A trial looking at datopotamab deruxtecan and durvalumab for breast cancer (TROPION-Breast04)
Cancer type:
Status:
Phase:
This trial is comparing datopotamab deruxtecan and durvalumab with pembrolizumab and standard chemotherapy before surgery for breast cancer. It is also comparing some of these treatments after surgery for breast cancer.
You pronounce datopotamab deruxtecan as day-toe-pot-oh-mab deh-rux-tee-can. It is also called Dato-DXd for short.
The trial is for people who haven’t had treatment yet and have:
triple negative breast cancer 
or- breast cancer that has low levels of receptors for the hormones oestrogen and progesterone and no receptors for HER2. Your doctor will know this.
More about this trial
Surgery is a usual treatment for breast cancer. You might also have an called pembrolizumab with chemotherapy for triple negative breast cancer. Sometimes the cancer comes back. So researchers are looking for new treatment options.
In this trial they are looking at 2 drugs called datopotamab deruxtecan and durvalumab.
Datopotamab deruxtecan is a type of drug called an . 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. It may also kill cancer cells nearby.
Durvalumab is a type of immunotherapy. It stimulates the body's immune system to fight cancer cells. It is already a treatment for a number of different cancer types.
There are 2 groups in this trial. One group has the new treatment. This is:
- datopotamab deruxtecan and durvalumab before surgery
- durvalumab with or without standard chemotherapy after surgery
The other group has . This is:
- pembrolizumab and chemotherapy before surgery
- pembrolizumab with or without standard chemotherapy after surgery
The main aims of the trial are to:
- compare the new treatment with standard treatment to see which works best
- see how long it is before the cancer comes back
- learn more about the side effects
- see how treatment 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 stage 2 breast cancer or stage 3 breast cancer. This is cancer that may have spread to nearby
lymph nodes , the skin of the breast or to the chest wall but no further. - have triple negative breast cancer or breast cancer that has low levels of oestrogen, progesterone or both and the breast cancer is
HER2 negative . Your doctor will know this. - have cancer cells that have grown through the lining of the ducts into the surrounding breast tissue (invasive cancer)
- are fit and active but might not be able to do heavy physical work (performance status of 0 or 1)
- have a sample of tissue (
biopsy ) that the trial team can access before you are put into a treatment group. You may need to give a new sample if there isn’t one available. - have satisfactory blood test results
- are willing to use reliable contraception during the trial and for a period after if there is any chance you or your partner could become pregnant
Who can’t take part
Cancer related
You cannot join this trial if any of these apply. You:
- have breast cancer that has spread to other parts of the body
- have had or are having treatment for breast cancer. This includes surgery, radiotherapy or any other cancer treatment that reaches the whole body. Your doctor will know this.
- have had a treatment called chloroquine or hydroxychloroquine within 14 days of being put into a treatment group
- have had medication that damps down the
immune system . This includes steroids within 2 weeks of starting trial treatment unless it was a low dose. - have had another cancer in the last 3 years unless it has been successfully treated and there have been no signs of it. You might be able to join if you have had
non melanoma skin cancer that has been removed. You might also be able to take part if you have had early cancers (carcinoma in situ ) and you have had treatment to try and completely remove them. - are taking an experimental drug or using a device as part of another clinical trial. This is if it is within 28 days of being put in a treatment group for this trial.
- have taken part in another treatment trial looking at datopotamab deruxtecan even if you didn’t have it
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. You can’t take part if you are taking medication for a heart condition called torsades de pointes. - have scarring on the lungs, active inflammation of the lungs (
pneumonitis ) or another serious lung condition - have had an
organ transplant - have an active bleeding problem
- have serious or ongoing
digestive problems causing diarrhoea - can’t swallow tablets or keep them down or there is any reason that could affect how you absorb them
- have a serious problem with the cornea in your eye
- have an
autoimmune condition that needs treatment apart from certain ones. Your doctor will know about this. - have HIV that is not well controlled with medication, an active or uncontrolled hepatitis B or hepatitis C infection,
tuberculosis (TB) or any other severe infection that needs treatment - 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 the start of treatment. Please note that the COVID-19 vaccine is allowed as it isn’t a live vaccine. - have a problem with drugs or alcohol
- are allergic or sensitive to datopotamab deruxtecan or any of the other treatments in the trial or anything they contain
- are pregnant or breastfeeding
Trial design
This phase 3 trial is taking place worldwide. The team need 1,728 people to take part. This includes 38 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 2 treatment groups.
Treatment group 1 have:
- datopotamab deruxtecan and durvalumab before surgery
- durvalumab with or without chemotherapy after surgery
Treatment group 2 have:
- pembrolizumab and chemotherapy before surgery
- pembrolizumab with or without chemotherapy after surgery
Treatment group 1 (new treatment)
Before surgery you have datopotamab deruxtecan and durvalumab. You have 8 before surgery. This takes about 6 months in total. You then have your breast surgery as planned. The trial team will tell you more about the surgery and how long you’ll be in hospital for.
After surgery you restart durvalumab. During surgery the team check if you have any signs of cancer. If this applies you also have standard chemotherapy. You have one or more of the following:
- doxorubicin or epirubicin
- cyclophosphamide
- paclitaxel
- carboplatin
- capecitabine
Your doctor will talk to you about the chemotherapy drugs they think will work best.
Everyone has 9 cycles of treatment after surgery. This takes about 7 months in total.
Treatment group 2 (standard treatment)
Before surgery you have pembrolizumab and standard chemotherapy. The standard chemotherapy includes one or a combination of the following:
- doxorubicin or epirubicin
- cyclophosphamide
- paclitaxel
- carboplatin
- capecitabine
You have 8 cycles of treatment before surgery. This takes about 6 months in total. You then have your breast surgery as planned. The trial team will tell you more about the surgery you’ll have and how long you’ll be in hospital for.
After surgery you restart pembrolizumab. During surgery the team check if you have any signs of cancer cells left. If this applies you also have capecitabine chemotherapy. You have 9 cycles of pembrolizumab with or without chemotherapy after surgery. This takes about 7 months in total.
Both groups
Some people might also have a targeted cancer drug called olaparib after surgery. This is only if you have a change in the or gene. To find this out, your doctor may test a sample of tissue. Those having olaparib have it for up to one year after surgery.
You stop trial treatment if your cancer gets worse. Your doctor will talk to you about other treatment options.
How you have treatment
You have treatment in cycles. Each cycle lasts 3 weeks.
The treatment you have depends on which group you are in.
You have the following drugs once every 3 weeks as a drip into a vein:
- datopotamab deruxtecan
- durvalumab
- pembrolizumab
- doxorubicin
- epirubicin
- cyclophosphamide
You have the other drugs in the trial as follows.
- You have paclitaxel as a drip into a vein once a week.
- You have carboplatin as a drip into a vein once a week or once every 3 weeks.
- Capecitabine is a tablet you take by mouth. You take them twice a day, every day for 2 weeks. You then have a week off.
- Olaparib is a tablet you take by mouth. You have them twice a day, every day.
We have information about all of these treatments in our Cancer drugs section.
Samples for research
The researchers take a sample of tissue when you have surgery. 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 datopotamab deruxtecan in the body if you have this
- 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 breast cancer
The team will also ask to take a sample of cancer tissue if your cancer starts to grow again or comes back. You can say no to giving this sample. You can also say no to the sample that looks at genes.
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 use it to record side effects, symptoms and how you are feeling. This information helps researchers to see how treatment affects your .
You do this at set times before, during and after treatment. The trial doctor will tell you more about this.
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 - mammogram or MRI scan of the breast
- eye tests
- breathing tests to see how your lungs are working
During treatment you see the doctor regularly. This is for blood tests and to see how you are. There are some shorter hospital visits that take about an hour or 2. Some hospital visits are longer and can take up to 6 hours. The team will give you a rough idea of how long each visit will take.
You have most of your treatment at the hospital on the daycare ward.
Scans
You have a mammogram or MRI of the breast when you join the trial. And if you have any remaining breast tissue following your surgery. You have these scans once a year after surgery.
Some people may have an ultrasound of the breast.
Follow up appointments
When you stop treatment you see the trial team for a check up once a month for 3 months.
The team then follow you up:
- every 3 months for the first 2 years
- every 6 months for the next 3 years and then
- once a year after that
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.
Datopotamab deruxtecan is a new drug so there may be side effects we don’t know about yet. The most common side effects we know about so far include:
- feeling sick or being sick
- sore mouth
- hair loss
- tiredness (fatigue)
- an
allergic reaction . 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 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.
- skin rash
- a drop in the number of red blood cells that might cause tiredness and breathlessness (
anaemia ) - dry eyes
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
- high temperatures (fever)
Getting medical treatment right away may keep these problems from becoming more serious.
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Durvalumab and pembrolizumab can affect the 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. |
The most common side effects of durvalumab are:
- diarrhoea
- skin rash or itchy skin
- tummy pain
- a sore throat, runny or stuffy nose – due to an upper respiratory tract infection
- cough
- fever
- too little thyroid hormone being made by the
thyroid gland . This can cause tiredness or weight gain.
Your doctor will talk to you about all the side effects of treatment. You’ll have a chance to ask them any questions you may have.
We have more information about:
You can read more about the side effects of the standard chemotherapy drugs used in this trial in our Cancer drugs section:
- doxorubicin
- epirubicin
- cyclophosphamide
- paclitaxel
- carboplatin
- capecitabine
Location
Recruitment start:
Recruitment end:
How to join a clinical trial
Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.
Chief Investigator
Professor Peter Schmid
Supported by
AstraZeneca
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
