Phase II Trial FAQ

What is the purpose of this study?

The purpose of this research study is to find out if the investigational study vaccine, VRP-HER2, as a single agent or in combination with pembrolizumab (another investigational drug) is safe and has beneficial effects in people with HER2-positive breast cancer.

How does this study work? What do patients receive?

Participants will be randomly assigned to one of three study groups: (A) VRP-HER2 alone, (B) pembrolizumab alone, or (C) VRP-HER2 + pembrolizumab. All participants will continue on their HER2 targeted therapy as directed by their physician, in addition to the study treatments. Participants will return for follow-up visits about 7-10 times over 24 weeks. If you decide to participate, you will also undergo two biopsies of your tumor tissue for research purposes. One before you receive the study drug(s), and another after the last dose of study drug(s).

Who will be my doctor on this study?

If you decide to participate, Dr. Force or one of the other medical oncologist investigators will be your doctor for the study and will be in contact with your regular health care provider throughout the time that you are in the study and afterwards, if needed.

Why is this study being done?

The purpose of this study is to find out what effects (good and bad) an investigational cancer vaccine called VRP-HER2, in combination with pembrolizumab, may have on your immune system’s activity and ability to control your cancer. The word “investigational” means that the vaccine is still being tested in research studies and is not approved by the U.S. Food and Drug Administration (FDA). Pembrolizumab has been approved by the FDA as a treatment for melanoma, non-small cell lung cancer, head and neck cancer, certain types of lymphoma, gastric cancer, cervical cancer, and urothelial cancer. However, it has not been FDA-approved for breast cancer, and therefore it is considered investigational for your type of cancer.
In HER2-positive breast cancer (the type of breast cancer you have), the HER2 gene is over-active and produces extra HER2 protein. A gene contains information that determines in part the traits, such as eye color, height, or disease risk, that are passed on from parent to child. Genes do this by producing proteins. Proteins are the building blocks of your body, organs, and cells. In this case, the HER2 gene produces HER2 protein present on cancer cells. This research is designed to use the HER2-overexpressing cancer cells as a target for a vaccine that will activate your immune system to fight the cancer cells.
The VRP-HER2 vaccine that will be studied in this research is made from a virus that contains a fragment of the HER2 gene. Once this virus is given to you as a vaccine, it can enter certain cells in your body such as some types of immune cells. The virus used in this vaccine was designed based on a virus called the Venezuelan Equine Encephalitis virus (an alphavirus). The virus has been changed so it is unlikely to cause an infection. Instead, the virus has been made to transfer a copy of the gene fragment that makes the HER2 protein to cells of the muscle, skin, and immune system. This transfer of a gene fragment should cause extra copies of the HER2 protein to be made in your cells. These cells will break up the HER2 protein and show pieces of it to other immune cells to tell them to attack cancer cells expressing HER2.

This is the first study of VRP-HER2 in combination with pembrolizumab in humans. A previous study has been performed to determine the safety of VRP-HER2 alone in cancer patients. The goal of thiss tudy is to find out if VRP-HER2 given in combination with pembrolizumab can cause an immune response against your cancer and whether it is safe.

How many people will take part in this study?

Up to 39 people will take part in this study all at Duke.

What is involved in this study?

All participants will continue on their HER2 targeted therapy as directed by their physician, in addition to study treatments.

Screening Procedures
If you agree to be in this study, you will be asked to sign and date this consent form. You will have the following tests and procedures to make sure that you are eligible. This is referred to as “Screening” for the study. Some of these are part of your routine care and others are being conducted only for research purposes. Ask your study doctor about which tests and procedures are for research purposes only.

Physical exam and medical history, including height, weight, and review of all medications
Vital signs (breathing rate, pulse, temperature and blood pressure)
Blood tests (for blood counts, chemistries, tumor markers, and research testing)
If you are a woman capable of becoming pregnant, a blood pregnancy test will be done. It must be negative for you to continue study participation.
12 lead electrocardiogram (EKG, which records the electrical activity of the heart)
Echocardiogram (ECHO), a noninvasive test that uses ultrasound to assess the function of your heart (only if you have not had a standard of care ECHO done within the 8 weeks preceding your first injection of study drugs).
Computerized tomography (CT) or magnetic resonance imaging (MRI) scans to evaluate the extent of your cancer (only if you have not had a standard of care scan done within the 4 weeks preceding your first injection of study drugs).
If you have a known history of HIV, you cannot participate in this study because you may have immunosuppression that may render you unable to respond to the vaccine.

Study Procedures
If you are eligible to participate in the study, you will be asked to return to the Duke Cancer Center for approximately 7-10 study visits over 24 weeks (about 6 months). The study will enroll patients who have been stable on trastuzumab and/or pertuzumab and who plan to continue this therapy during the trial. The number of visits will depend on which study group you are assigned to. The study staff will schedule your visits with you and let you know when you will need to come back.

Biopsies: As part of this research, you will be required to have two tumor tissue biopsies to collect samples of your tumor for research purposes. One biopsy will be done prior to receiving the first dose of study drugs, and the other will be done after the last dose of study drugs. Researchers will compare these samples to see what effect the study drugs had on the tumor cells in response to the antibodies activated by the vaccine. The tissue will not be examined by a pathologist or used to make treatment decisions. Depending on where the tumor is, you will have either a core needle biopsy (a wide, hollow needle is used to take out piece of breast tumor tissue) or a 3-5 mm punch biopsy of the skin. Your physician will tell you which type of biopsy you will have and discuss the procedure with you.
Exams and Blood Tests: At each visit of the study, a medical history and a complete physical examination will be performed. At some study visits you will also have up to 100 mL of blood (6 tablespoons) drawn from a vein by needle stick, for routine tests such as blood count and chemistries, as well as for testing for research purposes only (tests to determine the response of your immune system).
Immune monitoring: We will perform immune tests on your blood cells and serum isolated from your blood. We will collect up to 6 tablespoons of blood at your screening visit for the study, day 1 (cycle 1 day 1), day 43 (cycle 3 day 1), and 85 (cycle 5 day 1), and follow up visit (week 24).
ECHO: Around the time of the last dose of study drug(s) you will have an echocardiogram (ECHO) to assess the function of your heart.
CT/MRI: We will review the results of your standard of care CT or MRI scans around the time of the last dose of study drug(s) and at 24 weeks after the initial dose to evaluate the extent of your cancer.
Study Drugs: The first three subjects enrolled into the study will receive VRP-HER2 vaccine and pembrolizumab along with their current HER2 therapy (pertuzumab and/or trastuzumab). All subsequent study subjects will be placed into one of the three different study arms or groups. If you are not one of the first three subjects enrolled, you will be randomly assigned (like drawing numbers from a hat) to receive study drug designated by either arm A, arm B, or arm C. You have a 1 in 3 chance of receiving VRP-HER2 alone (arm A), pembrolizumab alone (arm B), or VRP-HER2 plus pembrolizumab in combination (arm C).

If you are assigned to study arm A, you will receive a total of four injections of the VRP-HER2 cancer vaccine in a muscle of your arm on the following days:

o Day 1 (cycle 1 day 1)

o Day 15 (cycle 1 day 15)
o Day 29 (cycle 2 day 8)
o Booster at day 85 (cycle 5 day 1)

Each time you receive VRP-HER2, you will be requested to remain at the hospital or clinic for one hour afterwards.
If you are assigned to study arm B, you will receive an infusion of pembrolizumab intravenously in your arm every three weeks for a total of five infusions. Each time you receive pembrolizumab, you will be requested to remain at the hospital or clinic for one hour afterwards.
If you are one of the first three subjects or if you are assigned to study arm C, you will receive an infusion of pembrolizumab intravenously in your arm every three weeks for a total of five infusions, and receive an injection of the VRP-HER2 cancer vaccine in a muscle of your arm on the following days:

o Day 1 (cycle 1 day 1)
o Day 15 (cycle 1 day 15)
o Day 29 (cycle 1 day 8)
o Booster at day 85 (cycle 5 day 1)

Each time you receive pembrolizumab and/or VRP-HER2, you will be requested to remain at the hospital or clinic for one hour afterwards.

Follow-up: About 30 days after the last dose of study drug(s) you will return for a safety follow-up visit where we will ask you how you are feeling and if you are experiencing any ongoing issues.
After 24 weeks, you will enter the follow-up phase of the study. Long-term follow-up for research involving a viral vector containing a gene fragment allows for the collection of important information on safety and side effects. We will also ask you to participate in the follow-up phase if you leave the study early.
The follow-up phase will consist of a review of your medical record by our study team, possible contact with your attending physician, or a member of our study team may contact you by phone every 12 weeks to inquire about your health since receiving the study drug(s). In each of these calls, we will ask about any medical problems you have had. We also may ask that you return to Duke so that we may draw up to 6 tablespoons (90 mls) of blood to test your body’s immune response to the study drug(s). This may be requested every three months for up to one year. We may contact you by phone, email or in person (if you come for a clinic visit) until the study is completed or until you withdraw your consent.
If you stop the study for a reason other than disease progression, you will have regular CT or MRI scans every six weeks for the first year, and then every nine weeks after.

Research Samples
By agreeing to participate in this research, you authorize Duke University Health System (DUHS) and members of its staff to use your tissue, blood or other samples for the purposes described in this consent form. DUHS will maintain these samples indefinitely or until they are exhausted. These samples will be analyzed as part of Pro00105388. These samples will not be available to you for diagnostic or therapeutic purposes. Tissue, blood, or other samples collected as part of this study may be valuable for scientific research, teaching purposes, or for the development of a new medical or commercial product. There is no plan to compensate you for any use of the samples.
If you decide to withdraw your permission to use your samples in this research project, please contact the study doctor, Jeremy Force, DO, in writing and let him know you are withdrawing your permission for your samples to be stored and used for current or future research. The mailing address is DUMC Box 3381, Durham, NC 27710. At that time, we will ask you to indicate in writing if you want your unused samples destroyed or if your samples (with all identifying information removed that would link the sample to you) could be used in research. Data collected using your sample before your withdrawal will continue to be used as part of the study.

Future Research and Genetic Testing
There may be blood and/or tissue samples left over from this study. We would like to save these samples to be used for research purposes that are not specifically related to this study. You do not have to allow the use of your samples for future research to participate in this study. If you do not wish to have your samples used in the future, they will be destroyed at the end of this study. If you agree to allow your specimens to be used for future research, the information may be used to study changes in genetic material (DNA) that is passed on in families, or that is influenced by environment and lifestyle. The results can then be studied to identify changes in DNA that may result in the development of diseases or the effectiveness of specific treatments. Genetic studies are for research purposes only.

Potential Risks and the Genetic Information Non-Discrimination Act (GINA):
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 at DUHS, 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.

The Genetic Information Nondiscrimination Act (GINA) is a Federal law that will protect you in the following ways:

Health insurance companies and group plans may not request genetic information from this research
Health insurance companies and group plans may not use your genetic information when making decisions regarding your eligibility or premiums
Employers with 15 or more employees may not use your genetic information when making a decision to hire, promote, or fire you or when setting the terms of your employment.

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.

How long will I be in this study?

You will be in the study drug phase of the study until 24 weeks from the first administration of the study drug. At that time, you will then continue into the follow-up phase of the study. The follow-up phase, as described above, will continue until the study is completed or until you withdraw your consent.
You can choose to stop participating at any time without penalty or loss of any benefits to which you are entitled. However, if you decide to stop participating in the study, we encourage you to talk to your doctor first.
Federal guidelines related to studies involving a viral vector containing a gene fragment require us to notify you that, if you should die at any point after having received the study vaccine, we will request permission from your family for an autopsy to be performed to find out if there have been any unexpected effects of the study vaccine on your body. You should speak to your family about your wishes regarding an autopsy. If an autopsy is requested by the study, there will be no cost to your family.

Can I continue to take my medications?

To participate in this study you may need to stop or change some of your current medications because they may affect how well the study drugs work. However, this is unlikely. For your safety, you must tell the study doctor or nurse about all the prescribed medical foods and drugs, herbal products, over-the-counter (OTC) drugs, vitamins, natural remedies, and alcohol that you are taking before you start the study and before starting to take any of these products while you are on the study. You will be notified if any of your current medications need to be stopped or changed to allow you to participate in this study. If there are any changes, your doctor will let you know of any risks that may be associated with changes in your current medications. If you participate in this study, there may also be limitations to the other medications and supplements or foods that you can take while you are taking the study drug. Changing or limiting the medications you take for other conditions may be associated with additional inconvenience, costs, and/or side effects.

What are the risks of the study?

This is the first time VRP-HER2 in combination with pembrolizumab has been given to humans. While on this study, you are at risk for side effects below and possibly others. There may be other side effects not listed that the researchers cannot predict. You should discuss these with your doctor.
VRP-HER2, which transfers a fragment of a gene into your cells, is designed so that it should not be able to survive and grow in your body. It is not designed to make any long-lasting changes to your cells or your DNA, and should only be in your cells for a short time. Although a viral vector containing a gene fragment can in rare cases cause a disease or a new cancer, the chance of this is very small. The VRP-HER2 virus has been designed to minimize this risk. The toxicity of the vaccine combined with standard of care drugs trastuzumab and pertuzumab is unknown, and there could be unforeseen side effects.
Many side effects go away shortly after the medications are stopped but, in some cases, side effects can be serious, long-lasting, permanent, or may result in death.
The known side effects and possible risks of this research study are:

VRP-HER2 Vaccine Risks
VRP-HER2 Injections may cause some, all or none of the side effects listed below.

Side Effects

Fever
Chills
Headache
Injection site reactions
Medications that might be needed to treat allergic reactions include antihistamines such as diphenhydramine (Benadryl), epinephrine and corticosteroids. Other medications may be given to make side effects less serious and uncomfortable.

What benefits are there to being in this study?

If you agree to take part in this study, there may be direct medical benefit to you. If the study drug(s) work for you, you may have better control of your cancer, which may extend your life, however this cannot be guaranteed. We hope the information learned from this study will benefit other people with cancer in the future.

Will my information be kept confidential?

Participation in research involves some loss of privacy. We will do our best to make sure that information about you is kept confidential, but we cannot guarantee total confidentiality. Your personal information may be viewed by individuals involved in this research and may be seen by people including those collaborating, funding, and regulating the study. We will share only the minimum necessary information in order to conduct the research. Your personal information may also be given out if required by law.
As part of the study, results of your study-related laboratory tests, x-rays, and procedures may be reported to Merck and its affiliates. In addition, your records may be reviewed in order to meet federal or state regulations. Reviewers may include representatives from the Food and Drug Administration, representatives and affiliates of Merck, the Duke University Health System Institutional Review Board, Duke Cancer Institute, Duke Office of Audit, Risk and Compliance and others as appropriate. If any of these groups review your research record, they may also need to review your entire medical record.

Will participating in this study cost me anything?

No. The study sponsor has agreed to pay for services and procedures that are done solely for research purposes, including providing the VRP-HER2 vaccine and pembrolizumab and the research biopsies that are not performed for standard of care. Please talk with the PI/study team about the specific services and procedures that the sponsor will pay for, and the ones for which you or your insurance will be responsible.
You or your insurance provider will be responsible and billed for all costs related to your routine medical care, including copayments and deductibles. Routine medical care services are those that you would have received for your condition if you were not participating in this research study. Not all services are covered by insurance. Some procedures or scans may require pre-authorization by your insurance plan. We will notify you if we learn that a service is not covered by your insurance plan as part of the pre-authorization process. If it is not covered, you will be responsible for paying for it. The amount of your out-of-pocket expense will depend on your insurance plan. For beneficiaries with Medicare Advantage Plans, traditional Medicare is billed for the routine cost of a research study. You may have more or higher co-pays than with a Medicare Advantage plan. Please discuss the costs of the study with Dr. Force. At your request, a Financial Counselor in the clinic may provide you with an estimate of costs for routine services.
We will monitor your DUHS patient care charges to make sure that costs are directed appropriately. If you have any questions or concerns about appropriate billing, contact your study team coordinator so that he/she can help find a resolution.