Clinical trial: NCT02280317
Section: Confidentiality
Subsections: 4 Will My Taking Part In The Study Be Kept Confidential?

ValiRx Plc, is the sponsor for this study based in the United Kingdom. We will be using information from you and your medical records in order to undertake this study and will act as the data controller for this study. This means that we are responsible for looking after your information and using it properly. ValiRx Plc, will keep identifiable information about you for a minimum of 15 years after the study has finished. Your rights to access, change or move your information are limited, as we need to manage your information in specific ways in order for the research to be reliable and accurate. If you withdraw from the study, we will keep the information about you that we have already obtained. To safeguard your rights, we will use the minimum personally-identifiable information possible.  
You can find out more about how we use your information at https://www.valirx.com/about- us/privacy-and-gdpr/ or contact George.morris@valirx.com.  
[NHS site] will collect information from you and your medical records for this research study in PIS and ICF version: 6.0 dated 05 August 2019 Page 12 of 17 accordance with our instructions.  
[NHS site] will keep your name, NHS number and contact details confidential and will not pass this information to ValiRxPlc. [NHS site] will use this information as needed, to contact you about the research study, and make sure that relevant information about the study is recorded for your care, and to oversee the quality of the study. Certain individuals from ValiRx Plc and regulatory organisations may look at your medical and research records to check the accuracy of the research study. ValiRx Plc will only receive information without any identifying information. The people who analyse the information will not be able to identify you and will not be able to find out your name, NHS number or contact details. [NHS site] will keep identifiable information about you from this study for at least 15 years after the study has finished.  
When you agree to take part in a research study, the information about your health and care may be provided to researchers running other research studies in this organisation and in other organisations. These organisations may be universities, NHS organisations or companies involved in health and care research in this country or abroad. Your information will only be used by organisations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research. Your information could be used for research in any aspect of health or care, and could be combined with information about you from other sources held by researchers, the NHS or government. Where this information could identify you, the information will be held securely with strict arrangements about who can access the information. The information will only be used for the purpose of health and care research, or to contact you about future opportunities to participate in research. It will not be used to make decisions about future services available to you, such as insurance. Where there is a risk that you can be identified your data will only be used in research that has been independently reviewed by an ethics committee. Throughout this study your doctors, nurses, and other study personnel will record information about you in forms provided by us (known as "case report forms"). This personal information will include information about your health and your demographic details (such as your date of birth, your sex, and your ethnic origin/race).  
All records and all other information about you entered into the case report forms will be identified by a unique study participant number, not your full name.  
The Sponsor may use the information collected by us:  By storing and analysing it electronically to find out what this study is telling us;  by sharing it with regulatory authorities that approve new medicines, or with groups that check that research is done properly;  by publishing the results of the study (this will not include any information that directly identifies you);  By sharing it as part of research with other companies or universities for the purpose of further understanding or developing this drug. If the information is sent to another country, ValiRx will apply the same level of protection to your information, to the extent permitted by local law;  By using it to plan new studies or other types of research or other medical purposes related to the development of the drug.
Clinical trial: NCT02280317
Section: Participant's Rights
Subsections: Participant Information Sheet And Consent Form

You are being invited to take part in a research study using an experimental (or investigational)
drug called VAL201. Before you decide whether to take part, it is important for you to understand why the study is being done and what it will involve. Please take as much time as you need to read the following information carefully and discuss it with friends, relatives and your GP if you wish. Please ask us if there is anything that is not clear or if you would like more information. It is important that you take your time to decide whether or not you wish to take part. There are 2 parts to this document:  
**Part 1** - This is to tell you about the study (why it is being done, how it will be carried out, possible benefits and potential risks of taking part) and what you will be expected to do.  
It will also explain how your medical information will be used and who may see it. If there is anything that is not clear or if you would like more information, you are free to ask us as many questions as you like.  **Part 2** - This provides more information on the study. If you agree to take part, you will be asked to sign an Informed Consent Form. You are free to change your mind and withdraw from the study at any time, without giving a reason.
A copy of this Participant Information Sheet and signed Informed Consent Form will be given to you to keep.
Clinical trial: NCT02280317
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: 8 What Are The Possible Disadvantages And Risks Of Taking Part?|Other Risks:|9 What Are The Side Effects Of Any Treatment When Taking Part?|<Add Study Doctor Contact Details Here> Harm To The Unborn Child:

Before participating in this study, you should consider if this will affect any personal insurance e.g.  
life insurance/assurance you have and seek advice if necessary.  
Surgery: Tissue sampling / Tumour *Biopsy* The surgical risks are similar to biopsies that you have previously had. These include a risk of bleeding and infection. In addition, there are risks associated with the anaesthesia used which may include feeling sick/nausea, vomiting, or infection at the site of the needle injection.  
Administration of study *drug* The study drug VAL201, will be injected under the skin (subcutaneously) into most likely your upper arm, leg (thigh) or stomach (approximately an inch away from your belly button). You may experience some discomfort in the injection area. Please report all discomfort experienced to your study doctor.

Blood Sampling Drawing blood results in local discomfort and may also cause bruising. No more than 631.5 ml
(just over a pint) of blood will be drawn over the 6–month period from screening to the Final Study visit. Placement of a cannula (small plastic tube placed directly into the blood vein) is a routine procedure that involves momentary discomfort at the time of insertion. Minor bruising may occur. In rare cases, phlebitis (irritation of the vein), extravasation (leaking of fluid outside the vein), and infection can also occur which resolves with or without antibiotic treatment.  
Electrocardiogram Some people have a skin reaction to the sticky electrode patches that attach to the chest for the electrocardiogram. This skin irritation usually disappears when the patches are removed. Some males may have some chest hair shaved to ensure adequate contact between the electrodes and the skin.  
Whole body radionuclide bone scan The scan involves one injection but, apart from that, it is painless. To have the scan, you first have a radioactive substance called a radionuclide injected into your bloodstream. Before you have the injection, the nurse or radiographer will ask you about allergies or asthma as some people can be allergic to it. The injection may make you feel hot and flushed for a minute or two. The doctor will ask you to pass urine just before you return (or when you return) to get rid of any radionuclide in your bladder. Otherwise this could interfere with the scan. When you are ready for the scan, you will lie down on an X-ray couch and will need to keep still. Your body goes through the scanner. This makes some people feel claustrophobic, so let your doctor or nurse know if you feel nervous as they can help to reassure you. The scan takes about an hour. The radiation dose of each bone scan is equivalent to about 14 months of natural background radiation. The risk of all the bone scans causing a cancer is about 1 in 1100. The body gets rid of the radionuclide in the urine. This takes up to 24 hours. If you need to take any precautions in the meantime, the doctor or nurses will tell you beforehand. CT scan or MRI A CT scan uses X-rays and a computer to create detailed images of the inside of the body. You'll be exposed to radiation in the form of X-rays for a full body scan. The radiation dose of each CT is equivalent to about 8 years of natural background radiation. The risk of all the potential CT scans including the possible CT biopsy causing a cancer is about 1 in 143. These risks (from the bone scans and the CT scans) should be considered in the context of 1 in 4  
naturally occurring risk and are the risks to the average population and not someone with your clinical condition. Therefore it is reasonable to say that the risk from the radiation from this study can be considered small.  
An MRI is a type of scan that uses strong magnetic fields and radio waves to produce detailed images of the inside of the body. An MRI scan is a painless and safe procedure. You may find it uncomfortable if you have claustrophobia and are nor suitable for people who have certain types of implants. Please talk to your doctor if you have any questions or concerns about these tests. Allergic Reactions Rare or unknown side effects could possibly occur, including life-threatening reactions. As with any drug, it is possible that you could experience an allergic reaction, such as itching, skin rash, facial swelling, and an acute or sudden drop in blood pressure. The latter may lead to shock with loss of consciousness and/or possible seizures, including the possibility of death. **If any of the**
above symptoms of an allergic reaction occurs, seek medical attention immediately. Please remember that as with any drug, there is a risk that a rare or previously unknown side effect will occur.

Patients that have received VAL201 in clinical study to date, have experienced the following side effects considered related to the VAL201 study drug:  Injection site reaction (rash/redness/pain/tenderness/itching/bruising)  Fatigue Raised blood pressure (hypertension)
If you experience any side effects that you are concerned about you should contact your study doctor immediately.

You must avoid becoming pregnant or fathering a child while participating in this study. If you are a woman that can bear children (that is, not surgically sterile or has not gone through menopause),
there may be a possibility that the study drug may harm an unborn child or nursing infant. For this reason, if you are pregnant, plan to become pregnant, or are breast- feeding, you CANNOT take part in this study. By signing the consent form, you confirm to the best of your knowledge that you are not pregnant now, you are not currently breast-feeding and you do not intend to become pregnant or start breast feeding during the study. If at any time during this study you think you might be pregnant, or later learn that you were pregnant during the study or wish to start breast feeding, you must contact the study doctor immediately for further instructions regarding your participation in this study and follow-up. If you become pregnant at any time during the study you will be immediately withdrawn from the study. If you are a woman that can bear children, you must have a negative blood pregnancy test at screening before you can enter the study. In addition, if you are a woman that can bear children, or a man whose female partner can bear children, you and your partner must BOTH be on a form of contraception during the treatment period and for at least 1month after the last dose of the study drug.  
If you are a male patient, you should use an effective method of contraception method upon enrolment, during the course of the study, and for 1month following the last study drug dosing. In the case of the woman who can bear children (whether study subject or partner of the study subject), you/she must already be using an effective method of contraception (e.g. barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine device
(a device which is placed within the uterus)).  
In the case of the man (whether study participant or partner of the study subject), an effective form of contraception must be used. 10 **What are the possible benefits of taking part?** It is possible that you may benefit from the care given and that your tumour may respond to the study treatment. VAL201 has not been tested in humans previously which means that there is no evidence that your treatment will be successful. You should not enrol in this study with any expectation that you will personally benefit, but your participation may help to provide information that will be useful for future patients needing treatment for tumours like yours.  
Research provides wider benefits to society / others with a similar condition and some indirect benefits might be foreseeable for participants themselves. 11 **What happens when the research study stops?** If the study drug results show that the growth of your tumour has slowed or halted and your study doctor feels you may benefit, you may be allowed to continue taking the study drug for more than 6 cycles as part of this protocol. You will be expected to continue to attend study visits as required by your doctor so that your progress can be monitored.  
12 **What if there is a problem?**
Any complaint about the way you have been dealt with during the study or any possible harm you might suffer will be addressed. The detailed information on this is given in Part 2. 13 **Will my taking part in the study be kept confidential?** Yes, we will follow ethical and legal practice and all information about you will be handled in confidence. The details are included in Part 2.
Clinical trial: NCT02280317
Section: Procedures
Subsections: As The Study Progresses, The Sponsor May Decide To Alter When The Study Dosing And Assessments Are To Be Performed Compared To The Above Summary. In This Case You Will Be Provided With A Separate Table Listing The Visits And The Assessments To Be Conducted.|Optional Tissue Sampling - Biopsy Collections

Table 2 - Study Schedule and Assessments –Cycle 7 onwards  
| Cycle 7 onwards                                                     | Final   |       |    |     |
|---------------------------------------------------------------------|---------|-------|----|-----|
| Day                                                                 |         | Visit |    |     |
| 1                                                                   | 8       |       |    |     |
| 15                                                                  |         |       |    |     |
| Assessment of disease and how it affects patients daily life (ECOG) |         | X     |    | X   |
| Physical examination                                                |         | X     |    | X   |
| Vital signs (heart rate/pulse, blood                                |         |       |    |     |
| pressure, temperature and breathing rate)                           | X       |       | X  |     |
| Electrocardiogram                                                   |         |       |    |     |
| -                                                                   |         |       |    |     |
| review of heart function                                            |         | X     |    | X   |
| Blood samples                                                       |         | X     |    | X   |
| Pregnancy test (females only)                                       |         | X     |    |     |
| Tumour assessment every                                             |         |       |    |     |
| 4                                                                   |         |       |    |     |
| cycles                                                              |         |       |    |     |
| (CT scan or MRI scan, and bone scan                                 |         |       |    |     |
| -                                                                   |         |       |    |     |
| disease specific)                                                   |         | X     |    | (X) |
| Review of side effects and ongoing subject health                   |         | X     | X  |     |
| X                                                                   |         |       |    |     |
| X                                                                   |         |       |    |     |
| Review of non-study medications                                     |         | X     | X  |     |
| X                                                                   |         |       |    |     |
| X                                                                   |         |       |    |     |
| VAL201 administration                                               |         | X     | X  |     |
| X                                                                   |         |       |    |     |
| Footnotes                                                           |         |       |    |     |  
Review of non-study medications X X X X  
VAL201 administration X X X  
Footnotes  
Additional assessments may be conducted as clinically indicated.  
Review of Medical History and Non-study *Medications* At the start of the study you will be asked to provide information about your medical history and a list of medications including any current or past drugs, any herbal therapies, any self- medications such as multivitamins and minerals and any over the counter medications you may be taking for pain, cold or allergies. At all subsequent visits, if your condition and/or medications change during the course of the study, you will need to inform the study staff of these changes.  
Disease assessment and effect on daily life The Eastern Cooperative Oncology Group (ECOG) performance scale is used by doctors and researchers to assess how a patient's disease is progressing. It will be used to assess how your disease affects your daily living abilities throughout the study.  
This will include an examination of your general appearance, head and neck, eyes and ears, nose and throat, chest, lungs, heart, abdomen, extremities and joints, lymph nodes, skin, and tests on your nervous systems (e.g., eye movement, knee jerk). Height and weight will also be measured at screening with weight checks taken over the study.  
Vital Sign Assessment Vital signs measurement (including your temperature, breathing rate, blood pressure, and heart rate/pulse) will be obtained.

New tumour tissue samples - the provision of tumour tissue samples or biopsy samples is completely optional to you. If you decide not to consent to the procedures to obtain such samples, your involvement in the study or future medical care will not be affected. The tissue samples will be taken for the assessment of biological activity of the study drug in the tumour tissue. If you provide consent to have tissue samples collected, after you have received an anaesthetic (the area will be numbed or the lower part of your body will be numbed with an injection at your spine), your doctor will look at your tumour and snip small pieces (biopsies) of it for storage and testing later in the laboratory. Imaging may be used to help locate the tumour when collecting the tissue sample. Two samples will be collected, one prior to the start of study drug e.g. at screening and one after treatment has commenced in Cycle 3 Day 15. During the study, the tissue samples will be stored in a secure laboratory, with a sub-sample prepared for storage and future evaluation of study drug. After completion of the study analysis of these samples, if there is any remaining tissue it will be returned to your local hospital for your Doctor to use to support your future medical treatment. If you do agree to provide a biopsy sample an additional 10 ml blood sample will be taken to enable a genetic comparison of your body's normal DNA to the tumour cell DNA. The results of the tests for this optional part are for research purposes only investigating mutations in tumour cell DNA. The results will not be of individual significance to you and they will not be used for your medical care. Therefore, results will not be provided to you or your study doctor.  
Access to previously collected tumour tissues *samples*– if you have previously had a biopsy of your tumour we may ask you to consent to have access to part of this sample tissue for study testing. The study Sponsor will only request access to this historical tissue sample from your doctor following specific written approval from yourself to do so. After completion of the study analysis of this sample, if there is any remaining tissue it will be returned to your local hospital for your Doctor to use to support your future medical treatment. If you do agree to provide a biopsy sample from tumour tissue that you have previously provided prior to this study, an additional 10 ml blood sample will be taken to enable a genetic comparison of your body's normal DNA to the tumour cell DNA. The results of the tests for this optional part are for research purposes only investigating mutations in tumour cell DNA. The results will not be of individual significance to you and they will not be used for your medical care. Therefore, results will not be provided to you or your study doctor. Review of Side Effects and Ongoing Subject *Health* Throughout the study you will be asked how you feel and will be encouraged to report to your study doctor if you feel unwell at any time. You will be given a card with contact details of your study doctor who you can contact to report any effects you are feeling throughout the study up until your final study assessment visit.  
Study Visits and *Dosing Days* The diagram below summarises the expected number of visits and the study design. The starting dose of VAL201 was 0.5 mg/kg (0.5 mg per every kg you weigh) in the first cohort of patients, and as the study progresses to the 6th cohort of patients, the dose will not exceed 16.0 mg/kg.  
You will receive doses of VAL201 once a week on a 21-day cycle.  
For Cycles 1, 3, 4 and 6 you will attend for visits on Days 1, 2, 8 and 15 and during Cycles 2 and 5 you will attend for visits on Days 1, 8, 15. If your doctor feels you are doing well and you are benefiting from treatment, you may continue  
to receive Cycles of treatment on Days 1, 8 and 15 after Cycle 6. A Follow-up visit will be completed 30 days after your last dose of treatment.  
Diagram 1 Summary of visits and dosing days *Cohorts 5&6*  
  
5 **Expenses and payments**
The study sponsor ValiRx is providing the study drug VAL201 free of charge and will cover all other study related costs or procedures not considered part of standard care for someone with your illness. Reasonable travel costs (by public transport or car, including parking) arising from attending study visits will be reimbursed in exchange for a receipt. You will not be paid for participating in this study. Your study doctor and study clinic/hospital are being paid by the study sponsor to conduct this research. Any data or specimens (for example, blood, urine, tissue samples) collected during this study and stored after study completion, may be used in research or in the development of future products.  
The sponsor does not intend to provide you with ownership or financial benefits that may result from this research or future commercial products.  
6 **What will I have to do?** You will be asked to attend the research unit for the screening visit and every assessment and dosing day as detailed in the study schedule (Table 1 or a separate schedule as provided to you by your research team) up until a final study assessment. However you may withdraw at any time or the study doctor may decide it is in your best interests to be removed from the study. It is important that, at all times during the study, you tell the study staff if you have taken any other medications than those given to you for the purpose of this study or agreed with your study doctor.  
This includes any over-the-counter medications, vitamins, herbal supplements or dietary supplements. If you have to see another doctor or are admitted into the hospital, please let them know that you are participating in this study and show them the patient card you will receive from your study doctor. Please notify the study staff as quickly as possible of these types of events.