A trial of pembrolizumab and chemotherapy for triple negative breast cancer (KEYNOTE-355)

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 for people with triple negative breast cancer that has come back (recurrent) or spread to another part of the body (metastatic).

Triple negative breast cancers are cancers without receptors Open a glossary item for: 

  • oestrogen
  • progesterone
  • HER2

More about this trial

Triple negative breast cancers are often treated with chemotherapy. You can have 1 of the following: 

Pembrolizumab (Keytruda) is a targeted cancer drug (biological therapy) called a monoclonal antibody. It works by stopping the cancer cells from switching off the body’s immune system Open a glossary item. This stimulates the immune system to attack the cancer. 

Pembrolizumab is already used to treat certain types of melanoma and lung cancer. But doctors want to find out if it can also help people with triple negative breast cancer.

This trial is in 2 parts. In part 1 the researchers want to find out if it is safe to have pembrolizumab and chemotherapy. People joining this part have 1 of the following:

  • pembrolizumab and nab-paclitaxel
  • pembrolizumab and paclitaxel 
  • pembrolizumab, gemcitabine and carboplatin   

Part 1 is now closed and doctors are looking for people to join part 2. In part 2 doctors want to collect information on how pembrolizumab and chemotherapy work as a treatment. Everyone in this part has 1 of the following: 

  • pembrolizumab and chemotherapy 
  • dummy drug (placebo Open a glossary item) and chemotherapy

The main aims of this trial are to: 

  • find out how well pembrolizumab and chemotherapy work as a treatment
  • learn about the side effects
  • find out more about people’s quality of life Open a glossary item
  • look for certain substances (biomarkers Open a glossary item) that can help to tell how well treatments work 

Who can enter

The following bullet points list 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. 

You may be able to join this trial if all of the following apply. 

  • You have triple negative breast cancer that has come back (recurrent) and you can’t have surgery to cure it. Or you have triple negative breast cancer that has spread to another part of the body (metastatic). And for both situations you haven’t had treatment with chemotherapy   
  • There has been 6 months or more since any treatment you had for early or locally advanced breast cancer (stages 1 to 3), that you had with the aim of curing your cancer, and your cancer coming back
  • If you have had treatment with chemotherapy in the past you must have had a drug called an anthracycline Open a glossary item unless you couldn’t have it for any reason or your doctor thought it wasn’t the best treatment for you 
  • You have at least 1 area of cancer that can be seen and measured on a scan 
  • You have a suitable sample of cancer available (or be willing to have a sample taken) to be tested for a biomarker Open a glossary item called PD-L1 and to confirm your cancer diagnosis 
  • You have satisfactory blood tests results
  • You are well enough to carry out your normal activities, apart from heavy physical work (performance status of 0 or 1) 
  • You are at least 18 years old
  • You are willing to use reliable contraception during treatment and for 4 months afterwards if there is any possibility you or your partner could become pregnant 

You cannot join this trial if any of these apply:

Cancer related

  • Your cancer has spread to your brain, the tissues surrounding your brain or your spinal cord Open a glossary item. You might still be able to take part if it has been stable, you don’t have side effects and you haven’t taken steroids in the past month
  • You have moderate or severe side effects from previous cancer treatment apart from hair loss 
  • You have moderate or severe problems with your nerves causing numbness or tingling (neuropathy) 
  • You have had another cancer in the past 5 years apart from successfully treated early cancer (carcinoma in situ Open a glossary item) of the cervix or non-melanoma skin cancer
  • You have had pembrolizumab or any other similar drug 

Medical conditions

  • You are taking part in another clinical trial or have taken part in a trial looking at a new treatment (drug or device) in the past 4 weeks  
  • You have an autoimmune disease Open a glossary item that needed treatment that reached your whole body (systemic) in the past 2 years, apart from treatment to replace something the body makes such as insulin or thyroxine
  • You have taken drugs that damp down your immune system (immunosuppressants), such as steroids, in the last week 
  • You have or have had lung problems such as inflammation of the lung (pneumonitis) that needs treatment with steroids or a lung condition called interstitial lung disease
  • You have a heart problem that causes shortness of breath during short physical activity or you have had a heart attack in the past 6 months 
  • You have an infection that needs treatment that reaches your whole body (systemic treatment)
  • You are known to be sensitive to pembrolizumab, the chemotherapy drugs used in this trial or anything they contain 
  • You take drugs that can interfere with how pembrolizumab or the chemotherapy drugs used in this trial work. You doctor can tell you more about this 
  • You have tuberculosis (TB)
  • You have HIV
  • You have hepatitis B or hepatitis C 
  • You have had a live vaccine Open a glossary item in the past month
  • You have any other medical condition or mental health problem that the trial team thinks could affect you taking part in this trial 

Other

  • You are pregnant or breastfeeding

Trial design

This is an international phase 3 trial. The researchers need up to 858 people to take part worldwide and hope that around 40 people from the UK will take part. 

This trial has 2 parts. Part 1 is now closed and doctors are looking for people to join part 2. 

Part 1
This part of the trial is randomised. The people taking part are put into 1 of the following treatment groups by computer:

  • pembrolizumab and nab-paclitaxel 
  • pembrolizumab and paclitaxel 
  • pembrolizumab, gemcitabine and carboplatin

Neither you nor your doctor are able to decide which group you are in.

study diagram

Everyone has pembrolizumab as a drip into a vein every 3 weeks. It takes about 30 minutes each time.

You also have chemotherapy as a drip into a vein. How often you have chemotherapy depends on the treatment you have. Your doctor can tell you more about this. 

You continue to have treatment for as long as it is helping you and the side effects aren’t too bad. You can have treatment with pembrolizumab for up to 2 years. 

You may be able to continue to have pembrolizumab after 2 years if your cancer got worse (progressed) at the end of treatment. This is called second course treatment. Your doctor can tell you more about this. 

Part 2
This part of the trial is also randomised. The people taking part are put into 1 of the following treatment groups by computer:

  • pembrolizumab and chemotherapy 
  • dummy drug (placebo) and chemotherapy

Neither you nor your doctor are able to decide which group you are in. And neither you nor your doctor will know which group you are in. This is a double blind trial Open a glossary item

You are 2 times more likely to have pembrolizumab and chemotherapy, than the dummy drug and chemotherapy. 

study diagram

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

You also have chemotherapy as a drip into a vein. How often you have it depends on the treatment you have. Your doctor will explain which chemotherapy drug they think is best for you. It can be:

  • nab-paclitaxel
  • paclitaxel
  • gemcitabine and carboplatin

You continue to have chemotherapy and pembrolizumab or a dummy drug for as long as it is helping you and the side effects aren’t too bad. You can have treatment with pembrolizumab for up to 2 years.

You may also be able to continue to have pembrolizumab after 2 years if your cancer got worse at the end of treatment with pembrolizumab (second course treatment). Your doctor can tell you more about this. 

Quality of life 
Everybody taking part completes quality of life questionnaires before the start of treatment and:

  • at set times during the trial
  • at the end of treatment 
  • a month after finishing treatment

The questionnaires ask about how you have been feeling and what side affects you have had.

Blood tests
You have some extra blood tests as part of this trial. Researchers want to:

  • look for certain proteins called biomarkers to see why treatments work better for some people than others
  • look at the cancer DNA Open a glossary item 
  • find out what happens to pembrolizumab in the body (pharmacokinetics) Open a glossary item

You have the extra blood tests before the start of treatment and then:

  • at set times during the trial
  • at the end of treatment 
  • 3 months after the end of treatment

Doctors will ask to store your blood samples and use them in future studies. This is called future biomedical research. You don’t have to agree to this if you don’t want to. You can still take part in this trial. 

Tissue sample
The trial team will ask to use a tissue sample of your cancer taken after your cancer came back or spread to another part of the body. If there isn’t a suitable sample available, you need to have a biopsy Open a glossary item.

Doctors might also ask you to have a biopsy if your cancer gets worse. You don’t have to agree to this if you don’t want to. You can still take part in this trial. 

Hospital visits

You see a doctor and have some tests before taking part. These tests might include: 

  • a physical examination
  • heart trace (ECG Open a glossary item)
  • a CT scan or MRI scan
  • a bone scan (if the cancer has spread to your bones)
  • blood tests
  • urine test

During treatment, you see the trial doctor for blood tests and a physical examination every 3 weeks. 

You have a CT scan or MRI scan every 8 weeks for about 6 months. After this you have a CT scan or MRI scan:

  • every 9 weeks for a year
  • then every 12 weeks for a year

You might have a bone scan if the cancer has spread to your bones and you have any new pain or any existing pain gets worse.

Your pembrolizumab treatment continues for as long as your cancer stays the same and the side effects aren’t too bad. 

When you finish treatment, you see the trial doctor after a month. You then speak with the trial team every 3 months. 

Side effects

The trial team monitor you during the time you have treatment and you have a phone number to call them if you are worried about anything. The team will tell you about all the possible side effects before you start the trial.

The most common side effect of pembrolizumab are: 

We have more information about pembrolizumab

And information about: 

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.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Peter Schmid

Supported by

Merck Sharp & Dohme 

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

14853

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Deborah wanted to help other breast cancer patients in the future

A picture of Deborah

“Deborah agreed to take part in a trial as she was keen to help other cancer patients in the future. "If taking part in a trial means others might be helped then I’m very happy with that."

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