A study looking at trastuzumab deruxtecan for breast cancer (DESTINY-breast07)

Cancer type:

Breast cancer

Cancer spread to the brain

Cancer spread to the liver

Cancer spread to the lung

Secondary cancers

Status:

Open

Phase:

Phase 1/2

This study is looking at trastuzumab deruxtecan by itself and with other cancer drugs for breast cancer. It is open to people with breast cancer that has spread to another part of the body and has large amounts of HER2 Open a glossary item .

More about this trial

Breast cancer that has spread to another part of the body is secondary breast cancer.

Trastuzumab deruxtecan is a type of drug called an antibody drug conjugate. It is trastuzumab with a chemotherapy Open a glossary item drug attached to it. Deruxtecan is the chemotherapy like drug. Trastuzumab finds and attaches to the HER2 protein on the cancer cell. Deruxtecan is then released into the cancer cell damaging or killing the cell. This stops the cancer from growing.

Trastuzumab deruxtecan is already a treatment in some countries for secondary breast cancer that has the HER2 protein.

In this study researchers are looking at trastuzumab deruxtecan by itself and in combination with other cancer drugs. These drugs are:

Tucatinib is a targeted cancer drug called a cancer growth blocker. It works by blocking a protein called tyrosine kinase Open a glossary item . Cancer cells use tyrosine kinase to grow and divide. Blocking it stops the cancer from growing. Doctors already use tucatinib to treat secondary breast cancer.

The aims of the study are to find out:

how well trastuzumab deruxtecan works by itself and in combination with other cancer drugs
how safe it is to give by itself and in combination with other cancer drugs
what happens to trastuzumab deruxtecan in the body
what happens to trastuzumab deruxtecan in combination with the other drugs in the body
how trastuzumab deruxtecan by itself and in combination with other cancer drugs 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 breast cancer that has spread to another part of the body (secondary breast cancer). Or you cannot have surgery with the aim to cure your cancer.
have a large amount of HER2 on the cancer cells (HER2 positive)
have cancer that the hormones oestrogen and or progesterone stimulate the cancer to grow (hormone receptor positive breast cancer)
have a previous tissue sample (biopsy ) that the team can ask for. If one isn’t available you must be willing to have a biopsy taken.
have had a least one course of treatment for your cancer spread such as chemotherapy or hormone therapy. And your cancer had got worse during the treatment or after it had finished.
are able to look after yourself but might not be able to do heavy physical work (performance status 0 or 1)
have satisfactory blood test results
have at least 1 area of cancer the doctor can measure
are willing to use contraception during the study and for a period of time after. This is if there is any chance you or your partner could become pregnant.
are at least 18 years old

Who can’t take part
There are a number of groups in this study and there are different reasons why you might not be able to join a certain group. Your doctor will know about these.

The reasons below apply to all the groups.

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

have another cancer. This is apart from successfully treated non melanoma skin cancer , any in situ cancer and an early type of melanoma skin cancer called lentigo maligna. You could also join if you had treatment for cancer with the aim to cure and there has not been any sign of the cancer for at least the past 5 years.
have spinal cord compression
have or had cancer spread to the tissues around the brain and spinal cord (leptomeningeal carcinomatosis)
have ongoing side effects from previous treatment. This is apart from mild ones or side effects that might not get worse. Your doctor will talk to you about this.
are having treatment
have had treatment with certain targeted cancer drugs . Your doctor will know which ones these are.
are taking part in another clinical trial or study using an experimental treatment or device within a month of starting treatment.

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

have heart problems that could affect you taking part
have lung problems that could affect you taking part
have HIV, hepatitis B or hepatitis C
have an infection that needs treatment
have an autoimmune disease . This is apart from certain ones which your doctor will know about.
had an immunotherapy called a checkpoint inhibitor . Your doctor will know if you have had one of these.
had a stem cell or bone marrow transplant from a donor (allogeneic transplant )
have had an organ transplant
are taking medication such as steroids that affect how well the immune system works within 2 weeks of starting treatment. This is unless it is a nasal spray, inhaler or a small dose of steroids.
cannot swallow tablets or capsules
have a problem with your digestive system that affects how well your body can absorb medicine taken by mouth
cannot have a targeted cancer drug called a monoclonal antibody
are taking medication including herbal preparations that affect certain CYP enzymes in the body. This is unless you can stop taking them or you can change them. Your doctor will know about this.
are not able to have an MRI scan using a contrast dye of the brain. This might be because you have surgical clips or other metal in your body. You are claustrophobic or you are allergic to the contrast dye.
have any other medical condition or mental health problem that could affect you taking part

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

are not able to have any of the combination of the study treatments. This includes if you are allergic or sensitive to any of the separate treatments used in the study or any of their ingredients.
have a live vaccine within 30 days of starting treatment, during treatment or for 30 days after. The COVID-19 vaccines are not live vaccines.
are pregnant or breastfeeding

Trial design

This is an international study. The team need 450 people worldwide to take part with 20 people from the UK.

In this study the team are looking at trastuzumab deruxtecan by itself and in combination with other cancer drugs. There are 8 groups. You are put into a group at random Open a glossary item . Neither you nor your doctor chooses the group you are in.

The first 6 groups are for people who don’t have cancer spread to the brain. And for people with cancer spread to the brain that is stable. They are:

trastuzumab deruxtecan
trastuzumab deruxtecan and durvalumab
trastuzumab deruxtecan and pertuzumab
trastuzumab deruxtecan and paclitaxel
trastuzumab deruxtecan, durvalumab and paclitaxel
trastuzumab deruxtecan and tucatinib

The other 2 groups are for people with cancer spread to the brain that is active. They are:

trastuzumab deruxtecan
trastuzumab deruxtecan and tucatinib

You have the following as a drip into a vein:

trastuzumab deruxtecan
durvalumab
pertuzumab
paclitaxel

You have them once every 3 weeks apart from paclitaxel which you have once a week.

Tucatinib is a tablet. You take them twice a day. Your doctor will tell you how many to take.

You continue to have treatment for as long as it is helping and the side effects aren’t too bad.

Samples when you join the study
The team ask everyone for a piece of a tissue sample (biopsy Open a glossary item ) of your secondary breast cancer. They can use a sample you have already had taken if there is one available. If there isn’t a previous tissue sample you must agree to have a fresh sample taken.

They use this sample to test for HER2. If there is no HER2 in your secondary breast cancer tissue then you can’t take part in the trial. In this case your doctor will talk to you about the best available treatments for you.

For people who have no secondary cancer in the brain or have secondary brain cancer that is stable the team will also test for PD-L1. This is so the team can put you into a treatment group. Whether your cancer has PD-L1 or not you can still take part in the trial. The study team will tell your doctor if your cancer has PD-L1 or not.

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

The team might ask for extra tissue samples (biopsies) during your treatment or after treatment. You don’t have to agree to this if you don’t want to.

Researchers will use these blood and tissue samples to:

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

Quality of life
You fill in questionnaires, you do this:

before starting treatment
during treatment
at the end of treatment
for a time after treatment

The questions ask about:

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

For people with secondary cancer in the brain you fill in an extra questionnaire at the same time. These questions ask about whether the treatment has affected:

how you talk
your nerves such as moving your limbs
your sense of touch
your memory
how fast you respond to surrounding things or reply to people

There is an application (app) you download onto your smart phone to do the questionnaires. If you don’t have a smart phone the team will provide an electronic device for you to do this. They will also train you how to use it.

These are quality of life questionnaires.

Interviewing people who get lung problems

One of the side effects of trastuzumab deruxtecan are lung problems such as scarring of the lung tissue and inflammation of the lungs.

Should you develop one of these side effects the team might ask for an interview. They ask someone outside the team (a third party person) to contact you.

The person will ask you about the side effect and how it has affected your daily life. The interview takes about an hour. They will tape record your answers.

Your answers and details are confidential. Your doctor will not know what you have said. Only the researchers will listen to the tape but they won’t know who you are.

You don’t have to agree to do the interview.

Hospital visits

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

a physical examination
blood tests
urine test
CT scan and an MRI scan
bone scan
heart trace (ECG )
heart scan (ECHO or MUGA )
eye test
breathing tests (lung function tests )

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

You have a device called a pulse oximeter to take and use at home. This records how much oxygen is in your blood. You need to use it every day while on treatment and to record what the result is. Your doctor will show you how to use the pulse oximeter.

You have a CT scan or an MRI scan:

every 6 weeks for up to a year
then every 9 weeks until your cancer starts to get worse

You see the doctor when you finish treatment and then:

about a month later then
every 3 months

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.

There may be some side effects we don’t know about trastuzumab deruxtecan when used by itself and in combination with other cancer treatments.

Side effects we do know about the cancer treatments the team use in the study are listed below.

Trastuzumab deruxtecan can affect the lungs. It can cause scarring or inflammation that may be life threatening. The symptoms may be similar to other lung problems or heart problems. Contact your doctor right away if you have any new or worsening lung symptoms, including:

trouble breathing
shortness of breath
cough
fever

These may be signs of inflammation of the lung known as interstitial lung disease (ILD) or pneumonitis, which may be serious or fatal. Getting medical treatment right away may keep these problems from becoming more serious.

Tell your doctor about any lung problems you have or have had in the past. In particular if you have a history of lung problems including inflammation of the lung known as interstitial lung disease (ILD) or pneumonitis. And if you have had or are having treatment with corticosteroids.

The most common side effects of trastuzumab deruxtecan are:

feeling or being sick
hair loss
constipation or diarrhoea
loss of appetite
a drop in blood cells causing an increased risk of infection, breathlessness, tiredness, bruising and bleeding
severe nose bleeds
coughing, difficulty breathing, lung problems
stomach (abdominal) pains and indigestion
infections of the nose, mouth, throat and voice box
headache
dry eyes
dizziness
sore mouth and ulcers
a change to how the liver works causing abnormal liver blood test results
skin rash
high temperature (fever)
swelling of the lower legs and hands

The most common side effects of tucatinib are:

diarrhoea – this can be severe talk to your doctor straightaway as soon as the diarrhoea starts
feeling or being sick
sore, inflamed mouth and ulcers
liver problems causing itching, yellowing of the eyes and skin, dark urine and pain or discomfort in the upper right area of your stomach (abdomen). Your doctor takes regular blood tests to make sure your liver is working properly. Talk to your doctor if you had any previous liver problems.
skin rash
weight loss
nose bleeds

Durvalumab can affect the immune system. It may cause inflammation in different parts of the body. This can cause serious side effects. They could happen during treatment, or some 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.

We have information about:

Your doctor will talk to you about the possible side effects of the treatments used in this study before you agree to take part.