A study of immunotherapy and targeted drugs for kidney cancer (sub study 03B)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Kidney cancer

Renal cell cancer

Secondary cancers

Status:

Closed

Phase:

Phase 1/2

The main study (KEYMAKER-U03) is looking at combinations of immunotherapy and targeted drugs for a type of kidney cancer called renal cell cancer.

Sub study 03B is part of the main study. It is open to people with a type of kidney cancer called renal cell cancer that has:

spread (advanced cancer ) or
got worse during or after treatment

More about this trial

Doctors can treat advanced renal cell cancer with the combination of pembrolizumab and lenvatinib.

Pembrolizumab is an immunotherapy. It works by helping the immune system Open a glossary item to find and attack cancer cells.

Lenvatinib is a targeted drug Open a glossary item called a cancer growth blocker. It works by stopping:

signals that tell the cancer cells to grow
the cancer making new blood vessels which they need to grow

This stops the cancer cells from growing.

In this sub study the study team are looking at the following drugs:

belzutifan (MK-6482)
MK-4280A
MK-1308A
MK-4830

Belzutifan is a drug doctors use to treat people with an inherited Open a glossary item disease called Von Hippel-Lindau syndrome and renal cell cancer.

MK-4280A and MK-1308A are combinations of pembrolizumab and another immunotherapy.

MK-4380 is an immunotherapy.

The main aims of the sub study are to find out:

how safe these treatments are
how well these treatments work
what happens to these treatments in the body and how they affect the body

Who can enter

The following bullet points are a summary of the entry conditions for this study. Talk to your doctor or the study 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 study if all of the following apply. You:

have a type of kidney cancer called renal cell cancer that has spread into the surrounding tissue (locally advanced) or to another part of the body (metastatic). This is stage 4 renal cell cancer.
have had certain targeted cancer drugs and immunotherapy. And your cancer spread got worse during or after treatment. Your doctor will know which treatments these are and if you have had them.
have an area of cancer that the doctor can measure
can take care of yourself but might not be able to do all your normal activities or do active work (Karnofsky performance score 70 to 100)
are able to swallow tablets
have a previous tissue sample (biopsy ) the team can access. If this is not available you are willing to have a fresh biopsy taken.
have satisfactory blood test results
are willing to use contraception during treatment and for a time after if there is any chance you or your partner could become pregnant
are at least 18 years old

You can join the trial if you are having medication such as bisphosphonates Open a glossary item for your bones. This is as long as you started it at least 2 weeks before going into one of the trial treatment groups (randomised).

Who can’t take part

Cancer related

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

have cancer spread to the brain or spinal cord. You might be able to join if you have had treatment for this spread. Your doctor will be able to tell you more about this.
have had a scan that shows the cancer that is either very close to a major blood vessel or that the cancer has changed and looks like it is full of air or similar. Your doctor will know if your scan shows this.
have another cancer that has needed treatment or has got worse in the past 3 years. This is apart from non melanoma skin cancer and any carcinoma in situ (CIS) that has been successfully treated.
have already had treatment or been put into a treatment group (randomised ) for another sub study that is part of the main study. Your doctor will know if you have.
have had an experimental drug or used a device as part of another clinical trial within 4 weeks of starting treatment
have had radiotherapy within 2 weeks of starting treatment. Or you are having corticosteroids due to side effects from radiotherapy.
have had more than 4 cancer treatments that reach the whole body (systemic treatment)
have had belzutifan or a similar drug already. Your doctor will know if you have.

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

have heart problems that could affect you taking part
have high blood pressure that isn’t well controlled
have major surgery within 3 weeks of starting treatment
have more than a certain amount of protein in your urine. Your doctor will do a urine test for this.
have lung problems such as inflammation or fluid on the lung that could affect you taking part. You might be able to take part if you had treatment for fluid on the lung. Your doctor will know if this is so.
are coughing up blood within the 3 weeks before starting treatment
have an inflammatory bowel disease such as irritable bowel syndrome (IBS) or Crohn’s disease
have an abnormal opening between 2 parts of the body or between the inside of the body and the outside of the body (a fistula). You might be able to join if it isn’t too bad. Ask your doctor they will know.
have a problem with your digestive system which affects how well your body absorbs medication taken by mouth
have an immune system that isn’t working very well or you are taking medication that damps down the immune system within the 7 days of starting treatment. You can take steroids as long as it is a small dose. Your doctor will know what the dose is.
have an autoimmune disease that has needed treatment in the past 2 years apart from certain ones. Your doctor will know which ones these are.
have HIV, hepatitis B or active hepatitis C. Or you have had any other infection that needs treatment.
don’t have enough oxygen in your blood. Your doctor will test for this. Or you need to have oxygen to help you breath.
have had an organ transplant . Or you have had a stem cell or bone marrow transplant from a donor (allogeneic transplant ).
have any other medical condition, mental health problem or social situation that could affect you taking part

Other
You cannot join this study if any of these apply. You:

are allergic or sensitive to any of the treatments or any of their ingredients
have a live vaccine within the 30 days of starting treatment. You cannot have a live vaccine for 3 months after finishing treatment. The COVID-19 vaccines and some seasonal flu vaccines are not live vaccines.
are pregnant or breastfeeding

Trial design

This is an international phase 1/2 study. The team need up to 370 people to take part with 40 people from the UK.

It is a randomised study. A computer puts you into a treatment group. Neither you nor your doctor chooses which group you go into. There are 6 treatment groups:

MK-1308A
MK-4280A
belzutifan and lenvatinib
pembrolizumab and belzutifan
pembrolizumab and MK-4830
pembrolizumab and lenvatinib

You have the following as a drip into a vein:

pembrolizumab
MK-1308A
MK-4280A
MK-4830

You have pembrolizumab once every 3 weeks or 6 weeks for up to 2 years.

You have MK-1308A once every 6 weeks for up to 2 years.

You have MK-4280A once every 3 weeks for up to 2 years.

Lenvatinib and belzutifan are tablets. You take the tablets once a day. Your doctor will tell how many to take and whether you take them on an empty stomach or with a meal.

You continue to have treatment as long as it is helping and the side effects aren’t too bad.

Samples for research
You give extra blood samples and tissue samples (biopsies Open a glossary item ) as part of the study. Where possible the team take theses samples when you have blood tests and tissue samples taken as part of your routine care.

The team use these samples to:

find out how the treatments affect the body and what happens to the treatments in the body
look at the genes in the cancer cells
look for substances (biomarkers )

This can help researchers to find out:

how well the treatments are working
what affects how well the treatments work
more about the treatments

They might also ask to store your samples for researchers to use in the future. Your samples will be anonymous.

Hospital visits

You see the doctor to have tests before taking part. These tests include:

a physical examination
blood tests
CT scan or an MRI scan
bone scan
heart trace (ECG)
heart scan (ECHO or MUGA )
urine test

You see the doctor regularly during treatment. This is:

for blood tests and urine tests
to see how you are
ask what daily activities you can do
ask about side effects

You have a scan at 6 weeks and then every 6 weeks while having treatment. If a scan shows your cancer is getting worse your doctor will talk to you about whether you should continue with the study treatment. They will also speak to you about what other treatments there might be if you do stop having the study treatment.

You will have regular heart traces if you are having lenvatinib or belzutifan. And heart scans done regularly if you are having lenvatinib. Your doctor will tell you how often you are to have them.

You see the doctor at the end of treatment and a month later. This is to see how you are and to ask about any side effects.

After finishing treatment a member of the trial team will contact you regularly to see how you are. This could by phone or in a clinic when you see the doctor.

Side effects

The study 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, MK-1308A and MK-4280A 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.

Researchers have looked at the combination of pembrolizumab and lenvatinib in other clinical trials. The side effects of these 2 drugs are the same whether you take them together or separately. The most common side effects from having pembrolizumab in combination with lenvatinib are:

a low level of thyroid hormones causing tiredness, weight gain, feeling cold and constipation
inflammation of the pancreas causing tummy pain, feeling or being sick
inflammation of the adrenal glands causing tiredness, weight loss, weak muscles, feeling faint, diarrhoea and aching tummy, joints or muscles
inflammation of the kidneys causing passing urine less often, cloudy urine, blood in the urine or lower back pain

MK-1308A is a new drug and there might be side effects we don’t know about yet. The most common side effects we do know of are:

skin rash and or itchy skin
inflammation of the lungs causing shortness of breath, a cough or both
too much thyroid hormone causing anxiety, feeling angry, trouble sleeping, weakness, trembling, sweating, tiredness and diarrhoea
a low level of thyroid hormones causing tiredness, weight gain, feeling cold and constipation

MK-4280A is a new drug and there might be side effects we don’t know about yet. The most common side effects we do know about are:

itchy skin, a rash or both
tiredness (fatigue)
diarrhoea
a low level of thyroid hormones causing tiredness, weight gain, feeling cold and constipation

Doctors use belzutifan to treat renal cell cancer that has a link to Von Hippel-Lindau syndrome. But not for renal cell cancer by itself so there might be side effects we don’t know about yet when treating renal cell cancer only. The most common side effects of belzutifan we do know about are: