A study of datopotamab deruxtecan with or without durvalumab for triple negative breast cancer that has spread or come back (TROPION-Breast05)
Cancer type:
Status:
Phase:
This study is looking at datopotamab deruxtecan with or without durvalumab. You pronounce datopotamab deruxtecan as dat-oh-pot-oh-mab deh-rux-tee-can. It is comparing it to standard chemotherapy with immunotherapy for triple negative breast cancer.
It is for people with breast cancer cells that have a high level of protein called PD-L1. And the cancer has either:
- spread from where it started to other parts of the body (metastatic breast cancer)
- come back in the area where it started after treatment (local recurrence) and cannot be fully removed with surgery
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
for people with triple negative breast cancer that has spread or come back may include chemotherapy with or without an drug.
Researchers would like to improve the treatment options available for people in this situation. 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 . 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. It 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. It stimulates the body's to fight cancer cells. Durvalumab seeks out cancer cells by looking for PD-L1 protein on the cancer cells and attaching to it. The immune system then recognises the marked cells and kills them.
In this trial one group of people have datopotamab deruxtecan alone. One group have datopotamab deruxtecan with durvalumab. And one group have the treatment their doctor think would be best for them. This is chemotherapy with a type of (immunotherapy) called pembrolizumab.
The possible treatments are:
- paclitaxel and pembrolizumab
- nab-paclitaxel and pembrolizumab
- gemcitabine with carboplatin (GemCarbo) and pembrolizumab
Please note - The group looking at datopotamab deruxtecan alone is not open in the UK.
The aims of the study are to find out:
- if datopotamab deruxtecan with or without duravlumab works better than your doctor’s choice of chemotherapy with pembrolizumab
- 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 study. Talk to your doctor or the study 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 study if all of the following apply. You:
- have triple negative breast cancer
- have cancer that has come back in the same part of the body as your original cancer (local recurrence), you are not able to have surgery and you are not having treatment to try and get rid of the cancer completely. Or your cancer has spread to other parts of the body (metastatic breast cancer).
- 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 ideally from the last 3 months that the study team can access. This might be from a
biopsy you have had before. Or you may need to give a new sample if your doctor thinks this is suitable for you. Your doctor can explain more. - have proteins on the cancer cells called PD-L1. Your doctor will know more.
- have not had chemotherapy or any cancer treatment that reaches your whole body (systemic treatment) for your metastatic breast cancer or locally recurrent breast cancer
- are suitable for the chemotherapy drugs you might have in the study
- have cancer that doctors can see on a scan
- have had a break from previous treatment before starting the study treatment. Your doctor will know how long the break is for each type of treatment or cancer drug.
- 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 study team can talk about suitable contraception for you and your partner if needed.
- agree not to donate or bank sperm during the time you are taking part in the study and for up to 6 months after you finish treatment
- won’t donate or bank eggs during the time you are taking part in the study and up to 7 months after you finish treatment
- won’t donate blood or platelets during the study and for the 90 days after your last study treatment
- are at least 18 years old
Who can’t take part
Cancer related
You cannot join this study if any of these apply. You:
- have, or had, another cancer unless it has been successfully treated, there have been no signs of it for at least 3 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. - are having any other cancer treatment at the moment
- 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
spinal cord compression - have cancer that has spread to the brain (brain metastases) which is causing you symptoms or means you need treatment
- have, or have had, cancer cells that have spread to the thin tissue layers covering the brain and spinal cord (the leptomeninges)
- have had a drug that targets a protein called TROP1 before or you have had a drug similar to datopotamab deruxtecan before. Your doctor will know more.
Medical conditions
You cannot join this study if any of these apply. You:
- have a build up of fluid somewhere in the body – for example in the tummy (abdomen) or lungs and you’re not able to keep having the fluid drained
- have an infection that needs treatment that reaches your whole body (systemic treatment) such as antibiotics into the bloodstream. Or you may be developing an infection, but your team is not sure.
- have an active or uncontrolled hepatitis B or hepatitis C infection. Or you have uncontrolled HIV.
- have uncontrolled or serious
heart problems - have
lung problems that could prevent you from taking part. This includes having had scarring or inflammation of the lungs in the past which needed treatment with steroids and was not caused by an infection. Or you have, or may have, scarring or inflammation of the lungs at the moment. - 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 a condition which causes loss of pigment from areas of the skin (vitiligo), alopecia or other specific autoimmune conditions. Your doctor can tell you more. - are having
hormone replacement therapy (HRT) that reaches the whole body (systemic) or you are 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 3 weeks of starting treatment. Or you might need surgery during the study.
Other
You cannot join this study if any of these apply. You:
- 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 starting treatment on the study.
- have been involved in the planning of the study or have been working on the study yourself
- have taken part in another study which looked at the same, or very similar, drugs. Your doctor will know which drugs these are.
- 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 more. - have taken an 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 any other serious medical condition or mental health problem that the study team think would affect you taking part
- are pregnant, breastfeeding or planning a pregnancy
Trial design
This is an international phase 3 trial. The team need around 1,950 people worldwide to join with 29 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. In the UK there are 2 groups open.
Group 1
You have datopotamab deruxtecan with durvalumab.
Group 2
You have the treatment that your doctor thinks is best for you. You have one of the following:
- paclitaxel and pembrolizumab
- nab-paclitaxel and pembrolizumab
- gemcitabine with carboplatin (GemCarbo) and pembrolizumab
Please note - Group 3 is not open in the UK. It is looking at datopotamab deruxtecan without durvalumab.
How you have treatment
You have all of the study treatments as drip into a vein.
Group 1
You have datopotamab deruxtecan once every 3 weeks.
You have durvalumab once every 3 weeks.
Group 2
You have pembrolizumab once every 3 weeks.
You have paclitaxel once a week for 3 weeks, then a rest for a week. You then start the paclitaxel again.
You have nab-paclitaxel once a week for 3 weeks, then a rest for a week. You then start the nab-paclitaxel again.
You have GemCarbo once a week for 2 weeks, then a rest for a week. You then start the GemCarbo again.
Both groups
You have t. Each cycle is 3 or 4 weeks depending on which treatment you are having. Your team will explain your treatment plan to you.
You continue treatment for as long as it is helping, and the side effects aren’t too bad.
The study team monitor you after you finish the study treatment for whatever reason. And you may be in the study for around 7 years.
The team will ask you to use an electronic application, TrialMax app, during the trial. You 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.
Samples for research
The researchers will ask for a sample of your cancer before you take part in the study. They can use a stored sample if there is one available from the last 3 months. If there is not one available, the team may ask for one from a . This is so that they can look at the levels of PD-L1 in the cancer cells and learn more about:
- your cancer
- 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 starts to grow or 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 study.
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:
- 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
- look at how the body processes datopotamab deruxtecan
Hospital visits
You see the doctor and have tests before you can take part. These include:
- a
physical examination - heart trace (
ECG) heart scan (echocardiogram or MUGA )lung function tests - vital signs checks – including blood oxygen levels
- chest CT scan
- eye tests
- looking at your mouth and making a mouthcare plan
- blood tests
- a pregnancy test - if there is any chance you may be pregnant
You also have scans such as a brain scan and bone scan. Your doctor can tell you more about this.
You go to the hospital once every 2 or 3 weeks to have:
- the treatment you have at the hospital
- blood tests
- a pregnancy test if this is appropriate
- a physical examination
- 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 CT scans or MRI scans, during treatment to see how well the treatment is working.
You usually have a scan to look at your cancer every 6 weeks from the start of the study treatment for 24 weeks. Then every 9 weeks for 18 months. You then have a scan every 3 months.
You have a CT scan if your team thinks you have a side effect called interstitial lung disease or . This is scarring of the lungs.
You stop having these scans if your cancer grows. Your doctor will talk to you about your treatment options if this happens.
If your cancer grows you have a final scan for the study around a month after the scan that showed the cancer growth.
Your study doctor will let you know your individual test and scan schedule.
Follow up
After treatment has finished, you go back to the hospital around a month later for some tests. This is so that the study team can check how you are getting on.
You have a follow up visit to the hospital to see your doctor and have some blood tests around a month after your last dose of study treatment. And then 2 and 3 months after treatment.
The study team checks in with you once every 3 months while you are taking part in the study. This can be in person, over the phone, or using your medical records. This is to find out:
- how you are feeling
- about your cancer
- about any other cancer treatment you may be having
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 ) - feeling or being sick
- sore mouth
- hair loss
- 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.
- loss of appetite
- diarrhoea
- skin rash
- dry eyes
- 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.
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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 include:
- diarrhoea
- the t
hyroid 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
- changes to liver function which can be seen on a
blood test - swelling from extra fluid in the body, such as in the legs
We have more information about:
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
