A trial looking at volrustomig, bevacizumab and lenvatinib for liver cancer that has spread (GEMINI-Hepatobiliary - Sub study one)

Cancer type:

Liver cancer

Secondary cancers

Status:

Open

Phase:

Phase 2

This trial is looking at having a new drug called volrustomig (MEDI5752) on its own for liver cancer. It is also looking at volrustomig in combination with bevacizumab or lenvatinib.

It is open to people with a type of liver cancer called hepatocellular carcinoma (HCC).

You might be able to join the trial if you have liver cancer that has spread into surrounding tissues or to another part of the body. Or you can’t have surgery to remove it.

More about this trial

Doctors are looking for ways to improve treatment for cancer that starts in the liver.

Volrustomig is a new immunotherapy drug. It is also called MEDI5752. It helps the immune system Open a glossary item to find and kill cancer cells. To do this it blocks 2 different proteins on the cancer cells. Researchers hope that by blocking 2 proteins it will boost the ability of your immune system to detect and fight cancer.

Lenvatinib and bevacizumab are targeted cancer drugs Open a glossary item . They are both usual treatments for liver cancer that has spread.

Bevacizumab blocks a growth factor that makes blood vessels. This growth factor is called VEGF. Blocking this protein stops the cancer from growing blood vessels, this starves the cancer of food and oxygen. This means that it can't grow.

Lenvatinib is a cancer growth blocker. It stops signals that cancer cells use to divide and grow. It also stops cancer cells from forming new blood vessels, which they need to keep growing.

Doctors think that volrustomig could improve treatment. But they aren’t sure so they want to find out more.

In this trial you have one of the following:

volrustomig
volrustomig and bevacizumab
volrustomig and lenvatinib

The main aims of the trial are to:

find out if it is safe to have volrustomig on its own or alongside bevacizumab or lenvatinib
find out how well treatment works
learn more about the side effects
see what happens to volrustomig in the body

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 hepatocellular liver cancer that has spread into surrounding tissues, to another part of the body or you can’t have surgery to remove it.
You have many tumours in your liver, but you feel well. This is BCLC stage B liver cancer. Or you have cancer that has spread, or you feel less well. This is BCLC stage C liver cancer.
Your liver is working normally.
You have at least 1 area of cancer that your doctor can measure on a scan that hasn’t been treated with radiotherapy.
There is a sample of tissue that the trial team can access or you are willing to give a new sample.
You weigh more than 35kg.
You are active but might not be able to do heavy physical work (performance status 0 or 1).
You have satisfactory blood test results.
You are willing to use reliable contraception during treatment and for a period after if there is any chance you or your partner could become pregnant.

Who can’t take part

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

have fibrolamellar or sarcomatoid hepatocellular liver cancer or you have a mix of bile duct cancer and hepatocellular liver cancer. Your doctor will know this.
have cancer that has spread to the brain or spinal cord or the thin tissues that cover the them
have spinal cord compression
are suitable to have local treatment to the liver such as heat treatment to destroy liver cancer
have had or are having chemotherapy, a targeted cancer drug or hormone therapy to treat your cancer
have had an immunotherapy or a similar drug in the past
have had another cancer in the past unless there have been no signs of it in the last 5 years and there is a low chance of it coming back. You can take part if you have had successfully treated non melanoma skin cancer , lentigo maligna melanoma or carcinoma in situ (CIS ).
are taking an experimental drug or using a device as part of another clinical trial
have already taken part in this trial

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

had changes in the brain that can occur with liver disease within a year of being put into a treatment group or you are taking medication to stop this happening. Your doctor will know this.
have had a heart attack in the last 6 months or another significant heart problem that isn’t well controlled with medication. Your doctor checks your heart before you join the trial.
have had a stroke in the last 6 months
have a serious wound, a wound that isn’t getting better or you have had a tummy ulcer or bone fracture within a month of being put into a treatment group
have had a blood clot in your lower leg or lung or a serious clot that developed in another part of the body within 3 months of being put into a treatment group
are taking or have recently taken medication to treat a blood clot. You might be able to take part if you are taking medication to prevent a this.
have inflammation of the blood vessels, a significant bleeding disorder or a significant bleed from your digestive tract within 6 months of being put into a treatment group
have had an organ transplant or you are on the waiting list to have one
have or had an autoimmune condition that needs treatment apart from certain ones. Your doctor will know about this.
have or had an inflammatory disorder such as Crohn’s disease
have a problem with how your immune system works
have HIV, tuberculosis, or any other active infection that needs treatment. You cannot join if you have both hepatitis B and hepatitis D. You can join if you have only hepatitis B or only hepatitis C that is being controlled with medication.
have bad side effects from past treatments that aren’t getting better. You can join if these are hair loss, loss of skin pigment (vitiligo) or other side effects that won’t get worse if you have the trial drug.
have scarring of the lungs
developed a hole or fistula in your digestive tract within 6 months of being put into a treatment group
can’t swallow tablets, keep them down or you have any other condition that affects how you absorb medication
have a problem with how your kidneys work
have a long term medical condition that means you have a lot of diarrhoea
have a collection of fluid around the tummy area (abdomen) and you had it drained within 6 months but it came back. You might be able to take part if you are on a stable dose of medication for at least 2 months to treat this.
have had major surgery within 28 days of starting trial treatment
have had treatment that damps down the immune system unless it is a low dose
have had radiotherapy to more than 30% of your bone marrow or to a wide area in the last 28 days
have a lot of protein in your urine
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:

are allergic to bevacizumab, lenvatinib, volrustomig or anything they contain
have had a live vaccine within 30 days of the first dose of trial treatment. You can have the approved COVID-19 vaccines as these aren’t live.
have had a herbal medication for liver cancer within 14 days of trial treatment
are pregnant or breastfeeding or you plan to become pregnant

Trial design

This is a phase 2 trial. It is taking place worldwide. The team need 120 people to take part.

There are 3 treatment groups. The treatment you have depends on when you join the trial. The treatment groups are:

volrustomig on its own
volrustomig and bevacizumab
volrustomig and lenvatinib

Treatment
You have volrustomig and bevacizumab as a drip into a vein. You have them once every 3 weeks. You have them on the same day.

Lenvatinib is a tablet. You take them once a day, every day. The trial team give you a diary to record when you take your tablets.

Everyone has treatment for as long as it is working and the side effects aren’t too bad.

You stop treatment if your cancer gets worse. Your doctor will talk to you about treatment options.

Samples for research
The researchers might ask you to give 3 extra tissue samples. 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
see what happens to treatment in the body
look at genes to understand more about hepatocellular cancer
look for substances called biomarkers to help work out why treatment might work for some people and not for others
measure circulating tumour DNA (ctDNA ) in the blood
look at immune cells

You can say no to giving the extra tissue samples and some of the blood samples. It won’t affect you taking part in the rest of the trial.

The team might ask to use any leftover samples for future research. You don’t have to agree to this if you don’t want to.

Hospital visits

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

blood tests
urine tests
a physical examination
heart trace (ECG)
heart scan (echocardiogram) or MUGA scan
CT scan or MRI scan

You might also need to have an endoscopy.

You have volrustomig and bevacizumab at the hospital. Some hospital visits take about an hour although you could be at the hospital for longer. Other hospital visits take longer and you may have some overnight stays. The trial team will give you more information about this.

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

Trial scans
You have a CT scan or MRI scan:

every 6 weeks for a year and then
every 3 months after that

You stop having the trial scans if your cancer gets worse.

Follow up visits
You see the trial team when you stop treatment for a check up at:

1 month
3 months

The team then follow you up every 3 months. You might see them at a routine hospital appointment or they may call or email you 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.

Volrustomig 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.

Volrustomig is a new drug and there may be side effects we don’t know about yet.

The possible side effects of volrustomig that affect the immune system include:

inflammation of the heart muscle which may cause chest pain, heart rate changes or the heart muscle not working well. Doctors can treat this but it is serious and can be life threatening.
skin rash or itchy skin
liver changes
cough or shortness of breath or a drop in oxygen levels in the blood
making too much or too little thyroid hormone
changes to how the adrenal glands work
high levels of sugar in the blood
diarrhoea that can be serious
problems with the pancreas that may cause high temperatures, feeling or being sick, tummy pain or swelling, tiredness or the yellowing of the skin or whites of the eyes
muscle pain or tenderness
kidney problems that may cause weeing more or less often, cloudy wee, blood in your wee, swelling of the face and ankles or puffy eyes
a nerve condition called myasthenia gravis. Symptoms may include double vision, problems swallowing or trouble breathing.
a nerve condition called Guillain-Barre syndrome. Symptoms may include unusual weakness of legs, arms, or face, numbness or tingling in hands or feet.
inflammation of the brain or lining of the brain

Other possible side effects of volrustomig include:

a reaction that can happen while you are having the infusion. This is called an infusion reaction. Signs include high temperatures (fever), chills, muscle pain or tenderness, feeling or being sick, itchy skin or skin rash, headache, flushing (redness of the skin), sweating, fast heartbeat, difficulty breathing, low blood pressure, dizziness or light-headedness.
a severe allergic reaction . This can happen while you are having volrustomig or up to 24 hours after you have it.
antibodies to volrustomig
your body might release a large amount of a substance called cytokines. This is called cytokine release syndrome. It includes symptoms such as high temperatures, headaches, skin rash, low blood pressure, low blood oxygen levels or a fast heartbeat. Your doctor can treat this but it is serious and can be life threatening.
some types of white blood cells being made too fast and becoming too active

The trial team keep a close eye on you and treat any side effects straight away.

Volrustomig and bevacizumab is a new combination of treatment and so is volrustomig and lenvatinib. There may be side effects of the combination of treatment that we don’t know about.

We have information about the following drugs and their side effects:

The trial team will talk to you about all the side effects of treatment before you join the trial. You will have a chance to ask any questions you may have.