A trial of datopotamab deruxtecan with or without durvalumab for triple negative breast cancer (TROPION-Breast03)

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

Cancer type:

Breast cancer

Status:

Closed

Phase:

Phase 3

This trial is comparing datopotamab deruxtecan with and without durvalumab to chemotherapy and immunotherapy. It is for triple negative breast cancer. It is open to people with stage 1-3 triple negative breast cancer that:

have had treatment to their cancer before surgery (neoadjuvant treatment) and
the cancer has not completely gone at the time of surgery (residual invasive disease)

More about this trial

Triple negative breast cancers are cancers whose cells don’t have receptors for:

the hormones oestrogen and progesterone
a protein called Her2

The main treatments for triple negative breast cancer are surgery, chemotherapy Open a glossary item and radiotherapy. Some people have an immunotherapy drug called pembrolizumab. You might have more than one type of treatment to give the best chance of them working well.

Researchers would like to improve the treatment options available for people with triple negative breast cancer. Researchers think datopotamab deruxtecan, on its own, or with another cancer drug called durvalumab might be a good treatment option. This trial aims to find this out.

Datopotamab deruxtecan (Dato-DXd) is a type of drug called an antibody drug conjugate. 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. This stops the cancer from growing.

Durvalumab is a type of immunotherapy Open a glossary item . It stimulates the body's immune system to fight cancer cells.

In this trial one group of people have datopotamab deruxtecan. This might be with or without durvalumab. And one group have the treatment their doctor think would be best for them. The possible treatments are:

capecitabine chemotherapy
pembrolizumab immunotherapy
both capecitabine and pembrolizumab

The aims of the trial are to find out:

if datopotamab deruxtecan with or without duravlumab is better than your doctor’s choice of chemotherapy, immunotherapy or both
more about how datopotamab deruxtecan works
more about the side effects of datopotamab deruxtecan
how datopotamab deruxtecan 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 triple negative breast cancer
have cancer cells that have grown through the lining of the ducts into the surrounding breast tissue (invasive cancer)
still have cancer cells after you have had treatment to try and shrink your cancer before surgery (neo adjuvant treatment). This will be seen when you have surgery. The cells are either in your breast or one or more lymph nodes under your arm (axillary).
have had at least 6 treatment cycles of certain chemotherapy drugs before surgery. You can still take part if you had this either with or without pembrolizumab. Your doctor will know more about the different types of chemotherapy drugs.
have had surgery to remove the cancer from the breast and lymph nodes. This could be a mastectomy or breast conserving surgery.
can look after yourself but might not be able to do heavy physical work (performance status 0 or 1). And your general health has not got worse in the 2 weeks before randomisation
have a tissue sample from surgery that the trial team can access
have satisfactory heart function tests in the 28 days before randomisation. Your doctor will know more.
can have at least one of either capecitabine or pembrolizumab. Your doctor will know which may be suitable for you.
have satisfactory blood test results
are willing to use contraception during treatment and for a time after if there is any chance you or your partner could become pregnant. Your trial team can talk about suitable contraception for you and your partner if needed.
won’t donate or bank sperm during the time you are taking part in the trial and for up to 4 months after you finish treatment
won’t donate blood or platelets during the study and for the 90 days after your last trial treatment
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 cancer that has come back in the same area or some distance from where it started
have had invasive breast cancer before. Or your cancer has come back after treatment before surgery and then surgery.
have changes (mutation) in the BRCA1 or BRCA2 genes
have, or had, another solid tumour unless it has been successfully treated, there have been no signs of it for at least 5 years and it is unlikely to come back. You might be able to join if you have had basal cell skin cancer or squamous cell skin cancer that has been removed. You might also be able to take part if you have had early (in situ) cancers and you have had treatment to try and completely remove them.
have side effects from your past cancer treatments unless they are mild. You might be able to take part if you have hair loss or a side effect that won’t get worse with treatment. Your doctor will know this.
have not had too many problems if you have taken pembrolizumab before. Your doctor can tell you more.
had, or are having, any cancer treatment as well as surgery which reaches the whole body (adjuvant systemic treatment)
are having radiotherapy at the same time you would be having the study drugs. You many still be able to take part if you have had radiotherapy before you have the study drug. Your doctor can explain more.

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

have had an organ transplant
have an active bleeding problem
have an active or ongoing infection
have serious or ongoing digestive problems causing diarrhoea
have a serious problem with the outermost lens (cornea) in your eye
have an autoimmune disease or inflammatory disorder. Or you have had one of these in the last 5 years. You might still be able to take part if you have vitiligo, alopecia or other specific autoimmune conditions. Your doctor can tell you more.
have HIV, an active hepatitis or an uncontrolled hepatitis B or hepatitis C infection, an active TB infection or any other infection that needs systemic treatment
have lung problems that could affect you taking part including scarring or inflammation of the lungs
have liver disease
have serious problems with your heart
have damage to nerves causing pain, numbness, changes in sensation and tingling (peripheral neuropathy). You still might be able to take part if you have mild symptoms. Your doctor can tell you more.
are having hormone replacement therapy (HRT) or using hormonal contraception. You can still take part if you are using hormone therapy not for cancer such as insulin.
have had medicine that damps down the activity of your body's immune system (immunosuppression) in the 2 weeks before randomisation. You can still take part if you have had small amounts of steroids. Your doctor will know more.
had major surgery or a major injury within 4 weeks of starting treatment. Or you might need surgery during the trial.

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

are taking anti malaria medication called chloroquine or hydroxychloroquine in the 2 weeks before randomisation
have had a live vaccine within the 30 days before starting treatment. The COVID-19 vaccines are not live vaccines.
have had treatment similar to datopotamab deruxtecan before. Your doctor can tell you more
are allergic or sensitive to datopotamab deruxtecan, any of its ingredients or are allergic to any similar drugs
are allergic to certain checkpoint inhibitors . Your doctor will know which drugs these are.
have already taken part in this study or have had an experimental drug or used a device as part of another clinical trial within 4 weeks of randomisation
have taken part in another study which looked at the same, or very similar, drugs. Your doctor will know which drugs these are.
have been involved in the planning of the trial or have been working on the trial yourself
are pregnant, breastfeeding or planning a pregnancy

Trial design

This is an international phase 3 trial. The team need around 1,075 people worldwide to join with 32 people from the UK.

It is a randomised trial. A computer puts you into a treatment group. Neither you nor your doctor choses which group you go into. There are 3 groups:

Group 1
You have datopotamab deruxtecan with durvalumab.

Group 2
You have datopotamab deruxtecan on its own.

Group 3
You have the treatment that your doctor thinks is best for you. You have one of the following:

capecitabine
pembrolizumab
capecitabine and pembrolizumab

For every 5 people who take part:

2 will be in group 1
1 will be in group 2
2 will be in group 3

Diagram 1

You have datopotamab deruxtecan as a drip into a vein. You have it once every 3 weeks.

You have durvalumab as a drip into a vein. You have it once every 3 weeks.

Capecitabine is a tablet. You take your tablet twice a day for 2 weeks then no capecitabine for a week. This is a three week treatment cycle.

You have pembrolizumab as a drip into a vein. You have it once every 3 weeks.

You have treatment in cycles Open a glossary item . Each cycle is 3 weeks. You may have up to 8 or 9 cycles of treatment, but you continue for as long as it is helping, and the side effects aren’t too bad.

The trial team monitor you after you finish the trial treatment. And you may be in the trial for around 8 years.

The team will ask you to use an electronic application, TrialMax app, during the trial. You also use it to record how you are feeling during and after treatment. You will be given an electronic device with the app on if you don’t have your own. The app will support you during the study. Your study doctor will tell you more about this. These are quality of life questionnaires.

Sample for research

The researchers will ask for a sample of your cancer before you take part in the trial. This is usually from surgery but could be from a biopsy Open a glossary item . This is so they can learn more about your cancer and:

substances in the tissue (biomarkers)
why some people might respond to treatment differently than others
how to improve treatment in the future

If your cancer comes back, the researchers would be interested in taking an extra sample for research. This is so they can learn more about why some cancers grow when you are having treatment. You don’t have to agree to having this biopsy if you don’t want to. You can still take part in the trial.

You give several blood samples during the trial. Where possible the team take these when you have your routine blood tests taken.

Researchers use these samples to:

find out more about triple negative breast cancer
look for substances (biomarkers) that might show how well treatment is working
learn more about why treatment may work better for some people than others

The researchers might also ask for a blood sample if you have inflammation in your lungs called pneumonitis Open a glossary item , to get more information on this condition. You don’t have to give this blood sample if you don’t want to.

Hospital visits

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

a physical examination including taking your temperature and pulse rate
heart scan (echocardiogram or MUGA)
lung function tests
CT scan
eye tests
blood tests
urine tests, including a pregnancy test – if there is a chance you could be pregnant

Usually, you go to the hospital once every 3 weeks to have:

the trial treatment you have at the hospital – you can take the rest of your capecitabine tablets at home
blood and urine tests
a physical exam
any other tests you might need

You have treatment as an outpatient. You should not need to stay overnight for any of the treatments in the trial.

You have tests and scans, such as an MRI scan or mammogram Open a glossary item , during treatment to see how well the treatment is working. Your doctor will let you know your schedule for this. They are usually every year. But your healthcare team might think you need one more regularly.

You see the doctor every 3 months for a check up. Your doctor will examine you and see how you are getting on.

Follow up
After treatment has finished, you go back to the hospital around a month later for some tests. This is so that the trial team can check how you are getting on.

You have follow up visits to the hospital to see the doctor and have some blood tests around:

every month for 3 months
every 3 months until it has been 2 years since randomisation
every 6 months for the next 3 years
every year after that

You have a mammogram or MRI scan once a year.

Side effects

The study 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.

Datopotamab deruxtecan is a new drug so there may be side effects we don’t know about yet. The possible side effects we know about so far include:

a drop in the number of red blood cells that might cause tiredness and breathlessness (anaemia )
dry eyes
feeling or being sick
sore mouth or inflammation in the lining of the digestive system
diarrhoea
tiredness (fatigue)
an allergic reaction. Symptoms could include swelling, skin rash, a fast heartbeat, difficulty breathing or a tight feeling in the throat or low blood pressure.
hair loss
loss of appetite
skin rash
inflammation of the moist linings of parts of the body. This is called mucosal inflammation. You might have stomach pain, be sick, have diarrhoea or be losing weight. This can be a serious side effect. Tell your trial doctor straight away if you have any of these side effects.

Datopotamab deruxtecan might cause a serious lung problem. In some cases, this could be life threatening. Symptoms are similar to other heart or lung diseases. Please contact your doctor straight away if you have any new lung symptoms or symptoms that are getting worse. These include:

a new or worsening cough
trouble breathing
new or worsening shortness of breath or other breathing problems
chest discomfort or chest pain
high temperatures (fever)

Getting medical treatment right away may keep these problems from becoming more serious.

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 durvalumab include:

diarrhoea
the thyroid gland not making enough hormone. This can cause tiredness or weight gain.
skin rash or dry itchy skin
infections of the sinuses and throat (upper respiratory tract infections)
cough
stomach (abdominal) pain
fever

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