A trial of ADP-A2M4 for certain types of soft tissue sarcoma (SPEARHEAD 1 STUDY)

Cancer type:

Sarcoma

Secondary cancers

Soft tissue sarcoma

Status:

Open

Phase:

Phase 2

This trial is looking at changing immune cells to recognize and attack sarcoma cells. The changed immune cells are called afamitresgene autoleucel SPEAR T-cells.

It includes people who have synovial sarcoma. And who can’t have surgery to remove the cancer or it has spread elsewhere in the body.

More about this trial

Doctors are looking for new ways to treat sarcoma. In this trial they are looking at afamitresgene autoleucel SPEAR T-cells. T cells are a type of white blood cell. They are part of your immune system Open a glossary item . They are very good at fighting infection but not so good at recognising and attacking cancer cells.

Afamitresgene autoleucel SPEAR T-cell treatment is a type of immunotherapy.

In this trial, doctors use your own T cells to make afamitresgene autoleucel. The T cells are changed (modified) in the laboratory by adding a gene. This helps the T cells recognise cancer cells that make the MAGE-A4 protein.

Once this is done you will have the changed T cells put back through a drip into your vein. This helps the T cells to recognise and attack sarcoma cells.

The main aims of this trial are to:

find out more about this type of treatment
find out how well it works
learn more about the side effects

Who can enter

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

Who can take part

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

have synovial sarcoma
can’t have surgery to remove the sarcoma or it has spread elsewhere in the body
have sarcoma with an HLA type that could work with the changed T cells (you are HLA-A2 positive). The trial team check this.
have sarcoma that has MAGE-A4 proteins on the surface of its cells. The trial team check this.
have had a type of chemotherapy drug called an anthracycline or a chemotherapy drug called ifosphamide. You might be able to join if you couldn’t have these types of chemotherapy due to side effects but you have had another type of chemotherapy.
have sarcoma that your doctor can measure on a scan
are able to have your T cells collected
are fit and active but might not be able to do heavy physical work (performance status 0 or 1)
have satisfactory blood test results
are willing to use reliable contraception during treatment and for a period of time after if there is any possibility that you or your partner could become pregnant
are at least 16 years old and less than 75 years old

Who can’t take part

You can’t join the trial if any of the following apply.

Cancer related
You:

have sarcoma that has certain other HLA proteins on its surface. The trial team check this.
have cancer that has spread to the brain or spinal cord
have side effects from past treatments that aren’t getting better unless they are mild. This is apart from hair loss, white patches on the skin or moderate numbness and tingling in the hands or feet (peripheral neuropathy )
have had another cancer that has got worse or needs treatment. This is apart from non melanoma skin cancer or other cancers that have been successfully treated with surgery and there have been no signs of cancer.

Medical conditions
You can’t join the trial if any of the following apply. You:

have or have had an autoimmune disease that needs treatment apart from certain ones. Your doctor will know this.
have had a heart attack, stroke or blood clot in the last 6 months or a significant heart problem that needs treatment. The trial team check if you have a heart problem before you join the trial.
have HIV, an active hepatitis B or hepatitis C infection or any severe infection that needs treatment
have high blood pressure that isn’t controlled with medication
have scarring on the lungs or active inflammation of the lungs (pneumonitis ) unless this was caused by radiotherapy
get very short of breath and need extra oxygen to help you breathe
have a blockage in your lungs, kidneys or large veins in the body and you can’t have a stent put in to fix it
have COVID-19 or a positive COVID-19 PCR test within 28 days of having the T cells collected or put back

Other
You can’t join the trial if any of the following apply. You:

are allergic to fludarabine, cyclophosphamide, other drugs used in the study or any ingredients that they contain
are pregnant or breastfeeding

Trial design

This phase 2 trial is taking place worldwide. The team need 120 people to take part including 6 from the UK.

There are 4 steps in this trial:

testing for biomarkers. This is to check you are suitable to join.
collecting your blood cells (leukapheresis)
a short course of chemotherapy
having the changed T cells back

Testing for biomarkers (pre screening tests)
The team ask you to give a blood sample. They test for certain HLA biomarkers Open a glossary item on your sarcoma cells. If these are present (you are HLA positive) your doctor looks at a sample of your cancer they took when you had a biopsy .

You might need to give a new sample if there isn't a suitable one available. Doctors use this sample to look for MAGE-A4 proteins on the surface of the sarcoma cells. It can take between 4 to 6 weeks for the results.

Some people do a pre screening test at home. To do this you swab the inside of your mouth for cells. The team give you a kit and instructions on what to do. You post the sample back. The team then analyse the sample. If you are HLA positive you then give the blood sample and have a tissue sample tested.

Please note, you can’t take part in the trial if you don’t have the HLA biomarkers or the MAGE-A4 proteins on your sarcoma cells. Your doctor will talk to you about other treatment options.

There are some other additional tests you will have done. We have information about these in the hospital visit section below.

Collecting your T cells
Leukapheresis is a procedure to collect white blood cells from your bloodstream. If you are having treatment for cancer, you may need to stop treatments for a certain amount of time before leukapheresis. Your doctor will let you know if you may restart these treatments after apheresis and before trial treatment.

You lie on a bed or reclining chair and have a tube into a vein in your arm. One tube removes blood and passes it into a machine that removes white blood cells. The rest of your blood goes back into your body through a central line Open a glossary item .

The researchers will then use gene therapy to change (modify) these cells in a laboratory. This is to make them able to recognise and attack sarcoma cells. It takes about 45 days to change and grow the T cells in the laboratory.

It isn’t always possible to grow enough cells. Your doctor will talk to you about this and about what other treatments might be available if this happens.

A short course of chemotherapy
A week before you have afamitresgene autoleucel SPEAR T-cell treatment, you have chemotherapy. This helps the changed T cells to survive and grow inside the body. Before this chemotherapy you will need to stop any current cancer treatments you are having for a certain period of time. This is for 1 week and up to 2 months depending on the treatment you had.

In the trial you have 2 drugs called:

You have them as a drip into a vein. You have this once a day for the first 4 days in hospital. You have both drugs for 3 days and then fludarabine only on day 4. Chemotherapy takes about 3 hours each time.

You might stay in hospital to have the chemotherapy or you may have it in the hospital outpatient department. Your doctor will tell you more about this.

Having the T cells back
You have the changed T cells back as a drip into a vein. It takes about 45 minutes. You need to stay in hospital after having the T cells. This is so doctors can monitor you for any side effects. They tell you how many days you need to stay in hospital. You might be able to go home after 10 days if you are well enough.

Follow up
After having the Tcells you see the trial team for regular check ups every week to begin with and then once a month. From 6 months onwards you see the trial team every 2 months.

Each visit takes 2 to 3 hours and may include blood tests.

Flow Chart 1

Samples for research
The researchers might ask you to give 3 extra tissue samples.

They plan to use the samples to:

see how well the treatment is working
look for substances called biomarkers to help work out why treatment might work for some people and not for others

Quality of life and health questionnaires
The trial team ask you to fill out some questionnaires:

before you start treatment
at set times during treatment

The questionnaires ask about side effects and how you’ve been feeling. This is called a quality of life study. They also ask about any other problems you have such as difficulties with moving around (mobility) or pain.

Hospital visits

You see the doctor and have tests before you can take part. These include:

blood tests
a physical examination
heart trace (ECG )
heart scan (echocardiogram or MUGA )
CT scan or MRI scan

After having your T cells collected the trial team tell you when you need to go back to hospital to have your chemotherapy.

You need to stay in hospital after having the T cells back. This is so doctors can check for any side effects. They tell you how many days you need to stay in hospital.

You then see the trial team for regular check ups every week to begin with and then once a month. From 6 months onwards you see the trial team every 2 months.

These visits stop if your cancer gets worse. Your doctor will talk to you about other treatment options.

You may continue in the study for long term follow up where you have a check up:

every 6 months for up to 5 years and then
once a year for up to 15 years

Side effects

The trial 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.

SPEAR T-cell treatment affects the immune system. This can cause serious side effects. They could happen during treatment, or after treatment has finished. In some cases, these side effects could be life threatening.

If you have any side effects tell your doctor or nurse as soon as possible.

Only a few people have had afamitresgene autoleucel SPEAR T-cells so there might be side effects we don’t know about yet. These are the side effects we know about so far.

The most common side effects of afamitresgene autoleucel are:

cytokine release syndrome (CRS). Afamitresgene autoleucel can cause the release of chemicals called cytokines. The side effects of the release of cytokines can be mild or severe. You may have flu-like symptoms such as fever, feeling sick, headache, confusion, rapid heartbeat, shortness of breath, and rash.
high temperature
skin rash
confusion or problems with speaking or writing
tiredness (fatigue)
loss of appetite
low levels of neutrophils (neutropenia ) and a fever
shortness of breath
headache
a drop in blood cells causing an increased risk of infection, bruising and bleeding or breathlessness
low blood pressure
feeling or being sick
chills
fast heartbeat
diarrhoea
low levels of phosphorus in the blood