A study looking at neo-antigen T cell therapy for non small cell lung cancer (CHIRON)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Lung cancer

Non small cell lung cancer (NSCLC)

Secondary cancers

Status:

Closed

Phase:

Phase 1/2

This study is looking at a type of immunotherapy Open a glossary item called ATL001 for non small cell lung cancer (NSCLC).

It is open to people with non small cell lung cancer that has either:

spread into the nearby tissue (locally advanced) and cannot be removed by surgery
spread to another part of the body (metastatic)

More about this trial

We know from research that cancer cells have changes (mutations Open a glossary item ) in the genes of their DNA 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 these surface 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 non small cell lung cancer (NSCLC) and your blood. The aim of ATL001 is to help your immune system recognise more of these changes on the surface of the cancer cells so they can be attacked.

There are 2 treatment groups in this study. Group A has ATL001 treatment by itself. Group B has ATL001 treatment combined with pembrolizumab treatment.

Pembrolizumab is also an immunotherapy Open a glossary item . Doctors use pembrolizumab to treat NSCLC. Pembrolizumab 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 pembrolizumab
more about the side effects of ATL001 by itself and in combination with pembrolizumab
how well ATL001 works by itself and in combination with pembrolizumab

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.

There are 2 treatment groups in this study. There are certain entry conditions for each group and reasons why you might not be able to join one of the groups. We haven’t listed them all. Your doctor will know what they are.

The entry conditions below apply to everyone.

Who can take part

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

have non small cell cancer (NSCLC) that your doctor thinks is caused by smoking
have NSCLC that is locally advanced (stage 3) that cannot be fully removed by surgery or your cancer has spread to another part of the body (stage 4)
have NSCLC that has got worse or come back after having the best available drug treatment for you
have an area of cancer that the doctor can measure
are able to have fludarabine, cyclophosphamide and IL-2
have satisfactory blood test results
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
are willing to use contraception during treatment and for a time after treatment. This is if you or your partner could become pregnant.
are at least 18 years old
have had previous targeted drugs treatment called PD-1 or PD-L1 inhibitor and a BRAF, unless you weren’t able to tolerate either of them. Your doctor will know this information.

There must also be enough of the lung cancer tissue that the surgical team can take a sample from 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 you symptoms or it is getting larger
are considered not to have smoked. That means that you have smoked less than 100 cigarettes in your life. Your doctor will talk to you about this.
have certain types of gene changes (mutations ) that caused your cancer or caused it to spread. Your doctor will know if you have one or more of these.
had standard treatment and the first scan after you started treatment showed that your cancer was getting worse. Your doctor will be able to tell you this.
have had another cancer in the past 3 years. This is apart from any cancers that have not spread from the tissue where it started (non invasive cancer), non melanoma skin cancer and early cancer of the prostate where you have a normal blood level of PSA .
are not able to have cyclophosphamide, fludarabine or IL-2

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

have hepatitis B, hepatitis C, syphilis, HIV or an active infection that needs treatment
have an autoimmune disease and you take medication that affects how well your immune system works
are taking steroids, apart from a small daily dose. Your doctor will know how much this is.
have a significant medical problem or condition with your heart , liver , kidneys , digestive system , bone marrow , lungs , brain, nerves, or any other part of the body, that the study team think will affect you taking part
have or had symptoms of a problem with the blood flow from your upper body to the heart (superior vena cava syndrome )
have had major surgery within the past 3 weeks
have had an organ transplant
have had treatment that is considered to be a gene therapy or cell therapy. Your doctor will know if you have had one of these.
have, had, or might have had a side effect that was caused by or thought to be caused by an immunotherapy that affected your brain or spinal cord
have or had moderate to severe diarrhoea or inflammation of the colon (colitis) caused by an immunotherapy within 6 months of being considered for this study

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

are allergic or sensitive to any of the treatments used in this study. This includes a penicillin allergy or sensitivity.
have a live vaccine within 28 days before starting fludarabine and cyclophosphamide study treatment. You should not have a live vaccine for at least 3 months after having fludarabine and cyclophosphamide study treatment. This does not apply to the COVID-19 vaccines as these aren’t live vaccines.
are pregnant or breastfeeding.

Trial design

This is an international phase 1/2 study. The team needs up to 50 people worldwide to join.

Everyone who is able to will have ATL001. Some people will also have pembrolizumab. Your doctor will tell you if you are having pembrolizumab.

To make ATL001
You have surgery to remove a sample of the NSCLC 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 NSCLC 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.

CHIRON trial flow chart of treatment

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 Open a glossary item 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 stay in hospital so the nurses can monitor you. This is because the treatment will have weakened your immune system Open a glossary item 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 injections of low dose Interleukin 2 (IL-2). You have it once a day for 10 days. You have IL-2 as an injection just under the skin This is called a subcutaneous injection. IL-2 helps immune cells to grow and how they work. This will help the ATL001 cells to work properly.

You stay in hospital for up to 2 weeks.

People having pembrolizumab
As well as having ATL001, some people also have pembrolizumab. You have pembrolizumab as a drip into a vein. You have pembrolizumab:

once a week for 2 weeks before having ATL001
at 2 weeks after having the ATL001
then every 6 weeks

You have pembrolizumab for up to a year as long as it is helping and the side effects aren’t too bad.

Samples for research
You give blood samples during the study. Where possible the team take these when you have your routine blood tests.

Researchers use these samples to look for substances in the blood (biomarkers Open a glossary item ) that might show how well the treatment is working.

The team ask for samples of tissue (biopsies) during the study. Your doctor will tell you more about this and when they will take the samples. You don’t have to agree to have these tissue samples taken.

Hospital visits

You see the doctor for tests before taking part in the study. These tests include:

a physical examination
blood tests
tissue sample collections
breathing tests (lung function tests ) if needed
heart scan if needed (ECHO)
MRI scan or CT scan
colonoscopy if needed. Your doctor will tell you if need to have this test.

You see the doctor a few times before you have fludarabine and cyclophosphamide. If you are having pembrolizumab you see the doctor a few times before having it. This is to see how you are, to check you are still able to take part in the study and for blood tests. At some of these hospital visits, they repeat some of the tests you had before and do other tests. They’ll tell you which tests you need to have done.

You have the first 2 days of treatment on the day care ward or outpatient ward. On the 3rd day you go into hospital where you have the rest of your treatment before having ATL001. You then have ATL001. You 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
then every 6 weeks to 6 months
then every 3 months up to about 2 years after you had ATL001

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

You have a CT scan or MRI scan after having ATL001:

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 pembrolizumab 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 a while. Side effects of ATL001 can include:

an allergic reaction. Symptoms can include fever, chill or headache. You have antihistamines 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.