A trial of Dato-DXd with durvalumab and carboplatin for non small cell lung cancer (AVANZAR)

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

Status:

Closed

Phase:

Phase 3

This trial is comparing the combination of Dato-DXd, durvalumab and carboplatin with the combination of pembrolizumab and chemotherapy.

It is open to people with advanced non small cell lung cancer (NSCLC) who have not had treatment for their advanced cancer Open a glossary item .

More about this trial

Doctors can treat advanced NSCLC that has spread with:

pembrolizumab, paclitaxel and carboplatin
pembrolizumab, pemetrexed and either carboplatin or cisplatin

They can also teat advanced NSCLC with durvalumab after having had chemoradiotherapy Open a glossary item .

Paclitaxel, carboplatin, pemetrexed and cisplatin are chemotherapy Open a glossary item drugs. They kill cancer cells by stopping them from dividing and growing.

Pembrolizumab is an immunotherapy drug. It works by helping the immune system to find, recognise and kill cancer cells.

Durvalumab is another type of immunotherapy drug. It also works by helping the immune system to find, recognise and kill cancer cells.

Datopotamab deruxtecan (Dato-DXd) is a type of drug called an antibody drug conjugate. It has two parts, they are:

Datopotamab a monoclonal antibody drug
deruxtecan a chemotherapy drug

Datopotamab finds a protein called TROP2 on the cancer cell. It attaches itself to the protein. It then releases the deruxtecan into the cancer cell damaging or killing the cell. This stops the cancer from growing.

Researchers think that the combination of Dato-DXd, durvalumab and carboplatin could be better than the pembrolizumab and chemotherapy.

The aims of this trial are to find out:

how well the combination of Dato-DXd, durvalumab and carboplatin works for people with advanced NSCLC
more about the side effects of this combination
how the combination affects quality of life

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) and cannot be removed by surgery or treated with chemoradiotherapy. Or you have NSCLC that has spread to another part of the body (stage 4).
There is a tissue sample (biopsy ) of your cancer that the team can access.
You 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.
You have at least 1 area of cancer that the doctor can measure on a scan and is a certain size or bigger. Your doctor will know what size this is.
You have adequate blood test results.
You are able to look after yourself but might not be able to do heavy physical work (performance status 0 or 1).
You are willing to use contraception during treatment and for a certain time after if there is any chance you or your partner could become pregnant.
You 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 already had treatment for your advanced NSCLC
have cancer spread to your brain or you have spinal cord compression. This is unless there are no symptoms, it is stable and you have not had steroids for 7 days before starting treatment.
have or had cancer spread to the tissues surrounding the brain
have NSCLC that has certain gene changes (mutations ) in the cancer cells. Or there is no record of certain gene changes in your medical notes. Your doctor will know about this.
have cancer that is a mix of small cell lung cancer and NSCLC. Or you have a type of NSCLC called sarcomatoid carcinoma.
have ongoing side effects from previous treatments. This is apart from certain ones which your doctor will know about.
have already had durvalumab and certain targeted treatments . If you had immunotherapy you must not have stopped treatment due to the side effects. And you have recovered from the side effects apart from certain ones. Your doctor will know about these.
are having or taking any other cancer treatment
have radiotherapy to relieve symptoms (palliative radiotherapy) within 2 weeks or 4 weeks of starting treatment. Your doctor will know more about this.
have already been in a clinical trial using durvalumab or Dato-DXd. This is regardless of whether you had these drugs or not.
are in a clinical trial using an experimental treatment or device within 4 weeks of being put into one of this trial’s treatment groups (randomisation )

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

have a disease or problem with the tissue covering the eyeball (cornea) that could affect you taking part
have or had an autoimmune disease apart from certain ones. Your doctor will know which autoimmune diseases these are.
have HIV that isn’t well controlled, active or uncontrolled hepatitis B, hepatitis C or active tuberculosis (TB). Or you have any other active infection that needs treatment.
have heart problems that could affect you taking part
have high blood pressure that isn’t controlled
have lung problems such as inflammation that is not caused by an infection. Or you have any other lung problems that could affect you taking part.
have major surgery within 3 weeks of starting trial treatment
have any other medical condition, mental health problem or social situation that could affect you taking part

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

are allergic or sensitive to any of the treatments or any of their ingredients
have a live vaccine within 30 days of starting treatment. The COVID-19 vaccines and some seasonal flu vaccines are not live vaccines.
are pregnant or breastfeeding

Trial design

This is an international phase 3 trial. The team need about 1,000 people to take part worldwide with 50 people from the UK.

It is a randomised trial. A computer puts you into 1 of 2 treatment groups. Neither you nor your doctor chooses which group you are in. The 2 groups are:

Dato-DXd, durvalumab and carboplatin
pembrolizumab and chemotherapy

Diagram 1

Dato-DXd, durvalumab and carboplatin
You have Dato-DXd, durvalumab and carboplatin as a drip into a vein. You have all 3 drugs on the same day once every 3 weeks. Each 3 week period is a cycle of treatment Open a glossary item .

You have all 3 drugs for 4 cycles of treatment. You then continue to have Dato-DXd and durvalumab as above. This is as long as it is helping and the side effects aren’t too bad.

Dato-DXd can cause side effects to your mouth. To prevent this your doctor will give you instructions and a kit for you to look after your mouth. You must follow the instructions and use the kit before starting and during treatment.

Pembrolizumab and chemotherapy
You have pembrolizumab and chemotherapy as a drip into a vein.

Which chemotherapy you have depends on whether you have non squamous NSCLC or squamous NSCLC.

For non squamous NSCLC you have pemetrexed and carboplatin or cisplatin.

For squamous NSCLC you have paclitaxel and carboplatin.

You have pembrolizumab and chemotherapy once a week every 3 weeks for 4 cycles of treatment.

After this you can continue to have pembrolizumab for up to 35 cycles (about 2 years) as long as it is helping and the side effects aren’t too bad.

People with non squamous NSCLC who have pemetrexed can continue to have it for up to 35 cycles (about 2 years) as long as it is helping and the side effects aren’t too bad.

Samples for research
You give blood samples and tissue samples (biopsies Open a glossary item ) as part of the trial. Wherever possible the team take these samples when you have bloods and tissue samples taken as part of your routine care.

Researchers will use these samples to:

look for substances (biomarkers ) that might tell them how well treatment is working and why treatment stops working for some people
find out what happens to the treatment in the body

You must agree to have some of these samples taken. Some you don’t have to agree to. Your doctor will tell you which these are. They will also tell you how often they take the samples.

Quality of life
You fill in questionnaires before starting treatment then:

during treatment
when you finish treatment
after treatment

The questions ask about:

your general health and wellbeing
what daily activities you can do
symptoms and side effects

These are quality of life questionnaires.

Symptoms diary
You have a diary to record any side effects of the mouth and throat you might have. A member of the team will go through the diary and explain it to you.

Hospital visits

You see the doctor to have tests before taking part. These include:

a physical examination
blood tests
urine test
heart trace (ECG)
a test to see how much oxygen is in the blood (Pulse oximeter)
eye test
a scan. This might be a CT scan, an MRI scan, a PET scan or a PET-CT scan. You might have one or more of these. Your doctor will tell you which scan or scans you are having.

You see the doctor regularly during treatment. This is to:

see how you are
have blood tests
ask if you have any side effects

You have scans during your treatment and after treatment. Your doctor will tell you about the scans and when you have them.

You see the doctor when you finish treatment then:

a month later
then every 3 months until your cancer starts to get worse

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.

Durvalumab 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.

The most common side effects of Dato-DXd are:

feeling and being sick
sore inflamed mouth
hair loss
feeling tired (fatigue)
loss of appetite
diarrhoea
inflammation of the digestive system
skin rash
dry eyes
a drop in the number of red blood cells causing tiredness and shortness of breath
reaction while having the Dato-DXd drip such as swelling, hives, skin rash, rapid heartbeat, difficulty breathing, tightening of the throat, drop in blood pressure and brief loss of consciousness