A trial looking at adding pembrolizumab to other cancer treatments for people with prostate cancer that has spread (KEYNOTE-365)

Cancer type:

Prostate cancer
Secondary cancers

Status:

Open

Phase:

Phase 1/2

This trial is looking at a drug called pembrolizumab in combination with other drugs in prostate cancer.

It is for people with metastatic castration resistant prostate cancer (mCRPC). This means that the cancer:

  • has spread to other parts of the body (advanced prostate cancer)
  • got worse despite having hormone treatment

More about this trial

Advanced prostate cancer is when the cancer has spread from the prostate to another part of the body (metastatic prostate cancer). A common treatment for advanced prostate cancer is hormone therapy. This can work well for a period of time, but the cancer can start to grow again.

Doctors are working on new treatments for when other treatments have stopped working.  

Pembrolizumab (Keytruda) is a type of targeted drug called a monoclonal antibody Open a glossary item. It targets and blocks a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the immune system cells to find and kill cancer cells.

The trial team are looking at giving pembrolizumab with other cancer drugs such as:

The aims of the trial are to:

  • see how safe it is to have pembrolizumab with other drugs for advanced prostate cancer
  • learn more about side effects
  • see how well pembrolizumab works alongside other drugs

Who can enter

Please note there are several treatment groups so the entry conditions for this trial are complex. Each group has specific entry conditions and we haven’t listed them all. Some groups are closed now.

The trial team will check if you are suitable to join the trial and which group you might join. They can tell you more about this.

Your doctor decides which group is best for you. To help them decide, they look at:

  • what type of treatment you have already had
  • the type of cells in your cancer – this is either adenocarcinoma or neuroendocrine cancer that has developed after previous treatment (treatment emergent neuroendocrine cancer)
  • what they think would be the best treatment for you
  • your medical history

The following bullet points are a summary of the main 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 prostate cancer that has spread to other parts of the body and got worse despite having hormone treatment (metastatic castration resistant prostate cancer)
  • have prostate cancer which has been getting worse (progressed) within the 6 months before joining the trial
  • have a cancer tissue sample from an area where you have not had radiotherapy before. Or you have a sample from an area where you have had radiotherapy before - but your cancer is growing again in the same place.
  • are receiving treatment to lower the amount of male sex hormones in your body (androgen deprivation). Your treatment must have started at least 4 weeks before the first dose of the study drug. Or you have had surgery to remove the testicles (orchidectomy).
  • have adequate blood tests results including testosterone level.
  • are willing to use reliable contraception if there is a chance your partner could become pregnant. The exact timing depends on which group you are in.
  • are at least 18 years old

Who can’t take part

Cancer related

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

  • are still experiencing significant side effects from having major surgery or from other cancer treatment you have had in the past
  • have had another cancer within the past 3 years that has been getting worse, or needed treatment – apart from basal cell skin cancer Open a glossary item or squamous cell skin cancer that have been treated with the aim to cure
  • have had certain monoclonal antibody treatments within the 4 weeks before starting treatment on this trial. You might still be able to take part if you are taking denosumab for cancer that has spread to the bone. Your doctor can explain more.
  • have had certain monoclonal antibodies more than 4 weeks before starting the study drug, but you have still not recovered from their side effects
  • have had radium therapy for your prostate cancer or any other types of radioisotope treatment for your prostate cancer
  • have had pembrolizumab before or had any very similar drugs to pembrolizumab in the past. Your doctor can explain more.
  • have cancer that has spread to the central nervous system Open a glossary item (CNS). You may be able to take part if you have had treatment in the past for cancer that has spread to the CNS and it is now stable. Your doctor will explain more.
  • have cancer that has spread to the leptomeningeal layers of the central nervous system 
  • have had chemotherapy, targeted cancer drugs, certain types of hormone therapy or radiotherapy in the 2 weeks before the first dose of the study drug. Your doctor can explain more.
  • have had a bone scan called a ‘superscan’. Your doctor can explain more.
  • have been taking bone strengthening drugs, for example bisphosphonates, for 4 weeks or less before the first dose of the study drug

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

  • have an immune deficiency Open a glossary item. Or you have been taking long term steroids that reach your whole body or other drugs that lower your immune system in the 7 days before your trial treatment is decided.
  • have an active autoimmune disease Open a glossary item which has required systemic treatment Open a glossary item in the past 2 years. You can still take part if you take replacement therapy, such as insulin or steroids, if your body does not make enough. Your doctor can explain more.
  • have inflammation of the lung tissue (pneumonitis) or if you have had pneumonitis which needed steroid treatment before
  • have an infection needing treatment that reaches the whole body
  • have any other medical problem, mental health condition or are taking any medication that the trial team think would affect you taking part
  • have HIV
  • have active hepatitis B or hepatitis C
  • have had an organ transplant or bone marrow transplant Open a glossary item in the past

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

  • have had a live vaccine Open a glossary item within 30 days before the first dose of the study drug
  • have taken any herbal medicines that may have affect prostate hormones or are known to decrease prostate specific antigen Open a glossary item levels (such as saw palmetto, ginko or turmeric) within the 4 weeks before your treatment group is decided
  • have had another trial drug or used a healthcare product as part of another clinical trial or study in the 4 weeks before the first dose of the study drug

As well as the above there are specific entry conditions and exclusion criteria for each treatment group. Speak to your doctor or research nurse if you want to find out more about the entry conditions for this trial.

Trial design

This is an international phase 1/2 trial. The trial team need around 1,000 people worldwide to join including 32 from the UK.

Because the trial team are looking at different combinations of drugs with pembrolizumab, everyone is put into one of 9 groups. And each group has a different drug combination.

Please note that groups A to D are closed to further recruitment. Groups E, F,G,H and I may be open for people to join. You can talk to the trial doctor about this.  

Group E
This group is for people with adenocarcinoma. You have pembrolizumab and lenvatinib. Lenvatinib is a type of targeted cancer drug called a cancer growth blocker.

You have pembrolizumab as a drip into a vein. You have lenvatinib as capsules.

Group F
This group is for people with neuroendocrine cancer that has developed after previous treatment. This is treatment emergent neuroendocrine cancer. You have pembrolizumab and lenvatinib. Lenvatinib is a type of targeted cancer drug called a cancer growth blocker.

You have pembrolizumab as a drip into a vein. You have lenvatinib as capsules.

Group G
This group is for people with adenocarcinoma. You have MK-7684A. This is a mixture of an immunotherapy drug called vibostolimab (MK-7684) and pembrolizumab. Vibostolimab is a type of monoclonal antibody.

You have MK-7684A as a drip into a vein.

Group H
This group is for people with neuroendocrine cancer that has developed after previous treatment. This is treatment emergent neuroendocrine cancer. You have MK-7684A. This is a mixture of an immunotherapy drug called vibostolimab and pembrolizumab. Vibostolimab is a type of monoclonal antibody.

You have MK-7684A as a drip into a vein.

Group I
This group is for people with neuroendocrine cancer that has developed after previous treatment. This is treatment emergent neuroendocrine cancer. 
There are two different treatment options for group I. 

It is a randomised part of the trial. You are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in.

You have 1 of the following:

Carboplatin and etoposide are chemotherapy drugs. 

You have pembrolizumab and the chemotherapy drugs as a drip into a vein.

Closed groups
The following groups are now closed and no more people can join. These groups are as follows.

Group A have pembrolizumab and olaparib
Group B have pembrolizumab, docetaxel Open a glossary item and prednisolone. 
Group C have pembrolizumab and enzalutamide
Group D have pembrolizumab, abiraterone acetate and prednisolone. 

Having treatment on the trial
The team tell you when you will have treatment and for how long. This is different for each group. 

For people having pembrolizumab this is for up to two years, as long as it is working, and the side effects are not too bad.

If you are having pembrolizumab or MK-7684A and all signs of your cancer disappear (complete response Open a glossary item) you might be able to stop these drugs early, after at least 8 doses. You and your doctor will talk about this at the time.

If the scan shows that your cancer is getting worse, the trial team will ask you to have another scan 4 or 6 weeks later. This is to confirm that your cancer is getting worse. Depending on the results of the second scan you might be able to continue with the study drugs or your doctor will advise other treatment options for you.

You may be able to have more treatment with pembrolizumab or MK-7643A. Your doctor can tell you more.

Research samples
You give blood samples and tissue samples during the trial. Your doctor will tell you how many and how often.

The trial team use these samples to:

  • look for substances called (biomarkers Open a glossary item)
  • find out how the treatment works
  • find out how your body responds to treatment
  • see why treatment might work better for some men and not others

The team are also using blood tests to look at:

  • your testosterone Open a glossary item levels
  • the amount of prostate specific antigen (PSA) in your blood, as a way of monitoring your prostate cancer
  • the amount of study drug in your body (pharmacokinetics Open a glossary item) – for people in group G only
  • natural antibodies Open a glossary item made by your body that attach to vibostolimab and pembrolizumab in your blood – for people in group G only

Future research
The trial team would like to collect some samples for future research if you are in a certain group. They will ask your permission for this. You can say no and still take part in the trial.

Hospital visits

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

  • physical examination
  • height, weight, temperature, pulse, breathing rate and blood pressure measured
  • taking a fresh sample of tissue (biopsy Open a glossary item) – if you have had a recent biopsy the trial team might be able to use this instead. Your trial doctor will explain more.
  • heart trace (ECG Open a glossary item)
  • blood tests
  • urine test
  • scans such as an MRI scan, CT scan or bone scan

You have a heart scan (ECHO) Open a glossary item – if you are in group E or F.

Each cycle of treatment Open a glossary item takes around 3 weeks. So, during treatment you see the doctor around every 3 weeks for bloods and to see how you are. You might be contacted by, or have to see, the study team more regularly depending on which treatment group you are in.

You might have your blood pressure measured in between hospital visits by a local healthcare professional.

Scans during treatment
You have an MRI scan or CT scan, and bone scan:

  • at the start of treatment
  • every 9 weeks after the start of the study treatment for the first year
  • every 12 weeks in the second year

After treatment and follow up
You have an end of treatment visit. You have some tests at this visit, these include:

  • physical examination
  • measuring your weight, temperature, pulse, breathing rate and blood pressure 
  • blood tests
  • urine test
  • heart trace (ECG]) (groups E&F only)

You see the team 30 days after the last dose of the study drug. This is to see how you are getting on, have some blood tests and an ECG (groups E&F only).

In the follow up stage, your doctor will let you know when you need to come into the hospital or when they will contact you. The trial team would like to keep in contact to see if there have been any changes and find out how you are feeling.

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 and MK-7684A can affect the immune system. They may cause inflammation in different parts of the body. This 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 tell your doctor or nurse as soon as possible. You should tell them that you are on or have been on an immunotherapy.

 

The most common side effects of pembrolizumab are:

  • rash, itching and loss of skin colour
  • diarrhoea
  • cough
  • high temperature (fever)
  • joint or back pain
  • pain in the tummy (abdomen)
  • the thyroid gland Open a glossary item not making enough hormones. This can cause tiredness, weight gain, feeling cold or constipation
  • a low amount of salt in the blood. This can cause tiredness, confusion, headaches, muscle cramps and or feeling sick.

We have more information about the side effects of pembrolizumab.

The trial team gives you separate information on the possible side effects of MK-7684A if you have this treatment. You can ask any questions you have before you start.

We have information about the possible side effects of lenvatinib

In general, the most common side effects of chemotherapy are:

We have more information on the side effects of:

Location

London

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 DeBono

Supported by

Merck Sharp & Dohme LLC

Freephone 0808 800 4040

Last review date

CRUK internal database number:

17603

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

Charlie took part in a trial to try new treatments

A picture of Charlie

“I think it’s really important that people keep signing up to these type of trials to push research forward.”

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