A trial of ATL001 for melanoma (THETIS)

Cancer type:

Melanoma
Skin cancer

Status:

Open

Phase:

Phase 3

This study is looking at a type of immunotherapy Open a glossary item called ATL001 by itself and in combination with nivolumab. 

It is open to people with melanoma that has either:

  • spread to another part of the body (advanced melanoma) or
  • come back after treatment

More about this trial

We know from research that cancer cells have changes (mutations Open a glossary item) in the genes Open a glossary item of the DNA Open a glossary item that aren’t found in healthy cells. Some of these changes are on the surface of the cancer cell. The immune system can recognise some of the changes but not well enough to control the cancer.

ATL001 is a type of immunotherapy called adoptive cell transfer Open a glossary item. ATL001 is made in the laboratory using immune cells taken from a sample of your melanoma and your blood. The aim of ATL001 is to help your immune system Open a glossary item recognise more of these changes on the surface of your cancer cells so they can be attacked.

There are 3 treatment groups in this study:

  • ALT001 and a standard dose of interlukin 2 (IL-2)
  • ALT001, nivolumab and a standard dose of IL-2
  • ALT001 and a higher dose of IL-2

Which group you go into depends on when you join the study and on your medical history Open a glossary item. Your doctor will discuss this with you.

Nivolumab is also an immunotherapy. Doctors use nivolumab to treat advanced melanoma and melanoma that has come back after treatment. Nivolumab works by helping the immune system find and attack cancer cells.

The main aims of this study are to find out:

  • how safe it is to give ATL001 by itself and in combination with nivolumab
  • more about the side effects of ATL001 by itself and in combination with nivolumab
  • how well ATL001 works by itself and in combination with nivolumab

Who can enter

The following bullet points are a summary of the main 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. 

Please note, there are 3 treatment groups. Each group has specific entry conditions and we haven’t listed them all.  Your doctor will know what they are.  

The entry conditions below apply to everyone regardless of the treatment group you are in.   

 

Who can take part

You may be able to join this study if all of the following apply. You:

  • have melanoma that has spread to another part of the body or has come back after treatment
  • have disease that has come back or got worse following treatment with the best current drugs available for you. Your doctor will know about this and can tell you more.
  • have areas of melanoma that the doctor can measure on a scan and the surgeon can safely remove by surgery
  • are able to look after yourself but might not be able to do heavy physical work (performance status 0 or 1) and your doctor thinks you are well enough to take part
  • have satisfactory blood test results
  • are willing to use reliable contraception during treatment and for a certain time after treatment. This is if you or your partner could become pregnant.
  • are at least 18 years old
  • have had previous targeted treatment with drugs called PD-1 or PD-L1 inhibitors and BRAF inhibitors (if applicable) unless you weren’t able to tolerate either of them. Your doctor will know this information.

There must also be enough of the melanoma tissue that the surgical team can remove to make the ATL001. Your doctor will know if there is enough. 

Who can’t take part

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

  • have cancer spread in your brain or spinal cord that is causing symptoms or that is growing bigger
  • have melanoma that first started in the eye (uveal melanoma) or a melanoma in the mucosal tissue (mucosal melanoma Open a glossary item). You cannot join if your melanoma is on the hands and feet.
  • have had another cancer in the past 3 years. This is apart from any non-invasive cancers, in-situ carcinoma Open a glossary item, early cancer Open a glossary item, prostate cancer and you have a normal blood level of PSA Open a glossary item and other types of non-melanoma skin cancer Open a glossary item.
  • are not able to have cyclophosphamide, fludarabine or IL-2

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

  • have HIV, hepatitis B, hepatitis C, syphilis or HTLV I/II or you are taking antibiotics for an infection
  • have an autoimmune disease Open a glossary item and you are having treatment that affects how well your immune system Open a glossary item works
  • are taking steroids, apart from a small daily dose. Your doctor will know how much this is.
  • have a major medical problem or condition with your heart Open a glossary item, liver Open a glossary item, kidneys Open a glossary item, digestive system Open a glossary item, bone marrow Open a glossary item, lungs Open a glossary item, brain, nerves or any other part of the body that the study team thinks will affect you taking part
  • have had, or might have had, a side effect of an immunotherapy Open a glossary item that affected your brain or spinal cord
  • have or had moderate to severe diarrhoea or inflammation of the bowels caused by an immunotherapy within 6 months before joining the study
  • have had major surgery within 3 weeks before joining the study
  • have had an organ transplant Open a glossary item
  • have already had an experimental drug that is considered to be a gene or cell therapy Open a glossary item. Your doctor will know if you have had one of these.

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

  • are allergic or sensitive to any of the treatments used in the study or any of their ingredients (this includes penicillin allergies).
  • have had a live vaccine Open a glossary item within the 28 days before starting treatment. You should not have a live vaccine for at least 3 months after fludarabine and cyclophosphamide treatment either. This does not apply to COVID-19 vaccines as these are not live vaccines.
  • are pregnant or breastfeeding

Trial design

This is an international phase 1/2 study. The team need up to 40 worldwide. Everyone who is able to will have ATL001 treatment.

To make ATL001
You have surgery to remove the melanoma tissue. You also give a blood sample at the same time or at a later date if needed. The team use both these samples to make ATL001 in the laboratory. It takes about 3 months to make ATL001. While waiting you may continue to have the standard treatments Open a glossary item for melanoma if your doctor thinks this is best for you. 

You might need to return to give another blood sample if for some reason the first sample couldn’t be used to make ALT001. 

 

Having ATL001
A week before having ATL001 you have fludarabine and cyclophosphamide chemotherapy. You have this once a day for 3 days through a drip into your vein. These treatments are not meant to treat your cancer but are used to lower the number of immune cells in your body. This is to make room for ATL001 when you have it. This helps the ATL001 cells to survive and work correctly. 

On the 3rd day of treatment you may stay in hospital so the nurses can monitor you. This is because the treatment will have weakened your immune system making it more likely for you to get an infection.

About 4 days after finishing chemotherapy you have ATL001 through a drip into your vein. You have 1 day of ATL001 treatment.

Within 3 to 12 hours after ALT001 treatment, you start treatment with Interleukin-2 (IL-2). IL-2 helps immune cell growth and activity so it will help the ATL001 cells to work properly.   

You will need to stay in hospital for up to 2 weeks after receiving ATL001.

There are 3 treatment groups in this study. 

Group A
You have fludarabine and cyclophosphamide a week before ATL001. You then have ATL001 by itself. This is followed by daily injections of the standard, low dose IL-2 for 10 days, just under this skin. This is called a subcutaneous injection.

Group B
You have nivolumab as a drip into a vein 1 to 2 weeks before ATL001. You then have fludarabine and cyclophosphamide. This is followed by ATL001 and the standard, low dose IL-2 injections for 10 days.  

You have nivolumab again 2 weeks after ALT001. You then continue to have nivolumab every 4 weeks for up to a year after having ATL001. This is as long as it is helping and the side effects aren’t too bad. 

Group C
You have fludarabine and cyclophosphamide a week before ATL001. You then have ATL001 by itself. This is followed by 6-doses of a higher dose of IL-2. You have IL 2 as a drip into a vein. This group is not yet recruiting.

Samples for research
You give blood samples during the study. Researchers will use these samples to look for substances in the blood biomarkers Open a glossary item that might show how well the ATL001 is working. 

The team will ask for samples of melanoma tissue biopsy Open a glossary item during the study. They will compare these samples to the samples of tissue taken before your treatment. This is to look for any differences between the 2 tissue samples that might have happened since the ATL001 treatment. 

You don’t have to agree to have these samples taken. Your doctor will tell you more about this when you join the study.
 

Hospital visits

You see the doctor to have some tests before taking part and to see if you can join the study. These include:

  • a physical examination Open a glossary item
  • blood tests
  • have samples of tissue taken
  • heart scan (ECHO) if needed
  • heart trace (ECG
  • MRI scan or CT scan
  • breathing tests (lung function test Open a glossary item) if you are in group C
  • colonoscopy if needed. Your doctor will tell you if need to have this test. 

You see the doctor a few times before you have chemotherapy and before you have nivolumab (if applicable). This is to see how you are, to check you can still join the study and for blood tests. At some of these hospital visits they repeat a few of the tests above and do other tests. They’ll tell you which tests you need to have done again and about any new tests. 

You have the first couple of chemotherapy treatments on the day care or outpatient ward. On the last day of chemotherapy, you may be admitted into hospital. You then have ATL001 and will stay in hospital for up to 2 weeks. 

After leaving hospital you see the doctor at:

  • 2 weeks after having ATL001
  • 3 weeks 
  • 4 weeks
  • 6 weeks 
  • every 6 weeks until 6 months 
  • every 3 months up to about 2 years

This is for blood tests and to see how you are. You may have extra tests at some of the visits. Your doctor will tell you more about these.  

You have a scan:

  • every 6 weeks for 24 weeks
  • then every 12 weeks

If a scan shows your cancer might have got worse or spread you have another scan 4 weeks later. If this scan confirms your cancer has got worse or spread you have no more scans for the study. 

Side effects

You stay in hospital for up to 2 weeks. This is so the team can monitor you for any side effects that you might have. You might have to stay in the hospital longer if your side effects are quite bad. 

After leaving hospital contact the hospital advice line or tell your doctor or nurse if any side effects are:

  • getting worse
  • not getting better 
  • if you notice any new side effects.
ATL001 and nivolumab can affect the immune system Open a glossary item. They may cause inflammation Open a glossary item in different parts of the body. This can cause serious side effects. These could happen during treatment, or some 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.

 

ATL001 is a new treatment and there might be side effects that we don’t know about. While you are having ATL001, your nurse will watch you closely to check for signs of an allergic reaction. If there are signs they will slow down the drip. Or they might stop it for awhile. Side effects of ATL001 can include: 

  • an allergic reaction. Symptoms can include fever, chill or headache. You have antihistamines Open a glossary item and paracetamol before having ATL001 to try to prevent this. 
  • cytokine release syndrome (CRS). Symptoms can include fever, chills, a headache, difficulty breathing, and dizziness.
  • immune cell associated neurotoxicity syndrome (ICANS). Symptoms can include confusion, drowsiness, restlessness, difficulty processing information, difficulty naming things and writing, hallucinations and seizures. Severe cases can cause swelling of the brain. These symptoms usually last between 2 to 10 days. But for some people it may last weeks. 

We have information about:

Your doctor will talk to you about the possible side effects of all the treatments used in this study before you agree to take part.

Location

Cambridge
London
Manchester
Newcastle upon Tyne
Southampton

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Samra Turajlic

Supported by

Achilles Therapeutics

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

17801

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Last reviewed:

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