Conditions: Breast Cancer Breast Neoplasms
Keywords: clinical stage I, II or III ER postive HER2 negative
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 58
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 estrogen-receptor (ER)-positive, HER2-negative breast cancer.

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)-positive, HER2-negative breast cancer.

This is a single-arm, multi-site Phase I/II study designed with the two goals being (1) to evaluate the feasibility of combining vaccination with the P10s-PADRE formulation with neoadjuvant chemotherapy and (2) to determine if the polymerase chain reaction (pCR) rate among ER-positive, HER2-negativebreast-cancer patients treated with the combination is significantly higher than the 8% rate observed among ER-positive breast-cancer subjects in a pooled analysis of seven randomized clinical trials. P10s-PADRE vaccine with MONTANIDE™ ISA 51 VG as adjuvant will be given in combination with neoadjuvant chemotherapy in female patients with clinical stage I, II or III ER-positive, HER2-negative breast cancer.

This combined Phase I/II feasibility-and-efficacy study will have three parts. Its first part will be a Phase I evaluation of the safety, tolerability, and feasibility of eliciting adequate IgG response with P10s-PADRE when administered in combination with SoC neoadjuvant chemotherapy. The study's second and third parts will respectively constitute Stages 1 and 2 of the Phase II primary-efficacy evaluation of Chemovax using a Simon optimal two-stage design

To evaluate the feasibility of eliciting adequate immune response with P10s-PADRE when it is administered in combination with neoadjuvant chemotherapy, we will sequentially evaluate different schedules of vaccination relative to chemotherapy, and stop evaluating as soon as we have identified a feasible schedule. To this end, we have defined five different Chemovax schedules, and named them A, B, C, D, and E;

Arms:
arm 1: Feasibility - Chemovax schedule A: Subjects will receive the first cycle of chemotherapy along with the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 1, the subsequent two injections of the vaccine one week apart (week 2 and 3), second cycle of chemotherapy on week 4, and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22). arm 2: Feasibility - Chemovax Schedule B: Subjects will receive the first cycle of chemotherapy on week 1, the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 2, the subsequent two injections of the vaccine one week apart (week 3 and 4), second cycle of chemotherapy on week 4 (along with second vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22). arm 3: Feasibility - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25). arm 4: Feasibility - Chemovax Schedule D: Subjects will receive the first injection of vaccine on week 1, the subsequent two injections of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine one week apart (week 2 and 3), the first cycle of chemotherapy on week 2 (along with second vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 5,8,11,14,17,20,23). arm 5: Feasibility - Chemovax Schedule E: Subjects will receive the first injection of vaccine on week 1, the subsequent two injections of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine one week apart (week 2 and 3), the first cycle of chemotherapy on week 3 (along with third vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 6,9,12,15,18,21,24). arm 6: Primary Efficacy - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25). arm 7: Expanded Efficacy - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25).

Interventions: intervention 1: P10s-PADRE/ MONTANIDE™ ISA 51 VG intervention 2: Doxorubicin intervention 3: Cyclophosphamide intervention 4: Docetaxel
Intervention descriptions: intervention 1: Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions concurrent with chemotherapy. intervention 2: Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles. intervention 3: Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles. intervention 4: Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.

If docetaxel is not tolerated, paclitaxel (175mg/m2) may be used in its place.

Protocol document:
ICF_002.pdf: 
 
 
 
 
 
 
 
 
 
 
Official Title: A Combined Phase I/II Feasibility-and-Efficacy Study of a Carbohydrate 
Mimotope-based Vaccine with MONTANIDE™ ISA 51 VG STERILE Combined with 
Neoadjuvant Chemotherapy 
 
“Vaccination of High Risk Breast Cancer Patients” 
IRB Number: 202556 
NCT Number: NCT02229084 
 
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 for Part 2/3 Schedule C 
Version 20 
Dated October 6, 2021 


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CONSENT FORM 
AND INFORMATION ABOUT 
 
 
“Vaccination of High Risk Breast Cancer Patients” 
 
 
A Combined Phase I/II Feasibility-and-Efficacy Study of a Carbohydrate Mimotope-based 
Vaccine with MONTANIDE™ ISA 51 VG STERILE Combined with Neoadjuvant 
Chemotherapy 
 
 
Schedule C 
 
 
 
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 breast cancer. 
 
Why is this research being done? 
The purpose of this research is to evaluate a new experimental breast cancer vaccine (used to 
stimulate immune cell production) with chemotherapy and then 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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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 may 
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 81 women in order to enroll up to 61 women, ages 18 and older with 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 61 women are enrolled at either site 
but the total combined enrollment for both sites will not be more than 61. At the beginning of the 
research, women were enrolled in groups of 5 to determine when the vaccine should be given in 
relation to the chemotherapy schedule. The timing of the vaccination relative to chemotherapy 
will be evaluated to see which schedule had the best immune response with the least harmful 
side effects. This part of the research, which involved 25 research participants, has been 
completed. Using the schedule determined to be the best, up to 36 additional women will now be 
enrolled to evaluate the effect of the vaccine and chemotherapy on the cancer. 
 
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. 
 
Summary of tests to be done prior to the study: 
Standard medical care for cancer treatments: 
 
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 prior to the study is one 
and a half teaspoons. 
 


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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 
 
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 to check the reaction of the immune system 
 
Notations of side effects and medications you are taking 
 
Investigational vaccine 
 
During this study, you will be asked to provide 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 73 weeks (about one year and six 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 
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: 
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. 
 


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This breakdown includes standard chemotherapy, growth factor (to stimulate growth of healthy 
white blood cells), and surgery, which are part of standard care. The chemotherapy, growth factor, 
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 1, 2 and 3. These visits are just for research. Research blood samples will 
be collected eight times during the study. 
 
Prior to receiving study vaccine 
 
Sign informed consent 
 
Clinic visit for history and physical examination 
 
Routine blood work 
 
Urine pregnancy test for women who are able to have children 
 
Week 1 
 
Urine pregnancy test for women who are able to have children 
 
Administer vaccine 
 
Review of side effects 
 
Clinic visit for history and physical examination 
 
Blood work for research 
 
Weeks 2 & 3 
 
Administer vaccine 
 
Review of side effects 
 
Week 4 
 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 (doses may 
be reduced) 
 
Growth factor may be given at physician’s discretion 
 
Review of side effects 
 
Clinic visit for history and physical exam 
 
Routine blood work 
 
Weeks 7, 10, & 13 
 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 (doses may 
be reduced) 
 
Growth factor may be given at physician’s discretion 
 
Review of side effects 
 
Clinic visit for history and physical examination 
 
Routine blood work 
 
Blood work for research 
 
Week 16 
 
Docetaxel 75 mg/m2 (dose may be reduced or replaced with Paclitaxel 175 mg/m2) 
 
Growth factor may be given at physician’s discretion 
 
Review of side effects 
 
Clinic visit for history and physical examination 
 
Routine blood work 
 
Blood work for research 
 


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Weeks 19 & 22 
 
Docetaxel 75 mg/m2 (dose may be reduced or replaced with Paclitaxel 175 mg/m2) 
 
Growth factor may be given at physician’s discretion 
 
Review of side effects 
 
Clinic visit for history and physical examination 
 
Routine blood work 
 
Week 25 
 
Docetaxel 75 mg/m2 (dose may be reduced or replaced with Paclitaxel 175 mg/m2) 
 
Growth factor may be given at physician’s discretion 
 
Review of side effects 
 
Clinic visit for history and physical examination 
 
Routine blood work 
 
Blood work for research 
 
Breast cancer surgery 
It is standard practice for surgery to be performed within 4-8 weeks after completion of 
chemotherapy. 
 
Week 49 (±4 weeks) & Week 73 (±4 weeks) 
 
Review of side effects 
 
Clinic visit for history and physical examination 
 
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. 
 
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 and you may be removed 
from the study. 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. 
 


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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. 
 
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 don't 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. If you have significant side effects or problems related to the chemotherapy, the 
remaining doses may be delayed, reduced, replaced or discontinued if the research doctor 
believes it is in your best interest. In general, the risks and side effects are lower than standard 
chemotherapy treatments and the blood draws are similar in the quantity of blood taken and the 
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 
 


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Risks and side effects related to blood collection: 
 
Pain or bruising at the injection site 
 
Rarely – infection 
 
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; 


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 
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. 
 
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 and HOG cannot and do 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. 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 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 controlled-access national database, so that other investigators can 
use them for research. This means that only researchers who apply for and get permission to use 
the information for a specific research project will be able to access the information. 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. 
 


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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. 
 
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 will 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) 686-8511. 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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Page 11 of 13 
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: 
 
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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Version 20 
10/06/2021 
 
Page 12 of 13 
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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Version 20 
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Page 13 of 13 
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: 
Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
 
“Vaccination of High Risk Breast Cancer Patients” 
 
 
A Combined Phase I/II Feasibility-and-Efficacy Study of a 
Carbohydrate Mimotope-Based Vaccine with MONTANIDE™ ISA 51 VG 
STERILE Combined with Neoadjuvant Chemotherapy 
 
 
Version 21 
06/02/2022 
 
 
University of Arkansas for Medical Sciences (UAMS) 
 
IRB 202556 
Principal Investigator: 
Sindhu Malapati, MD 
 
 
Highlands Oncology Group (HOG) 
 
IRB 204187 
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: NCT02229084 
 


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TABLE of CONTENTS 
 
1. ABBREVIATIONS ............................................................................................................................ 3 
2. PROTOCOL SUMMARY ................................................................................................................. 5 
3. BACKGROUND ............................................................................................................................... 7 
4. TRIAL OBJECTIVES ..................................................................................................................... 11 
5. PATIENT POPULATION ............................................................................................................... 12 
6. INVESTIGATIONAL PRODUCT – P10S-PADRE/ MONTANIDE™ ISA 51 VG STERILE ........... 13 
7. STUDY DESIGN ............................................................................................................................ 14 
8. TREATMENT PLAN ...................................................................................................................... 16 
9. STUDY CALENDARS .................................................................................................................... 17 
9.1. Study Calendar – Schedule A – Retired (Used only in Part 1) ............................................ 18 
9.2. Study Calendar – Schedule B – Retired (Used only in Part 1) ............................................ 19 
9.3. Study Calendar – Schedule C – Optimal Schedule (To be used in Parts 1, 2 & 3) ............ 20 
9.4. Study Calendar – Schedule D – Retired (Used only in Part 1) ............................................ 21 
9.5. Study Calendar – Schedule E – Retired (Used only in Part 1) ............................................ 22 
10. VISIT BREAKDOWN ..................................................................................................................... 23 
10.1. Visit Breakdown – Schedule A – Retired (Used only in Part 1) ........................................... 23 
10.2. Visit Breakdown – Schedule B – Retired (Used only in Part 1) ........................................... 27 
10.3. Visit Breakdown – Schedule C – Optimal Schedule (To be used in Parts 1, 2 & 3) ........... 31 
10.4. Visit Breakdown – Schedule D – Retired (Used only in Part 1) ........................................... 35 
10.5. Visit Breakdown – Schedule E – Retired (Used only in Part 1) ........................................... 40 
11. RISKS AND TOXICITIES TO BE MONITORED ........................................................................... 44 
12. SPECIMEN HANDLING ................................................................................................................ 47 
13. ENDPOINT DEFINITIONS, EVALUATION of IMMUNE-RESPONSE ENDPOINTS, and 
ENDPOINT-ASSAY METHODS .................................................................................................... 47 
14. STATISTICAL CONSIDERATIONS .............................................................................................. 51 
15. REGISTRATION GUIDELINES ..................................................................................................... 53 
16. DATA SUBMISSION SCHEDULE ................................................................................................. 53 
17. ETHICAL AND REGULATORY CONSIDERATIONS ................................................................... 53 
18. ADVERSE EVENTS ...................................................................................................................... 54 
19. CLINICAL SITE MONITORING ..................................................................................................... 56 
20. DEVIATIONS AND VIOLATIONS .................................................................................................. 56 
21. BIBLIOGRAPHY ............................................................................................................................ 57 


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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 
AST 
Aspartate Aminotransferase Test 
BUN 
Blood Urea Nitrogen 
CBC 
Complete Blood Count 
CCT 
Cancer Clinical Trials 
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 
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 
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 
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 
µg 
Microgram 


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mg 
Milligram 
mL 
Milliliter 
mm 
Millimeter 
MDSC 
Myeloid-Derived Suppressor Cells 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
NK 
Natural Killer 
P10s-MAP 
P10s-Multivalent-Antigen Peptide 
PBMC 
Peripheral Blood Mononuclear Cell 
PD-1 
Programmed cell death protein 
PE 
Physical Examination 
PRMC 
Protocol Review and Monitoring Committee 
pCR 
pathological Complete Response 
SAE 
Serious Adverse Event 
SC 
Subcutaneous 
SGOT 
Serum Glutamic-Oxaloacetic Transaminase 
SGPT 
Serum Glutamic-Pyruvic Transaminase 
SI 
Stimulation Index 
SoC 
Standard/Standard of Care 
STn 
sialosyl-TN 
TACA 
Tumor-Associated Carbohydrate Antigen 
TBAPS 
Tissue Biorepository and Procurement Service 
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 
 


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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 SoC neoadjuvant chemotherapy in subjects with clinical stage I, II 
or III estrogen-receptor (ER)-positive breast cancer. This combination of vaccine with chemotherapy 
will be called “Chemovax”. 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. 
 
A single-arm trial is designed with the goal being to evaluate the feasibility and efficacy of combining 
vaccination of the P10s-PADRE formulation with neoadjuvant chemotherapy. Feasibility will be based 
on the safety, tolerability, and immune-response adequacy of P10s-PADRE when it is administered in 
combination with neoadjuvant chemotherapy. Once a feasible schedule of Chemovax has been 
identified, efficacy will be based on the rate of pathologic Complete Response (pCR) observed among 
ER-positive breast-cancer subjects treated with the combination. 
 
The feasibility of schedule and clinical response to the vaccine will be assessed as follows: 
 
Primary Objectives: 
1) Identify a feasible schedule of vaccination relative to SoC neoadjuvant chemotherapy when 
the two are administered concurrently. Feasibility will be evaluated in terms of: 
a) Generation of a sufficiently high anti-P10s immunoglobulin-G response 
b) Safety and tolerability of the combination of vaccine and chemotherapy 
 
2) Demonstration of clinical response: 
Determine if the Chemovax regimen in ER-positive breast cancer would lead to a significantly 
higher rate of pCR in breast and axillary lymph nodes at time of definitive surgery compared to the 
corresponding rate reported by von Minckwitz et al (1, 2). 
 
Secondary Objectives: 
1) Determine Short-term Immune Responses Induced by Chemovax: 
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 Chemovax therapy. 
b) Determine the activation profile of NK cells before and after Chemovax therapy. 
c) Determine T-cell subpopulations and evaluate the effects of Chemovax therapy on the 
numbers of circulating T cells. 
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. 
 
2) Determine Long-term Immune Responses Induced by Chemovax: 
a) Determine antibody titers against P10s at approximately 6 and 12 months following the initial 
response evaluation. 
b) Measure anti-TACA cell-binding levels at approximately 6 and 12 months following the initial 
response evaluation. 
c) Determine the cytotoxic activity against TACA-expressing cell lines at approximately 6 and 12 
months following the initial response evaluation. 
d) Evaluate the functionality of T and NK cells. 
 


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Study Population: We plan to screen up to 81 women in order to enroll approximately 61 women, 18 
years of age and 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. 
 
Summary of Inclusion Criteria: Females, 18 years of age or older, with clinical stage I, II or III ER-
positive, HER2-negative breast cancer who qualify for SoC neoadjuvant treatment will be invited to 
participate. 
 
Summary of Exclusion Criteria: Females with ER-negative, HER2-positive, inflammatory, or 
metastatic breast cancer; women who are pregnant, breast-feeding, have 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: Chemovax - P10s-PADRE/MONTANIDE™ ISA 51 VG in combination with SoC 
neoadjuvant chemotherapy 
 
Study Design: This combined Phase I/II feasibility-and-efficacy study will have three parts. Its first 
part will be a Phase I evaluation of the safety, tolerability, and feasibility of eliciting adequate IgG 
response with P10s-PADRE when administered in combination with SoC neoadjuvant chemotherapy, 
and will require 25 subjects. The timing of vaccination relative to chemotherapy will be evaluated to 
identify a Chemovax schedule in which a sufficiently high proportion of subjects achieve an adequate 
IgG response. Once such a schedule is identified, the study will proceed with its second and third 
parts. The study’s second and third parts will respectively constitute Stages 1 and 2 of the Phase II 
primary-efficacy evaluation of Chemovax using a Simon optimal two-stage design, and will require a 
minimum of 19 subjects (5 subjects from Part 1 + an additional 14 subjects) and a maximum of 41 
subjects (19 subjects from Part 1 & 2 + an additional 22 subjects). The total sample size in the entire 
study will have a theoretical minimum of 25 subjects, a theoretical maximum of 61 subjects, and a 
most likely value of 41 subjects based on demonstrating both immune-response feasibility and clinical 
efficacy. 
 
To conduct this study, eligible subjects of all races, aged 18 years or older, will be enrolled and 
immunized by SC 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. 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 treatment evaluation to assess durations of the 
anti-P10s titer and anti-breast-cancer cytotoxicity. Tissue samples will be obtained from excess tissue 
collected as part of standard biopsy and/or surgery. These samples will be used for histology and 
immune cell isolation to identify immune cell infiltrates. Safety and tolerability of Chemovax will be 
evaluated throughout all parts/phases of the study. The primary efficacy endpoint is pCR and will be 
used to determine if Chemovax treatment in ER-positive breast cancer subjects will improve pCR at 
time of the definitive surgery to a rate significantly higher than the corresponding rate reported by von 
Minckwitz et al. (1). 
 
 


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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 
augment naturally occurring carbohydrate-reactive IgM antibodies that trigger apoptosis of tumor cells 
(4). TACAs are attractive targets 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 may, 
therefore, be more cytotoxic to tumor cells than antibodies that recognize protein antigens (8). 
 
Approaches to augment immune responses to TACA: 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 TACA 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 TACA. 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 (28). 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 (29). Thus, potential immunopathology due 
to destruction of normal tissue is minimized (30, 31). 
 


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Second, peptide mimotopes have the potential to overcome immune deficiencies that suppress 
vaccine-induced carbohydrate-directed responses (32). 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 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, 27). 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 (33-35). 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 (36, 37). 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 (38). The abundant gangliosides include GM3, GM2, GM1, and GD2, 
GD3 and GT3 (39). 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. (40), 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 (40). 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 affects 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 (41). 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 (42) and polarize Th1/Th2 responses (43). Our own 
studies indicate that immunization with a CMP followed by CY treatment can facilitate inhibition of 
tumor growth (44), including P10s-PADRE (data unpublished). The administration of docetaxel to 
patients with metastatic prostate or breast cancer, as well as that of cisplatin plus vinorelbine to non-


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small cell lung cancer patients, 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 
patients (45). 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 (46-48). 
 
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 (49). 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 (50), 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 completed. 
 
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 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 
ClinicalTrial.gov results database (number NCT01390064). 


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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 met the eligibility criteria. Six subjects consequently 
received the P10s-PADRE vaccine. P10s vaccination was well-tolerated. All 6 subjects displayed a 
persistent IgG response to P10s after vaccination, and induced antibodies in serum and plasma 
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. 
 
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 (51). 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) (51-55). Thus, improving pCR has become a valid 
strategy in the development of new treatment regimens. Specifically, the rate of pCR achieved in ER-
positive breast-cancer subjects following vaccination with P10s-PADRE administered concurrently 
with neoadjuvant chemotherapy will be compared with the corresponding pCR rate from a pooled 
analysis of seven randomized trials published in the Journal of Clinical Oncology (1) in which 287 of 
3,771 ER-positive breast-cancer subjects (approximately 8%) achieved the “ypT0 ypN0” definition of 
pCR following neoadjuvant chemotherapy. 
 
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).” (56) 
 
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. 
 


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This issue is perhaps best exemplified in the development of HER2-directed therapies, such as 
lapatinib (NeoALTTO trial) (57), and pertuzumab (NeoSphere trial) 58). 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 (59). 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, but no previous data are available on the immunogenicity of 
the investigational agent when administered concurrently with chemotherapy and steroids (used as 
antiemetics). Because of the above concerns, our study will begin by assessing the feasibility of 
achieving adequate immune response with P10s-PADRE when it is administered in combination with 
neoadjuvant chemotherapy. To this end, we have defined five different Chemovax schedules, and 
named them A, B, C, D, and E (see 8. Chemovax Schedules for the details of each schedule). There 
will be five subjects in each cohort enrolled onto a Chemovax schedule. Schedules will be evaluated 
for immune-response adequacy. 
 
Justification for 500ug 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 known to form 
granulomas. 
 
4. TRIAL OBJECTIVES 
 
Primary Objectives 
1) Identify a feasible schedule of vaccination relative to SoC neoadjuvant chemotherapy when 
the two are administered concurrently. Feasibility will be evaluated in terms of: 
a) Generation of a sufficiently high anti-P10s immunoglobulin-G response. 
b) Safety and tolerability of the vaccine-chemotherapy combination. 
 
2) Demonstration of clinical response: 
Determine if the Chemovax regimen in ER-positive breast cancer 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 8% observed among 3,771 ER-positive breast-cancer subjects in the pooled analysis of 
seven randomized clinical trials reported by von Minckwitz et al (1-2). 
 
 


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Secondary Objectives 
1) Determine Short-term Immune Responses Induced by Chemovax: 
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 Chemovax therapy. 
b) Determine the activation profile of NK cells before and after Chemovax therapy. 
c) Determine T-cell subpopulations and evaluate the effects of Chemovax 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 perform 
characterization of tumor infiltrating lymphocytes and their role in tumor response. 
 
2) Determine Long-term Immune Responses Induced by Chemovax: 
a) Determine antibody titers against P10s at approximately 6 and 12 months following the initial 
response evaluation. 
b) Measure anti-TACA cell-binding levels at approximately 6 and 12 months following the initial 
response evaluation. 
c) Determine the cytotoxic activity against TACA-expressing cell lines at approximately 6 and 12 
months following the initial response evaluation. 
d) Evaluate the functionality of T and NK cells. 
 
5. 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 clinical stage I, II, or III ER-positive, HER2 negative breast cancer who 
will undergo SoC neoadjuvant treatment. 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-negative, 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. 
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-


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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 tubal ligation, 
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. Concurrent enrollment in observational studies is allowed. 
 
6. 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. 
 
MONTANIDE™ ISA 51 VG STERILE will be supplied by SEPPIC, Inc. (Fairfield, NJ). See 
Investigator’s Brochure for formulation and storage conditions. 
 
 


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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 will receive 2 mL SC injections of the vaccine on each of 3 separate occasions 
according to each 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 MontanideTM 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. 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.” 
 
e. 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. Initial drug 
supply order will be placed by primary 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 will be the primary pharmacy for this study. All drug ordering and shipment 
to other sites will be described in the Pharmacy Instructions binder. 
 
f. 
Agent Accountability: P10s-PADRE and MONTANIDE™ ISA 51 VG STERILE will be stored in 
the UAMS Research 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. 
 
7. STUDY DESIGN 
 
This is a single-arm, multi-site Phase I/II study designed with the two goals being (1) to evaluate the 
feasibility of combining vaccination with the P10s-PADRE formulation with neoadjuvant chemotherapy 
and (2) to determine if the pCR rate among ER-positive breast-cancer subjects treated with the 
combination is significantly higher than the 8% rate observed among ER-positive breast-cancer 
subjects in a pooled analysis of seven randomized clinical trials (1). 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-positive breast cancer. 
 
This combined Phase I/II feasibility-and-efficacy study will have three parts. Its first part will be a Phase 
I evaluation of the safety, tolerability, and feasibility of eliciting adequate IgG response with P10s-
PADRE when administered in combination with SoC neoadjuvant chemotherapy, and will require 25 
subjects. The timing of vaccination relative to chemotherapy will be evaluated to identify a Chemovax 
schedule in which a sufficiently high proportion of subjects achieve an adequate IgG response. Once 
such a schedule is identified, the study will proceed with its second and third parts. The study’s second 
and third parts will respectively constitute Stages 1 and 2 of the Phase II primary-efficacy evaluation 
of Chemovax using a Simon optimal two-stage design, and will require a minimum of 19 subjects (5 
subjects from Part 1 + an additional 14 subjects) and a maximum of 41 subjects (19 subjects from Part 
1 & 2 + an additional 22 subjects). The total sample size in the entire study will have a theoretical 
minimum of 25 subjects, a theoretical maximum of 61 subjects, and a most likely value of 41 subjects 
based on demonstrating both immune-response feasibility and clinical efficacy. 


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To evaluate the feasibility of eliciting adequate immune response with P10s-PADRE when it is 
administered in combination with neoadjuvant chemotherapy, we will sequentially evaluate different 
schedules of vaccination relative to chemotherapy, and stop evaluating as soon as we have identified 
a feasible schedule. To this end, we have defined five different Chemovax schedules, and named 
them A, B, C, D, and E; see Chemovax Schedules for the details of each schedule. From one to five 
cohorts of subjects will be enrolled sequentially and used to evaluate the schedules in alphabetical 
order, beginning with Schedule A. There will be five subjects in each cohort enrolled onto a Chemovax 
schedule. A schedule that has a cohort enrolling onto it will be evaluated for immune-response 
adequacy. 
 
The best immune response with the least toxicity will be the Chemovax schedule that will be 
expanded and used to initiate the primary efficacy evaluation of Chemovax using a Simon optimal 
two-stage design (60, 61). 
 
 
Figure 1: Study Schema 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Part 1 
Feasibility 
Schedule A 
(n ≤ 5) 
Schedule B 
(n ≤ 5) 
Schedule C 
(n ≤ 5) 
Schedule D 
(n ≤ 5) 
Schedule E 
(n ≤ 5) 
Part 3 
Stage 2 of Simon 
two-stage design 
Final data analysis 
Enrolling additional 
22 subjects 
(n = [19+22] = 41) 
Yes 
Part 2 
Stage 1 of Simon 
two-stage design 
Enroll additional 14 
subjects on 
schedule determined 
in Part 1 (n = [5+14] 
= 19) 
End of Study 
≥ 2 subjects 
achieve 
pCR? 
No 
IgG 
increased 
≥4-fold in 
≥ 4 of 5 @ 
week ≥7
Yes 
No 
End of Study 


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Following Part 1 (feasibility), Cohort C and E displayed a significant average fold increase in anti-
peptide titers after immunization. Cohort C had a higher overall average fold increase and a higher 
number of responders. Therefore, Cohort C was identified as the best schedule for Part 2 (primary 
efficacy). Cohort C was expanded with an additional 14 subjects to test primary efficacy with a goal of 
at least 2 subjects from Cohort C achieving pCR. A total of 4 subjects obtained pCR. Cohort C will be 
expanded for Part 3 (expanded efficacy). 
 
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. All research participants will receive the Mimotope P10s-
PADRE/MONTANIDE™ ISA 51 VG vaccine via SC injection as well as SoC neoadjuvant 
chemotherapy according to the schedule on which they are enrolled (see Schedules below). 
 
b. Chemotherapy: For all subjects, doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) 
(AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 
mg/m2) every three weeks for four cycles, with growth factor at physician’s discretion. Subjects will 
be monitored for chemotherapy-related toxicities and, if clinically necessary, chemotherapy dosing 
may be modified per the Chemotherapy Dose Adjustment table. 
 
c. Chemotherapy Dose Adjustment: Any or all of the SoC neoadjuvant chemotherapies may 
be dose-reduced, as necessary, according to the table below. If docetaxel is not tolerated, 
paclitaxel 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 the first post-surgery study lab at Week 49 (Schedule C) will be followed 
for 30 days after the last vaccination and then be withdrawn from the study. 
 
Chemotherapy 
Starting Dose 
Reduction 1 
Reduction 2 
Reduction 3 
Doxorubicin 
60 mg/m2 
-20% 
-10% 
Discontinue 
Cyclophosphamide 
600 mg/m2 
-20% 
-10% 
Discontinue 
Docetaxel 
75 mg/m2 
-20% 
-10% 
Discontinue 
Paclitaxel* 
175mg/m2 
-20% 
-10% 
Discontinue 
* in case of docetaxel substitution only 
 
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 with 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 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. 
 
d. Chemovax Schedules: 
• 
SCHEDULE A: Subjects will receive the first cycle of chemotherapy along with the first dose 
of vaccine on week 1, the subsequent two doses of vaccine one week apart (week 2 and 3), 
second cycle of chemotherapy on week 4, and subsequent cycles of chemotherapy every 21 
days (week 7, 10, 13, 16, 19, 22). 
 


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• 
SCHEDULE B: Subjects will receive the first cycle of chemotherapy on week 1, the first dose 
of vaccine on week 2, the subsequent two doses of vaccine one week apart (week 3 and 4), 
second cycle of chemotherapy on week 4 (along with second vaccine dose) and subsequent 
cycles of chemotherapy every 21 days (week 7, 10, 13, 16, 19, 22). 
 
• 
SCHEDULE C: Subjects will receive three weekly doses of vaccine (week 1, 2, 3), then first 
cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 
7, 10, 13, 16, 19, 22, 25). 
 
• 
SCHEDULE D: Subjects will receive the first dose of vaccine on week 1, the subsequent two 
doses of vaccine one week apart (week 2 and 3), the first cycle of chemotherapy on week 2 
(along with second vaccine dose) and subsequent cycles of chemotherapy every 21 days 
(week 5, 8, 11, 14, 17, 20, 23). 
 
• 
SCHEDULE E: Subjects will receive the first dose of vaccine on week 1, the subsequent two 
doses of vaccine one week apart (week 2 and 3), the first cycle of chemotherapy on week 3 
(along with third vaccine dose) and subsequent cycles of chemotherapy every 21 days (week 
6, 9, 12, 15, 18, 21, 24). 
 
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 49 (Schedule C). Concurrent enrollment in observational trials 
is allowed throughout the study. 
 
f. 
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 treatment will be discontinued. 
 
• 
Any grade 3 or greater toxicity as per NCI CTCAE v4 toxicity criteria 
• 
Grade 2 or greater autoimmune toxicity, with the exception of vitiligo 
• 
Grade 2 or greater hypersensitivity reactions 
 
Subjects who develop any grade 3 or greater toxicity per NCI CTCAE v4.0 toxicity criteria, Grade 
2 or greater autoimmune toxicity with the exception of vitiligo, or Grade 2 or greater hypersensitivity 
reactions 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. 
 
g. Study Pausing Rules: 
• 
Death (other than due to disease progression or motor vehicle accident or to other 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 – Schedule A – Retired (Used only in Part 1) 
 
Procedures 
Pre-study/ 
Screeninga 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
7 
Wk 
10 
Wk 
13 
Wk 
16 
Wk 
19 
Wk 
22 
Surgery 
(4-8 weeks 
after chemo) 
Wk 46 
(± 4 wks) 
Wk 70 
(± 4 wks) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination with Mimotope 
P10s-PADRE/ 
MONTANIDE™ ISA 51 VG 
 
Xb 
Xb 
Xb 
 
 
 
 
 
 
 
 
 
 
Cyclophosphamidecd 
 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
 
Doxorubicincd 
 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
 
Docetaxelcd 
 
 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
AEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Concomitant Medications 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
History/PE/Vital Signsef 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
CBC with Diff 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Total Bilirubin 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
SGOT/AST 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
SGPT/ALT 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alk Phos 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
LDH 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Creatinine 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Calcium 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Urine Pregnancy Test 
X 
Xg 
 
 
 
 
 
 
 
 
 
 
 
 
Registration 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
 
Study Labi 
 
Xh 
 
 
X 
X 
X 
X 
 
 
X 
 
X 
X 
Surgeryj 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
                                                          
a Pre-study/Screening should be completed within 21 days prior to registration/week 1. 
b Post vaccine administration, the following vital signs will be monitored every 15 minutes (± 5 minutes) for one hour: blood pressure, temperature and pulse. 
c Chemotherapy administration date may be delayed up to 10 days at investigator discretion.  
d If clinically necessary, chemotherapy dosing may be modified per the Chemotherapy Dose Adjustment in Section 8c. 
e 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. 
f Tumor Assessments will be performed by physical exam according to standard practice. 
g To be completed prior to vaccine dose 
h Registration occurs after subject eligibility has been confirmed. Note: The registration process, as outlined in Section 15, may occur prior to Week 1. 
i Study lab: Up to 100 mLs of blood may be collected. Red Vacutainer tubes: Approximately 50 mL collected at all study lab timepoints. Lavender vacutainer tubes: 
 Approximately 50 mL will be collected at Weeks 1, 4, and 7 with the amount decreasing to 25 mL for Weeks 10, 13, 22, 46, and 70. 
j Surgery will be performed according to standard practice unless they are considered inoperable or if surgery is medically contraindicated. 


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IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 19 of 59 
 
9.2. Study Calendar – Schedule B – Retired (Used only in Part 1) 
 
Procedures 
Pre-study/ 
Screeninga 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
7 
Wk 
10 
Wk 
13 
Wk 
16 
Wk 
19 
Wk 
22 
Surgery 
(4-8 weeks 
after chemo) 
Wk 46 
(± 4 wks) 
Wk 70 
(± 4 wks) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination with Mimotope 
P10s-PADRE/ 
MONTANIDE™ ISA 51 VG 
 
 
Xb 
Xb 
Xb 
 
 
 
 
 
 
 
 
 
Cyclophosphamidecd 
 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
 
Doxorubicincd 
 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
 
Docetaxelcd 
 
 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
AEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Concomitant Medications 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
History/PE/Vital Signs ef 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
CBC with Diff 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Total Bilirubin 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
SGOT/AST 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
SGPT/ALT 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alk Phos 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
LDH 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Creatinine 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Calcium 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Urine Pregnancy Test 
X 
 
Xg 
 
 
 
 
 
 
 
 
 
 
 
Registration 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
 
Study Labi 
 
Xh 
 
 
 
X 
X 
X 
X 
 
X 
 
X 
X 
Surgeryj 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
                                                          
a Pre-study/Screening should be completed within 21 days prior to registration/week 1. 
b Post vaccine administration, the following vital signs will be monitored every 15 minutes (± 5 minutes) for one hour: blood pressure, temperature and pulse. 
c Chemotherapy administration date may be delayed up to 10 days at investigator discretion. 
d If clinically necessary, chemotherapy dosing may be modified per the Chemotherapy Dose Adjustment in Section 8c. 
e 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. 
f Tumor Assessments will be performed by physical exam according to standard practice. 
g To be completed prior to vaccine dose 
h Registration occurs after subject eligibility has been confirmed. Note: The registration process, as outlined in Section 15, may occur prior to Week 1. 
i Study lab: Up to 100 mLs of blood may be collected. Red Vacutainer tubes: Approximately 50 mL collected at all study lab timepoints. Lavender vacutainer tubes: 
 Approximately 50 mL will be collected at Weeks 1, 7, and 10 with the amount decreasing to 25 mL for Weeks 13, 16, 22, 46, and 70. 
j Surgery will be performed according to standard practice unless they are considered inoperable or if surgery is medically contraindicated. 


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IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 20 of 59 
 
9.3. Study Calendar – Schedule C – Optimal Schedule (To be used in Parts 1, 2 & 3) 
 
Procedures 
Pre-study/ 
Screeninga 
Wk 
1 
(± 2 
days) 
Wk 
2 
(± 2 
days) 
Wk 
3 
(± 2 
days) 
Wk 
4 
(± 2 
days) 
Wk 
7 
(± 2 
days) 
Wk 
10 
(± 2 
days) 
Wk 
13 
(± 2 
days) 
Wk 
16 
(± 2 
days) 
Wk 
19 
(± 2 
days) 
Wk 
22 
(± 2 
days) 
Wk 
25 
(± 2 
days) 
Surgery 
(4-8 weeks 
after chemo) 
Wk 49 
(± 4 wks) 
Wk 73 
(± 4 wks) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination with Mimotope 
P10s-PADRE/ MONTANIDE™ 
ISA 51 VG 
 
Xb 
Xb 
Xb 
 
 
 
 
 
 
 
 
 
 
 
AC Chemotherapycd 
 
 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Docetaxel (75 mg/m2)d 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
AEs 
 
X 
X 
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/PE/Vital Signs ef 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
CBC with Diff 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Total Bilirubin 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SGOT/AST 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
SGPT/ALT 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Alk Phos 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
LDH 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Chemistryg 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Urine Pregnancy Test 
X 
Xh 
 
 
 
 
 
 
 
 
 
 
 
 
 
Registration 
 
Xi 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Labj 
 
X 
 
 
 
X 
X 
X 
X 
 
 
X 
 
X 
X 
Surgeryk 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
                                                          
a Pre-study/Screening should be completed within 21 days prior to registration/week 1. 
b Post vaccine administration, the following vital signs will be monitored every 15 minutes (± 5 minutes) for one hour: blood pressure, temperature and pulse. 
c Cyclophosphamide (600 mg/m2) and Doxorubicin (60 mg/m2) (AC) to be administered concurrently every three weeks for four cycles 
d SoC growth factor may be given at physician’s discretion. Chemotherapy administration date may be delayed up to 7 days at investigator discretion. If clinically 
necessary, chemotherapy dosing may be modified per the Chemotherapy Dose Adjustment in Section 8c. 
e 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. 
f Tumor Assessments will be performed by physical exam according to standard practice. 
g Chemistry (OP Chem 7) includes blood urea nitrogen (BUN), carbon dioxide, creatinine, calcium, chloride, potassium, sodium. 
h To be completed prior to vaccine dose. Week 1 test may be omitted if screening urine pregnancy test is performed within the 72 hours prior to first vaccine dose. 
i Registration occurs after subject eligibility has been confirmed. Note: The registration process, as outlined in Section 15, may occur prior to Week 1. 
j Study lab for Week 1 should be completed prior to the vaccine. Study lab: Up to 100 mLs of blood may be collected. Red Vacutainer tubes: Approximately 50 mL 
collected at all study lab timepoints. Lavender vacutainer tubes: Approximately 50 mL will be collected at Weeks 1, 7, and 10 with the amount decreasing to 25 mL for 
Weeks 13, 16, 25, 49, and 73. 
k Surgery will be performed according to standard practice unless they are considered inoperable or if surgery is medically contraindicated. 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 21 of 59 
 
9.4. Study Calendar – Schedule D – Retired (Used only in Part 1) 
 
Procedures 
Pre-study/ 
Screeninga 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
5 
Wk 
8 
Wk 
11 
Wk 
14 
Wk 
17 
Wk 
20 
Wk 
23 
Surgery 
(4-8 weeks 
after chemo) 
Wk 47 
(± 4 wks) 
Wk 71 
(± 4 wks) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination with Mimotope 
P10s-PADRE/ 
MONTANIDE™ ISA 51 VG 
 
Xb 
Xb 
Xb 
 
 
 
 
 
 
 
 
 
 
Cyclophosphamidecd 
 
 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
Doxorubicincd 
 
 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
Docetaxelcd 
 
 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
AEs 
 
X 
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/PE/Vital Signs ef 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
CBC with Diff 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Total Bilirubin 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
SGOT/AST 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
SGPT/ALT 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alk Phos 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
LDH 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Creatinine 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Calcium 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Urine Pregnancy Test 
X 
Xg 
 
 
 
 
 
 
 
 
 
 
 
 
Registration 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
 
Study Labi 
 
Xh 
 
 
X 
X 
X 
X 
 
 
X 
 
X 
X 
Surgeryj 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
                                                          
a Pre-study/Screening should be completed within 21 days prior to registration/week 1. 
b Post vaccine administration, the following vital signs will be monitored every 15 minutes (± 5 minutes) for one hour: blood pressure, temperature and pulse. 
c Chemotherapy administration date may be delayed up to 10 days at investigator discretion. 
d If clinically necessary, chemotherapy dosing may be modified per the Chemotherapy Dose Adjustment in Section 8c. 
e 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. 
f Tumor Assessments will be performed by physical exam according to standard practice. 
g To be completed prior to vaccine dose 
h Registration occurs after subject eligibility has been confirmed. Note: The registration process, as outlined in Section 15, may occur prior to Week 1. 
i  Study lab: Up to 100 mLs of blood may be collected. Red Vacutainer tubes: Approximately 50 mL collected at all study lab timepoints. Lavender vacutainer tubes: 
 Approximately 50 mL will be collected at Weeks 1, 5, and 8 with the amount decreasing to 25 mL for Weeks 11, 14, 23, 47, and 71. 
j  Surgery will be performed according to standard practice unless they are considered inoperable or if surgery is medically contraindicated. 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 22 of 59 
 
9.5. Study Calendar – Schedule E – Retired (Used only in Part 1) 
 
Procedures 
Pre-study/ 
Screeninga 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
6 
Wk 
9 
Wk 
12 
Wk 
15 
Wk 
18 
Wk 
21 
Wk 
24 
Surgery 
(4-8 weeks 
after chemo) 
Wk 48 
(± 4 wks) 
Wk 72 
(± 4 wks) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination with Mimotope 
P10s-PADRE/ 
MONTANIDE™ ISA 51 VG 
 
Xb 
Xb 
Xb 
 
 
 
 
 
 
 
 
 
 
Cyclophosphamidecd 
 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Doxorubicincd 
 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Docetaxelcd 
 
 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
AEs 
 
X 
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/PE/Vital Signs ef 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
CBC with Diff 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Total Bilirubin 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
SGOT/AST 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
SGPT/ALT 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alk Phos 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
LDH 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Creatinine 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Calcium 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Urine Pregnancy Test 
X 
Xg 
 
 
 
 
 
 
 
 
 
 
 
 
Registration 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
 
Study Labi 
 
Xh 
 
 
X 
X 
X 
X 
 
 
X 
 
X 
X 
Surgeryj 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
                                                          
a Pre-study/Screening should be completed within 21 days prior to registration/week 1. 
b Post vaccine administration, the following vital signs will be monitored every 15 minutes (± 5 minutes) for one hour: blood pressure, temperature and pulse. 
c Chemotherapy administration date may be delayed up to 10 days at investigator discretion. 
d If clinically necessary, chemotherapy dosing may be modified per the Chemotherapy Dose Adjustment (Section 8c). 
e 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. 
f Tumor Assessments will be performed by physical exam according to standard practice. 
g To be completed prior to vaccine dose 
h Registration occurs after subject eligibility has been confirmed. Note: The registration process, as outlined in Section 15, may occur prior to Week 1. 
i Study lab: Up to 100 mLs of blood may be collected. Red Vacutainer tubes: Approximately 50 mL collected at all study lab timepoints. Lavender vacutainer tubes: 
 Approximately 50 mL will be collected at Weeks 1, 6, and 9 with the amount decreasing to 25 mL for Weeks 12, 15, 24, 48, and 72. 
j Surgery will be performed according to standard practice unless they are considered inoperable or if surgery is medically contraindicated. 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 23 of 59 
 
10. VISIT BREAKDOWN 
10.1. Visit Breakdown – Schedule A – Retired (Used only in Part 1) 
 
Pre-study/Screening (within 21 days prior to initiating study treatment) 
• 
Complete medical history and physical examination: vital signs to include height, weight, blood 
pressure, temperature and pulse. 
• 
Informed Consent 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
Total Bilirubin 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Creatinine 
○ 
Calcium 
• 
Urine pregnancy test for women of childbearing potential 
 
Week 1 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse 
• 
Urine pregnancy test for women of childbearing potential (within 72 hours prior to dosing) 
• 
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 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0 
• 
Concomitant medications 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 
• 
SC administration of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine. 
• 
Post vaccine administration, the following vital signs will be monitored every 15 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
 
Week 3 
• 
SC administration of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine. 
• 
Post vaccine administration, the following vital signs will be monitored every 15 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
 
 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 24 of 59 
 
Week 4 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 7 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 10 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 25 of 59 
 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 13 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 16 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
 
Week 19 
• 
Complete medical history and physical examination: vital signs to include: weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
 
Week 22 
• 
Complete medical history and physical examination: vital signs to include: weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 26 of 59 
 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Breast cancer surgery 
• 
Definitive surgery will be performed according to standard practice 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. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Creatinine 
○ 
Calcium 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 70 (±4 weeks) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Creatinine 
○ 
Calcium 
 
 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 27 of 59 
 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
10.2. Visit Breakdown – Schedule B – Retired (Used only in Part 1) 
 
Pre-study/Screening (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. 
• 
Concomitant medications will be collected from consent to end of treatment 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
Total Bilirubin 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Creatinine 
○ 
Calcium 
• 
Urine pregnancy test for women of childbearing potential 
 
Week 1 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 
• 
Urine pregnancy test for women of childbearing potential (within 72 hours prior to dosing) 
• 
SC administration of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine. 
• 
Post vaccine administration, the following vital signs will be monitored every 15 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
 
 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 28 of 59 
 
Week 3 
• 
SC administration of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine. 
• 
Post vaccine administration, the following vital signs will be monitored every 15 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
 
Week 4 
• 
Complete medical history and physical examination: vital signs to include weight, 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 (± 5 minutes) minutes for one 
hour: blood pressure, temperature, and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
 
Week 7 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 10 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 29 of 59 
 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 13 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 16 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 19 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 30 of 59 
 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
 
Week 22 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Breast cancer surgery 
• 
Definitive surgery will be performed according to standard practice 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. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Creatinine 
○ 
Calcium 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 70 (±4 weeks) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 31 of 59 
 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Creatinine 
○ 
Calcium 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
10.3. Visit Breakdown – Schedule C – Optimal Schedule (To be used in Parts 1, 2 & 3) 
 
Pre-study/Screening (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. 
• 
Concomitant medications will be collected from consent to end of treatment. 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
Total Bilirubin 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Urine pregnancy test for women of childbearing potential. 
 
Week 1 (± 2 days) 
• 
Complete medical history and physical examination: vital signs to include weight, 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 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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. 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 32 of 59 
 
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 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
 
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 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
 
Week 4 (± 2 days) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 (SoC growth factor 
may be given at physician’s discretion) 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
 
Week 7 (± 2 days) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 (SoC growth factor 
may be given at physician’s discretion) 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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. 
 
 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 33 of 59 
 
Week 10 (± 2 days) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 (SoC growth factor 
may be given at physician’s discretion) 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 13 (± 2 days) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 (SoC growth factor 
may be given at physician’s discretion) 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 16 (± 2 days) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 (SoC growth factor may be given at physician’s discretion) 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 34 of 59 
 
○ 
Alkaline Phosphatase 
○ 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 19 (± 2 days) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 (SoC growth factor may be given at physician’s discretion) 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
 
Week 22 (± 2 days) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 (SoC growth factor may be given at physician’s discretion) 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
 
Week 25 (± 2 days) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 (SoC growth factor may be given at physician’s discretion) 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 35 of 59 
 
Breast cancer surgery 
• 
Definitive surgery will be performed according to standard practice 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 49 (±4 weeks) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 73 (±4 weeks) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Chemistry (BUN, carbon dioxide, creatinine, calcium, chloride, potassium, sodium) 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
10.4. Visit Breakdown – Schedule D – Retired (Used only in Part 1) 
 
Pre-study/Screening (within 21 days prior to initiating study treatment) 
• 
Complete medical history and physical examination: vital signs to include height, weight, blood 
pressure, temperature and pulse. 
• 
Informed Consent 
• 
Concomitant medications will be collected from consent to end of treatment 
 
 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 36 of 59 
 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
Total Bilirubin 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Creatinine 
○ 
Calcium 
• 
Urine pregnancy test for women of childbearing potential 
 
Week 1 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Urine pregnancy test for women of childbearing potential (within 72 hours prior to dosing) 
• 
SC administration of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine. 
• 
Post vaccine administration, the following vital signs will be monitored every 15 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 
• 
Complete medical history and physical examination: vital signs to include: weight, 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 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
 
Week 3 
• 
SC administration of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine. 
• 
Post vaccine administration, the following vital signs will be monitored every 15 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
 
 


Vaccination of High Risk Breast Cancer Patients 
IRB 202556 & 204187 
Sponsor: UAMS 
Version 21 
06/02/2022 
Page 37 of 59 
 
Week 5 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 11 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 


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• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 14 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 17 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
 
Week 20 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
 
Week 23 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 


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• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Breast cancer surgery 
• 
Definitive surgery will be performed according to standard practice 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 47 (±4 weeks) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Creatinine 
○ 
Calcium 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 71 (±4 weeks) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Creatinine 
○ 
Calcium 
 


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• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
10.5. Visit Breakdown – Schedule E – Retired (Used only in Part 1) 
 
Pre-study/Screening (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. 
• 
Concomitant medications will be collected from consent to end of treatment. 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
Total Bilirubin 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Creatinine 
○ 
Calcium 
• 
Urine pregnancy test for women of childbearing potential 
 
Week 1 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Urine pregnancy test for women of childbearing potential (within 72 hours prior to dosing) 
• 
SC administration of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine. 
• 
Post vaccine administration, the following vital signs will be monitored every 15 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 
• 
SC administration of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine. 
• 
Post vaccine administration, the following vital signs will be monitored every 15 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
 
 


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Week 3 
• 
Complete medical history and physical examination: vital signs to include weight, 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 (± 5 minutes) 
minutes for one hour: blood pressure, temperature, and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
 
Week 6 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 9 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
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 


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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 12 
• 
AC Chemotherapy - cyclophosphamide 600 mg/m2 and doxorubicin 60 mg/m2 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 15 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Week 18 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
Week 21 


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• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications. 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
 
Week 24 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Docetaxel 75 mg/m2 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
Breast cancer surgery 
• 
Definitive surgery will be performed according to standard practice 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 48 (±4 weeks) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Creatinine 
○ 
Calcium 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 


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Week 72 (±4 weeks) 
• 
Complete medical history and physical examination: vital signs to include weight, blood pressure, 
temperature and pulse. 
• 
Adverse Events: events will be monitored using the NCI CTCAE Version 4.0. 
• 
Concomitant medications 
• 
Blood Tests to include the following: 
○ 
Complete blood count with differential 
○ 
SGOT/AST 
○ 
SGPT/ALT 
○ 
Alkaline Phosphatase 
○ 
LDH 
○ 
Creatinine 
○ 
Calcium 
• 
Study Lab: 
○ 
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 to determine cytotoxicity effect on breast cancer cells. 
○ 
Isolation of plasma: Approximately 25 mL of blood will be collected in potassium EDTA tubes 
to collect plasma. 
 
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. 


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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, 
hypoalbuminemia 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 
complete blood count (CBC) with 
differential, liver function tests, etc. 
- Close and frequent monitoring of 
subjects by qualified staff 
- Emergency equipment including crash 
carts, advanced cardiac life support 
(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, serious adverse 
events (SAEs) and unanticipated 
problems. 
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. 


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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. 
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 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 the first post-
surgery study lab (e.g. Week 49 for Schedule C), 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 Chemovax will be at least as high 
as would be expected were the patient to receive only SoC neoadjuvant chemotherapy. Chemovax 
may potentiate an immune response, which could improve the rate of pCR compared to SoC 
therapy alone. 
 


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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 relabel 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 -65ºC 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. 
 
Tissue specimens will be obtained from archival tissue collected as part of standard biopsy and/or 
surgery. Whenever available, a total of 4 H&E slides and 36 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 the 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 ENDPOINTS, and 
ENDPOINT-ASSAY METHODS 
 
a. Primary Feasibility Endpoint: Adequate IgG Response 
This will be defined as a >4-fold increase in a subject’s anti-P10s-MAP IgG titer at Week 7 or later 
(at least 4 weeks after the 3rd immunization) relative to her pre-immune titer. 
 
b. Primary Efficacy Endpoint: Pathologic Complete Response (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) (59). 
 
c. Secondary Endpoints for determining short-term immune responses to Chemovax 
• 
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. 
○ 
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. 


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○ 
The anti-TACA cell-binding level will be determined on each subject from serum and 
plasma samples drawn as specified in the study calendar. 
 
• 
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. 
○ 
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. 
 
d. Secondary Endpoints for determining persistence of immune responses 
We will further determine the persistence of a subject’s immune responses upon treatment with 
the Chemovax therapy. 
 
• 
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. 
 
e. Tolerability and Safety Endpoints 
Subjects will receive 3 planned vaccine doses unless they withdraw from the study or develop any 
grade 3 or greater toxicity as per NCI CTCAE v4.0 toxicity criteria, Grade 2 or greater autoimmune 
toxicity with the exception of vitiligo, or Grade 2 or greater hypersensitivity reactions. These 
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 4.0 will be used for toxicity and SAE reporting. A copy of the CTCAE 
Version 4.0 can be downloaded from the Cancer Therapy Evaluation Program (CTEP) home page. 
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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 AEs, the most serious of which will be reported as 
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. 
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. 
 
• 
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. 
 
 


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• 
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 -80ºC. 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. 
 
• 
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 
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• 
Immunohistochemistry: In those subjects with enough pathological specimens, tumor-tissue 
slides will be requested from tissue collected at both the original biopsy before treatment (2 
H&E and 8 unstained slides) and at time of definitive surgery (2 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 4 H&E slides and 
16 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 (two slides per antibody from both biopsy and surgery). In addition to the slides for 
immunohistochemistry, 20 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. 
 
14. STATISTICAL CONSIDERATIONS 
 
General Considerations: The primary objectives of this multi-center study are (1) to identify a 
Chemovax schedule that is “feasible” in the sense of being safe, tolerable, and capable of generating 
adequate immune response in enough subjects, and (2) determine if ER-positive breast-cancer 
subjects treated with the Chemovax regimen experience a significantly higher rate of pCR than ER-
positive subjects treated with SoC neoadjuvant chemotherapy. The size of the study population was 
purposely chosen to provide adequate power (>90%) to properly evaluate the clinical efficacy of the 
vaccine-chemotherapy combination. 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 Feasibility Endpoint: To evaluate the feasibility of eliciting adequate 
immune response with P10s-PADRE when it is administered in combination with neoadjuvant 
chemotherapy, we will sequentially evaluate different schedules of vaccination relative to 
chemotherapy, and stop evaluating as soon as we have identified a feasible schedule. Immune-
response adequacy will be evaluated using the previously described Schedule Evaluation Rule and 
will be defined as four or more of the 5 subjects exhibit a ≥4-fold increase in anti-P10s serum IgG titer 
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Analysis Plan for Primary Efficacy Endpoint: If a feasible Chemovax schedule is identified, then 
that schedule’s cohort will be expanded and used to initiate the primary efficacy evaluation of 
Chemovax using a Simon optimal two-stage design (60, 61). 
 
The following is a Simon two-stage optimal design intended to test the null hypothesis that the pCR 
rate with Chemovax will be 8% or less versus the alternative that the pCR rate with Chemovax will be 
23% or more. Nineteen subjects will be accrued, treated with Chemovax, and evaluated during the 
first stage of the primary efficacy evaluation. If one or none achieve pCR, then the trial will be 
terminated for futility; if two or more achieve pCR, then the second stage of the primary efficacy 
evaluation will open. If the second stage opens, it will accrue 22 additional subjects, so that a total of 
41 subjects will be accrued, treated with Chemovax, and evaluated. If and only if the total number of 
subjects who achieve pCR is 6 or more, then the null hypothesis (that the pCR rate is ≤8%) will be 
rejected in favor of the alternative hypothesis (that the pCR rate is ≥23%). When the null hypothesis 
is true, this design will have a true Type I error rate of 9.6%, and an expected sample size of 29.03 
based on a 54.4% probability of early termination. This design will attain 90.8% power to reject the null 
hypothesis in favor of the alternative when the true rate of pCR is 23%. 
 
Determination of Sample Size: The primary efficacy evaluation just described will be preceded by 
an immune-response feasibility stage during which a sequence of up to five schedules of vaccination 
relative to chemotherapy will be evaluated. Each schedule will accrue a cohort of five subjects, and 
be evaluated using the previously described Schedule Evaluation Rule to identify a feasible Chemovax 
schedule that does not interfere with subjects’ ability to mount an adequate IgG response. Therefore: 
1. If a feasible Chemovax schedule is identified, then there could be from zero to 20 subjects 
who are accrued to unsuccessful schedules, in addition to the 19 or 41 subjects who are 
accrued to the successful schedule. Under this scenario, the final sample size of the entire 
study would range from 25 to 61 subjects. 
2. If all five Chemovax schedules are evaluated and none of them are identified as feasible then 
none of the cohorts will be expanded, and the primary efficacy analysis will not take place. 
Under this scenario, the final sample size of the entire study would be 25. 
 
Thus, the final sample size of the entire study will have a theoretical minimum of 25 subjects, and a 
theoretical maximum of 61 subjects. 
 
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-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. 
 
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. 
 
 


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Data Safety Monitoring Plan: AEs and safety will be evaluated throughout the study by a Data Safety 
Monitoring Board (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. 
 
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 Trial Management Suite (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 records will be destroyed as well as links between identifiers of the research 
subjects and their 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: Potential subjects will be recruited from the WPRCI on the 
UAMS campus and clinics at HOG. The potential subjects will be identified by the research 
physician or staff. Prior to any research activities, the potential 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 potential 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 


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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 (21CFR50) and the Office for 
Human Research Protections: Protection of Human Subjects (Code of Federal Regulations 
45CFR46). 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 21CFR56 and the Office for Human Research Protections: Protection of 
Human Subjects 45CFR46. 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 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. 
[21CFR312.32 (a)] 
 


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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 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 21CFR312. All other AEs will be reported to the Sponsor 
and FDA in the Annual Progress Report. 
 


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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 and will be reported at continuing review and the Annual 
Progress Report. 
 
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. 
 
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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21. BIBLIOGRAPHY 
 
1. von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact 
of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast 
cancer subtypes. J Clin Oncol. 2012;30(15):1796-804. doi:10.200/JCO.2011.38.8595. Epub 2012 Apr 16. 
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