Last year in the UK over 60,000 cancer patients enrolled on clinical trials aimed at improving cancer treatments and making them available to all.
A trial looking at pembrolizumab and chemotherapy for advanced non small cell lung cancer (KEYNOTE-789)
This trial is for people with advanced non small cell lung cancer (NSCLC). Advanced NSCLC can mean one of the following:
- the cancer is in both lungs
- the cancer has spread outside of the lung into the surrounding area, or elsewhere in the body
- there is a collection of fluid around the lung (pleural effusion) and this fluid contains cancer cells
It is for people who have a NSCLC that has a change (mutation) in receptors called epidermal growth factor receptors (EGFR). And that have had treatment with drugs called tyrosine kinase inhibitors (TKI).
More about this trial
For advanced non small cell lung cancer, you usually have a combination of chemotherapy drugs. Chemotherapy uses anti cancer (cytotoxic) drugs to destroy cancer cells. Possible chemotherapy combinations are:
Pembrolizumab (also called Keytruda) is a type of immunotherapy called a monoclonal antibody. It helps the immune system to attack the cancer and stop it from growing. Pembrolizumab is already a possible treatment for people with advanced NSCLC.
Everyone taking part in this trial has one of the following:
- pembrolizumab with pemetrexed and cisplatin or carboplatin
- dummy drug (placebo) with pemetrexed and cisplatin or carboplatin
The main aims of this trial are to:
- find out how well pembrolizumab and chemotherapy work together
- learn more about the side effects of pembrolizumab 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 non small cell lung cancer that is stage 4
- you have a change (mutation) in receptors called epidermal growth factor receptors (EGFR)
- your cancer came back and got worse after treatment with a type of cancer growth blocker called a tyrosine kinase inhibitor such as erlotinib and afatinib
- you have at least 1 area of cancer that can be seen and measured on a scan
- you are willing to have a sample of your cancer taken (a biopsy) if there isn’t a suitable sample available taken after you finished your last cancer treatment
- you are at least 18 years old
- you are well enough to carry out your normal activities, apart from heavy physical work (performance status of 0 or 1)
- you have satisfactory blood test results
- 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
You cannot join this trial if any of these apply.
- your NSCLC has spread to the brain or the membranes surrounding the brain (carcinomatous meningitis) unless you have had treatment, it has been stable for the past 4 weeks and you have stopped taking steroids more than 2 weeks ago
- your NSCLC is mainly a type called squamous cell cancer
- you have fluid in your lung (pleural effusion) or a collection of fluid in the abdomen (ascites) that is causing symptoms (you may be able to take part if you have had treatment and the symptoms are stable)
- you have had treatment with pembrolizumab or any other similar drug
- you have had treatment that reached your whole body (systemic treatment) for advanced NSCLC unless it was a tyrosine kinase inhibitor or chemotherapy that you had before surgery (neo adjuvant therapy) or after surgery (adjuvant therapy)
- you have had radiotherapy in the past 2 weeks and you still have side effects from it (one week if it was radiotherapy to help with symptoms and 6 months if it was a large dose of radiotherapy to your lungs)
- you have had another cancer in the last 5 years unless it was non melanoma skin cancer or an early cancer (carcinoma in situ) of the bladder or breast that have been successfully treated
- have had treatment with a new drug or device in the last 4 weeks
- take drugs that damp down your immune system such as steroids unless it is a very small dose
- have an autoimmune disease that needed systemic treatment in the last 2 weeks, unless it was treatment to replace something that the body makes such as insulin or thyroxine
- have lung problems such as pneumonitis
- have an active infection that needs systemic treatment
- have HIV
- have hepatitis B or hepatitis C
- have active tuberculosis
- have any other serious condition or mental health problem that the trial team think could affect you taking part
- are pregnant or breastfeeding
- have had a live vaccine in the past 30 days
- are sensitive to the drugs used in this trial or anything they contain
This is an international phase 3 trial. Researchers need about 480 people worldwide and 24 people from the UK to join.
It is a randomised trial. The people taking part are put into one of the following groups at random:
- pembrolizumab with pemetrexed and cisplatin or carboplatin (group 1)
- dummy drug with pemetrexed and cisplatin or carboplatin (group 2)
Neither you nor your doctor will be able to choose with group you go into. And neither you nor your doctor will know which group you are in. This is called a double blind trial.
How do I have treatment?
You have all drugs as a drip into your bloodstream on set days during the trial. It takes:
- about 30 minutes to have pembrolizumab or the dummy drug
- about 10 minutes to have pemetrexed
- up to 60 minutes to have cisplatin or carboplatin
Your doctor will tell you whether you have cisplatin or carboplatin.
When do I have treatment?
You have treatment in cycles of treatment that last 3 weeks. You have the first 4 cycles of treatment (about 3 months) in the following way:
- you have pembrolizumab or the dummy drug on day 1 of each cycle of treatment
- you have pemetrexed and cisplatin or carboplatin on day 1 of each cycle of treatment
After 4 cycles of treatment, you stop having cisplatin and carboplatin. You continue to have pembrolizumab, or the dummy drug, and pemetrexed on day 1 of each cycle of treatment.
You can have up to 35 treatment cycles of pembrolizumab, or the dummy drug, and pemetrexed. It takes about 2 years.
After 2 years, you may be able to continue to have pemetrexed alone. This is called second course treatment. Your doctor can tell you more about this.
If you have the dummy drug and your cancer gets worse, you may be able to cross over to the other group and have pembrolizumab. Your doctor will discuss this with you.
Blood tests and tissue samples
You have extra blood tests as part of this trial. Doctors want to look for:
- substances that can tell how the treatment is working (biomarkers)
- abnormal cells in your blood called circulating tumour cells (CTCs)
They will also ask you to have a blood test to study your genes. Doctors want to find out how genes affect the way people respond to treatment and the side effects they have.
You have the extra blood tests before the start of treatment and at set times during the trial.
Your doctor will ask to use a sample of your cancer taken after your cancer got worse. You need to have a biopsy if there isn’t a suitable sample available. This is so your doctors can find out whether the cancer still has a change in the epidermal growth factor receptors (EGFR).
Quality of life
Everybody taking part completes a quality of life questionnaire before starting treatment and:
- on day 1 of each cycle of 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.
You see a doctor and have some tests before taking part. These tests might include:
During treatment, you see the doctor every 3 weeks. You have blood tests and a physical examination each time you see them.
You have a CT scan or MRI scan 6 weeks after you start treatment. You then have a CT scan or MRI scan every 9 weeks. This continues for about a year. You then have a CT scan or MRI scan every 12 weeks.
Your treatment continues for as long as your cancer stays the same 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 them every 12 weeks.
The trial team monitor you during treatment and afterwards. You have a phone number to call them if you are worried about anything. The team will tell you about all the possible side effects before you start the trial.
The most common side effects of pembrolizumab are:
- skin rashes, itching and loss of skin colour
- joint, back and tummy (abdomen) pain
- high temperature (fever)
- low levels of thyroid hormones in your body that can cause tiredness, weight gain and feeling cold
- low levels of salt in the body that can cause muscle cramps and feeling sick (nausea)
We have more information about the possible side effects of pembrolizumab.
We also information about the possible side effects of:
How to join a clinical trial
Professor Samreen Ahmed
Merck, Sharp & Dohme