A trial looking at HTL0039732 and other cancer drugs for solid tumours that have spread

Cancer type:

All cancer types

Status:

Open

Phase:

Phase 1/2

This trial is looking at the best dose of HTL0039732 for solid tumours Open a glossary item that have spread to another part of the body. It is also looking at the best dose of HTL0039732 to have with atezolizumab or other cancer drugs.

The trial is for people whose cancer is getting worse and there is no standard treatment available.

A solid tumour is any cancer apart from cancers of the blood such as leukaemia Open a glossary item and lymphoma .

Cancer Research UK supports this trial.

More about this trial

Cancer that has spread to another part of the body is sometimes called advanced cancer. Doctors are trying to improve treatment for people with advanced cancer.

In this trial they are looking at a new drug called HTL0039732. This is the first time people are having it. HTL0039732 is a type of immunotherapy Open a glossary item . It blocks a protein that stops the immune system from attacking cancer cells. Doctors think this will stop or slow cancer growth.

They also want to see if having HTL0039732 with atezolizumab or other cancer drugs could work to stop or slow cancer growth. Atezolizumab is also an immunotherapy.

In this trial, some people have HTL0039732 on its own and some people have HTL0039732 and atezolizumab. This is part 1 of the trial. At a later stage, the team plan to see how well HTL0039732 works alongside other cancer drugs. This is part 2 of the trial.

To begin with, the researchers need to find the best dose of HTL0039732 to give by itself and in combination with atezolizumab.

The main aims of the trial are to:

find the best dose of HTL0039732 to have
find the best dose of HTL0039732 to have with atezolizumab
find out more about the side effects of treatment
see what happens to HTL0039732 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

Part 1 (group A)
You may be able to join this part to have HTL0039732 on its own if all of the following apply. You have:

cancer that has spread elsewhere in the body and standard treatment has stopped working, there isn’t a suitable standard treatment available or you don’t want to have it
at least one area of cancer that your doctor can measure accurately and this has got worse since your last treatment

Part 1 (group B)
You may be able to join this part to have HTL0039732 and atezolizumab if all of the following apply. You have:

cancer that has spread elsewhere in the body and standard treatment has stopped working, there isn’t a suitable standard treatment available or you don’t want to have it
at least one area of cancer that the trial team can see on a scan that has got worse. This doesn’t apply to people who have prostate cancer but tests must show your cancer must has got worse.
a cancer type that the team think the combination of HTL0039732 and atezolizumab might work for

These include one of the following:

bowel cancer that is microsatellite stable
squamous cell cancer of the head and neck
prostate cancer and hormone treatment has stopped working or you have had surgery to remove the testicles
oesophageal cancer
stomach cancer
pancreatic cancer
lung cancer
bladder cancer
mesothelioma
cervical cancer
a type of kidney cancer called renal cancer
soft tissue sarcoma or bone sarcoma
phaeochromocytoma
any cancer that has a P13K, AKT or mTOR gene change (mutation) . Your doctor will know this.

As well as the above, for both parts, all of the following must also apply. You:

have a sample of tissue (biopsy ) available that the trial team can access or you are willing to give a new sample
have satisfactory blood test results
are active but might not be able to do heavy physical work (performance status 0 or 1)
are willing to use reliable contraception during the trial and for a period after
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 spread to the brain unless you have had treatment, the cancer is stable and you haven’t had steroids for at least 4 weeks
have had radiotherapy in the last 4 weeks unless it was to help with symptoms of cancer (palliative radiotherapy)
have had chemotherapy, another treatment to the whole body or an experimental treatment in the 4 weeks before joining the trial. You might be able to take part if you are having certain hormone treatments for prostate cancer or it has been more than 6 weeks since you had chemotherapy drugs called nitrosoureas or a drug called mitomycin C .
have had an immunotherapy in the 12 weeks before having HTL0039732
have side effects from past treatments that aren’t getting better unless they are mild. You can take part if you have hair loss or some other side effects that the doctor thinks won’t get worse if you join the trial.
are taking an experimental drug as part of a clinical trial or you are due to join one

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

have had major surgery to your chest or tummy area (abdomen) and you aren’t better yet
have or have had TB, HIV, hepatitis B, hepatitis C or any other active infection that needs treatment
have had treatment with HTL0039732 or a similar drug in the past. Your doctor will know this.
have had treatment with a type of drug called a COX-2 inhibitor in the 8 weeks before you join the trial. Your doctor will know this.
have had treatment that damps down the immune system. This includes steroids within 2 weeks of starting trial treatment unless it was a low dose
have a significant heart problem or heart condition that isn’t well controlled with medication. Your doctor checks your heart before you join the trial.
have a problem swallowing or a digestive problem that means you can’t absorb medication
have a stomach ulcer, inflammation of the stomach, indigestion or heartburn that is causing symptoms
have any other medical condition or mental health problem that could affect you taking part

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

are allergic to the substance that the capsules are made of
are pregnant or breastfeeding

As well as the above, to join part 1, group B, the following can’t apply. You

have had a live vaccine in the 4 weeks before joining the trial. Please note, this doesn't apply to the approved COVID-19 vaccines or flu vaccines as they aren't live.
have a problem with how your immune system works
have an autoimmune condition that needed treatment in the last 2 years
have scarring of the lungs, active inflammation of the lungs (pneumonitis ) or you had inflammation of the lungs that needed treatment in the past
are allergic to atezolizumab or anything it contains

Trial design

This is a phase 1/2 trial. It has 2 parts. The team need 150 people to join.

Part 1 is looking at the best dose of HTL0039732 to have on its own or with atezolizumab. This is the dose escalation phase.
Part 2 is looking at HTL0039732 to have with other cancer drugs. This is the dose expansion phase.

Part 1 (group A dose escalation)
This part of the trial opens first. It is open to recruitment.

It is looking at the best dose of HTL0039732 to have on its own. The best dose is the highest dose with the fewest side effects. The first few people have a low dose. The next few people have a higher dose if they don’t have any side effects. And so on until they find the best dose to give.

You have treatment in cycles Open a glossary item that last 3 weeks.

HTL0039732 is a capsule. You take:

a dose about a week before the first cycle of treatment and then
you take the capsules every day. The team will tell you how many to take.

You swallow the capsules whole with a glass of water. The team may ask you to not eat or drink anything (except water) for 2 hours before you take your capsules and for 1 hour afterwards. The team let you know how many capsules to take and when to take them. This depends on when you join the trial.

You have HTL0039732 for up to a year as long as it is working and the side effects aren’t too bad.

Part 1 (group B dose escalation)
This part of the trial opens soon after part 1, group A begins.

It is looking at the best dose of HTL0039732 to have with atezolizumab.

You have:

HTL0039732 on its own for the first 3 weeks and then
you continue to have it with atezolizumab

You have HTL0039732 once a day, every day. You have atezolizumab as a drip into a vein, once every 3 weeks.

You have HTL0039732 and atezolizumab for up to a year.

Part 2 (dose expansion)
This part won’t start until part 1 (group A and group B) are complete.

You have HTL0039732 in combination with other cancer drugs. We’ll add more information about this part of the trial when it opens.

Samples for research
In part 1, group B, the researchers ask you to give an extra tissue sample before you start treatment and one extra sample during the trial. You need to say yes to this to join this part.

The team ask everyone to give some extra blood samples. Where possible, you have these at the same time as your routine blood tests. They also ask for some urine samples.

The researchers plan to use the samples to:

look at genes to understand more about your cancer type
look for substances to help work out why treatment might work for some people and not for others
see what happens to treatment in the body

Hospital visits

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

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

You might also need to have a bone scan if you have prostate cancer.

Those having atezolizumab have it at the hospital in the outpatients department.

You see the doctor often while having treatment. This is to see how you are and for blood tests. Some of the hospital visits are long and might take a full day. The team can tell you roughly how long you can expect to be at the hospital. You also have some overnight stays. The trial team can tell you when these take place.

Trial scans
You have a CT scan or MRI scan:

every 6 weeks for the first 18 weeks and then
every 9 weeks

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

Follow up
You see the trial team a month after you stop treatment. The team then follow you up every month to see how you are getting on. They might see you at a routine hospital appointment or give you a call. They may also check your medical notes.

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.

HTL0039732 and atezolizumab 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.

This is the first time people are having HTL0039732 on its own and with atezolizumab. So there may be side effects we don’t know about yet.

The possible side effects of HTL0039732 include: