by study personnel. 
Subject study numbers will be used for 
identification of samples so that they may 
be retained for future research and 
confidentiality is ensured. 
Investigators will provide certification of 
completion of Human Subject Protection 
training course. 
UAMS shall retain the records and reports 
for 2 years after a marketing application is 
approved for the drug; or, if an application 
is not approved for the drug, until 2 years 
after shipment and delivery, or for 2 years 
after the IND (Investigational New Drug 
Application) is closed and discontinued 
with the Food and Drug Administration 
(FDA). After such time all study records 
will be destroyed as well as the links 
between identifiers of the research 
subjects and their research study numbers 
according to UAMS’ record destruction 
policy. 
 
Any subject may voluntarily revoke consent and withdraw from the study at any time. A subject may 
be terminated early (completely withdrawn from the study) for the following conditions: (i) non-
compliance, (ii) an unrelated intercurrent illness that may affect assessment or place the subject at 
risk for AEs or require systemic steroids, (iii) deterioration in performance status so as to make 
participation a hardship for the subject, or (iv) for any reason that the investigator feels it is not in the 
subject’s best interest to continue (i.e. different chemotherapy regimen prior to Week 46 study labs, 
etc.). These subjects must be followed for at least 30 days after the last dose of study vaccine. 
 
b. Benefits: There is no guarantee that subjects will experience direct benefit from participation in this 
study. However, it is expected that the rate of pCR following chemo+vaccine will be at least as high as 
the rate observed among subjects who receive only SoC neoadjuvant chemotherapy. Adding 
vaccination with P10s to SoC therapy may potentiate an immune response, which could improve the 
rate of pCR compared to SoC therapy alone. 
 
12. SPECIMEN HANDLING 
 
A trained phlebotomist or registered nurse will draw the blood required for clinical and research purposes. 
Research staff will pick up specimens from the Cancer Institute Blood Draw or Infusion Center. Research 
staff will re-label specimens with a subject identifier, date of specimen, and name of visit. Specimens will 
then be delivered to the UAMS Tissue Biorepository and Procurement Service (TBAPS) in the Cancer 
Institute. The serum tubes will remain in the UAMS TBAPS and will be stored frozen at -65°C or lower. The 
EDTA tubes will be delivered to Dr. Kieber-Emmons’ research laboratory for processing and analysis. 
Samples will be kept for the duration of this study and may be used for future P10s-PADRE vaccine 
research. At the end of this cancer vaccine research, any unused specimen will be mixed with bleach and 
disposed in a sink. 
 


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Tissue specimens from archival tissue collected as part of standard biopsy and/or surgery will be 
requested for each subject at the time of enrollment. Whenever available, a total of 2 H&E slides and 20 
unstained slides (half from the original biopsy and half from tissues collected at surgery) per subject will 
be requested for all analyses (see Immunohistochemistry and Characterization of tumor infiltrating 
lymphocytes (TILs)). 
 
All specimen containers (tubes and containers) will be disposed into biohazard red plastic bags according 
to UAMS Occupational Health & Safety policy. Red bag waste will be picked up by Occupational Health & 
Safety for final disposal. 
 
HOG will have study specimens brought to UAMS by courier service. Study specimen will be delivered to 
the UAMS TBAPS the same day they are drawn following the same process above. 
 
13. ENDPOINT DEFINITIONS, EVALUATION of IMMUNE RESPONSE, and ENDPOINT-ASSAY METHODS 
 
a. Primary Efficacy Endpoint: pCR 
We will employ the definition of pCR proposed by the FDA in their May 2012 Draft Guidance for 
Industry, “Pathologic Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast 
Cancer: Use as an Endpoint to Support Accelerated Approval”. The FDA’s proposed definition reads 
as follows: 
Pathological Complete Response is defined as the absence of any residual invasive cancer on 
hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral 
lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in 
the current AJCC staging system)(58). 
 
The baseline tumor pathology, final tumor pathology, and tumor response will also be collected. 
• 
Baseline Tumor Pathology: tumor size, tumor stage and grade, lymph node status 
• 
Final Tumor Pathology (at surgery): tumor size, tumor stage and grade, lymph node status 
• 
Tumor Response: clinical complete response (cCR), clinical partial response (cPR), disease 
progression, and stable disease 
• 
Pathological Response Status: (i.e. pCR, residual disease, etc.). 
 
b. Secondary Endpoints for determining short-term immune responses to Treatment 
• 
P10s-MAP-reactive immunoglobulin titers: The anti-P10s binding level will be measured via ELISA 
method after incubation with a subject’s serum or plasma sample. 
o 
The P10s-MAP-reactive immunoglobulin titers will be determined on each subject from serum 
and plasma samples drawn as specified in the study calendar. 
 
• 
Anti-TACA cell-binding level: The anti-TACA cell-binding level will be measured via flow-cytometry 
methods as the median fluorescence intensity of TACA-expressing tumor cells obtained after 
incubation with a subject’s serum or plasma sample. 
o 
The anti-TACA cell-binding level will be determined on each subject from serum and plasma 
samples drawn as specified in the study calendar. 
 
 


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• 
Anti-breast-cancer cytotoxicity: The cytotoxicity of a sample towards a breast cancer cell line will 
be measured as the percent decrease (relative to a control) in the cells’ survival following 
incubation with pre- and postimmune serum and plasma. 
o 
The anti-breast-cancer cytotoxicity will be determined on each subject from serum and 
plasma samples drawn as specified in the study calendar. 
 
• 
Frequencies of circulating T cells, B cells, NK cells, and regulatory T cells (Tregs): Peripheral blood 
mononuclear cells (PBMCs) will be isolated and the above populations of immune cells will be 
determined by flow cytometry. See Section f below for additional details. 
 
• 
Activation profiles of NK cells: Activated-NK-cell profiles will be determined via flow cytometry as 
the expression levels of different activation markers on NK cells in the subject’s blood sample. See 
Section f below for additional details. 
 
• 
Functionality of T cells and NK cells: Effector functions will be determined through stimulation 
with anti-CD3-coated plates, phytohemagglutinin (PHA; Sigma) and tumor cell lysate, and 
production of cytokines will be measured. The effector function of NK cells will be measured by 
Antibody Dependent Cell Cytotoxicity (ADCC) assay monoclonal antibodies or using serum 
samples. See Section f below for additional details. 
 
• 
Biomarkers of response and efficacy: The expression of glycan antigens and proliferation/ 
apoptosis markers will be determined on tumor tissues. 
 
• 
Characterize infiltrating lymphocytes: TILs will be characterized and frequency of subpopulation 
with efficacy will be correlated. 
 
c. Secondary Endpoints for determining persistence of immune responses 
We will further determine the persistence of a subject’s immune responses upon treatment according 
to the arm to which they are randomized. 
• 
The anti-P10s antibody titer will be determined on each subject’s serum and plasma samples 
drawn approximately 6 and 12 months, as specified in the study calendar. 
• 
The anti-TACA cell-binding level will be determined on each subject’s serum and plasma samples 
drawn approximately 6 and 12 months as specified in the study calendar. 
• 
The anti-breast-cancer cytotoxicity will be determined on each subject’s serum and plasma 
samples drawn approximately 6 and 12 months as specified in the study calendar. 
• 
Functionality of T and NK cells will be evaluated. 
 
d. Determining DTH Responses 
To evaluate DTH responses, subjects will be skin-tested according to the time points in the study 
calendar against Candida albicans antigen (week 1) and the Mimotope P10s-PADRE (week 10). The 
Candida albicans antigen serves as a control antigen. DTH responses to the control antigen will be 
assessed at pre-study to determine immunocompetency of study subjects. DTH responses to the 
P10s-PADRE will be assessed at week 10 to determine cellular immunogenicity of the vaccine. All 
antigens will be administered intradermally on the subject’s back. Induration will be measured using 
calipers or a ruler and reported in mm across one diameter at 48-72 hours post injection. An 
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e. Safety and Tolerability Endpoints 
Subjects on Arm 2 will receive 3 planned vaccine doses unless they withdraw from the study or 
develop any Grade 3 or greater toxicity as per NCI CTCAE Version 5.0 toxicity criteria, Grade 2 or 
greater autoimmune toxicity with the exception of vitiligo, or Grade 2 or greater hypersensitivity 
reactions. Subjects will be treated and referred for additional care as indicated with systemic steroids, 
topical steroids, epinephrine or Benadryl, at which time they will discontinue the vaccine injections 
and will continue to have assessments per the study calendar defined in the protocol. Subjects will be 
followed until resolution of toxicity. There will be no dose modifications for toxicity. 
 
The NCI CTCAE Version 5.0 will be used for toxicity and SAE reporting. A copy of the CTCAE Version 
5.0 can be downloaded from the Cancer Therapy Evaluation Program (CTEP) home page. All 
appropriate treatment areas have access to a copy of the CTCAE Version 5.0. 
 
The study will be paused upon Death (other than disease progression or motor vehicle accident) or 
two Grade 4 Toxicity events that are possibly/probably related to the study agent. 
 
The endpoints used to monitor tolerability will mirror safety endpoints, and will be classified into 
reactogenicity endpoints and vaccine-related adverse events (AEs), the most serious of which will be 
reported as serious adverse events (SAEs). Reactogenicity endpoints will be further divided into: (1) 
systemic symptoms that include fever, malaise, and myalgia; and (2) local symptoms that include pain, 
tenderness, and induration at the injection site. 
 
f. Immunological assay methods for determining the endpoints will follow established SOPs 
The following are brief descriptions of the methods by which the study’s endpoints will be 
determined. 
 
• 
Sample cytotoxicity towards MDA-MB-231 and HCC1954: This assay will be conducted on both 
serum samples and plasma samples. Cells from each cell line will be grown in 24-well plates, and 
exposed in triplicate to the samples from each subject, and to fetal bovine serum (FBS) as a 
control. Cells will be incubated for 24, 48 and 72 hours, after which wells will be photographed 
and then dead cells and debris will be removed and viable cells will be fixed and stained. More 
pictures will be taken and the number of viable cells for each treatment will be counted. The 
number of alive cells in sample-treated wells will be expressed as a percentage of the number of 
cells in FBS-treated wells. 
 
• 
Anti-P10s antibody titer: In each sample, the anti-peptide reactivity will be determined by ELISA 
methods using P10s-MAP adhered to 96-well microtiter plates, with secondary antibody being 
HRP-conjugated anti-human antibody. Endpoint titers will be determined from reactivities via the 
serial 2-fold dilution method. Both the IgG titer and the IgM titer will be determined. 
 
• 
Binding of antibody to TACA-expressing tumor cells: From each sample, aliquots will be removed 
and used to incubate 1-to-2 x 105 cells from each of three human breast-cancer cell lines: MCF-7 
(which expresses LeY), MDA-MB-231 (which expresses gangliosides), and HCC1954. Serum-
incubated cells will be post-incubated with FITC-labeled goat antihuman antibody, then fed 
through the flow cytometer. The median fluorescence intensity of the treated cells will be 
determined and reported as the measure of binding of serum antibody to TACA-expressing tumor 
cells. The monoclonal antibodies BR55-2 and 14G2a will be used as positive controls. 


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• 
Determining NK-cell activation: To count the number of NK cells in a blood sample, PBMCs will be 
separated from blood using Histopaque® (Sigma), washed and stained with anti-CD3 and anti-
CD56 (BD biosciences), and the number of cells that are determined to be CD3-/CD56+ will be 
counted and used as the total number of NK cells in the sample. To determine the expression 
levels of activation markers CD69, CD94, CD16, and NKp46, cells will be stained with a third color 
specific for each marker. The expression level of each activation marker will be determined in CD3-
/CD56+ cells (NK cells) via flow cytometry as either the median or geometric mean of the marker’s 
fluorescence-intensity histogram. 
 
• 
Determine T-cell and B-cell subpopulations: Both lymphocytes and CD3+ cells will be stained for 
CD4 and CD8 markers. The CD19+ B cell subpopulations, including naive B cells (IgD+CD27−), 
marginal zone–like/natural effector B cells (IgD+CD27+), class-switched memory B cells 
(IgD−CD27+), transitional B cells (IgM++CD38++) and plasmablasts (IgM−CD383+) will be determined. 
Percentage of CD40+, CD69+, CD83+ and IgG+ CD19 B-cells will be determined. 
 
• 
Determine T-cell subpopulations: Peripheral blood mononuclear cells (PBMCs) will be isolated by 
density gradient centrifugation using Ficoll-Paque solution. Lymphocytes will be stained and the 
expression levels of CD69, PD-1, and CTLA-4 among CD4 and CD8 T cells will be determined. The 
regulatory subpopulation of CD4+/CD25hi/CD127-/lo (FOXP3+) and MDSC populations with 
granulocytic (Lin− HLA-DR−/lo CD15+ CD33+CD11b+) and monocytic (HLA-DR−/lo CD14+) phenotype 
will be determined. The expression of PD-L1 on monocytes will also be determined. The above 
cell populations will be assessed and assays performed in each subject’s pre- and post-immune 
blood samples and comparisons will be made to understand whether vaccination affects immune 
cell profile and function. 
 
• 
Proliferation assay and cytokine detection: The effector functions through stimulation of T cells 
with P10s and P10s-PADRE peptides, tumor cell lysate, and anti-CD3-coated plates will be 
conducted and production of cytokines will be measured. 2x10^5 PBMCs will be incubated in 200 
µl of RPMI 1640 medium containing 5% heat inactivated fetal calf serum. Proliferation will be 
induced using P10s, P10s-PADRE, PHA (10 μg/ml), anti-CD3-coated plates (5 μg/ml) or lysate of a 
representative breast cancer cell line. After 24 (PHA or anti-CD3) to 72 (tumor lysate) hours of 
incubation 3H thymidine will be added and incubated for another 8 hours. Cells stimulated with 
lysate may need another round of stimulation (total of 6 days) before thymidine addition. A 
fraction of supernatant from each well will be collected before thymidine addition for detection 
of cytokines by ELISA. The cells will be harvested and 3H thymidine incorporation determined 
using a liquid scintillation counter (Perkin Elmer Inc.) and expressed as counts per minute (cpm). 
The stimulation index (SI) will be obtained by calculating total cpm/control cpm. PBMCs that had 
not been subjected to PHA addition will be used as controls. The collected supernatant will be 
frozen and kept at -80°C. Supernatants will thawed and used for detection of cytokines (IFN-γ, IL-
2, TNFα, IL-4, IL-10, and IL-13) by ELISA using kits from R&D Systems. 
 
• 
ELISPOT assay: ELISPOT will be used to further confirm T-cell effector function. PBMCs will be 
stimulated with P10s, P10s-PADREE, tumor cell lysate, and anti-CD3 and cytokine secretion profile 
will be determined using human BD™ ELISPOT kit set following manufacturer’s instructions. 
 
 


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• 
ADCC assay: ADCC assays will be performed to evaluate functionality of post-immune serum in 
inducing immune cell-mediated cell death and compare it to pre-immune serum for each subject, 
where breast cancer cell lines will be used as targets. Target cells will be labelled with calcein AM 
and 10^4 cells per well in 50 µl of medium will be added to 96 well microtiter plates and then 50 
µl serum will be added and incubated for 30 minutes. Effector cells will be added in 100µl volume 
of medium to give serially diluted effector:target cell ratios (E:T) with maximum E:T of 50:1. 
Primarily, PBMCs from healthy donors or NK-92 cells will be used as effectors. After 4 hours of 
incubation imaging with Cytation 5 cell imaging reader (BioTek, Winooski, VT) will be performed 
to count live target cells in wells with and without effector cells and percent cytotoxicity will be 
calculated as [1-(calcein AM target cells with effector cells /calcein AM target cells without 
effector cell)]X100. In separate experiments, pre- and post-immune PBMCs from responder 
subjects will be compared using mAb BR55-2 (mediates ADCC on LeY-positive cells). This will show 
whether vaccination results in more potent effector cells. 
 
• 
Immunohistochemistry: In those subjects with enough pathological specimens, tumor-tissue 
slides will be requested from tissue collected at both the original biopsy before treatment (1 H&E 
and 8 unstained slides) and at time of definitive surgery (1 H&E and 8 unstained slides). The tumor-
tissue slides from the original biopsy will be compared to the tumor-tissue slides from surgery in 
order to learn more about the mechanism of action. These slides will be stained for anti-glycan 
mAbs (anti-LeY and GD2 mAb), to evaluate potential correlation of expression of LeY and GD2 
gangliosides levels with clinical response. Caspase-3 and activated caspase-3 (Abcam Inc., MA) 
expression will also be determined. Ki67 staining will be performed and its expression 
determined. Besides pCR, potential tumor response by evaluating invasion burden and location 
will be evaluated. Staining of provided slides will be performed by the UAMS experimental 
Pathology Core Facility. To perform these analyses, a total of 2 H&E slides and 10 unstained will 
be requested, whenever available, for each procedure (half from original biopsy and half from 
tissues collected at surgery) per subject. 
 
• 
Characterization of tumor infiltrating lymphocytes (TILs): The characterization of TILs in tumor 
tissues of subjects of this study is planned to help us to understand whether vaccination efficacy 
relate to pre-treatment immune infiltrates or whether vaccination affect lymphocyte infiltration 
and the composition of the infiltrates. We also seek to understand whether any response to 
vaccination is associated with immune infiltrates and their compositions. Therefore, we will first 
evaluate H&E and Ki67 expression in tumor specimens collected at original biopsy before 
treatment and tissues collected at surgery. Whenever available, tumor-tissue slides will be 
requested to perform staining to detect subpopulations of infiltrating immune cells. Staining will 
be performed with anti-CD3, -CD4, -CD8, -FOXP3, and -CD56 mAbs (one slide per antibody from 
both biopsy and surgery). In addition to the slides for immunohistochemistry, 10 unstained slides 
(half from original biopsy and half from tissues collected at surgery) will be requested per subject 
for TILs characterization. Staining will be performed through the UAMS Experimental Pathology 
Core Facility. 
 
 
Genome-wide gene expression and methylation analyses using plasma, immune and tumor cells: 
Genetic and epigenetic variation in plasma samples, immune cells and tumors before and after 
immunization will be explored to study the potential biomarkers of immune and tumor responses. 
 


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14. STATISTICAL CONSIDERATIONS 
 
General Considerations: The primary objectives of this Phase I/II, randomized, multi-center safety and 
efficacy study are (1) to monitor the safety of P10s-PADRE vaccine when used in combination with SoC 
chemotherapy and (2) to evaluate the efficacy of the combination of chemo+vaccine as illustrated by the 
pCR rate. The secondary objectives are to evaluate immunologic endpoints. The size of the study 
population was purposely chosen to provide adequate power (>80%) to properly evaluate the clinical 
efficacy of the vaccine-chemotherapy combination while allowing for a formal interim analysis. In 
addition, the translational effectiveness of any cancer vaccine in a large population depends on both the 
level and the functionality of the resultant immune responses. 
 
Analysis Plan for Primary Efficacy Endpoint and Determination of Sample Size: SoC chemotherapy is 
expected to result in a pCR rate of 40%, consistent with rates reported elsewhere (62). pCR is defined as 
the absence of invasive cancer in the breast and the lymph nodes (ypT0/Tis, ypN0). The presence of in-
situ cancer in the breast is acceptable and does not disqualify a subject from the pCR definition. We 
hypothesize that the combination of chemo+vaccine will result in an increase of the pCR rate to 65% or 
higher. The two arms will be compared for evidence of this increase using the one-sided Z test with pooled 
variance at a 10%-alpha significance level. A sample size of 102 subjects, 68 on the chemo+vaccine arm 
versus 34 on the control arm, will provide the planned Z test with 85.8% power at 10% target alpha to 
detect the hypothesized increase in pCR between arms. The true attained alpha will be 9.6%. Assuming 
that the planned interim analysis (see below) does not lead to early closure, this study will be declared a 
success if the planned Z test yields a Z-score of +1.316 or greater (1-sided P≤0.094) 
 
Interim Analysis Plan for Efficacy and Futility: A formal interim analysis will take place when 51 subjects 
(half the planned total) have been evaluated for response to treatment. We expect this analysis to occur 
when approximately 75% of the planned study sample has been enrolled. Unless there are toxicity 
concerns or extenuating circumstances, the study will not close during this interim assessment. To 
conduct the interim analysis, the treatment arms will be compared via 1-sided pooled-variance Z test, 
Results will be evaluated using the following decision boundaries, which were calculated in East version 
6.4 software (Cytel, Inc., Cambridge, MA, USA) using O’Brien-Fleming spending functions for both alpha 
and beta. 
• 
If the test yields a Z-score of +2.054 or greater (1-sided P≤0.0200 or less), then the chemo+vaccine 
arm will be declared efficacious enough to warrant closing the study early for efficacy. 
• 
On the other hand, if the test yields a Z-score of -0.045 or less (1-sided P≥0.518), then that result 
will be considered negative enough to warrant closing the study early for futility. 
 
Findings of either kind that warrant closing the study early will not be binding, but will be evaluated along 
with other evidence by a formal meeting of the Data Safety Monitoring Board (DSMB). 
 
Analysis Plans for Secondary Endpoints: To analyze the secondary endpoints, data will be summarized by 
collection time as means, standard deviations, medians, and ranges, and displayed graphically using 
profile plots and box plots. Residuals analysis will be used to examine adherence to distributional 
assumptions, and data transformations will be applied if warranted. Each endpoint will be analyzed 
longitudinally using either generalized estimating equations or mixed-models analysis. In particular, post-
immune levels of each endpoint will be compared to its pre-immune level for (a) occurrence of a 
significant increase, and (b) duration of the significant increase if one occurred. In addition, subjects will 
be classified individually with respect to each endpoint as a “responder” if any of that endpoint’s post-


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immune levels attains an increase of at least two folds relative to its pre-immune level, and the number 
and proportion of “responders” with respect to each endpoint will be reported. Finally, a mixed-models 
regression approach will be used to determine how much of the samples’ cytotoxicity towards HCC1954 
and MDA-MB-231 can be predicted by the secondary endpoints. 
 
DTH-test results will be summarized by subpopulation as the number and proportion responding. Subjects 
with positive versus negative DTH-test results will be compared via Wilcoxon rank-sum tests for 
differences in their anti-P10s-MAP IgG titers. 
 
Missing, Unused and Spurious Data: Missing data will be treated as missing, and will not be imputed. All 
data collected will necessarily be reported to the FDA. Spurious data will be corrected at the source 
document. Any data documented as spurious that is unable to be corrected at the source will be treated 
as missing. 
 
Data Safety Monitoring Plan: AEs and safety will be evaluated throughout the study by a DSMB. The DSMB 
will meet at predetermined intervals set forth in the DSMB Charter to review toxicities and serious and/or 
unexpected AEs. The DSMB will primarily evaluate safety data; efficacy data will only be reviewed in the 
event of a serious safety concern. Minutes for all DSMB meetings will be generated and a copy provided 
to the Sponsor. 
 
15. REGISTRATION GUIDELINES 
 
Screening logs will be maintained by research staff at UAMS and HOG. 
 
Subject registration will occur in Clinical Trials Office (CTO) within the UAMS WPRCI after the IRB-approved 
consent is signed and eligibility has been confirmed. Subjects will be registered in the Clinical Trials 
Management System (CTMS) and will be assigned a study number by CTO. The study number will be used 
for identification of the research subject during the study. 
 
HOG will send registrations to research staff at CTO. CTO will register the subject in the CTMS and will 
assign each subject a study number. Once registration has been completed, the information will be sent 
back to HOG. 
 
16. DATA SUBMISSION SCHEDULE 
 
Data must be submitted according to protocol requirements for ALL subjects registered to the treatment 
portion of this trial, whether or not assigned treatment is administered. 
 
For subjects deemed to be ineligible to participate in the study or for whom documentation is inadequate 
to determine eligibility, only the eligibility case report form will be completed. Data obtained during the 
study will be collected at each subject visit and entered into the clinical trial management suite. Data will 
be captured on the case report forms (CRFs). 
 
UAMS and HOG shall retain the records and reports for 2 years after a marketing application is approved 
for the drug; or, if an application is not approved for the drug, until 2 years after shipment and delivery of 
the drug for investigational use is discontinued and the FDA has been notified. After such time all study 


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records will be destroyed as well as the links between identifiers of the research subjects and their 
research study numbers according to UAMS’ record destruction policy. 
 
17. ETHICAL AND REGULATORY CONSIDERATIONS 
 
a. Study Personnel: Study personnel must have completed training in Good Clinical Practice (GCP) and 
Protection of Human Subjects. 
 
b. Recruitment and Informed Consent: Research subjects will be recruited from the WPRCI on the UAMS 
campus and clinics at HOG. The research subjects will be identified by the research physician or staff. 
Prior to any research activities, the research subject will be approached for participation in the study 
by her physician, who will discuss the protocol along with the risks and potential benefits of 
participating in it. A clear statement will be made concerning the voluntary nature of her participation 
and that her decision will have no effect on her remaining care. The research nurse or research staff 
will follow with a detailed review of the informed consent document. The research subject will be 
encouraged to have family or friends participate in any or all of the process. The potential subject will 
be given time to ask questions, will be questioned to be certain she understands the information, and 
if she agrees to proceed, will sign consent. Subjects will be allowed time to reflect, ask questions or 
withdraw. The consent process will be documented in the medical record. A copy of the informed 
consent document will be given to the subject. The original informed consent will be filed with the 
subject file. The consent process will occur in a private exam room. There will be no additional 
recruitment materials. The principles of informed consent are described by Federal Regulatory 
Guidelines (Code of Federal Regulations 21 CFR 50) and the Office for Human Research Protections: 
Protection of Human Subjects (45 CFR 46). These principles must be followed to comply with FDA 
regulations for the conduct and monitoring of clinical investigations. 
 
c. Institutional Review: This study will be approved by the sites’ IRBs as defined by Federal Regulatory 
Guidelines 21 CFR 56 and the Office for Human Research Protections: Protection of Human Subjects 
45 CFR 46. This study will also undergo scientific review by the Cancer Institute’s Protocol Review and 
Monitoring Committee (PRMC). Approval by both the UAMS PRMC and the IRB of record for each 
institution is required before the clinical trial can be activated. 
 
d. Investigational Agent Accountability: Documentation of drug disposition (drug receipt, dispensing, 
transfer or return) will be maintained on the UAMS Investigational Agent Accountability Record or its 
equivalent that is on file with FDA. Drug supplies (long-term storage) will be kept in a secure, limited 
access storage area under the recommended storage conditions in the research pharmacy at the 
WPRCI under the direction of the research pharmacist. During the course of the study, the following 
information will be noted on the Investigational Agent Accountability Record; the study number, the 
research subject’s initials, the research subject’s assigned number, the dose of drug, the date(s) and 
quantity of drug dispensed to the subject, the balance forward, the lot number and the recorder’s 
initials. These Investigational Agent Accountability Records will be readily available for inspection and 
are open to FDA inspection at any time. 
 
e. Dissemination of Data: The data collected in this study may be used for presentations, posters, and 
publications or uploaded into open or controlled-access databases, like NIH database of genotypes 
and phenotypes and Gene expression omnibus, upon request. The publications or data uploaded will 
not contain any identifiable information that could be linked to a participant. We are fully committed 


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to the responsible data sharing and therefore, the de-identified data, including analyzed and raw, 
supporting the conclusions made in any publications will be made available to any qualified researcher 
upon legitimate request. The study will be listed on clinicaltrials.gov in accordance with FDA 
requirements. 
 
18. ADVERSE EVENTS 
 
Following consent, safety will be measured by assessment of adverse events through the duration of the 
study, which is approximately 16 months post first vaccination. 
 
a. Adverse Event (AE): Any unfavorable and unintended sign, symptom or disease temporally associated 
with the use of a medical treatment or procedure regardless of whether it is considered related to the 
medical treatment or procedure. Each AE is a unique representation of a specific event used for 
medical documentation and scientific analysis. [ICH E6 1.2] 
 
b. Serious Adverse Event (SAE): Any adverse drug experience occurring at any dose that results in any 
of the following outcomes: death, a life-threatening adverse drug experience, inpatient 
hospitalization, prolongation of existing hospitalization, a persistent or significant disability/incapacity 
or a congenital anomaly/birth defect. Important medical events that may not result in death, be life 
threatening or require hospitalization may be considered a serious adverse drug experience when, 
based upon medical judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. FDA requires IND sponsors to 
report qualified AEs and SAEs through the expedited reporting system. [21 CFR 312.32 (a)] 
 
To avoid confusion, as the terms “serious” and “severe” are not synonymous, the following 
clarification is given: The term “severe” is often used to describe the intensity (severity) of a specific 
event (as in mild, moderate or severe myocardial infarction); the event itself, however, may be of 
relatively minor medical significance (such as severe headache). This is not the same as “serious,” 
which is based on subject/event outcome or action usually associated with events that pose a threat 
to a subject’s life or functioning. Seriousness (not severity) serves as a guide for defining regulatory 
reporting obligations. [ICH-E2A(II)(B)] 
 
c. Related: An event is related if more likely than not it was caused by the research activity. 
 
d. Unexpected: An event is unexpected when its specificity, nature, severity or incidence is not 
accurately reflected in the consent form, protocol, or investigator’s brochure previously reviewed and 
approved by the IRB. Examples include a lower rate of response to treatment or a side effect that is 
more severe than initially expected. 
 
e. Monitoring, Recording and Reporting of AEs: All subjects will be monitored for AEs during the study. 
Assessments may include monitoring the subject’s clinical symptoms; laboratory, pathological, 
radiological, or surgical findings; physical examination; or other appropriate tests and procedures. 
 
Any condition, laboratory abnormality, or physical finding with an onset date prior to the subject 
signing consent for study participation is considered to be pre-existing in nature and part of the 
subject’s medical history. All relevant historical medical conditions that are known/diagnosed prior to 
the administration of study vaccine are to be recorded. All AEs, which completely resolve and then 


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recur should be recorded as a new AE, regardless of whether it is related or not. In addition to new 
events, any increase in the severity or frequency of a pre-existing condition that occurs after the 
administration of the first vaccine is considered an AE. 
 
All AEs occurring during the study period must be recorded. The clinical course of each event should 
be followed until resolution, stabilization, or until it has been determined that the study treatment or 
participation is not the cause. SAEs that are still ongoing at the end of the study period must be 
followed for up to 30 days to determine the final outcome. Any SAE that occurs after the study period 
and is considered to be possibly related to the study treatment or study participation should be 
recorded and reported immediately to the Sponsor. 
 
All AEs and SAEs must be recorded in the appropriate section of the CRF. The report should include, 
whenever possible, the investigator’s written medical judgment as to the relationship of the AE/SAE 
to the vaccine and/or to the study (not the chemotherapy) (i.e., “definite”, “probable”, “possible” or 
“unrelated”). 
 
Expedited Reporting: Any instance of a Guillain-Barre Syndrome event will require expedited reporting 
to the FDA, IRB, and IND Sponsor. 
 
AEs that are serious, unanticipated/unexpected, and possibly related to the vaccine qualify for 
expedited reporting. Any adverse experience that meets expedited reporting guidelines for SAEs must 
be reported immediately to the Sponsor. The CRA will follow AE reporting plans per institutional 
policies and applicable regulations. All qualified AEs will be reported to the Investigators, FDA, IRB, 
Medical Monitor, and the UAMS Office of Research Regulatory Affairs (Sponsor) according to this plan. 
The Sponsor will report all events that meet expedited reporting requirements to FDA in accordance 
with 21 CFR 312. All other AEs will be reported to the Sponsor and FDA in the Annual Progress Report. 
 
Only AEs meeting UPIRTSO (Unanticipated Problem Involving Risks to Subjects or Others) will be 
reported to the UAMS IRB within the required 10-day allotment of being notified of the event. 
UPIRTSO requires that an unanticipated problem meet the following qualifications: a) unanticipated 
or unexpected; b) related to the research; and c) involves new or increased risk to the subject(s). All 
other AEs should be recorded and reported to the UAMS IRB at continuing review. 
 
Deaths that are related to research will be reported to the Sponsor immediately upon Investigator 
notification. A death due to a terminal condition of the research participant would be considered 
anticipated and not related to the research. 
 
19. CLINICAL SITE MONITORING 
 
Clinical site monitoring will be conducted by the UAMS Office of Research Regulatory Affairs (ORRA) to 
ensure that the rights and well-being of human subjects are protected, that the reported trial data are 
accurate, complete, and verifiable from source documents, and that the conduct of the trial is in 
compliance with the currently approved protocol/amendment(s), ICH GCP, and applicable regulatory 
requirements. 
 


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Monitoring specialists from ORRA will conduct periodic on-site, comprehensive monitoring as determined 
by a protocol specific monitoring plan, which will be provided by the ORRA Monitoring Unit to the 
Investigator. 
 
20. DEVIATIONS AND VIOLATIONS 
 
a. Protocol Deviation: A deviation is any unintentional change, divergence, or departure from the study 
design or procedures defined in the protocol. Protocol deviations will be tracked and compiled in a 
Protocol Deviation Log. Deviations that potentially cause concern for the subject health, safety, or 
rights will be reported to the Sponsor as soon as possible for guidance on reporting. 
 
b. Protocol Violation: A violation is a change to, or non-compliance with, the IRB-approved procedures 
without prior Sponsor and IRB approval (excluding changes made to eliminate apparent immediate 
hazard to subjects). A violation may affect health, safety, or rights of a subject. Any violation will be 
reported immediately to the Sponsor for guidance on reporting. 
 
If the protocol deviation/protocol violation does not represent a significant alteration in the approved 
protocol and/or affect the safety or welfare of the subject, it will be reported to the UAMS IRB at the 
time of Continuing Review. If the protocol deviation/violation represents a significant alteration in the 
approved protocol and/or if it affects the safety or welfare of the subject, it must be reported to the 
Sponsor and UAMS IRB immediately. 
 
 


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