A trial looking at pembrolizumab combined with enzalutamide for prostate cancer (KEYNOTE 641)

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

Cancer type:

Prostate cancer




Phase 3

This trial is for men with prostate cancer that has spread and is getting worse despite having hormone therapy or having their testicles removed. This is called metastatic castration resistant prostate cancer. 

The trial is comparing pembrolizumab and enzalutamide with a dummy drug (placebo) and enzalutamide. 

More about this trial

Enzalutamide is a hormone treatment doctors use to treat prostate cancer that has spread to another part of the body. 

Pembrolizumab is an immunotherapy. It works by stimulating the immune system Open a glossary item to fight cancer. Pembrolizumab is used to treat other types of cancer. 

Researchers think the combination of enzalutamide and pembrolizumab might work well for men with prostate cancer that has spread and is getting worse. 

To find this out in this trial:

  • half the men have enzalutamide and pembrolizumab 
  • half the men have enzalutamide and a dummy drug (placebo Open a glossary item)

The aims of this trial are to find out:

  • how well the combination of enzalutamide and pembrolizumab works
  • how safe it is 
  • how it affects quality of life Open a glossary item

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. 

Who can take part

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

  • have adenocarcinoma of the prostate
  • have cancer that is getting worse while having hormone therapy or surgery to remove your testicles. Your doctor can give you details about how long you need to have had hormone therapy for.
  • have a CT scan Open a glossary item or MRI scan Open a glossary item or bone scan Open a glossary item that shows your cancer has spread to another part of the body
  • have had abiraterone for at least 4 weeks for your cancer spread without it getting worse or you had abiraterone for your cancer spread and it got worse after at least 8 weeks of treatment. If the cancer spread is in the bones it must have got worse after at least 14 weeks of treatment.. Your disease must have got worse since you stopped this treatment. If you stopped due to side effects, you must have received at least 4 weeks of treatment before this. 
  • are having treatment that stops the production of testosterone Open a glossary item (anti androgens or luteinising hormone blockers) and your testosterone level in the blood is less than 50 ng/dL. If you are having luteinising hormone-releasing (LHRH) agonists or antagonist (if you have not had surgery to remove the testicles) you must have started the LHRH 4 weeks before randomisation Open a glossary item in this trial
  • had flutamide at least 4 weeks ago or bicalutamide or nilutamide at least last 6 weeks ago if you had any of these three drugs before joining this trial
  • have satisfactory blood test results
  • are willing to use a condom during treatment and for 3 months after if there is any chance you can pass your ejaculate to another person of any sex. You should not store any sperm during treatment or for 3 months after. 
  • are fit and able to do all your daily activities but might not be able to heavy physical work (performance status 0 or 1)
  • have a sample of tissue (biopsy Open a glossary item) available of your cancer spread that was taken within the past year. If not you are willing to have a fresh sample done, it may be possible to use older tissue. 
  • are at least 18 years old   

Who can’t take part

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

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

  • have areas of small cell type cancer in your prostate
  • have cancer spread only to the lymph nodes Open a glossary item in the area between your hips (pelvis)
  • have had ketoconazole and your cancer got worse while having it
  • have had chemotherapy for your cancer spread unless it was docetaxel for cancer spread while hormone therapy was still working and the last dose of docetaxel was more than 4 weeks ago
  • have cancer that has spread to your brain or spinal cord unless it has been treated and you’ve had a scan within 4 weeks of randomisation which  shows there is no sign of it getting worse, you have no symptoms and have not needed steroids for 7 days before randomisation
  • have cancer spread into the tissue covering the brain or spinal cord (carcinomatosis meningitis)
  • have had radiotherapy within 2 weeks of randomisation. If you have had any radiotherapy you must have no remaining side effects, not take corticosteroids and have no lung inflammation caused by radiotherapy. For radiotherapy for symptom control (palliative radiotherapy) it is 1 week. 
  • have had radium Open a glossary item treatment or similar radioactive Open a glossary item drugs to treat prostate cancer  
  • have had treatment to slow or prevent bone damage such as a bisphosphonate or denosumab and the dose has not been the same for 4 weeks or more before randomisation  
  • have had enzalutamide, apalutamide or darolutamide 
  • have had a monoclonal antibody Open a glossary item (MAB) within 4 weeks of randomisation or still have side effects within 4 weeks of randomisation
  • have ongoing moderate side effects from cancer treatment apart from hair loss (alopecia) or nerve damage (neuropathy)
  • have another cancer that is getting worse or that has needed treatment in the past 3 years apart from successfully treated non melanoma skin cancer Open a glossary item or carcinoma in situ Open a glossary item

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

  • have an autoimmune disease Open a glossary item that has needed treatment that reaches the whole body (systemic treatment) in the past 2 years apart from medication to replace substances in the body such as hormones for an underactive thyroid or insulin for diabetes 
  • have a problem with your digestive system Open a glossary item that affects how well it absorbs medication, such as an operation to remove part of the stomach or a stomach ulcer (peptic ulcer), in the past 3 months
  • have inflammation of the lung (pneumonitis) that isn’t caused by an infection or you had pneumonitis in the past that needed treatment with steroids
  • have an active infection including tuberculosis (TB) that needs treatment
  • have HIV, hepatitis B or hepatitis C
  • have a condition that affects the immune system Open a glossary item
  • are taking steroids equal to or more than 10mg of prednisolone or any other medication that affects your immune system within 7 days of starting the study treatment
  • have had a fit (seizure) or you have a medical condition that means you are more likely to have fits such as a cerebrovascular accident (CVA) or a mini stroke (TIA) 
  • have had a loss of consciousness within the past year
  • have had a heart attack or chest pain (angina) within 6 months of randomisation. You can take part if you had an operation to improve the blood flow in the vessels in your heart within 3 months of randomisation. 
  • have an abnormal heart rhythm such as a fast or slow heartbeat that is affecting your daily life
  • have moderate to severe heart block and don’t have a pacemaker 
  • have low blood pressure, or you have high blood pressure that isn’t controlled by medication
  • have had major surgery within 28 days of randomisation and you have not recovered from the side effects or complications
  • have taken herbal products that might affect the prostate or lower the PSA such as saw palmetto within 4 weeks before randomisation
  • have had treatment with a drug that blocks the proteins PD-1 ,PD-L1 or PD-L2 or a drug that stimulates or blocks T cells Open a glossary item of the immune system. Your doctor will be able to discuss this further with you. 
  • have had a targeted drug Open a glossary item within 4 weeks of randomisation or you still have ongoing side effects apart from hair loss or nerve damage (neuropathy). Your doctor will be able to discuss this further with you.
  • are taking finasteride, dutasteride or similar drugs, oestrogens or cyproterone acetate within 4 weeks of randomisation
  • have had an experimental drug or used an experimental device as part of a clinical trial within 4 weeks of randomisation
  • have had a bone marrow transplant using a donor’s bone marrow (allogeneic transplant), double umbilical cord transplant or a solid organ transplant
  • have any other medical condition or mental health problem that your doctor or the trial team think might affect you taking part

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

  • are sensitive or allergic to any of the drugs used in this trial or any of their ingredients
  • are not able swallow tablets or capsules
  • have had a live vaccine  Open a glossary itemwithin 30 days of randomisation
  • are expecting to father a child from when you join the trial, during and within 3 months after your last treatment in the trial 
  • have had a type of bone scan called a superscan

Trial design

This is an international phase 3 trial. The trial team need about 1,200 men to join worldwide with around 70 men in the UK.

This is a randomised trial. You go into 1 of 2 groups. Neither you nor your doctor chooses which group. The 2 groups are:

  • enzalutamide and pembrolizumab
  • enzalutamide and a dummy drug (placebo)

You have pembrolizumab as a drip into a vein. You have it once a week every 3 weeks. You continue to have pembrolizumab for up to 2 years as long as it is working and the side effects aren’t too bad. 

Enzalutamide is a capsule or tablet. You take it once a day. You continue taking it as long as the side effects aren’t too bad and it is still working. 

Research samples
When you join the trial you give a fresh tissue sample (biopsy Open a glossary item). If this isn’t possible the team may ask for a piece of tissue from when you had an earlier biopsy. 

You give blood samples and urine samples during the trial. The team use these samples to see what happens to the drugs in your body and how they affect your body. They also use them to look for substances (biomarkers Open a glossary item) that might show how well the drugs are working. 

Quality of life
You fill in a questionnaire at the hospital:

  • when you join the trial
  • several times during treatment
  • when you finish treatment and 
  • a month after finishing treatment

The questions ask about:

  • your general health
  • what you can do
  • how you are feeling

This is a quality of life questionnaire

You will also have an electronic device similar to a mobile phone to take home with you to complete other quality of life questionnaires. The device alerts you when to fill in the questionnaire.

Pain questionnaire
The trial team want to know if you have any pain and what medication you take if you do. You have a diary to write down what pain medication you use at home.

You bring both the device and the diary to all your clinic visits in the hospital. 

Hospital visits

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

During the treatment you see the doctor every 3 weeks for blood tests and to see how you are. 

You see the doctor when you stop treatment and again a month later. 

If your cancer has not yet got worse and you haven’t started another treatment, you then see the doctor every 9 weeks for a year and then every 12 weeks. You have a scan every 9 weeks for the first year and then every 12 weeks.

If your cancer has got worse or you have started another treatment, your doctor or study team will contact you at least every 12 weeks to see how you are.

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. It may cause inflammation in different parts of the body which 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.

If you have any of these side effects, you should tell the doctor or nurse as soon as possible that you are on or have been on an immunotherapy. 

The most common side effects of pembrolizumab are:

  • itching, rash, loss of skin colour
  • diarrhoea
  • cough
  • joint and back pain
  • high temperature (fever)
  • stomach pain
  • your thyroid not making enough hormones (hypothyroidism) causing weight gain, feel cold, tiredness and lack of energy, or having infrequent or hard poo (stool) 
  • low levels of salt in the blood (hyponatremia) causing tiredness, confusion, headaches, muscle cramps and feeling sick

We have information on enzalutamide

Your doctor or a member of the trial team will talk to you about the possible side effects before you agree to join the trial, and regularly throughout the trial. 

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

Professor Johann de Bono

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.

Last reviewed:

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