A trial of pembrolizumab with olaparib for prostate cancer (KEYLYNK 010)

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

Cancer type:

Prostate cancer

Status:

Closed

Phase:

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 the combination of pembrolizumab and olaparib with:

  • abiraterone and prednisolone or  
  • enzalutamide on its own
     

More about this trial

Abiraterone is a hormone treatment doctors use to treat prostate cancer. You have the steroid prednisolone with abiraterone to help reduce some of its side effects.

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. 

Olaparib is a targeted drug Open a glossary item called a PARP inhibitor. It stops a protein called PARP from working. Some cancer cells use PARP to repair damaged DNA Open a glossary item. When olaparib stops PARP from repairing the DNA the cancer cells die. 

Doctors use pembrolizumab and olaparib on their own to treat other types of cancer. 

Researchers think the combination of pembrolizumab and olaparib might help men with prostate cancer that has spread. 

In this trial some men have pembrolizumab and olaparib. And some have either abiraterone and prednisolone or enzalutamide on its own. 

The aims of this trial are to find out:

  • how well the combination of pembrolizumab and olaparib works
  • how safe it is 
  • how this combination 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 after surgery to remove the testicles within 6 months of randomisation Open a glossary iteminto this trial. If you were having flutamide your cancer must have got worse 4 weeks or more after your last treatment. If you were having bicalutamide or nilutamide it must have got worse 6 weeks or more after your last treatment. 
  • 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 either abiraterone or enzalutamide
  • have had docetaxel for prostate cancer that had spread and the cancer spread got worse during or after treatment
  • 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 (LRHR) agonists or antagonists and have not had surgery to remove the testicles you must have started the LRHR 4 weeks before you go through randomisation for this trial
  • have satisfactory blood test results
  • are willing to use a condom during treatment and for 6 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 6 months after. 
  • are fit and able to do all your daily activities but might not be able to do 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. You may still be allowed to join if you have an older sample available. 
  • 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 areas of small cell type cancer in your prostate 
  • have had both abiraterone and enzalutamide before  
  • 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. You must have no side effects from previous radiotherapy, must not be taking 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 itemtreatment or similar radioactive Open a glossary itemdrugs 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 apalutamide or darolutamide, or enzalutmide for prostate cancer which is responding to hormone therapy (hormone sensitive prostate cancer)
  • have had olaparib or another PARP inhibitor
  • 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
  • have a myelodysplastic syndrome Open a glossary item (MDS) or  acute myeloid leukaemia Open a glossary item (AML) or symptoms which might indicate you have these conditions 
  • have had a certain type of bone scan called a bone ‘superscan’

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

  • have had growth factors Open a glossary item such as G-CSF or GM-CSF within 28 days of randomisation
  • 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 a hereditary Open a glossary itemcondition where your body is unable to absorb certain sugars such as galactose, lactose or glucose
  • 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 of more than 10mg of prednisolone or any other medication that affects your immune system
  • have had a fit (seizure) within 6 months of giving consent to take part in the trial (informed consent) 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 fluid on the abdomen (ascites) or you have fluid on the lung (pleural effusion) that needs medical attention
  • have had a loss of consciousness within the past year
  • have symptoms of congestive heart failure 
  • 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 can tell you more about this. 
  • 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. Your doctor can tell you more about this.  
  • are taking medication or herbal products that affect the CYP enzymes. You might be able to join the trial if you can stop taking these but there needs to be a number of weeks before stopping them and starting olaparib. You doctor can talk to you about this. 
  • are taking finasteride, dutasteride or similar drugs, oestrogens or cyproterone acetate 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 had a whole blood transfusion within 120 days of randomisation. For red blood cells Open a glossary itemon their own and or platelets Open a glossary itemon their own it is within 28 days of randomisation. 
  • have had an experimental drug or used an experimental device as part of a clinical trial within 4 weeks of randomisation
  • have moderate nerve damage (neuropathy) causing weakness, numbness, and pain apart from when caused by an accident
  • have any other medical condition or mental health problem that your doctor or the trial team think might affect you taking part

Other
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 item within 30 days of randomisation
  • are expecting to father a child from when you join the trial, during and within 6 months (180 days) after your last treatment in the trial
     

Trial design

This is an international phase 3 trial. The team need up to 780 people to join worldwide with around 40 joining in the UK. 

It is a randomised trial. There are 2 groups. Neither you nor your doctor choses which group you are in. You and your doctor will both know which group you are in. The groups are:

  • pembrolizumab and olaparib
  • abiraterone with prednisolone or enzalutamide on its own

Out of every 3 people who join, 2 go into the pembrolizumab and olaparib group.

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. 

Olaparib is a tablet or a capsule. You take it twice a day. 

Abiraterone is a tablet. You take it once a day. 

Prednisolone is a tablet. You take it twice a day. 

Enzalutamide is a capsule. You take it once a day. 

You continue taking which ever treatment you are on as long as they are still working and the side effects aren’t too bad.  

Men having pembrolizumab and olaparib should not eat or drink the following while on treatment:

  • grapefruit and grapefruit juice
  • Seville oranges and Seville orange juice
  • St John’s wort both tea and tablets

This is because they can affect how pembrolizumab and olaparib work. Your doctor will talk to you about this.

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

You give blood samples and urine samples regularly 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:

  • 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

Some of these questionnaires are completed at home in between treatment visits on an electronic device similar to a mobile phone. 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.

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 then again a month after you finish treatment. After this you see the doctor every 9 weeks for a year and then every 12 weeks.  

During the trial if your cancer gets worse, or you have started another cancer treatment, the study team will see you every 12 weeks. For some of them they might phone you. 

You have a scan every 9 weeks and then every 12 weeks. If your disease has gotten worse, you may not need to have any more scans as part of the study.
 

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, tiredness and lack of energy
  • low levels of salt in the blood (hyponatremia) causing tiredness, confusion, headaches, muscle cramps and feeling sick
  • diarrhoea

The most common side effects of olaparib are:

  • feeling or being sick
  • tiredness and weakness (fatigue)
  • indigestion and heartburn
  • loss of appetite
  • changes to taste
  • headache
  • dizziness
  • diarrhoea (tell your doctor straightaway if this gets severe)
  • cough and shortness of breath
  • rash
  • sore mouth
  • stomach pain
  • a drop in blood cells causing tiredness, an increased risk of infection, bruising and bleeding
  • an increase in blood creatinine. This test is used to check how your kidneys are working.

We have information about:

Your doctor or a member of the trial team will talk about the possible side effects from treatment before you agree to join 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

Freephone 0808 800 4040

Last review date

CRUK internal database number:

17104

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

Keith took part in a trial looking into hormone therapy

A picture of Keith

"Health wise I am feeling great. I am a big supporter of trials - it allows new treatments and drugs to be brought in.”

Last reviewed:

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