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

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  or MRI scan  or bone scan  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  (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  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 ) 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  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  treatment or similar radioactive  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  (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  or carcinoma in situ

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

• have an autoimmune disease  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  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
• 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  of the immune system. Your doctor will be able to discuss this further with you. 
• have had a targeted drug  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

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  within 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