A study of pembrolizumab and epacadostat for advanced non small cell lung cancer (KEYNOTE-654)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Lung cancer
Non small cell lung cancer
Secondary cancers




Phase 3

This study is looking at pembrolizumab and epacadostat as the first treatment for non small cell lung cancer that has spread elsewhere in the body.

More about this trial

The usual treatment for advanced non small cell lung cancer is chemotherapy, radiotherapy or a targeted cancer drug. You might have a type of targeted drug called pembrolizumab. It is a type of immunotherapy. It stimulates the body’s immune system Open a glossary item to recognise and attack cancer cells.

But sometimes it stops working and the cancer starts to grow again. So researchers are always looking for ways to improve treatment. In this study, they are looking at a new drug called epacadostat.

Epacadostat also works on the immune system but in a different way to pembrolizumab. It blocks a protein which can help the immune system to work better.

Researchers think that adding epacadostat to pembrolizumab will improve treatment. But they aren’t sure, so want to find out more. 

In this study, some people have pembrolizumab and epacadostat. And some pembrolizumab alone.

The aims of the study are to:

  • find out if pembrolizumab and epacadostat works better than pembrolizumab alone
  • learn more about the side effects

Who can enter

The following bullet points list 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 the following apply.

  • have non small cell lung cancer that has spread to another part of the body (metastatic cancer)
  • haven’t had treatment for the cancer spread
  • have high levels of PD-L1 in the lung cancer cells
  • have cancer that the doctor can see and measure on a scan
  • are willing to use reliable contraception during treatment and for 120 days afterwards if there is any chance you or your partner could become pregnant
  • are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
  • have satisfactory blood test results
  • are at least 18 years old

Who can’t take part
You cannot join this study if any of these apply.

Cancer related

  • have cancer that has spread to the brain unless you have had treatment, it  hasn’t got worse in the past 4 weeks and you haven’t taken steroids in the last 2 weeks before joining the study
  • have certain gene mutations in the lung cancer cells including EGFR Open a glossary item and ALK
  • have had chemotherapy or other targeted drugs
  • have had pembrolizumab, epacadostat or similar drugs in the past
  • have had radiotherapy within 14 days of starting study treatment or radiotherapy to the lung within 6 months
  • have had steroid treatment within 7 days of starting study treatment
  • have had another cancer unless this was treated with the aim to cure and there haven’t been any signs of it for at least 5 years - you can take part if you had successful treatment for basal cell skin cancer Open a glossary item, early bladder cancer, squamous cell skin cancer, Open a glossary item carcinoma in situ Open a glossary item of the cervix Open a glossary item or other carcinomas in situ
  •  have had an experimental treatment as part of another clinical study in the past month

Medical conditions

  • have, or have had, certain lung problems such as inflammation of the lungs (pneumonitis) or interstitial lung disease
  • you have an autoimmune disease Open a glossary item and you had treatment in the past 2 years, apart from treatment to replace something that the body makes such as insulin or thyroxine
  • have a collection of fluid on your lung or in your tummy (abdomen) unless you have had successful treatment
  • have a problem with your immune system or you are having steroid treatment that is more than 10mg a day or any other drug that dampens down the immune system in the 7 days before starting study treatment
  • have had an organ transplant or a transplant with somebody else’s stem cells
  • have HIV
  • have an active hepatitis B or hepatitis C infection
  • have a problem with your digestive system Open a glossary item that might affect how you absorb the study drug
  • have problems with your heart, such as a heart attack in the last 6 months, angina that is not well controlled, an abnormal rhythm of your heart or congestive heart failure
  • have tuberculosis that needs treatment
  • developed a condition called serotonin syndrome after having certain drugs such as phenelzine
  • an active infection that needs treatment
  • are sensitive to monoclonal antibodies Open a glossary item, pembrolizumab, epacadostat or anything they contain
  • have taken meperidine, linezolid, or methylene blue or similar drugs in the 21 days before starting treatment
  • have any other serious medical condition or mental health problem that the study team thinks could affect you taking part


  • are pregnant or breastfeeding
  • have a problem with drugs or alcohol
  • have had a live vaccine Open a glossary item within 30 days of starting study treatment

Trial design

This is a phase 3 trial. The researchers hope to find 588 people to join the study including 6 from the UK.

It is a randomised study. A computer will put you into a treatment group. Neither you nor your doctor will be able to decide which group you are in. And neither of you will know which group you are in. We call this a double blind study.

You have 1 of the following treatments:

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

KEYNOTE-654 diagram

You have pembrolizumab as a drip into a vein. You have it once every 3 weeks.

Epacadostat and the dummy drug are tablets. You have either epacadostat or the dummy drug twice a day, everyday.

You have treatment for up to 2 years, for as long as it is working and the side effects aren’t too bad.

After 2 years of treatment you might be able to continue if the treatment is working. The trial doctor can tell you more about this.

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

Quality of life
The study team will ask you to complete some questionnaires before treatment starts and then regularly throughout treatment. We call these quality of life Open a glossary item questionnaires. They look at how the treatment affects you physically and emotionally.

Research samples
The researchers will ask you to have some extra blood tests. They will also ask to use a tissue sample (biopsy) of your cancer that you had taken when you were diagnosed. You need to have a biopsy if there isn’t a suitable sample available.

They plan to use the samples to:

  • look for gene changes (mutations Open a glossary item)
  • look at substances called biomarkers Open a glossary item to help work out why treatment might work for some people and not for others
  • find out what happens to the drugs in the body (we call this pharmacokinetics Open a glossary item)

They might ask to use any leftover samples for future research. You don’t have to agree to this if you don’t want to. You can still take part in the study. 

Hospital visits

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

  • physical examination
  • heart trace (ECG) Open a glossary item
  • blood tests
  • urine tests
  • CT scan or MRI scan

You might need to give a tissue sample (biopsy) Open a glossary item if there isn’t a sample available for the study team to do some tests on.

You have a CT or MRI scan every:

  • 9 weeks for 1 year
  • 3 months after that

The study team will follow you up every 3 months if your cancer gets worse. They will phone you to see how you are getting on.

Side effects

Having epacadostat and pembrolizumab together is a new combination of treatment. And epacadostat is a new drug, so there might be some side effects we don’t know about yet.

The study team will monitor you during the time you have treatment and you’ll have a phone number to call them if you are worried about anything.

The most common side effects of epacadostat include:

The most common side effects of pembrolizumab include:

  • tummy pain
  • constipation or diarrhoea
  • feeling sick
  • tiredness (fatigue)
  • itchy skin or skin rash
  • high temperature (fever)
  • loss of appetite
  • back pain
  • headache
  • cough
  • difficulty breathing
  • a drop in the number of red blood cells in your blood which can cause tiredness – we call this anaemia Open a glossary item
  • liver damage that will get better when you finish treatment
  • joint pain

The study team will talk to you about all the possible side effects of having treatment. We have more information about pembrolizumab.

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 Katy Clarke

Supported by

Merck, Sharp & Dohme

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:


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

Wendy took part in a new trial studying the possible side effect of hearing loss

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