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

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

Cancer type:

Lung cancer

Non small cell lung cancer

Secondary cancers

Status:

Closed

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) 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 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) 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 in the last year
have lung problems such as pneumonitis
have an autoimmune disease 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 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 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.

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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:

pembrolizumab as a drip into a vein over 30 minutes, every 3 weeks
lenvatinib as tablets that you swallow whole every day

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) that can tell how well the treatment is working. They will also ask you to have a blood test to study your genes.

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)
a heart scan (MUGA or ECHO)
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

Recruitment start:

31/01/2019

Recruitment end:

14/10/2019

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.

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Questions to ask your doctor about clinical trials

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

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

Freephone 0808 800 4040

Email

Last review date

22 January 2020

CRUK internal database number:

15982