A trial of chemoradiotherapy, pembrolizumab, and olaparib for small cell lung cancer (KEYLYNK-013)

Cancer type:

Lung cancer

Small cell lung cancer

Status:

Open

Phase:

Phase 3

This trial is looking at adding a drug called pembrolizumab to chemoradiotherapy for newly diagnosed small cell lung cancer. It is also looking at having pembrolizumab on its own or with olaparib after chemoradiotherapy.

It is for people who:

haven’t had treatment for small cell lung cancer and
whose cancer is in only one lung. This is called limited small cell lung cancer.

More about this trial

You might have a combination of radiotherapy and chemotherapy to treat small cell lung cancer that hasn’t spread. This is called chemoradiotherapy. It is a standard treatment for some people with limited small cell lung cancer.

Doctors are looking for ways to improve treatment for this group of people. They think that adding 2 drugs called pembrolizumab and olaparib may help.

Pembrolizumab is a type of immunotherapy. It helps your immune system Open a glossary item to find and kill cancer cells. It is already a treatment for another type of lung cancer and for small cell lung cancer that has spread.

Olaparib is a type of targeted cancer drug called a PARP inhibitor Open a glossary item . It blocks an enzyme called PARP which helps damaged cells to repair themselves.

The main aims of the trial are to find out:

if it is safe to have pembrolizumab and olaparib for limited stage small cell lung cancer
if having pembrolizumab and olaparib improves treatment
more about the side effects of treatment
what happens to olaparib and pembrolizumab in the body
how treatment 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:

have limited small cell lung cancer that is newly diagnosed
have cancer that is contained in a single area on one side of the chest and it can be treated with radiotherapy
have cancer that the doctor can measure on a scan
have a sample of cancer tissue (biopsy or fluid sample) available for the trial team to do some tests on or you are willing to give a new sample
are well enough to carry out all your normal activities but might not be able to do heavy physical work (performance status 0 or 1)
have satisfactory blood test results
are willing to use reliable contraception during the trial and for a certain period of time after if there is any chance you or your partner could become pregnant
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 cancer that has spread to other parts of the body or it isn’t possible to have radiotherapy to treat it
have had treatment for lung cancer. This includes having chemotherapy, radiotherapy or surgery.
need surgery to remove the cancer during the trial
might need to have a large dose of radiotherapy
have had an immunotherapy in the past
have already had olaparib or another PARP inhibitor in the past
might need another cancer treatment while you are on this trial
have had treatment to boost the number of blood cells in your body within 28 days of starting trial treatment
have or had a type of blood cancer called acute myeloid leukaemia or myelodysplastic syndrome
are taking an experimental treatment or using a device as part of a clinical trial in the 4 weeks before joining this trial
have another cancer that is getting worse or needed treatment in the past 5 years. You can join if you have non melanoma skin cancer , early bladder cancer or CIS that has been successfully treated.

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

have a problem with how your lungs work
have a heart problem that needs treatment, an abnormal heartbeat or you had a heart attack in the last 3 months
have had a problem with seizures (fits) in the last 3 months
have lost more than 10% of your body weight in the 3 months before you join the trial
have spinal cord compression that needs treatment
have a blockage in a major blood vein in your upper body (superior vena cava obstruction )
have a problem with how your immune system works or you are taking medication to damp down the immune system unless it is a low dose
have an autoimmune condition that needed treatment in the last 2 years apart from certain ones
have scarring on the lungs or active inflammation of the lungs (pneumonitis ) that is not caused by an infection
have had major surgery in the 4 weeks before starting treatment in this trial
have HIV, an active hepatitis B or hepatitis C infection or you have another infection that needs treatment
have a problem with your nerves caused by cancer. This can cause problems with coordination, changes to your senses, memory or thinking skills, or sleep problems. Your doctor will know about this.
can’t swallow medication or you have a problem with your digestive system that affects how you absorb medication
have had a stem cell transplant with somebody else’s cells or you had an organ transplant in the past
are taking medication that affects the CYP enzymes
have any other 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:

have had a live vaccine within a month of starting trial treatment. This doesn’t include the approved COVID-19 vaccines as they aren’t live.
have a problem with drugs or alcohol
are allergic to treatments in this trial or anything they contain
are pregnant or breastfeeding

Trial design

This is a phase 3 trial. The trial team need 672 people to take part.

It is a randomised trial. A computer puts you into a treatment group. Neither you nor your doctor can decide which group you are in. Nor will you know which group you are in. The trial doctor can find this out if necessary.

There are 3 groups. You have one of the following:

dummy (placebo ) pembrolizumab and chemoradiotherapy. This is followed by dummy pembrolizumab and dummy olaparib. (Group 1)
pembrolizumab and chemoradiotherapy. This is followed by pembrolizumab and dummy olaparib. (Group 2)
pembrolizumab and chemoradiotherapy. This is followed by pembrolizumab and olaparib. (Group 3)

KEYLYNK-013 trial randomisation

Chemotherapy and radiotherapy (standard treatment)
To begin with, everyone has chemotherapy and radiotherapy.

You have chemotherapy every 3 weeks. Each 3 week period is a cycle of treatment Open a glossary item .

Day 1 is the first day of the treatment cycle. In each cycle you have:

cisplatin or carboplatin on day 1 (your doctor decides which drug they think is best for you)
etoposide on day 1, day 2 and day 3

You have chemotherapy as a drip into a vein. You have it for up to 12 weeks in total.

You have radiotherapy from Monday to Friday. You start this when you begin your second cycle of chemotherapy. You have either:

radiotherapy once a day, Monday to Friday for 6 ½ weeks or
radiotherapy twice a day Monday to Friday for 3 weeks

Your doctor will talk to you about the schedule of radiotherapy they think is best for you. Before your radiotherapy starts you have a planning appointment.

Chemotherapy and radiotherapy take up to 4 months in total.

Pembrolizumab with chemoradiotherapy
During chemoradiotherapy you also have pembrolizumab or the dummy pembrolizumab. You have this as a drip into a vein once every 3 weeks. You have it for up to 12 weeks in total.

Radiotherapy to the brain
Small cell lung cancer can spread to the brain. After radiotherapy and chemotherapy your doctor might suggest that you also have radiotherapy to the brain. This is to reduce the risk of cancer spreading there. The team can tell you more about this if you have this treatment. It is a standard treatment Open a glossary item you might have even if you weren’t in this trial.

Pembrolizumab and olaparib after chemoradiotherapy
After chemoradiotherapy you have pembrolizumab or the dummy pembrolizumab. You have this once every 6 weeks. You have it for up to a year as long as the cancer does not get worse and the side effects aren’t too bad.

You also have olaparib or the dummy olaparib. Olaparib is a tablet. You take it twice a day, every day. You have it for up to a year as long as the cancer does not get worse and the side effects aren’t too bad.

Samples for research
The researchers ask for a sample of cancer tissue from a previous biopsy Open a glossary item . You may need to give a new sample if there isn’t one available. The team also ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests.

They plan to use the samples to:

see how well the treatment is working
look at genes to understand more about small cell lung cancer
look for substances called biomarkers to help work out why treatment might work for some people and not for others
see what happens to pembrolizumab and olaparib in the body

Quality of life
The trial team ask you to fill out a questionnaire:

before you start treatment
at set times during treatment

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

Hospital visits

You see the doctor and have tests before you can take part. These include:

blood tests
urine tests
a physical examination
heart trace (ECG)
breathing tests (lung function tests )
CT scan or MRI scan
PET-CT scan

You might also have a hearing test if you have cisplatin.

You have chemotherapy and pembrolizumab or the dummy pembrolizumab in the hospital day care ward. You also have radiotherapy at the hospital.

You see the doctor regularly during treatment. This is to see how you are and for blood tests.

Trial scans
You have a CT scan or MRI scan 12 weeks after you start chemotherapy. You then have the scans every:

9 weeks until the end of the second year of the trial
3 months in the 3rd year
4 months in the 4th year
6 months in the 5th year of the trial and then
once a year after that

You stop having the trial scans if your cancer gets worse. The team will talk to you about other treatment options.

Follow up
When you finish treatment, you see the trial doctor a month later for a check up. You then see them regularly to see how you are. If your cancer gets worse or you start another cancer treatment the team call you every 3 months to see how you are getting on.

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. Open a glossary item This may cause inflammation and other reactions in different parts of the body. For many people the inflammation and reactions are not too bad. For some people they can cause serious side effects.

These side effects could happen during treatment or months after treatment has finished. Rarely, these side effects could be life threatening. Your doctor or nurse can explain what these side effects are, the risk of them happening and what to look out for.

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

Pembrolizumab and olaparib are new treatments for limited small cell lung cancer. So there may be some side effects we don’t know about yet.

The common side effects of pembrolizumab include:

itchy skin or skin rash
diarrhoea
cough
joint pain
high temperatures (fever)
back pain or stomach pain
loss of skin colour
low levels of thyroid hormone. You may feel tired, gain weight, feel cold, or have constipation.
low levels of salt in the blood. This may cause you to feel tired, confused, have a headache, have muscle cramps, feel or be sick.

The most common side effects of olaparib include:

feeling or being sick
tiredness and weakness (fatigue)
indigestion or heartburn
loss of appetite or taste changes
headache
dizziness
diarrhoea
cough
shortness of breath
a drop in the number of blood cells causing an increased risk of infection, bleeding or bruising, tiredness and shortness of breath