A trial looking at different types of immunotherapy to have with chemotherapy and radiotherapy for locally advanced lung cancer (CheckMate 73L)

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

Status:

Closed

Phase:

Phase 3

This trial is looking at adding nivolumab to chemoradiotherapy and comparing it to chemoradiotherapy alone.

It is also comparing 3 different immunotherapy treatments to have after these first treatments. These are nivolumab plus ipilumumab, nivolumab on its own and durvalumab.

It is for people with locally advanced lung cancer.

More about this trial

There are different treatment options for stage 3 non small cell lung cancer. Stage 3 lung cancer can also be called locally advanced cancer.

One common treatment is chemotherapy Open a glossary item and radiotherapy together, this is called chemoradiotherapy .

You might also have immunotherapy.

Immunotherapy uses our immune system to fight cancer. It works by helping the immune system recognise and attack cancer cells. But researchers don’t know if giving a type of immunotherapy at the same time as chemoradiotherapy is better than chemoradiotherapy on its own.

They also want to see if follow up treatment with two immunotherapy drugs that work slightly differently, helps people more than just one. Doctors call this follow up treatment maintenance. It is to try and keep the cancer under control.

Nivolumab blocks a protein called PD-L1 on the surface of immune cells. Blocking this protein triggers the immune system to find and kill cancer cells.

Ipilimumab works by attaching itself to normal immune cells. This changes the way these cells work and helps the immune system destroy cancer cells.

Durvalumab seeks out cancer cells by looking for the PD-L1 protein and attaching to it. The immune system then recognises the marked cells and kills them.

The aims of this trial are to find out:

if having nivolumab with chemoradiotherapy works better than chemoradiotherapy alone
if having nivolumab and ipilimumab as maintenance treatment works better than just nivolumab
if having nivolumab with chemoradiotherapy, then nivolumab and ipilimumab maintenance, works better than chemoradiotherapy with durvalumab maintenance
how safe the treatment is
more about the side effects
more about 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.

There are some additional entry conditions for the second part of the trial.

Who can take part (chemoradiotherapy stage)

You may be able to join the chemoradiotherapy part of trial if all of the following apply. You:

have non small cell lung cancer that has spread outside your lung (Stage 3). You might need a sample of tissue biopsy to check whether the cancer has spread to the lymph nodes
have cancer that the doctor can measure on a scan
haven’t had treatment for your cancer
are not able to, or not planning to, have surgery for your cancer
have a sample of tissue (biopsy) available that the trial team can do some tests on or you are willing to give a new sample
your lungs are healthy enough to receive the radiotherapy
have satisfactory blood results
have satisfactory lung function test results
are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
are at least 18 years old
are willing to use reliable contraception during treatment. Women should continue to use it for 5 months after treatment and men for 7 months, if there is any chance you or your partner could become pregnant.

Who can’t take part

Cancer related
You cannot join the chemoradiotherapy part of the trial if any of these apply. You:

have a type of lung cancer called a Pancoast tumour
are able to have surgery as part of your treatment plan
have cancer cells that have receptors for a protein called epidermal growth factor (EGFR positive), this means other treatment could be available to you
have a change in the ALK gene with or without a change in the ROS1 gene
have had similar immunotherapy drugs before, your doctor can tell you more
have had another cancer within the past 3 years apart from successfully treated non melanoma skin cancer , early non muscle invasive (superficial) bladder cancer or breast, cervical or prostate carcinoma in situ

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

have an autoimmune disease apart from certain types. Your doctors can tell you more about this.
have taken steroids or any other medication that dampens down your immune system within the last 2 weeks before randomisation . You might be able to take part if you are taking lower doses of steroids, steroids in skin creams or inhalers. Or you are taking steroids because your body doesn’t make enough
have had a solid organ transplant or stem cell transplant from a donor and need to take drugs to help stop your body rejecting the organ or tissue (immunosuppression)
have ever had chest radiotherapy
have had radiotherapy to a part of the body other than the chest within the last 30 days of starting treatment
have had any of the study drugs in the last 28 days before starting treatment
have HIV or AIDS, hepatitis B or hepatitis C
have an active infection which needs treatment that reaches the whole body within the last 2 weeks before randomisation
have an abnormal collection of fluid between the sheets of skin (pleura) which cover the lungs or a build up of blood or fluid in the area around the heart
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 a live vaccine within 30 days before starting treatment
are taking or have taken herbal medicines or traditional Chinese medicines within the last 2 weeks before randomisation or treatment
have an allergy to the study drugs or had an allergic reaction to a monoclonal antibody in the past
are being cared for in prison

Maintenance treatment
There are some additional entry conditions for the second part of the trial. This is the maintenance part of the trial.

Who can take part (maintenance stage)

You may be able to join the maintenance part of trial if all of the following apply:

your cancer has not grown by a fifth (20%) or more and there are no new areas of cancer, this is measured by a scan during or after the chemoradiotherapy stage of the trial
you have any side effects that from the chemoradiotherapy part of the trial that have gone back to how they were before you started treatment. Or they are mild. You might be able to take part if you have moderate tiredness (fatigue). If you have low numbers of white blood cells at this stage, you still might be able to take part.
you are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
you have satisfactory blood test results

You might not be able to take part in the maintenance part of the trial if any of these apply. You:

are taking medication that dampens down your immune system within the last 2 weeks of starting maintenance treatment. You might be able to take part if you are having steroids in nose sprays or inhalers, or steroids because your body does not make enough. You can take part if you have had steroids to help prevent or treat any problems with side effects of previous treatment in this trial.
have any other serious condition or mental health problem that the trial team think could affect you taking part

Trial design

This is a phase 3 trial. The researchers hope 888 people will take part worldwide including 30 from the UK.

The trial is split into 4 stages:

screening stage – the trial team makes sure you are able to take part in the trial. This takes up to 28 days.
chemoradiotherapy stage – this takes around 9 weeks
maintenance stage – this takes around a year
follow up stage – this is up to 5 years after you started on the trial

It is a randomised trial. You are put into 1 of the following treatment groups by computer:

Group A - chemotherapy, radiotherapy and nivolumab, followed by nivolumab and ipilimumab maintenance treatment
Group B - chemotherapy, radiotherapy and nivolumab, followed by nivolumab maintenance treatment
Group C - chemotherapy and radiotherapy then durvalumab maintenance treatment

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You have chemotherapy and immunotherapy as a drip into a vein. You have radiotherapy from a machine outside the body.

Chemoradiotherapy stage

Everyone has chemotherapy with or without immunotherapy in cycles. Each 3 week period is a cycle of treatment. The trial team will let you know how often you have treatment, which chemotherapy drugs you have, and how long each cancer drug takes.

Everyone has radiotherapy, this is usually Monday to Friday for 6 to 7 weeks. You start radiotherapy with your second cycle of chemotherapy.

Maintenance stage

Everyone has immunotherapy:

Group A - you have nivolumab every 3 weeks and iplimumab every 6 weeks
Group B - you have nivolumab every 4 weeks
Group C - you have durvaulmab every 2 weeks

The maintenance stage is up to a year. You have treatment for as long as it is working, and the side effects aren’t too bad.

Quality of life
The trial team will ask you to fill out questionnaires:

before you start treatment
at set times during treatment

The questionnaires will ask about side effects and how you’ve been feeling. This is called a quality of life study.

Samples for research
The trial team will ask you to give some extra blood samples. Where possible you have these at the same time as your routine samples.

They will ask to look at a sample of tissue you gave when you were first diagnosed.

The researchers plan to look at:

substances called biomarkers to help work out why treatment might work for some people and not for others
what happens to the drugs in your body
genes to learn more about lung cancer

They might also ask you to give a new sample if your cancer gets worse.

Treatment during follow up

You might be able to have more treatment if your cancer gets bigger during the follow up period. To have this you need to have completed a year of treatment with nivolumab, with or without ipilimumab.

This will be the same treatment you had as maintenance treatment.

Hospital visits

You’ll see a doctor and have some tests before you can take part. These include:

a physical examination
heart trace (ECG)
lung function tests
blood tests
urine tests
PET scan or CT scan of your whole body, you might also have an MRI or CT scan of your chest and tummy or brain to see whether cancer has spread from the lung
a test to look for cancer cells in the lymph nodes near the lungs
a biopsy so the study doctors can look at the tumour tissue – if a sample is available from the past 3 months, the team will use this

Hospital visits during treatment

You have treatment at the hospital. How often you go depends on which treatment group you are in.

At each visit, you see the trial doctor for a check up and blood tests. You have extra blood tests to check the levels of nivolumab and ipilimumab, if you are in these study groups.

CT or MRI Scans

You have a scan:

about 3 weeks after the chemoradiotherapy
about 6 months after starting chemoradiotherapy
then every 12 weeks during the maintenance part of the trial

The trial team think you will have 10 more scans during the trial, than you would if receiving standard of care treatment. It’s likely that you will have to visit the hospital as an extra visit for these.

After the maintenance treatment phase, you see the trial doctor for a check up and blood tests:

a month later
at 3 months

After that, the trial team will catch up with you every 3 months. This will be either at the hospital or over the phone.

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.

Nivolumab, ipilimumab and durvalumab can affect the immune system. They may cause inflammation in different parts of the body. This can cause serious side effects. They could happen during treatment, or some months after treatment has finished. Rarely, these side effects could be life threatening.

In particular, the team caring for you will look out for signs of breathlessness or other signs of lung inflammation.

If you have any of these side effects, you should tell the doctor or nurse as soon as possible that you are on or have been on an immunotherapy.

The most common side effects of nivolumab include:

The most common side effects of having nivolumab and ipilimumab together are:

an increased level of enzymes in the liver and pancreas
decreased function of the thyroid gland
diarrhoea
tiredness (fatigue)
itching
feeling sick
decreased appetite
skin rash or itching
fever

The most common side effects of durvalumab are:

tummy (abdominal) pain
cough
diarrhoea
tiredness (fatigue)
fever
itching
lung inflammation (pneumonitis)
lung infection (pneumonia) or upper respiratory tract infections
shortness of breath
rash
decreased function of the thyroid gland

We have information about:

The side effects of radiotherapy to the chest include:

inflammation of the food pipe (oesophagus)
inflammation of the lungs (pneumonitis)
skin changes
lower numbers of red cells, white cells and platelets in the body. This can lead to feeling breathless and tired (anaemia), increased risk of getting an infection and more regular bruising or bleeding.

We have more information on possible side effects of lung chemoradiotherapy. Your doctor will talk to you about all the possible side effects before you agree to take part.