A trial looking at rilvegostomig and datopotamab deruxtecan for non small cell lung cancer that has spread (TROPION-Lung10)

Cancer type:

Lung cancer

Non small cell lung cancer

Secondary cancers

Status:

Open

Phase:

Phase 3

This trial is looking at rilvegostomig on its own or with datopotamab deruxtecan for non small cell lung cancer. It is comparing this to standard treatment Open a glossary item .

The trial is for people whose cancer has spread into surrounding tissues or to distant parts of the body. This is locally advanced Open a glossary item or metastatic cancer.

You pronounce rilvegostomig as ril–veh–gost-oh-mig.

You pronounce datopotamab deruxtecan as day-toe-pot-oh-mab deh-rux-tee-can. It is also called Dato-DXd for short.

More about this trial

Pembrolizumab is a standard treatment Open a glossary item for non small cell lung cancer (NSCLC) that has spread. It is a type of immunotherapy . It targets and blocks a certain protein. Blocking this protein triggers the immune system to find and kill cancer cells. Sometimes pembrolizumab stops working so researchers are looking at ways to improve treatment.

In this trial they are looking at datopotamab deruxtecan and rilvegostomig.

Datopotamab deruxtecan is a new type of drug called an antibody drug conjugate Open a glossary item . It is datopotamab with a chemotherapy drug attached to it. Deruxtecan is the chemotherapy drug. Datopotamab finds a protein called TROP2 on the cancer cell. It attaches itself to it. Datopotamab deruxtecan then releases the deruxtecan into the cancer cell damaging or killing the cell.

Rilvegostomig is a new type of immunotherapy. It works in a similar way to pembrolizumab. Rilvegostomig also blocks another protein called TIGIT. By blocking TIGIT, rilvegostomig could help the immune system recognise cancer cells and stop the cancer growing.

Researchers think that rilvegostomig on its own or with Dato-DXd could work better than standard treatment. But they aren’t sure so want to find out more. In this trial you have one of the following:

pembrolizumab
rilvegostomig on its own
Dato-DXd and rilvegostomig

The main aims of the trial are to find out:

which treatment works best
what the side effects are
how treatment affects quality of life
what happens to rilvegostomig and Dato-DXd in the body

Who can enter

The following bullet points are a summary of the 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 non small cell lung cancer (NSCLC) that has spread into the nearby tissue (stage 3B or 3C lung cancer) and cannot be treated with surgery or chemoradiotherapy . Or you have NSCLC that has spread to another part of the body (stage 4 lung cancer).
have NSCLC that has a certain amount of the protein PD-L1. And the doctors know whether your cancer has a certain biomarker called TROP2.
have an area of lung cancer that the trial team can see on a scan that measures at least 10mm across
have a sample of tissue (biopsy ) available that the trial team can use to test for certain proteins or you are willing to have a new sample taken
are fit and active but might not be able to do heavy physical work (performance status of 0 or 1)
have satisfactory blood test results
are willing to use reliable contraception during the trial and for a time after if there is any chance you or your partner could become pregnant
weigh at least 30kg. This is 4 stone 10lb.
are at least 18 years old

Who can’t take part

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

have one of the following types of lung cancer: squamous cell lung cancer, a mix of small cell and non small cell lung cancer, sarcomatoid lung cancer, a less common type of lung cancer or your cancer is made up mostly of squamous cells. Your doctor will know this.
have cancer that has spread to the brain or spinal cord or the thin tissue layers that cover them. You can take part if you had treatment, the cancer is stable and you stopped taking steroids.
have NSCLC that has certain gene changes (mutations ) in the cancer cells. Your doctor will know about this.
have already had treatment to the whole body (systemic treatment ) for locally advanced or advanced cancer. You might be able to take part if you had chemotherapy that included a platinum drug , radiotherapy or chemoradiotherapy for early lung cancer and the cancer got worse at least 12 months after the last dose of treatment.
have had pembrolizumab, rilvegostomig, Dato-DXD or similar drugs in the past or you have had a cancer vaccine
are having another cancer treatment
have side effects from past treatments unless they are mild. You can take part if you have hair loss. You also might be able to take part if you have moderate long term side effects from treatment as long as they are stable. Your doctor asks about this.
have spinal cord compression
have already been put into a treatment group as part of this trial even if you didn’t have treatment
have had treatment that damps down the immune system . This includes steroids within 2 weeks of starting trial treatment unless it was a low dose.
have had recent radiotherapy to a small area to help with symptoms or you have had radiotherapy in the last month to a large area or to more than 30% of the bone marrow . Your doctor checks if and when you had this.
have taken an experimental drug or used a device as part of another clinical trial in the last 12 months, unless the treatment has already been cleared from your body. Your doctor will know this.
have had another cancer in the last 3 years unless it has been successfully treated with the aim to cure and it has a low chance of coming back. You can join if you have had non melanoma skin cancer that has been removed.

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

have had a heart attack or serious chest pain in the last 6 months or a significant heart problem that needs treatment. The team check if you have a heart condition before you join the trial.
have high blood pressure that is not controlled
have active inflammation of the lungs (pneumonitis ) that needs treatment or another serious lung condition
have an active bleeding problem and the trial doctor thinks this could affect you taking part
have serious or ongoing digestive problems causing diarrhoea and the trial doctor thinks this could affect you taking part
have had an organ transplant and the trial doctor thinks this could affect you taking part
have a hepatitis B or hepatitis C infection unless you have had or are having treatment and it is under control. You have tuberculosis or you have another active infection that needs treatment to the whole body.
have HIV unless you are having treatment and it is under control
have a serious problem with the clear covering (cornea) in your eye
have an autoimmune condition that needs treatment apart from certain ones. Your doctor will know about this.
have a problem with how your immune system works
have had major surgery or an injury that happened suddenly and needed medical attention such as a fall in the 3 weeks before starting treatment. Or you might need to have major surgery during the trial.
have had a blood clot in a vein the last 3 months
have a collection of fluid in an area of the body where it should not be such as in the lung that the doctor can’t drain
have had a treatment called chloroquine or hydroxychloroquine within 14 days of being put into a treatment group. Your doctor will know this.
have another medical condition, mental health problem or there is any other reason that could affect you taking part in the trial

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

have had a live vaccine within 30 days of starting treatment. Please note that the approved COVID-19 vaccines are allowed as they aren’t live. You can’t have the COVID-19 vaccination within 72 hours of having the first dose of rilvegostomig and pembrolizumab.
are allergic to Dato-DXd, rilvegostomig, pembrolizumab, similar drugs or anything they contain
are pregnant, breastfeeding or planning a pregnancy

Trial design

This phase 3 trial is taking place worldwide. The team need 675 people to take part. This includes 21 from the UK.

It is a randomised trial. You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in. There are 3 treatment groups.

You have one of the following:

pembrolizumab
rilvegostomig
Dato-DXd and rilvegostomig

19891-randomisation.png

Out of every 5 people who join:

2 go into the pembrolizumab group
1 goes into the rilvegostomig group
2 go into the Dato-DXd and rilvegostomig group

You have treatment for as long as it is working and the side effects aren’t too bad. You stop trial treatment if your cancer gets worse. Your doctor will then talk to you about other treatment options.

How you have treatment
You have all your treatment as a drip into a vein. Depending on the group you are in you have:

pembrolizumab once every 3 weeks to begin with. You might then have this once every 6 weeks later on in the trial.
rilvegostomig on its own once every 3 weeks
Dato-DXd and rilvegostomig once every 3 weeks

Samples for research
The researchers ask to take 2 extra samples of tissue. They also ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests.

They plan to use the samples to:

see what happens to Dato-DXd and rilvegostomig in the body
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
look at genes to understand more about NSCLC

You can say no to having the tissue samples taken. You can also say no to the samples that look at the genes. It won’t affect you taking part in the rest of the trial.

The team will ask to store away any remaining samples for future research. You don’t have to agree to your samples being stored. You can still take part in the trial.

Quality of life
The team will ask you to use an electronic application during the trial. This is called the TrialMax app. The team give you a small electronic handheld device that has the app on it. You can also download this on your phone. You use it to record side effects, symptoms and how you are feeling. This information helps researchers to see how treatment affects your quality of life.

You do this at set times:

before you start treatment
during the trial and
after treatment finishes

The trial doctor will tell you more about this.

Symptoms diary
You record any side effects of the mouth and throat you might have on the TrialMax app. This is because some of the treatments can cause side effects in the mouth and throat. A member of the team will go through this and explain it to you. The app will provide some guidance to help based on your reported symptoms.

Hospital visits

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

blood tests
urine tests
a physical examination
heart trace (ECG )
heart scan (echocardiogram ) or MUGA scan
eye test
breathing tests to check how your lungs are working
CT scan or MRI scan

You might also need to have a bone scan or a PET-CT scan.

You have all your treatment at the hospital in the outpatient department. The team will give you an idea of how long each hospital visit will take. You might have some overnight stays. The team will let you know if this applies to you.

During treatment you see the doctor regularly. This is for blood tests and to see how you are.

Trial scans
You have a CT or MRI scan:

every 6 weeks in the first 3 months
every 9 weeks for a year and then every
3 months after that

You stop having the trial scans if your cancer gets worse. Your doctor will then talk to you about other treatment options.

Follow up
When you finish treatment you see the doctor 1 month later for a check up.

The team then see how you are every 3 months when you finish treatment. You might see them at a routine hospital appointment or they may call you to see how you are getting on.

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.

Rilvegostomig and pembrolizumab 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.

Dato-DXd and rilvegostomig are new drugs so we don’t know what all the side effects are.

Only a few people have had rilvegostomig. The possible side effects we know about so far include:

inflammation in different parts of the body. The team will explain what to look out for.
a severe reaction during or shortly after the infusion. You might get a rash, shortness of breath, redness or swelling of the face and dizziness. Tell your healthcare team straight away if this happens.
changes to the levels of chemicals in your blood due to the breakdown of tumour cells. This is tumour lysis syndrome. You have regular blood tests to check for this.
cytokine release syndrome. Symptoms include fever, headache, rash, low blood pressure, low blood oxygen levels, rapid heart rate, and shortness of breath. These are usually mild to moderate but can sometimes be life threatening.
skin rash or other skin problems
developing anti-drug antibodies to rilvegostomig. This can cause aching joints, rash, high temperatures, kidney problems or inflammation in blood vessels.

The most common side effects of Dato-DXd we know about include:

feeling or being sick
sore mouth
hair loss
tiredness (fatigue)
an allergic reaction to Dato-DXd. Symptoms could include swelling, skin rash, a fast heartbeat, difficulty breathing, a tight feeling in the throat or low blood pressure.
loss of appetite
diarrhoea
inflammation of the lining of the digestive system
skin rash
a drop in the number of red blood cells (anaemia )
dry eyes

There is a chance that the side effects of treatment could be worse if you have both Dato-DXd and rilvegostomig. The side effects of these drugs that overlap include: