A study of the drug tebentafusp for melanoma (TebeMRD)

Cancer type:

Melanoma

Status:

Open

Phase:

Phase 2

This study is looking at a type of immunotherapy Open a glossary item called tebentafusp. It is for people with melanoma of the skin (cutaneous), or of the eye (uveal), that:

have finished treatment, or are about to finish treatment
are at an increased risk of their melanoma coming back

More about this trial

Surgery is the main treatment for melanoma. You might also have other treatments if you are at an increased risk of your cancer coming back or if your cancer has spread. Possible treatments include:

immunotherapy
targeted cancer drugs

You may have treatment with radiotherapy Open a glossary item if you have melanoma of the eye (uveal melanoma).

These treatments can work well, but some people have a small number of cancer cells left at the end of treatment. This is called molecular relapsed disease (MRD). Doctors can find the cancer cells in a blood test. But they cannot see the cancer on a scan at that time.

Researchers would like to improve treatment for people with melanoma that have an increased risk of it coming back. They think giving a new treatment early, when they find MRD, might help people in this situation.

Tebentafusp is a type of immunotherapy Open a glossary item . It is made from two different proteins that are joined together. One of the proteins recognises and attaches to a protein called gp100. There are high levels of gp100 in some melanoma cells.

The other protein recognises and attaches to a protein called CD3. CD3 is on certain cells of the body’s immune system. By sticking to gp100 and CD3, tebentafusp activates your immune system Open a glossary item to recognise and destroy cancer cells.

To work, your immune system needs to recognise the tebentafusp. This is only possible for people with a HLA protein Open a glossary item called HLA-A*0201. Around 50 in 100 people (around 50%) have this HLA protein on most of their cells.

We know from research that tebentafusp has helped people with melanoma that has spread (advanced melanoma). Now, doctors would like to find out if it could help people at an earlier stage. This trial is looking into this.

This study is in 3 parts. The 1st part, called pre screening, is to find people with HLA-A*0201.

The 2nd part is called molecular screening. It is for people with HLA-A*0201. You have blood tests to see if you have MRD.

The 3rd part of the study is the main study. It is for people with HLA-A*0201 and MRD. Everyone joining the 3rd part of this study will have tebentafusp.

The main aims of the trial are to find out:

how well tebentafusp works for people with cutaneous melanoma with MRD and HLA-A*0201
how well tebentafusp works for people with uveal melanoma with MRD and HLA-A*0201
about the safety of tebentafusp
how tebentafusp works in the body
about the side effects of treatment
about cutaneous and uveal melanoma

Who can enter

The following bullet points are a summary of the entry conditions for this study. Talk to your doctor or the study team if you are unsure about any of these. They will be able to advise you.

You must have melanoma of the skin (cutaneous), or melanoma of the eye (uveal).

Who can take part – Pre screening
You may be able to join the 1st part of this study, called pre-screening, if:

you have a blood sample that the study team can access, or you are willing to give a new blood sample and
your doctor thinks that you may be able to take part in the 2nd and 3rd parts of the study

Who can take part – Molecular screening
You may be able to join the 2nd part of this study, called molecular screening if:

you have a protein called HLA-A*0201 on your cells. Your doctors use the pre screening blood test to find this out.
your doctor thinks that you may be able to take part in the 3rd part of the study

As well as the above, one of the following must apply:

you are due to finish adjuvant treatment in the next 3 months. Or you have finished adjuvant treatment in the last 9 months for intermediate or high risk melanoma of the skin (cutaneous melanoma) that has been removed. Your doctor can explain your risk group to you.
within the last 3 years you have finished all your treatment for melanoma that started in the eye (uveal melanoma)
within the last 3 years you have finished all your treatment for melanoma that came back in no more than 5 areas (oligometastatic disease)

Who can take part – Main study
You may be able to join the 3rd part of the study (main study) if all of the following apply. You:

have a small amount of cancer cells left after treatment (MRD positive). Your team will find this out during the molecular screening part of the trial.
might not be able to carry out heavy physical work, but can do anything else (performance status 0 or 1)
have satisfactory blood test results
are willing to use reliable contraception during treatment and for 6 months after the last dose if there is any possibility that you or your partner could become pregnant
are at least 18 years old

Who can’t take part in the main study

Cancer related
You cannot join the main study if any of these apply. You:

have melanoma that your team can see on a scan , or when they examine you, while you are having tests to check if you can take part in the study
have melanoma that has spread
have another type of cancer apart from those that were treated with the aim to cure and has not come back after at least 2 years with no treatment. You may be able to take part if you had basal cell or squamous cell skin cancer that has been removed, a slow growing cancer that has not needed treatment or any type of early cancer (carcinoma in situ ) that has been removed.
have had certain cancer drugs recently. Your doctor can explain how long the gap must be for each drug you have had.
have ongoing side effects from previous cancer treatment, apart from hair loss, nerve damage, hearing or balance problems that are mild
have had immunotherapy treatment before and you are still having certain side effects. You might still be able to take part if you have certain hormonal side effects which are well managed on replacement drugs. Your doctor can explain more.

Medical conditions
You cannot join the main study if any of these apply. You:

have an active infection that needs antibiotic treatment that reaches the whole body (systemic treatment)
have a serious physical or mental health condition that the team think will make it difficult for you to take part
are known to have hepatitis B, hepatitis C or HIV
have had any serious problems with your heart , including a heart attack within the last 6 months
have an autoimmune disease or have had one in the last 3 years. You may still be able to take part if you have diabetes, vitiligo or psoriasis. Or if you have well managed asthma or hypothyroidism . Your doctor can explain more.
are having steroids that reach your whole body (systemic treatment) and you need them for longer than 2 weeks. You may be able to take part if you are taking them because your body does not make enough (renal or adrenal insufficiency). You may also be able to take part if you are having steroid ear or eye drops, steroid inhalers or a steroid injection directly into a joint.
have had major surgery within 2 weeks of having the first dose of the study treatment

Other
You cannot join the main study if any of these apply. You:

have had a live vaccine within 4 weeks of starting the trial drug
are pregnant, breastfeeding or planning a pregnancy
have taken part in another clinical trial or research study, or have had an experimental treatment, in the 4 weeks before joining the study

Trial design

This is a phase 2 study. Researchers hope that around 850 people from the UK will agree to take part in the pre screening part of the study. They think that around 350 to 380 people will take part in the molecular screening part of the study. And the team think that around 50 people will have tebentafusp in the main study.

Pre screening

The study team want to find people who have HLA-A*0201. This is called HLA-A*0201 positive. You have a blood test to find this out. If you are HLA-A*0201 positive, you go onto the molecular screening part of the study.

If you don’t have HLA-A*0201, your doctor will discuss other treatment options with you. You will no longer be part of this study.

Molecular screening

The study team want to find people who have HLA-A*0201 and MRD but do not have cancer on a scan. You have a MRD blood test around once every 3 months for a year to find out.

If you are not found to have MRD at any of your molecular screening visits you are not able to join the main study. This is because the trial team think that tebentafusp will not be able to help you.

Main study

This is for people with HLA-A*0201 and MRD. You can move from molecular screening to the main study at any point if your team find you have MRD.
You have tebentafusp as a drip into your bloodstream every week.

The amount of tebentafusp increases each time you have the drug for the first month. This is to make sure the side effects are not too bad.
You have tebentafusp for up to 6 months as long as:

you are not feeling worse
your doctor can’t see any signs of melanoma when they examine you
the side effects are not too bad

Samples for research

The researchers ask for a sample of your cancer that was removed if you had a biopsy Open a glossary item

. This is to look at the DNA Open a glossary item

in the melanoma tissue and see if it has a protein called gp100. You don’t have to give these samples if you don’t want to. You can still take part in the trial.

The study team use your blood tests from molecular screening to look at genetic Open a glossary item changes in the DNA. This might help doctors predict which patients will benefit from treatment in the future.

The study team will ask if you are happy for blood samples to be used in future research. This is because genetic research is changing all the time. You don’t have to give these samples if you don’t want to. You can still take part in the trial.

Hospital visits

Pre screening
You go to the hospital to have a blood test. You might not need to if there is a recent sample available for the team or if your HLA status is already known.

Molecular screening
There will be up to 5 hospital visits in total.

You see the study team and have some tests first of all. The tests include:

a physical examination
blood tests
a CT scan

You also have a liver MRI scan if you have uveal melanoma.

You might go to the hospital more than once to complete these tests.

During molecular screening you go to the hospital about every 3 months for a physical examination and blood test. You have these blood tests for up to a year.

Main study
You are likely to go to one of up to 10 specialist hospitals for the main study. This might mean you have to go to a different hospital from where you took part in molecular screening.

You see the study team and have some tests before you start treatment. These include:

a physical examination, including checking your pulse, blood pressure , height and weight
blood tests
urine tests
a CT scan
an electrocardiogram (ECG)

You might also have a liver MRI scan if you have melanoma of the eye (uveal melanoma).

You might go to the hospital more than once to complete these tests.

You go to the hospital once a week to have tebentafusp. You might have up to 6 months of treatment, which would be 24 hospital visits. The drip takes around 15 to 20 minutes. You stay in hospital overnight the first 3 times you have tebentafusp. This is so your healthcare team can see how you are feeling after the drug.

You usually have the rest of the doses in the outpatient department of the hospital. You are monitored between 30 minutes and 4 hours after each dose. How long you stay for monitoring depends on any side effects.

At each visit for tebentafusp you have some tests, these include:

a physical examination, including checking your pulse, blood pressure, height and weight
routine blood tests and research blood tests
urine tests

You may also have a heart trace (ECG). After the first 3 doses of tebentafusp you have an ECG only if your doctor thinks this is needed.

Around 28 days after your last dose of tebentafusp you go to the hospital for a follow up visit. The team see how you are getting on. You have some of the same tests you had during your treatment visits.

Follow up
You see the study team every 3 months for a year. This is called follow up. You have research blood tests and see the team to talk about how you have been feeling.

Side effects

The study team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.

Tebentafusp can affect the immune system Open a glossary item . This may cause inflammation and other reactions in different parts of the body. For many people the inflammation and reactions are not too bad. For some people they can cause serious side effects.

These side effects could happen during treatment or months after treatment has finished. Rarely, these side effects could be life threatening. Your doctor or nurse can explain what these side effects are, the risk of them happening and what to look out for.

If you have any of these side effects tell your doctor or nurse as soon as possible. You should tell them that you are on or have been on an immunotherapy.

The most common side effects of tebentafusp are:

skin problems such as a rash, dry skin, red skin or skin peeling or flaking
itching
swelling of the face, body or the skin around the eyes
fever and, or chills
tiredness and lacking energy (fatigue)
feeling or being sick
low blood pressure or high blood pressure
headache
constipation or diarrhoea
coughing
increased risk of infection due to low white blood cells
pain in the tummy (abdomen), arms and legs, back, muscles, bones, joints and neck
flu-like illness
liver changes
lightening of the skin, vitiligo or darkening of the skin
decreased appetite
flushing or tingling of the skin
hair colour changes
dizziness
heartburn or acid reflux
difficulty sleeping
blocked or runny nose
urine infection
taste changes
skin lumps
breathlessness or difficulty breathing
fast heart rate
breathlessness or looking pale due to a low red blood count (anaemia)
an increase in the levels of pancreas enzymes in the bloodstream
low levels of a mineral called phosphate in the bloodstream
low levels of a protein called albumin in the bloodstream