A trial of pembrolizumab, olaparib and chemotherapy for non small cell lung cancer

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 for people with non small cell lung cancer (NSCLC) that has spread to other parts of the body. This is metastatic or advanced NSCLC.

It is for people who are going to have treatment for advanced NSCLC the first time.

More about this trial

Chemotherapy and targeted drugs are common treatments for non small cell lung cancer (NSCLC) that has spread to other parts of the body.

Chemotherapy uses cytotoxic drugs to kill cancer cells. Carboplatin and paclitaxel are common chemotherapies treatments for advanced NSCLC.

Targeted drugs work by targeting differences that a cancer has that help them to survive and grow. There are many different types of targeted drugs such as pembrolizumab and olaparib.

Pembrolizumab (Keytruda) is a type of targeted drug called immunotherapy. It works by targeting and blocking a protein called PD-1 on the surface of immune cells called T-cells. Blocking PD-1 triggers the immune system Open a glossary item

to find and kill cancer cells. Pembrolizumab is already a possible treatment for some people with NSCLC.

Olaparib (Lynparza) is a type of targeted drug called a cancer growth blocker. It works by stopping cancer cells from repairing themselves. Olaparib is already a possible treatment for some people with ovarian cancer.

This trial is in 2 parts. The first part is called the induction phase. Everyone taking part has pembrolizumab and one of the following chemotherapy treatments:

carboplatin and paclitaxel
carboplatin and nab-paclitaxel

After the induction phase, you might be able to have maintenance treatment with one of the following:

pembrolizumab and olaparib
pembrolizumab and dummy drug (placebo)

The main aim of this trial is to find out how well pembrolizumab, olaparib and chemotherapy work for people with advanced NSCLC.

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 the first part of this trial (induction phase) if all of the following apply. You:

have stage 4 NSCLC
have a type of NSCLC called squamous cell cancer. Your doctor can tell you more about this
have at least 1 area of cancer that can be seen and measured on a scan
are going to have treatment for advanced NSCLC for the first time. You might be able to take part if you had had treatment for NSCLC that was contained within the lungs and you have finished it more than a year ago
are willing to have a sample of your cancer taken (biopsy) for some tests if there isn’t a suitable sample available. The trial team confirm with the laboratory that the sample is adequate before you can join the trial.
are well enough to carry out your normal activities apart from heavy physical work (performance status of 0 or 1) and that hasn’t changed in the last week
have satisfactory blood tests results
are at least 18 years old
can swallow and absorb tablets
are willing to use reliable contraception during treatment and for 6 months afterwards if there is any possibility that you or your partner could become pregnant

You might be able to join the second part of this trial (maintenance phase) if after the induction phase your cancer:

• stayed the same (stable disease Open a glossary item

)

• got better (partial response Open a glossary item

)

• disappeared (complete response Open a glossary item

)

Who can’t take part

Cancer related

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

have cancer spread in your brain, the spinal cord or layers of tissue that surround the brain (carcinomatous meningitis) unless you have had treatment, it has been stable for the past 2 weeks and you have stopped taking steroids more than 3 days ago
have had chemotherapy or a targeted drug for advanced NSCLC
have had radiotherapy in the last 6 months unless it was radiotherapy to help with symptoms (palliative radiotherapy) and you have finish it more than 7 days ago
have fluid in your lungs (pleural effusion) or a collection of fluid in your tummy (ascites) that is causing symptoms. You might be able to take part if you have had treatment and the symptoms are stable
have had olaparib, pembrolizumab or any other similar drug
have another cancer that is getting worse, or that got worse in the past 3 years unless it was a non melanoma skin cancer or a 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:

have had a major surgery in the last 3 weeks and you still have side effects from it
are taking part in another trial or have taken part in a trial looking at a new drug or device in the past month
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
take or have taken drugs that damp down your immune system (corticosteroids) in the last week
have lung problems such as pneumonitis
have heart problems such as an abnormal heart rhythm or you have had a heart attack in the past 3 months
have an infection that needs treatment that reaches your whole body (systemic)
have had drugs that stimulate your body to produce blood cells such as G-CSF
have seizures (fits) that aren’t controlled
have had an organ transplant from a donor
have HIV
have hepatics B or hepatitis C
have active tuberculosis
take certain drugs that affect the CYP enzymes. Your doctor can tell you more about this
have any other serious condition or mental health problem that the trial team think could affect you taking part
take an amount of drugs or drink an amount of alcohol that is a concern for your doctor

Other

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

are sensitive to any of the drugs used in this trial or anything they contain
are pregnant or breastfeeding
have had a live vaccine in the last month

Trial design

This is an international phase 3 trial. Researchers hope that around 735 people worldwide and 30 people from the UK will agree to take part.

This trial is in 2 parts:

induction phase
maintenance phase

Induction phase

Everyone has one of the following treatments:

pembrolizumab, carboplatin and paclitaxel
pembrolizumab, carboplatin and nab-paclitaxel

Your doctor can tell you which treatment you will have.

You have treatment in cycles of treatment that last 3 weeks. This means that after each round of treatment you have a break to allow your body to recover. You have up to 4 cycles of treatment, taking around 3 months in total.

You have each cycle of treatment in the following way. You have:

pembrolizumab as a drip into your bloodstream on day 1
carboplatin as a drip into your bloodstream on day 1
paclitaxel as a drip into your bloodstream on day 1 OR nab-paclitaxel on day 1, 8 and 15

After 4 cycles of treatment, you have a scan to find out how well the treatment is working. You stop this trial if your cancer got worse (progressed) after induction treatment. Your doctor can tell which other treatments you might be able to have.

You join the second part (maintenance phase) of this trial if your cancer stayed the same, got better or disappeared.

Maintenance phase

This part of the trial is randomised. The people taking part are put one of the following groups at random:

pembrolizumab and olaparib
pembrolizumab and dummy drug

Neither you nor your doctor are able to decide which group you are in.

You have pembrolizumab as a drip into your vein every 3 weeks. It takes about 30 minutes each time you have it. You continue to have pembrolizumab for as long as it helps you and the side effects aren’t too bad. You can have treatment for up to 2 years.

You have olaparib or the dummy drug as tablets that you swallow whole, twice a day. You continue to have olaparib or the dummy drug for as long as it helps you and the side effects aren’t too bad.

16403.png

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 a protein called PD-L1 on the surface of the cancer cells.

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 help to tell how well the treatment is working. They also want to look for small amounts of cancer DNA Open a glossary item

in the blood. This is called circulating tumour DNA.

Quality of life

Everybody taking part in the maintenance phase 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.

Hospital visits

You see a doctor have some tests before taking part. These tests might include:

a physical examination
heart trace (ECG )
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 MRI scan after 28 days of the start of treatment. You then have a CT scan or MRI scan:

every 6 weeks during the induction phase
at the end of the induction phase
then every 6 weeks for the first year during the maintenance phase
then every 9 weeks until the end of this trial

When you finish treatment, you see the trial team after a month. You have blood tests and a physical examination. You then see or speak with the trial team:

every 9 weeks for a year
then 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 affects the immune system. This 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 which can cause muscle cramps and feeling sick

We have more information about the possible side effects of pembrolizumab.

The most common side effects of olaparib are:

feeling or being sick
tiredness
indigestion, loss of appetite and taste changes
headaches
dizziness
diarrhoea
cough and shortness of breath
tummy pain
a decrease in the number of blood cells in your body which can cause breathlessness, increased risk of infection, bruising and bleeding