A trial of pembrolizumab and chemotherapy for breast cancer (KEYNOTE-B49)

Cancer type:

Breast cancer

Secondary cancers

Status:

Open

Phase:

Phase 3

This trial is looking at adding pembrolizumab to chemotherapy for breast cancer that has come back or spread.

It is for people whose cancer has:

come back in the same area of the breast and you can’t have an operation to remove it or it has spread elsewhere in the body
a large number of receptors for the hormone oestrogen (ER positive )
none or a small number of the HER2 receptors (HER2 negative )
cells that have certain proteins (receptors) called PD-L1 on the surface (PD-L1 positive)

More about this trial

Doctors can use chemotherapy to treat HER2 negative breast cancer that has come back or spread. Sometimes it stops working so they are looking for ways to improve treatment for this group of people.

In this trial they are looking at the combination of pembrolizumab and chemotherapy. Pembrolizumab is a type of immunotherapy. It helps your immune system Open a glossary item to find and kill cancer cells.

Having pembrolizumab and chemotherapy together is a new combination of treatment for breast cancer in this group of people. The researchers aren’t sure how well it will work so they are doing this trial to find out more.

In this trial, some people have chemotherapy and pembrolizumab. And some have chemotherapy and a dummy drug (placebo Open a glossary item ).

The main aims of the trial are to find out:

how safe it is to have pembrolizumab and chemotherapy
if adding pembrolizumab to chemotherapy improves treatment
more about the side effects of treatment
how treatment affects people’s 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 breast cancer that has come back and the doctor can’t remove it with surgery or it has spread to another part of the body
have cancer that got worse on hormone treatment and you are suitable to have chemotherapy. Your doctor will check the previous treatments you had including the chemotherapy drugs to see if you are suitable for the trial.
have cancer that has a large number of receptors for the hormone oestrogen (ER positive )
have breast cancer that has none or a small number of the HER2 receptors (HER2 negative [Gloss/HER2 negative])
have a biomarker on your cancer cells called PD-L1
have cancer that the doctor can measure on a scan
have had a scan or given a tissue sample (biopsy ) that showed your cancer is getting worse
have a sample of tissue the team can access to do some tests on
are well enough to carry out all your normal activities but you might not be able to do heavy physical work (performance status 0 or 1)
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
are willing not to donate sperm if you are male
are on a stable dose of bisphosphonates or certain treatments such as denosumab if you are having this treatment. You must have had this dose for at least 4 weeks.
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:

breast cancer and you can’t have treatment with the aim to cure
already had chemotherapy for breast cancer that has come back and can’t be removed with surgery or has spread to another part of the body
breast cancer that has spread only to the skin
cancer that has spread to the brain unless you have had treatment and it is stable
inflammation of the covering of the brain (carcinomatous meningitis) caused by your cancer
the BRCA gene change and you haven’t had treatment with a drug called a PARP inhibitor
had radiotherapy within 2 weeks of starting treatment or you needed to have steroids for side effects from radiotherapy
had treatment with certain types of immunotherapies . Your doctor will know about this.
cancer that has spread to organs in the body such as the liver or lungs and this is causing symptoms. If your doctor can treat these symptoms, you might be able to take part in this trial.
another cancer that is getting worse or needed treatment in the last 3 years
had an experimental treatment or used an experimental device within 4 weeks of being put into a treatment group

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

have had a heart attack in the last 6 months or another significant heart problem that needs treatment
have an autoimmune condition that needed treatment in the last 2 years apart from certain ones. Your doctor will know about this.
have or had scarring on the lungs or active inflammation of the lungs (pneumonitis ) and you needed to have steroid treatment
have HIV, tuberculosis (TB) or an active infection that needs treatment
have an active hepatitis B or hepatitis C infection. You might be able to take part if you are having treatment and there are no signs of it.
have a COVID-19 infection
have a problem with how your immune system works
have had treatment that damps down the immune system. This includes steroids within 2 weeks of starting trial treatments unless it was a low dose
have had a transplant with someone else’s cells (allogeneic transplant or you have had an organ transplant
have another medical condition or mental health problem that could affect you taking part

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

are allergic to pembrolizumab or any of the chemotherapy drugs they plan to use in this trial
have had a live vaccine within 30 days of starting trial treatment. This doesn’t apply to the approved COVID vaccines as they aren’t live.
are pregnant or breastfeeding

Trial design

This phase 3 trial is taking part worldwide. The team need 800 people to join including 32 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. Nor will you know which treatment you are having. The doctor can find this out if necessary.

There are 2 treatment groups. You have 1 of the following:

chemotherapy and pembrolizumab
chemotherapy and a dummy drug (placebo )

You have pembrolizumab or the dummy drug as a drip into a vein. You have it once every 3 weeks.

You also have one of the following chemotherapy drugs:

These are all standard treatments. Your doctor will talk to you about which one they think will work best.

You have:

paclitaxel every week for 3 weeks followed by a week with no treatment
nab-paclitaxel every week for 3 weeks followed by a week with no treatment
liposomal doxorubicin once every 4 weeks
capecitabine twice a day every day for 2 weeks. You then have a week that you don’t take it.

You have paclitaxel, nab-paclitaxel or liposomal doxorubicin as a drip into a vein. Capecitabine is a tablet.

Everyone has treatment for up to 2 years as long as it is safe and the side effects aren’t too bad. Some people in the pembrolizumab group might be suitable to have treatment for another year. Your doctor will talk to you if this applies.

You stop treatment if the cancer gets worse. Your doctor will talk to you about other treatment options.

Samples for research
The researchers might ask you to give a tissue sample if there isn’t already a suitable one they can access. 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 how well the treatment is working
look at genes to understand more about breast cancer
look for substances called biomarkers to help work out why treatment might work for some people and not for others

Quality of life
The trial team ask you to fill out some questionnaires:

before you start treatment
at set times during treatment
at set times after treatment

The questionnaires ask about side effects and how you’ve been feeling. This is called a quality of life study.

Hospital visits

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

blood tests
a physical examination
heart trace (ECG)
heart scan (echocardiogram) or MUGA scan
bone scan
CT scan or MRI scan

You see the doctor for regular blood tests and check ups.

You have a CT or MRI scan every:

9 weeks in the first year and then
every 12 weeks

You stop having the trial scans if your cancer gets worse.

You see the team a month after you stop treatment. After that they follow you up every 9 to 12 weeks. This might be at a hospital appointment or they might 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.

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 common side effects of pembrolizumab include:

itchy skin or a skin rash
diarrhoea
cough
joint, back or tummy pain
fever
loss of skin colour
not enough thyroid hormone. This might cause you to feel tired, gain weight, feel cold or have constipation.
low levels of salt in the blood. This might cause you to feel tired, confused, have a headache, have muscle cramps or feel sick.