A trial looking at pembrolizumab with or without sacituzumab govitecan for non small cell lung cancer that has spread (KEYNOTE D46/EVOKE-03)
Cancer type:
Status:
Phase:
This trial is looking at a targeted cancer drug called sacituzumab govitecan in combination with the immunotherapy drug pembrolizumab. The trial team are comparing this treatment to pembrolizumab alone.
You pronounce sacituzumab govitecan as sass-ih-too-zo-mab go-vih-tee-kan.
It is for people with non small cell lung cancer and:
- the cancer has spread from where it started to other parts of the body (advanced cancer)
- more than half (more than 50%) of the lung cancer cells have a protein called PD-L1 on their surface
- they have not had treatment for their advanced lung cancer before
More about this trial
There are a number of treatments for non small cell lung cancer that has spread.
Treatments such as chemotherapy, radiotherapy or targeted cancer drugs can help to shrink the cancer, reduce symptoms and help people to feel better.
Doctors are trying to improve treatment for people with advanced lung cancer. They think an 
drug called pembrolizumab and a called sacituzumab govitecan could work well together but they aren’t sure. They are doing this trial to try and find out.
Sacituzumab govitecan is an . This means that it is a type of drug with two parts:
- sacituzumab - a
monoclonal antibody - SN-38 - a
chemotherapy drug
The sacituzumab finds specific proteins on cancer cells and delivers chemotherapy to the cell to kill it.
Pembrolizumab stimulates the body's to fight cancer cells. It does this by targeting and blocking a protein called PD-1 on the surface of certain immune cells called . Blocking PD-1 triggers the T cells to find and kill cancer cells.
The main aims of the trial are to:
- look at the safety of pembrolizumab with and without sacituzumab govitecan for advanced non small cell lung cancer
- see how well pembrolizumab and sacituzumab govitecan work together compared to pembrolizumab alone
- find out about the
quality of life of people taking part - get more information about the side effects of treatment
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 non small cell lung cancer that has spread outside the lungs. This is stage 4 non small cell lung cancer (NSCLC). You might be able to take part if your cancer is a mix of NSCLC and another type, unless you have any small cell lung cancer cells. Your doctor can explain more.
- have cancer that your doctor can see on a scan
- don’t have
gene changes in EGRF, ALK and ROS1 on your cancer cells. Your doctor can explain more. - have a tissue sample available that the trial team can access. Or you are willing to give a new sample from a
biopsy . The sample shows that more than half (more than 50%) of the lung cancer cells have a protein called PD-L1 on their surface. - are willing to use reliable contraception during treatment and for a time after if there is any chance you or your partner could become pregnant. The trial team can let you know reliable methods of contraception and for how long after you must use them.
- agree to not donate sperm during treatment and for some time afterwards. The trial team can let you know how long this will be.
- have satisfactory blood test results
- are fit and active but might not be able to do heavy physical work (performance status 0 or 1)
- 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 had another cancer before unless you had treatment with the aim to get rid of the cancer completely and there has been no sign of the cancer for 3 years. You might be able to take part if you have had
basal cell skin cancer , squamous cell skin cancer or a very early stage cancer (in situ) apart from bladder cancer and you have had treatment to try and get rid of the cancer completely. - have had any treatment that reaches the whole body (
systemic treatment ) for your NSCLC that has spread. You might still be able to take part if you have had chemotherapy or radiotherapy for NSCLC before it spread. And it finished at least 12 months before you were diagnosed with advanced non small cell lung cancer. - have no side effects of previous treatment unless they are mild. You might be able to take part if you have a moderate side effect related to your nervous system (neuropathy) or you have
hormonal side effects and need treatment. Your doctor can explain more. - have had treatment with a type of chemotherapy called a topoisomerase 1 inhibitor before. Or you have had a treatment that targets the TROP2 protein before. Your doctor will know this.
- have had certain
checkpoint inhibitors before. Your doctor will know which drugs these are. - have had radiotherapy in the 2 weeks before starting the study drugs or you have side effects of radiotherapy that needs treatment with steroids. You might be able to take part if you have had two weeks or less of radiotherapy to help with symptoms (apart from for cancer in the brain and spinal cord) and you’ve had at least a week’s break before treatment in the study.
- have had a certain amount of radiotherapy to the lung within 6 months of the first dose of the study drug. Your doctor will know more.
- have had cancer that has spread to the
central nervous system or the thin layer between the brain and the spinal cord. You might be able to take part if you have had cancer that has spread to the brain before and it has not grown or got worse over 4 weeks, you don’t need treatment and you’ve not had steroids for this within 2 weeks of having the first dose of the study drug.
Medical conditions
You cannot join this trial if any of these apply. You:
- have had serious
heart problems , such as having a heart attack within 6 months of joining the trial. Your doctor can explain more. - have active, long term bowel inflammatory bowel disease such as Crohn’s disease or
ulcerative colitis - have had a hole in your bowel in the 6 months before joining the study
- have got an immunodeficiency disorder, meaning you have a lowered resistance to infection
- are having treatment with steroids long term, this is apart from small doses. Or you are having any other treatment that dampens down your
immune system within the 7 days before your first dose of study treatment. - have an active
autoimmune disease that has needed treatment in the last 2 years apart from certain ones. Your doctor can explain more. - have
pneumonitis or inflammation and scarring of the lungs (interstitial lung disease). Or you have had these in the past, they were not caused by infection, and you needed steroid treatment. - have an active infection that needs treatment that reaches the whole body (
systemic treatment ) - have ever had hepatitis B, have active hepatitis C or have HIV
- have any other serious physical or mental health condition, or social circumstances, that could prevent you from taking part
- have had major surgery and have not recovered fully. Or you are still having side effects from surgery.
- have had a solid
organ transplant
Other
You cannot join this trial if any of these apply. You:
- have had a
live vaccine in the 30 days before your first dose of study drug. The COVID vaccines are not live. - have had treatment that affects the UGT1A1 protein before. Your doctor will know this.
- have had another trial medication, or used a trial medical device, within 4 weeks of having the first dose of study drug
- are allergic to pembrolizumab or sacituzumab govitecan or anything they contain
- are pregnant or breastfeeding
Trial design
This phase 3 trial is taking place worldwide. The trial team need 614 people to take part.
It is a randomised trial. You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in. There are 2 treatment groups.
You have 1 of the following:
- pembrolizumab and sacituzumab govitecan
- pembrolizumab
You have . Each cycle lasts for 3 weeks. You have all your treatment as a drip into a vein.
Pembrolizumab and sacituzumab govitecan
You have sacituzumab govitecan on the trial for as long as it is working, and the side effects are not too bad.
You have pembrolizumab for up to 2 years on the trial. This is as long as the drug is working, and the side effects are not too bad.
Pembrolizumab alone
You have treatment for up to 2 years on the trial, as long as it is working, and the side effects are not too bad.
Everyone taking part
You stop treatment if your cancer gets worse. The trial doctor will talk to you about other treatment options.
Samples for research
The researchers might ask you to give a sample of cancer tissue if there isn’t already a suitable one that they can access. They 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 non small cell lung cancer - look for substances called
biomarkers to help work out why treatment might work for some people and not for others - help develop and improve tests for people with cancer
Quality of life
The trial team ask you to use a computer at the clinic to answer questions about how you are feeling and your day-to-day life. This is called a quality of life study.
You fill in the questionnaires:
- before you start treatment
- before every cycle of treatment for a year
- before every other cycle of treatment after a year
Hospital visits
You see the doctor and have tests before you can take part. These might include:
- blood tests
- urine tests
- a
physical examination - a pregnancy test - if there is any chance you could become pregnant
- heart trace (
ECG ) - CT scan or
MRI scan - a biopsy - if there is not a recent tumour sample available
Having treatment
You have treatment as an outpatient in the hospital. This means you don’t need to stay overnight.
You have pembrolizumab on day 1 of your 3 week cycle. And sacituzumab govitecan on day 1 and day 8 of your 3 week cycle.
So you go into hospital:
- around twice every 3 weeks if you are having pembrolizumab and sacituzumab govitecan
- around once every 3 weeks if you are having just pembrolizumab
The trial team will also contact you about 1 week after each visit to check how you are getting on.
Tests during treatment
You have some tests at each hospital visit, including blood and urine tests. Your doctor will let you know which tests to expect and when.
You have during treatment to see how well the treatment is working.
You have a scan around every 6 weeks for the first 4 months after . You then have a scan around every 9 weeks for the rest of the first year of treatment.
You then have a scan around every 3 months until you stop treatment.
You have a scan when you finish treatment on the trial. The trial team will ask you to still have scans every 3 months if you stop treatment, but your cancer has not got worse.
Follow up
The trial team monitor you on the trial after you finish treatment.
You have a hospital visit about 30 days after you finish treatment. You have some tests at this visit, including blood tests. Your doctor will let you know which tests to expect.
You have hospital visits every 9 to 12 weeks unless your cancer gets worse, or you start other cancer treatments. The trial doctor will let you know your follow up schedule.
Then the trial team will get in touch with you around every 3 months to see how you are feeling and 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.
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Pembrolizumab can affect the 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. |
The most common side effects of pembrolizumab are:
- itchy skin or a skin rash
- diarrhoea
- cough
- joint, back or tummy pain
- fever
- loss of skin colour
- not enough
thyroid hormone. This might mean you feel tired, gain weight, feel cold or have constipation. - low levels of salt in the blood. This might mean you feel tired, confused, have a headache, have muscle cramps or feel sick.
The most common side effects of sacituzumab govitecan include:
- an
allergic reaction . This could cause a skin rash or hives, breathing problems, wheezing, feeling dizzy or lightheaded, fast pulse, sweating or swelling around the mouth, throat or eyes. - a drop in the number of blood cells causing an increased risk of infection, tiredness, and breathlessness
- feeling or being sick
- diarrhoea or constipation
- pain in the tummy (abdomen) or joint pain
- tiredness (fatigue)
- urine infections
- weight loss, loss of appetite or both
- low levels of magnesium, potassium, or phosphate in the blood
- lack of fluids in the body (dehydration)
- headache
- dizziness
- shortness of breath with or without exercise
- cough
- skin rash or itchy skin
- hair loss
You might have more severe side effects with a combination of the drugs. Your doctor will talk to you about this. You’ll have a chance to ask any questions you may have.
Let your doctor know if you know you have the UGT1A1*28 gene. This means you may be more likely to have side effects from sacituzumab govitecan including changes to the production of blood cells. Your doctor can explain more.
We have more information about pembrolizumab including possible side effects.
Location
Recruitment start:
Recruitment end:
How to join a clinical trial
Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.
Chief Investigator
Professor Samreen Ahmed
Supported by
Merck, Sharp and Dohme
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
