A trial of pembrolizumab for cancer of unknown primary (CUPem)

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

Cancer type:

Cancer of unknown primary (CUP)
Secondary cancers




Phase 2

This trial is looking at pembrolizumab for people who have cancer of unknown primary (CUP).

Cancer of unknown primary means that cancer spread has been found in your body (secondary cancer). But your doctors can't find where the cancer started (the primary cancer).

More about this trial

Chemotherapy is one of the main treatments for cancer of unknown primary (CUP). But sometimes it doesn’t work or the cancer comes back. So doctors are looking for ways to improve treatment. In this trial they are looking at a drug called pembrolizumab.     

Pembrolizumab is a type of immunotherapy. It stimulates the body's immune system Open a glossary item to fight cancer cells.

Some people in this trial have already had chemotherapy for CUP. And some haven’t and are having pembrolizumab as their first treatment. 

The main aims of the trial are to:

  • find out if pembrolizumab works better than chemotherapy
  • learn more about the side effects
  • see how treatment affects quality of life

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 if all of the following apply. You:

  • have cancer spread in your body but the doctors don’t know where the cancer started (cancer of unknown primary or CUP)
  • have had chemotherapy for CUP but it didn’t work, your cancer came back or you had to stop treatment because of bad side effects, or you haven’t had chemotherapy 
  • have cancer that your doctor can measure on a scan 
  • have a sample of tissue (biopsy Open a glossary item) available for the trial team to test
  • are well enough to be up and about for at least half the day (performance status 0, 1 or 2
  • have satisfactory blood test results 
  • are willing to use reliable contraception during treatment and for 120 days afterwards if you or your partner could become pregnant
  • are at least 18 years old 

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

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

  • have cancer spread in your brain or spinal cord. You might be able to take part if the cancer has been stable for 4 weeks and you haven’t had steroids in the 7 days before starting trial treatment.
  • have cancer spread in the tissues that surround the brain (carcinomatous meningitis)
  • have taken part in a trial that used an experimental drug or device within 4 weeks of starting trial treatment
  • have had a monoclonal antibody Open a glossary item or immunotherapy Open a glossary itemwithin 4 weeks of starting trial treatment or you have side effects from these treatments unless they are mild
  • have had chemotherapy, targeted drugs Open a glossary item or radiotherapy within 2 weeks of starting trial treatment or you have side effects that aren’t better unless they are mild
  • have had treatment with pembrolizumab or a similar drug in the past
  • have another cancer that is getting worse or needs treatment apart from non melanoma skin cancer Open a glossary itemor carcinoma in situ (CIS Open a glossary item) of the cervix that has been successfully treated

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

  • have an active autoimmune disease Open a glossary item that needed treatment in the last 2 years apart from diabetes or hormone problems that are controlled by medication 
  • have a problem with your immune system Open a glossary item or you are having steroids or any other medication that damps down the immune system within 7 days of starting trial treatment 
  • have or have had tuberculosis (TB)
  • have or have had inflammation of the lung caused by treatment (pneumonitis) and you needed treatment with steroids
  • have an active infection that needs treatment
  • have HIV
  • have an active hepatitis B or hepatitis C infection
  • have any other medical condition, mental health problem or problem with drugs or alcohol that the trial team think would affect you taking part 

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

  • are sensitive to pembrolizumab or anything it contains
  • are pregnant or breastfeeding
  • are planning a pregnancy or to father a child during the trial
  • have had a live vaccine  Open a glossary itemwithin 30 days of starting trial treatment

Trial design

This is a phase 2 trial.  It is taking place in the UK. The researchers need 77 people to join. 

Everyone has pembrolizumab. You have treatment as a drip into a vein. You have treatment once every 3 weeks. The treatment takes 30 minutes each time. But you will be at the hospital for longer than this. 

You have treatment for as long as it is working and the side effects aren’t too bad. 

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

Samples for research
The researchers ask for a sample of your cancer (biopsy) Open a glossary item that doctors took when you were diagnosed.  

They also ask for some extra blood samples. Where possible, you have these at the same time as your routine blood tests.

They plan to use the samples to: 

  • look at genes Open a glossary item
  • look for biomarkers Open a glossary itemto predict who will benefit from treatment

Quality of life
The study team will ask you to fill out a questionnaire before you start treatment and at set times during treatment. The questionnaire asks about side effects and how you’ve been feeling. This is called a quality of life study.

    Hospital visits

    You see a doctor and have some tests before you can take part in the trial. These include:

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

    You have your treatment at the hospital in the outpatient department. You see the trial doctor once every 3 weeks for a check up and blood tests. 

    You have a CT scan every 3 months until your cancer gets worse. 

    If you stop treatment but your cancer isn’t worse, you continue to have a CT scan every 2 months.

    When you stop treatment you see the trial team 1 month later for a check up.

    You continue to see or speak with the trial team every 4 months. This is to check how you are getting on.

    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. You should tell them that you are on or have been on an immunotherapy. 

    The common side effects of pembrolizumab are:

    • itchy skin or skin rash 
    • diarrhoea
    • cough
    • joint pain
    • fever
    • back pain
    • pain in your belly
    • loss of skin colour
    • low levels of thyroid hormone that may cause you to feel tired, gain weight, feel cold, or be constipated
    • low levels of salt in the blood that may cause you to feel tired, feel confused, have a headache, have muscle cramps or feel sick  

    The trial doctor or a member of the trial team talk to you about all the possible side effects of treatment.

    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 Harpreet Wasan

    Supported by

    Imperial College London
    Merck Sharp & Dohme Ltd

    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.

    Cara took part in a clinical trial

    A picture of Cara

    "I am glad that taking part in a trial might help others on their own cancer journey.”

    Last reviewed:

    Rate this page:

    Currently rated: 5 out of 5 based on 1 vote
    Thank you!
    We've recently made some changes to the site, tell us what you think