A trial comparing usual treatment with pembrolizumab for bowel cancer that has spread (KEYNOTE 177)

Cancer type:

Bowel (colorectal) cancer
Colon cancer
Rectal cancer

Status:

Open

Phase:

Phase 3

This trial is open to people with certain gene changes (mutations) in the bowel cancer genes. These gene changes are microsatellite instability high (MSI-H) or mismatch repair deficiency (dMMR).

More about this trial

Chemotherapy is the usual treatment for bowel (colorectal) cancer that has spread to another part of the body (advanced cancer). You might have this alongside a monoclonal antibody Open a glossary item therapy drug such as bevacizumab or cetuximab. 

Pembrolizumab (also known as MK-3475) is a type of biological therapy Open a glossary item. It helps the immune system Open a glossary item to recognise and attack cancer cells. 

Researchers think it might work better than usual treatment for people with the gene changes (mutations Open a glossary item) microsatellite instability high (MSI-H) or mismatch repair deficiency (dMMR). But they aren’t sure, so they want to find out more. Your doctor will test for the gene changes before you can take part. 

In this trial, some people have usual treatment Open a glossary item and some have pembrolizumab. 

The aims of this trial are to 

  • compare usual treatment with pembrolizumab to see which works best
  • learn more about the side effects

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. 

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

  • Have bowel (colorectal) cancer that has spread to another part of the body
  • Have microsatellite instability high (MSI-H) or mismatch repair deficiency in the bowel cancer genes
  • Have cancer that can be seen on a scan
  • Are well enough to carry out all your normal activities, apart from heavy physical work (performance status 0 or 1)
  • Have satisfactory blood test results 
  • Are willing to use reliable contraception during treatment and for up to 6 months afterwards if there is any chance that you or your partner could become pregnant
  • Are at least 18 years old 

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

  • Have cancer that has spread to your brain and is causing symptoms. You might be able to take part if you have had treatment and the cancer isn’t causing any symptoms, it has not got any worse or you haven’t taken steroids Open a glossary item in the last 28 days
  • Have inflammation of the covering of the brain (carcinomatous meningitis)
  • Have already had treatment that reaches the whole body (systemic treatment) for advanced bowel cancer. You might still be able to take part if you had chemotherapy after surgery and it finished more than 6 months ago. 
  • Have had radiotherapy in the last 4 weeks and haven’t recovered from side effects. You might be able to take part if you had radiotherapy to areas of cancer spread to help with symptoms and have recovered from short term side effects
  • Have had previous treatment with any anti-PD1, anti-PDL1, anti-PD2 or anti-CTLA-4 drugs such as ipilimumab, nivolumab or any similar drugs 
  • Are having or have had treatment or used an experimental device as part of a clinical trial within 4 weeks of joining this trial
  • Are sensitive to any of the drugs used in the trial or there is any other reason you might not be able to have them
  • Have another cancer that is getting worse or needs treatment apart from non melanoma skin cancer Open a glossary item or very early cancer of the cervix (CIS) that has been successfully treated
  • Have an autoimmune disease Open a glossary item such as rheumatoid arthritis or multiple sclerosis and you have had treatment in the last 2 years. If you have had treatment to replace hormones in the body, you might still be able to take part.
  • Have problems with your immune system Open a glossary item or have taken drugs that suppress your immune system in the last 7 days
  • Have a inflammation of the lung called pneumonitis or interstitial lung disease
  • Have had major surgery, a biopsy or a traumatic injury in the last 28 days
  • Have had a live vaccine Open a glossary item in the last 30 days
  • Have an infection that needs treatment as a drip into a vein
  • Are known to have HIV 
  • Have or have had hepatitis B or hepatitis C
  • Have a significant problem with drugs or alcohol 
  • Have any other serious medical condition or mental health problem that the trial team think could affect you taking part
  • Are pregnant or breastfeeding

Trial design

This is an international phase 3 trial. Researchers need 270 people to take part including at least 4 from the UK. 

It is a randomised trial. You are put into 1 of 2 treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in.

  • One group have pembrolizumab 
  • The other group have 1 of the following usual treatments

              o    FOLFOX
              o    FOLFORI
              o    FOLFOX and bevacizumab
              o    FOLFOX and cetuximab
              o    FOLFIRI and bevacizumab
              o    FOLFIRI and cetuximab

Diagram for KEYNOTE 177 trial design

Usual treatment 
If you are having usual treatment, your doctor will explain which drugs they think are best for you. They will also explain how often you have them. You have treatment for as long as it is helping you and the side effects aren’t too bad. 

If your cancer gets worse, you stop treatment. You might be able to start having pembrolizumab. Your doctor can tell you more if this applies. 

Pembrolizumab
You have pembrolizumab through a drip into a vein once every 3 weeks. Each 3 week period is called a cycle of treatment. You have it for up to 2 years as long as it is helping you and you don’t have any severe side effects.

After having pembrolizumab for 2 years, if your cancer then starts to get worse you might be able to have it again. Your doctor can tell you more if this applies.

Tissue samples 
Before starting treatment, the research team might ask you to have a biopsy Open a glossary item of your cancer. Or they might be able to use an older sample.

The sample is used to confirm the gene changes being looked at in this trial

They will ask if any samples left over can be used for research purposes. You don’t need to agree to this, if you don’t want to. You can still take part in the trial.

Blood samples
You have some extra blood tests as part of this trial. The researchers want to find out what happens to pembrolizumab in the body. 

The doctors will ask to look at substances called biomarkers Open a glossary item that can help them see how a treatment is working. Where possible you have the blood samples at the same time as your routine blood tests. You don’t have to agree to this research if you don’t want to. You can still take part in the trial.

Hospital visits

You see the doctor and have some tests before you start treatment. The tests include

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

You go to hospital to have treatment. You probably won’t need to stay overnight. 

You see the doctors regularly for a check up and blood tests

  • once every 3 weeks if you are have pembrolizumab
  • about twice a month if you are have usual treatment

You see the trial team a month after you finish treatment. They will repeat some of the tests you had when you joined the trial. You have an MRI or CT scan and see the trial team every 9 weeks for a check up. 

You see the doctors until either your cancer gets worse or you start another anti cancer treatment.

Side effects

The most common side effects of pembrolizumab are

We have information about the side effects of 

Location

Aberdeen
Belfast
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

Dr Kai-Keen Shiu

Supported by

Merck Sharpe & Dohme

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

14095

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

Over 60,000 cancer patients enrolled on clinical trials in the UK last year.

Last reviewed:

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