A trial of pembrolizumab, lenvatinib and 2 new drugs called MK-4280 and MK-1308 for non small cell lung cancer (KEYNOTE 495)

Cancer type:

Lung cancer
Non small cell lung cancer
Secondary cancers

Status:

Open

Phase:

Phase 2
This trial is for people with advanced non small cell lung cancer (NSCLC). Advanced NSCLC can mean one of the following:
  • the cancer is in both lungs
  • the cancer has spread outside of the lungs into the surrounding area, or elsewhere in the body
  • there is a collection of fluid around the lung (pleural effusion) and this fluid contains cancer cells

More about this trial

Targeted drugs are a possible treatment for advanced non small cell lung cancer (NSCLC). They work by ‘targeting’ those differences that help a cancer cell to survive and grow. 
 
Pembrolizumab, MK-4280 and MK-1308 are 2 types of targeted drugs called monoclonal antibodies. They help the immune system to attack the cancer and stop it from growing. Pembrolizumab is already a possible treatment for people with advanced NSCLC.
 
Lenvatinib (Lenvima) is also a targeted drug. It works by blocking certain proteins that help cells to grow new blood vessels. All cancer cells need blood vessels to survive and grow. Lenvatinib is already a possible treatment for people with certain types of thyroid cancer. 
 
Everyone taking part in this trial has 1 of the following:
  • pembrolizumab and MK-4280 (group 1)
  • pembrolizumab and lenvatinib (group 2) 
  • pembrolizumab and MK-1308 (group 3)
The main aims of this trial are to:
  • find out how well pembrolizumab, MK-4280, MK-1308 and lenvatinib work as a treatment for advanced NSCLC
  • 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. 
 
Who can take part
You may be able to join this trial if all of the following apply:
  • you have stage 4 NSCLC  
  • you have at least 1 area of cancer that can be seen and measured on a scan 
  • you are willing to have a sample of your cancer taken (biopsy Open a glossary item) if there isn’t a suitable sample available. Your doctor can tell you more about this
  • your blood pressure is normal and your heart is working well 
  • you are at least 18 years old  
  • you are well enough to carry out your normal activities apart from heavy physical work (performance status of 0 or 1)
  • you have satisfactory blood tests results 
  • you are willing to use reliable contraception during treatment and for about 4 months afterwards if there is any possibility that you or your partner could become pregnant 
Who can’t take part
You cannot join this trial if any of these apply. 
 
Cancer related
  • your NSCLC has spread to the brain, the spinal cord or the membranes surrounding the brain (carcinomatous meningitis) unless you have had treatment, it has been stable for the past 4 weeks and you have stopped taking steroids more than 4 weeks ago 
  • you have had chemotherapy that reached your whole body (systemic treatment) for advanced NSCLC unless it was chemotherapy that you had before or after surgery or radiotherapy (neo adjuvant or adjuvant therapy) and that you finished more than 6 months ago
  • doctors think that you can have treatment such as surgery or radiotherapy to try to cure the cancer   
  • your doctors are planning surgery, radiotherapy or any other cancer treatment during this trial
  • you have fluid in your lungs (pleural effusion) or a collection of fluid in your tummy (ascites) that is causing symptoms. You may be able to take part if you have had treatment and the symptoms are stable 
  • your cancer has spread to a major blood vessel Open a glossary item and your doctor thinks that you have a high risk of bleeding  
  • you have had a large bleeding from your cancer in the past 2 weeks 
  • you have had pembrolizumab, lenvatinib or any other similar drug 
  • you have had anti cancer treatment such as chemotherapy in the last 4 weeks and you still have moderate or severe side effects apart from numbness and tingling in fingers and toes 
  • you have had radiotherapy in the past 3 weeks (2 weeks if it was radiotherapy to help with symptoms) 
  • you have had another cancer in the past 3 years unless it was non melanoma skin cancer or an early cancer (carcinoma in situ Open a glossary item) of the breast and cervix that have been successfully treated 
Medical conditions 
You cannot join this trial if any of these apply. You:
  • are taking part in another clinical trial or have taken part in a trial looking at a new treatment (drug or device) in the past 4 weeks  
  • have heart problems such as an abnormal heart rhythm, congestive heart failure, angina that isn’t stable or you have had a heart attack in the past year 
  • have had a stroke Open a glossary item in the last year 
  • have lung problems such as pneumonitis Open a glossary item
  • have an autoimmune disease Open a glossary item that needed systemic treatment in the past 2 years unless it was to replace something that the body makes such as thyroxine or insulin
  • have taken drugs that damp down your immune system such as steroids in the past week unless it was a very small dose 
  • have had an organ transplant Open a glossary item from a donor
  • have protein in your urine 
  • have an active infection that needs systemic treatment 
  • have HIV 
  • have hepatitis B or hepatitis C 
  • have active tuberculosis 
  • have had a major surgery and still have side effects from it 
  • have problems with your gut and you can’t absorb tablets 
  • have coughed up a large amount of blood in the past 2 weeks 
  • have any other serious condition or mental health problem that the trial team think could affect you taking part 
Other
You cannot join this trial if any of these apply. You:
  • are pregnant or breastfeeding 
  • have had a live vaccine Open a glossary item in the last month 
  • are sensitive to pembrolizumab, lenvatinib, MK-4280 or anything they contain 

Trial design

This is an international phase 2 trial. Researchers hope that around 288 people worldwide will agree to take part. 
 
It is a randomised trial. The people taking part are put into 1 of the following groups at random:
  • pembrolizumab and MK-4280 (group 1)
  • pembrolizumab and lenvatinib (group 2)
  • pembrolizumab and MK-1308 (group 3)
Neither you nor your doctor are able to decide which group you are in. 

Pembrolizumab and MK-4280 (group 1)
You have both drugs as a drip into your vein (intravenously) every 3 weeks. It takes about 30 minutes each time you have pembrolizumab and 30 minutes each time you have MK-4280. 
 
You continue to have pembrolizumab and MK-4280 for as long as it helps you and the side effects aren’t too bad. You can have them for up to 2 years. 
 
Pembrolizumab and lenvatinib (group 2)
You have:
You continue having pembrolizumab and lenvatinib for as long as it helps you and the side effects aren’t too bad. You can have them for up to 2 years. 
 
After 2 years, you may be able to continue taking lenvatinib alone. This continues for as long as it helps you and the side effects aren’t too bad. 
 

Pembrolizumab and MK-1308 (group 3)
You have:
  • pembrolizumab as a drip into a vein over 30 minutes, every 3 weeks 
  • MK-1308 as a drip into a vein over 30 minutes, every 6 weeks
This continues for as long as it is helping you and the side effects aren’t too bad. You can have treatment for up to 2 years. 
 
Blood tests 
You have extra blood tests as part of this trial. You have them before the start of treatment and then:
  • at set times during the trial
  • at the end of treatment
Doctors want to look for certain proteins (biomarkers Open a glossary item) that can tell how well the treatment is working. They will also ask you to have a blood test to study your genes Open a glossary item
 
Tissue sample
The trial team will ask to use a tissue sample of your cancer taken when you had surgery or a biopsy. You need to have a new sample taken if there isn’t a suitable sample available. 
 
Researchers want to look for certain changes in the cancer. 

Hospital visits

You see a doctor and have some tests before taking part. These tests might include:
  • a physical examination
  • heart trace (ECG Open a glossary item
  • a heart scan (MUGA Open a glossary item or ECHO Open a glossary item)
  • blood tests 
  • urine test 
  • a CT scan or MRI scan 
During treatment, you see the trial team every 3 weeks. You have blood tests and a physical examination every time you see them. 
 
You have a CT scan or a MRI scan every 9 weeks for a year. You then have a CT scan or a MRI scan every 12 weeks. 
 
Your treatment continues for as long as your cancer stays the same and the side effects aren’t too bad. 
 
When you finish treatment, you see the trial doctor after a month. You then see or speak with the trial team every 3 months. 

Side effects

The trial team monitor you during treatment and afterwards. You have a phone number to call them if you are worried about anything. The team will tell you about all the possible side effects before you start the treatment. 
 
Pembrolizumab affects the immune system. This 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. In some people, these side effects could be life threatening. 
 
The most common side effects of pembrolizumab are: 
  • skin rashes, itching and changes to your skin colour 
  • loose or watery poo (diarrhoea)
  • cough 
  • pain in your joints, back and tummy (abdomen)
  • high temperature (fever)
  • low levels of thyroid hormones in your body that can cause tiredness, weight gain and feeling cold
  • low levels of salt in your body that can cause muscle cramps and feeling sick (nausea)
We have more information about the possible side effects of pembrolizumab
 
The most common side effects of lenvatinib are:
  • a stroke or bleeding in the brain that might cause numbness or weakness on one side of your body
  • a blood clot in the veins of your legs or lungs 
  • heart problems such as palpitations or a heart attack 
  • an abnormal opening (fistula) between organs or to the outside of your body
  • a hole in your bowel (bowel perforation)
  • bleeding from the gut
  • feeling or being sick 
  • diarrhoea 
  • loss of fluid in your body (dehydration) 
  • heart problems that can cause shortness of breath
  • liver problems which may cause yellowing of the skin and eyes (jaundice), tiredness, fever and confusion
MK-4280 is a new drug and there might be side effects we don’t know about yet. Side effects may include:
  • inflammation of the lungs (pneumonitis) which can cause shortness of breath, cough and pain in your chest 
  • an allergic reaction during treatment which can cause fever, dizziness and shortness of breath
  • pain in your joints 

MK-1308 is also a new drug and there might be side effects we don’t know about yet. Side effects may include:

  • skin rash and itchy skin
  • diarrhoea 
  • inflammation of the lungs
  • tiredness
  • changes in the levels of thyroid hormones
  • high levels of liver enzymes

Location

Cambridge
Derriford
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 Martin Forster

Supported by

Merck, Sharp & Dohme Limited

 

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

15982

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

Wendy took part in a new trial studying the possible side effect of hearing loss

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"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”

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