A trial of datopotamab deruxtecan for cancer that has spread (TROPION PanTumour03)

Cancer type:

Bowel (colorectal) cancer
Ovarian cancer
Prostate cancer
Secondary cancers
Stomach cancer
Womb (uterine or endometrial) cancer

Status:

Open

Phase:

Phase 2

This trial is looking at a new drug called datopotamab deruxtecan (Dato Dxd) on its own, or with other treatments, for some solid cancers Open a glossary item. It is for people whose cancer has spread to nearby tissues or to another part of the body.

It is open for a number of different cancer types, to find out which look in ‘who can enter’. 

More about this trial

Cancer that has spread is called advanced cancer Open a glossary item. And cancer that has spread further away from where it started is called metastatic cancer Open a glossary item. Advanced or metastatic cancer can be more difficult to treat. 

Researchers think datopotamab deruxtecan might help people with certain types of advanced or metastatic cancer. Researchers are trying to find out whether it will help in the types of cancers in this trial. The side effects seen so far in other studies have been manageable and this trial will find out more.

Datopotamab deruxtecan is called an antibody drug conjugate (ADC). It’s a combination of 2 drugs. Datopotamab is a monoclonal antibody Open a glossary item. It attaches to cancer cells that have a protein called TROP2 on them. It then releases deruxtecan into the cancer cell. Deruxtecan is the chemotherapy Open a glossary item part of the drug. It kills or damages the cancer cell.

In this trial everyone has datopotamab deruxtecan. You might also have it with other cancer drugs. These include:

  • durvalumab 
  • AZD5303
  • capecitabine, fluorouracil or carboplatin - chemotherapy Open a glossary item drugs

Durvalumab is a type of immunotherapy Open a glossary item. It stimulates the body's immune system Open a glossary item to fight cancer cells.

AZD5305 is a drug called a PARP inhibitor. PARP is a protein (enzyme) found in our cells. It helps damaged cells to repair themselves. PARP inhibitors stop the PARP from doing its repair work in cancer cells and the cell dies.

The other drugs you may have depend on your cancer type.

The aims of the trial are to:

  • find out how well datopotamab deruxtecan works on its own or with other cancer drugs for people with advanced cancer
  • learn more about how datopotamab deruxtecan works
  • get more information about the side effects  
  • find out more about cancer that has spread

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. 

Please note, there are several study groups so the entry conditions for this trial are complex. Each study has specific entry conditions, and we haven’t listed them all. 

The study you join depends on your cancer type.

Who can take part

You may be able to join the trial if you have one of the following cancers:

And all of the following apply: You:

  • have cancer that has spread into nearby tissues, or to another part of your body, and your team think the treatments used in the trial could be suitable for you
  • can look after yourself but might not be able to do heavy physical work (performance status 0 or 1). Your general health has not got worse in the 2 weeks before you have your first tests with the trial team or your first dose of the trial drug.
  • have a tissue sample (biopsy) Open a glossary item that the trial team can access. If not, you are willing to have a fresh tissue sample taken.
  • have at least 1 area of cancer that the doctor can measure on a scan Open a glossary item. You must not have had radiotherapy to this area before. Those with prostate cancer might be able to take part if the cancer has spread to the bone marrow Open a glossary item and the doctor can confirm this with a test.
  • have satisfactory blood test results 
  • 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. Your trial team can talk about suitable contraception for you and your partner if needed.
  • won’t donate or bank sperm during the time you are taking part in the trial  
  • won’t donate blood or platelets during the study and for the 28 days after your last trial treatment
  • won’t use contact lenses during the trial and for 28 days after the last dose of datopotamab deruxtecan
  • are able to use artificial tears during the trial and for 28 days after the last dose of datopotamab deruxtecan
  • are at least 18 years old

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related

You:

  • have, or had, another solid tumour Open a glossary item unless it has been successfully treated, there have been no signs of it for at least 3 years and it is unlikely to come back. You might be able to join if you have had basal cell skin cancer Open a glossary item or squamous cell Open a glossary item skin cancer that has been removed. You might also be able to take part if you have had early (in situ) cancers and you have had treatment to try and completely remove them.
  • have side effects from your past cancer treatments unless they are mild. You might be able to take part if you have hair loss or a side effect that won’t get worse with treatment. Your doctor will know this.
  • have cancer spread to the brain or spinal cord unless it is stable and doesn’t need treatment.
  • have had whole brain radiotherapy or stereotactic radiotherapy Open a glossary item in the 2 weeks before joining the trial
  • have had radiotherapy to a smaller area to help with symptoms in the 2 weeks before starting the trial treatment 
  • have had radiotherapy to just over a quarter (30%) of your bone marrow Open a glossary item in the 4 weeks before starting the trial treatment. Your doctor will know this. 
  • have cancer that has spread to the membranes that surround the brain (leptomeningeal carcinomatosis)
  • are having, or have had, cancer treatment within a certain time of starting the trial treatment. Your doctor will know how long this is for each cancer treatment. You may be able to take part if you are having hormone therapy not for cancer (such as HRT Open a glossary item )
  • have had treatment similar to datopotamab deruxtecan before. Your doctor can tell you more.

Medical conditions
You:

  • have had an organ transplant Open a glossary item
  • have an active bleeding problem
  • have a serious problem with the outermost lens (cornea) in your eye
  • have HIV that isn’t well controlled with medication, an active hepatitis or an uncontrolled hepatitis B or hepatitis C infection, an active TB infection or any other infection that needs systemic treatment Open a glossary item 
  • have lung problems Open a glossary item that could affect you taking part including scarring or inflammation of the lungs 
  • have had a heart attack in the last 6 months or any other heart problem Open a glossary item that might affect you taking part. The trial team check if you have a heart condition before you join the trial.
  • had major surgery or a major injury within 3 weeks of starting treatment. Or you might need surgery during the trial.
  • have any other medical condition or mental health problem that could affect you taking part 

Other
You:

  • have already taken part in this trial or have had an experimental drug or used a device as part of another clinical trial within 4 weeks of starting treatment
  • are allergic or sensitive to datopotamab deruxtecan or any of its ingredients
  • are taking anti malaria medication called chloroquine or hydroxychloroquine within 2 weeks of your first dose of the trial drug
  • have a live vaccine Open a glossary item within 30 days of starting treatment. The COVID-19 vaccines are not live vaccines.
  • are pregnant, breastfeeding or planning to become pregnant
  • have been involved in the planning of the trial or have been working on the trial yourself

As well as the above there are specific entry conditions and exclusion criteria for each treatment group. Speak to your doctor or research nurse if you want to find out more about the entry conditions for this trial.
 

Trial design

This is an international phase 2 trial. The team need up to 550 people worldwide to join, including 40 from the UK.

There are 5 studies which together make up the trial. Each study is looking at a cancer type.

Womb (endometrial) cancer - study 1
There are 4 different treatment groups in this study.

Not all study treatment groups will be open at the same time. Your study doctor will let you know which treatment groups are open and which is right for you.

Group 1 – you have datopotamab deruxtecan only
Group 2 – you have datopotamab deruxtecan and durvalumab
Group 3 – you have datopotamab deruxtecan and AZD5305
Group 4 – you have datopotamab deruxtecan, durvalumab and AZD5305

You have datopotamab deruxtecan as a drip into a vein. You have it once every 3 weeks.

You have durvalumab as a drip into a vein. You have it once every 3 weeks.

AZD5305 is a tablet. Your study doctor will tell you how often you take your tablets.

Stomach (gastric) cancer - study 2
Please note, 
if one of these groups is not open when you join, the team will let you know. The doctor will give you information about what group is open and you will join the group.

There are 2 different treatment groups in this study. It is a randomised study. 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. 

Group 1 – datopotamab deruxtecan and capecitabine chemotherapy 
Group 2 – datopotamab deruxtecan and fluorouracil (5FU) chemotherapy 

You have datopotamab deruxtecan as a drip into a vein. You have it once every 3 weeks. 

You have capecitabine chemotherapy as a tablet, one in the morning and one in the evening.

You have fluorouracil chemotherapy as a drip into a vein by a small pump that you carry around for 5 days.

Your team will explain to you which of the drugs you have and when.

Prostate cancer - study 3
There are 2 different treatment groups in this study. Your study doctor will let which treatment group you will be in.

Group 1 – you have datopotamab deruxtecan only
Group 2 – you have datopotamab deruxtecan and AZD5305

You have datopotamab deruxtecan as a drip into a vein. You have it once every 3 weeks. 

You have AZD5305 as a tablet. Your study doctor will tell you how often you take your tablets.

Ovarian cancer - study 4
There are 2 different treatment groups in this study.

Not all study treatment groups will be open at the same time. Your study doctor will let you know which treatment groups are open and which one you will be in.

Group 1 – you have datopotamab deruxtecan only
Group 2 – you have datopotamab deruxtecan, carboplatin chemotherapy and AZD5305

In group 1, you have datopotamab deruxtecan as a drip into a vein. You have it once every 3 weeks.

In group 2 you have datopotamab deruxtecan and carboplatin chemotherapy for 6 cycles of treatment Open a glossary item. You also have carboplatin as a drip into a vein.

After this, you have datopotamab deruxtecan and AZD5305 as maintenance treatment. This is to try and stop the cancer coming back. AZD5305 is a tablet. Your doctor will let you know when to take your tablets and for how long.

Bowel (colorectal) cancer - study 5
Everyone has datopotamab deruxtecan as a drip into a vein. You have it once every 3 weeks. You might have other cancer drugs alongside the datopotamab deruxtecan. Your doctor will let you know which other drugs you have and when.

For all groups
You have treatment in cycles Open a glossary item. You may be in the trial for around 18 months. But you continue to have treatment for as long as it is working, and the side effects aren’t too bad.

The team will ask you to use an electronic application, TrialMax app, during the trial. You will be given an electronic device with the app on if you don’t have your own. The app will support you during the study. You also use it to record how you are feeling. Your study doctor will tell you more about this.

Samples for research

The researchers ask for a sample of your cancer biopsy Open a glossary item before you have the trial drug. They will use a sample that is already available if it is suitable. And they ask for a tissue sample when you are having treatment with the trial drug. This is so they can learn more about how the treatment works for your type of cancer.

The researchers might also ask for a lung tissue sample if you have disease in your lungs called pneumonitis Open a glossary item, to get more information on this condition.

If your cancer starts to grow, the researchers would be interested in taking a sample for research. This is so they can learn more about why some cancers grow when you are having treatment.

If your cancer grows, or comes back, in the future the team might ask to take another tissue sample. They would like to look at:

  • substances in the tissue (biomarkers) Open a glossary item
  • using the samples to help develop tests for people in the future
  • if using computers can tell us more about your type of cancer – by using photos taken of the tissue samples
  • why your cancer may have got worse

You don’t have to give these samples if you don’t want to. You can still take part in the trial.

Blood samples for research

The trial team 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 look more closely at the genes Open a glossary item involved in developing cancer.

You don’t have to give these samples if you don’t want to. You can still take part in the trial.

Hospital visits

You see the doctor and have tests before you can take part. This might be over 1 or 2 days.

The tests you have depend on your cancer type but include:

  • a physical examination Open a glossary item including taking your temperature and pulse rate
  • lung function tests Open a glossary item
  • blood tests
  • urine tests, including a pregnancy test – if there is a chance you could be pregnant
  • heart trace Open a glossary item (ECG)
  • heart scan (echocardiogram or MUGA) Open a glossary item
  • CT scan or MRI scan
  • eye tests

You might also have:

  • x-rays Open a glossary item
  • a biopsy Open a glossary item - if the trial team do not have a tissue sample that they can use
  • a bone scan
  • a PET-CT scan

Usually, you go to the hospital once every 3 weeks to have:

  • datopotamab deruxtecan and any other trial treatment you have at the hospital
  • blood tests
  • your weight checked
  • a physical exam
  • any other tests you might need

You have datopotamab deruxtecan as an outpatient. You should not need to stay overnight for any of the treatments in the trial.

You might need to go to the hospital more often than every 3 weeks. It depends on what treatments you are having and how you are feeling. 

Follow up
After treatment has finished, you go back to the hospital between a month and 3 months after the last dose of the trial drug. This is so that the trial team can check how you are getting on.

You might have extra visits for scans every 6 weeks. A member of the trial team will call you every 3 months to ask about your health.

Follow up is different depending on your cancer type and treatment group. Your doctor will let you know your individual follow up plans.
 

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. 

Datopotamab deruxtecan is a new drug so there may be side effects we don’t know about yet. The possible side effects we know about so far include:

  • a drop in the number of red blood cells that might cause tiredness and breathlessness (anaemia) Open a glossary item
  • dry eyes
  • feeling or being sick
  • sore mouth or inflammation in the lining of the digestive system Open a glossary item
  • diarrhoea
  • tiredness (fatigue
  • an allergic reaction. Symptoms could include swelling, skin rash, a fast heartbeat, difficulty breathing or a tight feeling in the throat or low blood pressure.
  • hair loss
  • loss of appetite
  • skin rash
  • inflammation of the moist linings of parts of the body. This is called mucosal inflammation. You might have stomach pain, be sick, have diarrhoea or be losing weight. This can be a serious side effect. Tell your trial doctor straight away if you have any of these side effects.

Datopotamab deruxtecan might cause a serious lung problem. In some cases, this could be life threatening. Symptoms are similar to other heart or lung diseases. Please contact your doctor straight away if you have any new lung symptoms or symptoms that are getting worse. These include:

  • a new or worsening cough
  • trouble breathing
  • new or worsening shortness of breath or other breathing problems
  • high temperatures (fever)

Getting medical treatment right away may keep these problems from becoming more serious.

Using AZD5305 with other drugs is new, so there may be more side effects we don’t know about yet. The possible side effects of AZD5305 we know about so far include:

Please note, if you have any fast or uneven heartbeats, light headedness, shortness of breath, fainting or vision problems you should contact your trial doctor immediately.

Durvalumab can affect the immune system Open a glossary item. This may cause inflammation Open a glossary item 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.

The most common side effects of durvalumab include:

  • diarrhoea
  • the thyroid gland Open a glossary itemnot making enough hormone. This can cause tiredness or weight gain 
  • skin rash or dry itchy skin
  • infections of the sinuses and throat (upper respiratory tract infections)
  • cough

We have more information about:

Location

Cambridge
Dundee
London
Manchester

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.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Rebecca Kristeleit

Supported by

AstraZeneca

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

18801

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Last reviewed:

Rate this page:

Currently rated: 5 out of 5 based on 3 votes
Thank you!
We've recently made some changes to the site, tell us what you think