A trial of amivantamab, lazertinib and osimertinib for non small cell lung cancer (MARIPOSA)

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 3

This trial is looking at whether amivantamab with lazertinib is better than osimertinib by itself or lazertinib by itself for non small cell lung cancer.

It is open to people with non small lung cancer (NSCLC) that has spread into the nearby tissue (locally advanced Open a glossary item ) or to another part of the body (advanced). It is only for people whose cancer has a gene change (mutation) in the epidermal growth factor receptor (EGFR).

More about this trial

Amivantamab is a targeted drug Open a glossary item called a monoclonal antibody. It works by attaching to different proteins on cancer cells and blocking them. One protein is EGFR.

Osimertinib and Lazertinib are targeted drugs called TKI growth inhibitors. They work by attaching to EGFR that have certain gene changes (mutations) and blocking them.

Blocking EGFR can stop or slow down the growth of NSCLC.

Doctors already use amivantamab for NSCLC that has spread to nearby tissue or another part of the body. They also use osimertinib for NSCLC that has spread to another part of the body.

Researchers think that combining amivantamab with lazertinib might be better than osimertinib by itself or lazertinib by itself.

In this trial you have either:

amivantamab and lazertinib or
lazertinib and a dummy drug (placebo ) or
osimertinib and a dummy drug

The aims of the trial are to find out:

how well the combination of amivantamab and lazertinib works for NSCLC
what the side effects are
how it affects quality of life

Who can enter

The following bullet points are a summary of 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:

are newly diagnosed with non small cell lung cancer (NSCLC) that has grown into the nearby tissue (locally advanced) or to another part of the body (advanced).
have not had treatment and your cancer cannot be treated with the aim to cure
have cancer with certain changes (mutations) in EGFR. Your doctor will know about this.
have had tissue samples (biopsies) that the team can access. Or you are willing to give a new sample if these are not available.
have at least 1 area of cancer that has not been treated with radiotherapy and the doctor can measure
have satisfactory blood test results
can look after yourself but might not be able to do heavy physical work (performance status 0 or 1)
are willing to use reliable contraception during treatment and for a period of time after if there is any chance you or your partner could become pregnant. You must also agree to not donating eggs or sperm during treatment and for a time after.
are at least 18 years old

Who can’t take part

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

have already had systemic treatment such as chemotherapy for locally advanced or advanced NSCLC (stage 3 or 4). You could join if you had treatment for stage 1 or 2 cancer as long as it was completed more than a year before your diagnosis of locally advanced or advanced cancer.
have cancer spread to the brain that isn’t causing symptoms. You could join if the cancer spread has been treated.
had or have cancer spread to the tissue surrounding the brain
have cancer that is pressing on the spine causing spinal cord compression unless it has been treated
have cancer pain that can’t be controlled
have ongoing side effects from any previous treatment unless they are mild
have or had another cancer. This is apart from some cancers that were successfully treated in the past 2 years or the past 5 years. Your doctor will know which ones these are.

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

have diabetes that isn’t controlled
have an ongoing or an active infection
bleed or bruise easily
need to have continuous oxygen
have a problem with your digestive system that affects how well your body absorbs medication. This includes having part of your bowel removed.
have a problem swallowing tablets or capsules
have an eye problem that can get worse at any time
have heart problems
are taking medication that affects the CYP enzymes unless you are able to stop taking them. This includes herbal preparations.
have had medication that works in the same way as the trial treatment. Your doctor will know about this.
are taking an experimental drug or using a device as part of a clinical trial. Or you have done so in the past year.
had or have scarring of the lung tissue or inflammation of the lung
have hepatitis B, hepatitis C or any other active liver infection
have HIV unless you have had the same antiviral treatment for the past 6 months, your CD4 count is more than 350. And you have not had an opportunistic infection in the past 6 months.
have had major surgery or a major injury within in 4 weeks of being put in to a treatment group in this trial
have any other medical condition or mental health problem that could affect you taking part

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

allergic or sensitive to any of the treatments used or any of their ingredients
are pregnant or breastfeeding

Trial design

This is an international phase 3 trial. The team need about 1,000 people to join with 11 people from the UK.

This is a randomised trial. A computer puts you into a group. Neither you nor your doctor chooses which group you are in.

There are 3 groups:

amivantamab and lazertinib - group A
osimertinib and a dummy drug (placebo) - group B
lazertinib and a dummy drug - group C

People in group A and their doctors know what treatment they are having. This is an open label trial group.

People in group B and group C and their doctors don’t know what treatment they are having. These are double blinded trial Open a glossary item groups. But your doctor can find out what treatment you are having if necessary.

For every 5 people joining the trial 2 go into group A, 2 into group B and 1 into group C.

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You have amivantamab as a drip into a vein. You have it once a week for 4 weeks and then every 2 weeks.

Lazertinib, osimertinib and the dummy drugs are tablets. You take them once a day every day. Your doctor will tell how many to take and how often.

You continue treatment as long as it is working and the side effects aren’t too bad.

Quality of life
You fill in questionnaires before you start treatment and then:

during treatment
at the end of treatment
then every 12 weeks for a year after treatment

The questions ask about your general health and wellbeing.

You complete the questionnaires on a smart phone or tablet.

These are quality of life questionnaires.

Research samples
You give extra blood samples as part of the trial. Where possible the team take these when you have your routine bloods.

The team ask for a piece of a tissue sample (biopsy Open a glossary item ) you had previously. If this is not available you must agree to have a new tissue sample taken. They will also ask for another tissue sample when you finish treatment.

They will use these samples to learn more about lung cancer and treatment for it.

Hospital visits

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

a physical examination
blood tests
urine test
eye examination
heart trace (ECG)
MRI scan or CT scan
heart scan (ECHO or MUGA )

You see the doctor at regular times during treatment to see how you are and for blood tests.

You see the doctor at the end of treatment and then every 3 months for 3 years.

You have a scan every 8 weeks for 2½ years and then every 3 months until your cancer gets worse.

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.

Combining amivantamab with lazertinib is new and there might be side effects we don’t know about yet. The side effects that have been reported are:

reaction when having amivantamab. These include feeling or being sick, chills, shortness of breath and chest discomfort.
rash, itching or dry and cracked skin
infection or inflammation of the skin around the nails
inflamed mouth or mouth sores
feeling or being sick
muscle pain
dizziness
diarrhoea or constipation
low levels of albumin in the blood
loss of appetite
swelling of the hands, feet, legs or arms
tiredness
inflammation of the lungs
a change to the way the liver works
abnormal sensations such as pins and needles
eye problems
heartburn

The common side effects of osimertinib are:

rash, itching, dry skin and other skin changes that might be painful
diarrhoea
inflammation of the mouth and lips
redness around fingernails
a drop in white bloods and platelets
inflammation of the lungs
a change to how well the heart works and inflammation of the heart that could cause heart failure