A study looking at V940 immunotherapy with pembrolizumab for people with high risk melanoma (INTerpath-001)

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

Cancer type:

Melanoma
Secondary cancers
Skin cancer

Status:

Closed

Phase:

Phase 3

This study is looking at an immunotherapy Open a glossary item treatment called V940 (mRNA-4157) with pembrolizumab to treat melanoma. Each V940 treatment is made individually for each person taking part.

It’s for people who have:

  • had all their melanoma removed with surgery and 
  • not had any other cancer treatment for their melanoma

More about this trial

Often the first type of treatment for melanoma skin cancer is surgery.

Depending on how big the cancer is, and if it has spread, treatments after surgery can include:

  • immunotherapy
  • targeted cancer drugs Open a glossary item

Treatment can work well, but some people with stage 2,3 or 4 melanoma have a higher risk of their cancer coming back after surgery. Doctors would like to improve treatment for people in this situation.

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

Pembrolizumab targets and blocks a protein called PD-1 on the surface of certain immune cells called T cells Open a glossary item. Blocking PD-1 triggers the T cells to find and kill cancer cells.

Some people with melanoma already have pembrolizumab after surgery or if their cancer has spread.

V940 is a type of personalised immunotherapy. It’s a new drug. It is also called mRNA-4157. Scientists make each treatment individually for everyone taking part. It uses the genes Open a glossary item in your melanoma cells to teach your immune system to kill the cancer cells. It doesn’t permanently change your genes or stay in your body after treatment.

Scientists make each V940 treatment for each person taking part using:

  • a tissue sample from their melanoma
  • a blood test they have before they take part

In this study, researchers are looking at pembrolizumab and V940 to see if they work well together.

The main aims of this study are to find out:

  • more about the safety of V940 with pembrolizumab when compared to pembrolizumab and a dummy drug (placebo Open a glossary item)
  • how well V940 with pembrolizumab works when compared to pembrolizumab with a dummy drug
  • more about the side effects of treatment
  • about the quality of life Open a glossary item of the people taking part

Who can enter

The following bullet points are a summary of the entry conditions for this study. Talk to your doctor or the study 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 study if all of the following apply. You:

  • have melanoma skin cancer that is at least 2mm thick and the skin covering the cancer may, or may not, be broken (ulcerated). The cancer may have spread to the nearby lymph nodes Open a glossary item or to another area of the body. This is stage 2b to stage 4 melanoma. You may be able to take part if your melanoma has come back (recurred) after you’ve had it removed. This is as long as you have had surgery again. Your doctor can explain more.
  • have a good quality tissue sample from a recent surgery available for the study team to look at. There must be enough of the sample so that the trial team can do some tests on it called next generation sequencing. Your doctor can tell you more. 
  • have not had any treatment that reaches the whole body for melanoma (systemic treatment). You might be able to take part if you have had radiotherapy Open a glossary item to where the cancer started (primary site Open a glossary item) or after surgery to remove one or more lymph nodes. To take part your radiotherapy must have finished by 11 weeks after surgery and 2 weeks before you have your first dose of the study drug.
  • have had your surgery to remove the melanoma at the most 13 weeks before having your first dose of pembrolizumab in this study. And there is now no sign of your melanoma.
  • have no signs of melanoma either on a scan or when your doctor examines you within 28 days before randomisation Open a glossary item
  • have had a biopsy Open a glossary item of any part of your skin that looked like it could be melanoma. Other than the melanoma you are having treatment for, the test results must show that it was not cancer.
  • are fit and active but might not be able to do heavy physical work (performance status 0 or 1) and this hasn’t changed within the 7 days before your first dose of pembrolizumab in the study
  • are willing to use reliable contraception during the study and for at least 4 months after your last dose of treatment if there is any chance you could become pregnant
  • are willing to avoid breastfeeding during the study and for at least 4 months after your last dose of treatment
  • have satisfactory blood test results and tissue sample quality results. Your doctor can tell you more.
  • are at least 18 years old

Who can’t take part

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

  • have melanoma of the eye (ocular melanoma) or melanoma of the layer of tissue that covers the inside surface of certain parts of the body (mucosal melanoma)
  • have had certain checkpoint inhibitors Open a glossary item before. Your doctor will know which drugs these are.
  • have had any cancer treatment that reaches your whole body (systemic anti cancer therapy or SACT) before randomisation Open a glossary item
  • have cancer cells that have spread further than 2cm from the primary tumour Open a glossary item but before the nearest lymph node (in-transit metastases). And they are not able to be removed with surgery.
  • have side effects of radiotherapy that are causing you problems
  • you are having treatment with steroids long term, this is apart from small doses. Or you are having any other treatment that dampens down your immune system Open a glossary item within the 7 days before your first dose of study treatment.
  • have another cancer that has been getting worse, or has needed treatment, in the past 3 years. You might be able to take part if you have had basal cell skin cancer Open a glossary item, squamous cell skin cancer Open a glossary item or a very early stage cancer (in situ) apart from bladder cancer. You might be able to take part if you have early stage, low risk prostate cancer. You might be able to take part if you have had another primary melanoma.
  • have had melanoma that has spread to the central nervous system Open a glossary item or the thin layer between the brain and the spinal cord
  • have had treatment with a cancer vaccine before
  • have had a red blood cell transfusion, platelet transfusion Open a glossary item  or any colony stimulating factors such as G-CSF Open a glossary item in the 2 weeks before having blood tests to see if you’re able to take part in the study

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

  • have a wound that is not healing well
  • have had heart failure within the last 6 months unless it is well controlled. Your doctor will know more. 
  • have got an immunodeficiency disorder
  • have an active autoimmune disease Open a glossary item that has needed treatment in the last 2 years apart from certain ones. Your doctor can explain more.
  • have active hepatitis B or hepatitis C
  • have HIV unless it is well controlled on antiretroviral medication. Your doctor can explain more.
  • have pneumonitis Open a glossary item or inflammation and scarring of the lungs (interstitial lung disease). Or you have had these in the past, they were not caused by infection, and you needed steroid treatment.
  • have any other serious physical or mental health condition, or social circumstances, that could prevent you from taking part
  • have had a solid tissue or organ transplant Open a glossary item
  • have had major surgery and have not recovered fully. Or you are still having side effects from surgery.

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

  • are allergic to V940 or pembrolizumab or anything they contain
  • have had a live vaccine Open a glossary item in the 30 days before your first dose of study drug. You can have a COVID-19 or flu vaccine at certain times while taking part in this study.
  • have had another study medication within 4 weeks of having the first dose of study drug
  • are pregnant or breastfeeding

Trial design

This is a phase 3 study. The researchers need around 1,089 people to take part. 

It is a randomised double blind study. You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in. Nor will you or your doctor know which treatment you have. During the study your doctor will be able to find out what treatment you are having, if necessary. There are 2 treatment groups:

  • Group 1 - pembrolizumab and V940
  • Group 2 - pembrolizumab and a dummy drug (placebo)

Out of every 3 people taking part:

  • 2 people will be in group 1 and will have pembrolizumab and V940
  • 1 person will be in group 2 and will have pembrolizumab and a dummy drug

You have pembrolizumab as a drip into a vein. You have it every 6 weeks. This is a cycle of treatment Open a glossary item.

You have up to 9 cycles of pembrolizumab, as long as it is working, and the side effects are not too bad.

You have V940, or the dummy drug, as an injection into the muscle. You have V940, or the dummy drug, once every 3 weeks. You have up to 9 doses, as long as it is working, and the side effects are not too bad.

Treatment on the study can take up to about a year.

Blood samples for research
The team take extra blood samples during the study. Where possible they take these when you have your routine bloods done. 

Researchers use these samples for:

  • genetic Open a glossary item testing
  • biomarker Open a glossary item testing

The researchers want to use the results to learn more about melanoma and:

  • how the study drugs work in the body
  • why treatment works better for some people than for others
  • any link between your HLA proteins Open a glossary item and the study treatment or melanoma

Tissue samples for research
As well as to make your treatment, the study team may use your tissue sample to improve and develop tests to help people with cancer. The study team can give you more information.

The study team ask for another biopsy Open a glossary item sample if your melanoma comes back during the study. The researchers want to use the sample to learn more about melanoma and develop tests for people with cancer. 

Quality of life
You fill in questionnaires on an electronic tablet at certain points during the study. This is to find out about your daily life and how you are feeling. This is to find out more about your quality of life.

Hospital visits

You see the doctor to have tests before taking part. These tests include:

  • a physical examination Open a glossary item
  • a scan, such as a CT scan, of the chest, tummy (abdomen) and pelvis Open a glossary item
  • a brain scan Open a glossary item
  • heart trace (ECG Open a glossary item)
  • blood tests
  • urine test
  • pregnancy test – if there is any chance you could become pregnant

You might have a bone scan if needed.

This might be slightly different if the team ask you to think about joining the study before surgery. The study team will explain this to you in more detail. It’s called limited screening. You then sign the main consent form Open a glossary item later. And you start having the other tests to see if you’re able to take part then.

You have your treatment as an outpatient in hospital. You also have some tests and scans at certain visits. Your team will let you know your schedule. Tests include:

  • scans, such as an MRI scan or CT scan
  • a heart trace (ECG)
  • blood tests
  • urine test
  • having a picture taken of any new melanomas that develop while you’re taking part – the team try and make sure you can’t be recognised from the picture if it is on your face

If your cancer comes back
You stop having treatment on the study if your melanoma comes back. Your team will discuss the next treatment options with you. You go back to the hospital up to 30 days after you stop having study treatment for a check up and blood tests. You may also have other tests at this visit.

Follow up
After treatment, the team monitor your progress for up to another 6 years. This is called follow up.

You see the study team for a check up and tests around 30 days after having the last dose of study treatment then:

  • around every 3 months for year 1 and 2
  • around every 6 months for year 3 and 4
  • once in year 5

You may continue to visit the hospital after the first 5 years. The study team will let you know your follow up schedule. The tests you have at treatment visits are similar to the ones you had before and during treatment.

After 5 years, the study team get in touch with you around once every 3 months to see how you are getting on.

Side effects

The study 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. 

V940 is a new drug. Because of this there might be side effects we don’t know about yet.

Possible side effects of V940 include:

Pembrolizumab can affect the immune system Open a glossary item. This may cause inflammation Open a glossary item and other reactions in different parts of the body. For many people the inflammation and reactions are not too bad. For some people they can cause serious side effects. 

These side effects could happen during treatment or months after treatment has finished. Rarely, these side effects could be life threatening. Your doctor or nurse can explain what these side effects are, the risk of them happening and what to look out for.
 
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:

  • skin changes such as skin rash, itchy skin or loss of skin colour
  • diarrhoea
  • cough
  • joint pain
  • fever
  • back pain
  • tummy (abdominal pain)
  • low levels of thyroid Open a glossary item hormones. You may feel tired, feel cold or gain weight.
  • low levels of salt in the blood. You may feel tired, confused, or sick. You might also have a headache or muscle cramps.

We have more information about pembrolizumab including possible side effects.

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 Heather Shaw

Supported by

Merck, Sharp and Dohme UK

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

19866

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

Last reviewed:

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