A trial of pembrolizumab and lenvatinib for people who have had treatment for non small cell lung cancer (LEAP-008)

Cancer type:

Lung cancer
Non small cell lung cancer
Secondary cancers

Status:

Open

Phase:

Phase 3

This trial is for people with non small cell lung cancer (NSCLC) that has spread. This is metastatic NSCLC. It means that the cancer has spread outside the lungs into the surrounding area. Or it has spread elsewhere in the body. 

It is for people who have had treatment with immunotherapy Open a glossary item and chemotherapy. Possible previous treatments include:

  • pembrolizumab
  • nivolumab
  • atezolizumab
  • durvalumab
  • and chemotherapy regimens with carboplatin or cisplatin 

More about this trial

For metastatic NSCLC, you usually have chemotherapy and immunotherapy. This treatment can help to control the cancer for some time and reduce your symptoms. 

But sometimes NSCLC continues to grow despite chemotherapy and immunotherapy. This is called progressive disease. If this happens, you might have treatment with a chemotherapy drug called docetaxel (Taxotere)

Doctors are trying to help people in this situation. In this trial, they are looking at the combination of pembrolizumab and lenvatinib. 

Pembrolizumab (Keytruda) is a type of immunotherapy. It helps the immune system Open a glossary item attack the cancer and stop it from growing. 

Lenvatinib (Lenvima) is a type of 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. 

Everyone taking part in this trial has 1 of the following treatments: 

  • pembrolizumab and lenvatinib (group 1) 
  • docetaxel (group 2) 
  • lenvatinib (group 3)

The main aim of this trial is to find out how well pembrolizumab and lenvatinib work for metastatic NSCLC for people who have had previously immunotherapy and chemotherapy. 

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 NSCLC that has spread outside the lungs into the surrounding area or elsewhere in the body 
  • your cancer got worse (progressed) after treatment with chemotherapy which included cisplatin or carboplatin
  • your cancer got worse after at least 2 doses of immunotherapy such as pembrolizumab, nivolumab, atezolizumab or durvalumab  
  • you have at least one area of cancer that can be seen and measured on a scan 
  • you are willing to have a sample of cancer taken (biopsy Open a glossary item) to look for potential causes of why some cancers are resistant to immunotherapy and chemotherapy
  • your heart is working well and your blood pressure is normal 
  • you have satisfactory blood tests results 
  • you are well enough to carry out your normal activities apart from heavy physical work (performance status of 0 or 1)
  • you are at least 18 years old 
  • you are willing to use reliable contraception during treatment and for up to 6 months afterwards if there is any possibility that you or your partner could become pregnant 

Who can’t take part

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

  • your cancer has receptors for proteins called epidermal growth factor (EGF), ALK or ROS1. Your doctor can tell you more about this 
  • you have cancer spread in your brain, spinal cord or the membranes that surround the brain (carcinomatous meningitis) unless you have had treatment, it has been stable for the past month and you have stopped taking steroids more than 2 weeks ago
  • you have had a high dose of radiotherapy in the past 6 months and still have moderate or severe side effects from it, or you have had radiotherapy in the past 2 weeks if it was a small dose (less than 30Gy)  
  • you have had docetaxel or lenvatinib 
  • you have had bleeding from your cancer in the last 2 weeks 
  • your cancer has spread to a major blood vessel Open a glossary item for example the heart or lung arteries
  • you have had another cancer in the past 3 years unless it was non melanoma skin cancer, a superficial bladder cancer or carcinoma in situ of the cervix

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

  • have had a major surgery and still have side effects from it 
  • have coughed up a large amount (1/2 teaspoon) of bright red blood in the past 2 weeks 
  • have heart problems such as an abnormal heart rhythm, congestive heart failure, angina Open a glossary item that isn’t stable or you have had a heart attack in the past year 
  • have any other heart problems such as your heart has a lower than normal ability to pump blood around the body. You have a heart scan called ECHO Open a glossary item to check for this
  • have problems with your gut and you can’t absorb tablets 
  • have a moderate or severe opening (fistula) in your digestive system Open a glossary item or elsewhere in the body
  • are taking part in another clinical trial or have taken part in a trial looking at a new drug or device in the last month 
  • have an autoimmune disease Open a glossary item that needed treatment that reached your whole body (systemic) in the past 2 years unless it was something that the body makes such as thyroxine or insulin
  • take or have taken drugs that damp down your immune system such as steroids in the past week unless it was a very small dose 
  • have or have had lung problems such as pneumonitis Open a glossary item
  • have an active infection 
  • have HIV 
  • have hepatitis B or hepatitis C 
  • have active tuberculosis 
  • have protein in your urine
  • have had an organ transplant Open a glossary item from a donor
  • have any other serious medical 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, docetaxel or anything they contain 

Trial design

This is an international phase 3 trial. Researchers hope that around 405 people worldwide and 43 people form the UK 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 lenvatinib (group 1)
•    docetaxel (group 2)
•    lenvatinib (group 3)

Neither you nor your doctor are able to decide which group who are in. And you are 4 times more likely to join group 1 or group 2, than group 3. 

Everyone who receives pembrolizumab and lenvatinib or docetaxel has treatment in cycles of treatment that last 3 weeks. The first day of each cycle is called day 1.  Everyone who receives lenvatinib only has treatment every day.

Pembrolizumab and lenvatinib (group 1)
You have pembrolizumab as a drip into your bloodstream (intravenously) every 3 weeks. It takes about 30 minutes each time you have it. 

Lenvatinib comes as tablets that you swallow whole every day. 

You have pembrolizumab and lenvatinib for as long as they are helping you and the side effects aren’t too bad. You can have up to 35 pembrolizumab treatments, taking about 2 years in total.  

You may be able to have a second course of treatment with pembrolizumab with or without lenvatinib if your cancer comes back after you stop treatment. And if you stop having lenvatinib due to its side effects, you may still continue to have pembrolizumab.  Your doctor can tell you more about this. 

Docetaxel (group 2)
You have docetaxel as a drip into your bloodstream every 3 weeks. It takes around 60 minutes each time you have it. This continues for as long as it is helping you and the side effects aren’t too bad. 

Lenvatinib (group 3)
You take lenvatinib tablets every day, for as long as you don’t have any serious side effects and they are helping you. 

Quality of life
Everyone taking part completes quality of life questionnaires before the start of treatment and:

  • every 3 weeks during treatment
  • at the end of treatment 
  • a month after finishing treatment 

The questionnaires ask about how you have been feeling and what side effects you have had. 

Blood tests 
You have extra blood tests as part of this trial. You have them before you start treatment and at set times during the trial. 

Researchers want to:

  • look for certain proteins (biomarkers) that can help to tell how well the treatment is working
  • find out what happens to the drugs inside your body (pharmacokinetics Open a glossary item)
  • look at the cancer DNA Open a glossary item

Tissue sample
The trial team ask to use a tissue sample of your cancer taken when you had surgery or a biopsy. Researchers want to look for a protein called PD-L1 in the cancer. 

You also need to have a new sample taken (biopsy). Doctors want to learn more about why some cancers are resistant to treatment with chemotherapy and immunotherapy. 

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)
  • 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 on day 1 and day 15 of each treatment cycle. This continues for 2 months. You then see the trial team every 3 weeks. You have blood tests and a physical examination each time you see them. 

You have a CT scan or MRI scan every 6 weeks for 9 months. You then have a CT scan or MRI scan:

  • every 9 weeks for 4 months
  • then every 12 months for as long as you are taking part in this trial 

This continues for as long as the treatment is helping you and the side effects aren’t too bad. 

When you finish treatment, you see the trial team 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. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better. 

Pembrolizumab can affect the immune system. It may cause inflammation in different parts of the body which can cause serious side effects. Side effects can happen during treatment or some months after treatment has finished. Rarely, some side effects can 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 causing tiredness, weight gain and feeling cold
  • low levels of salts in your body causing muscle cramps and feeling sick 

We have more information about the possible side effects of pembrolizumab

The most common side effects of lenvatinib are:

  • a stroke Open a glossary item 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)
  • shortness of breath
  • liver problems which may cause yellowing of the skin and eyes (jaundice), tiredness, fever and confusion

We also have information about the side effects of docetaxel

Location

Aberdeen
Birmingham
Cottingham
Coventry
Leeds
Leicester
London
Northwood
Nottingham

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 Samreen Ahmed

Supported by

Merck Sharp & Dohme Limited (MSD), a subsidiary of Merck & Co., Inc., of Kenilworth, New Jersey, USA

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

16541

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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