A trial of trastuzumab deruxtecan for stomach cancer (DESTINY-Gastric03)

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

Cancer type:

Secondary cancers
Stomach cancer

Status:

Closed

Phase:

Phase 1/2

This trial is looking at trastuzumab deruxtecan for stomach cancer that has spread into the nearby tissue or to another part of the body. 

It is also looking at adding another drug called pembrolizumab to trastuzumab deruxtecan. This is to find out whether this combination might work better than trastuzumab deruxtecan on its own. 

The trial is open to people with stomach cancer and cancer where the food pipe meets the stomach (gastro oesophageal junction cancer) that:

  • has many HER2 Open a glossary item receptors (HER2 positive) 
  • and doctors can’t remove by surgery

More about this trial

One of the standard treatments Open a glossary item for stomach cancer and gastro oesophageal junction is chemotherapy. Some of these cancers have many HER2 receptors on the cancer cells. In this case you might have trastuzumab with chemotherapy. 

Trastuzumab is a targeted drug Open a glossary item called a monoclonal antibody Open a glossary item. It works by attaching to the HER2 receptors on the cancer cells. This stops the cancer dividing and growing. 

Trastuzumab deruxtecan is a combination of trastuzumab and deruxtecan. Deruxtecan is similar to chemotherapy. When trastuzumab attaches to the HER2 receptors on the cancer cells it releases deruxtecan into the cell. 

Deruxtecan becomes active when inside the cancer cell. It works by blocking an enzyme Open a glossary item that cancer cells need to divide and grow.

Researchers think that trastuzumab deruxtecan might help people with stomach cancer or gastro oesophageal junction cancer that has many HER2 receptors. 

When you agree to join the trial, the trial team will test a piece of cancer tissue from a previous tissue sample (biopsy Open a glossary item). This is to see how many HER2 receptors your cancer cells have. 

Pembrolizumab is a targeted drug called an immunotherapy Open a glossary item. It works by stimulating the immune system Open a glossary item to find and kill cancer cells.  

Research suggests that combining pembrolizumab with trastuzumab deruxtecan might work better for people with cancers that have many HER2 receptors.

In this trial you have one of the following:

  • trastuzumab deruxtecan - closed
  • trastuzumab deruxtecan with chemotherapy - closed
  • trastuzumab deruxtecan, chemotherapy and pembrolizumab
  • trastuzumab deruxtecan and pembrolizumab

The aims of this trial are to find out:

  • how well trastuzumab deruxtecan works in combination with chemotherapy and pembrolizumab
  • what the side effects are

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 adenocarcinoma Open a glossary item of the stomach, oesophagus (food pipe) or where the food pipe meets the stomach (gastro oesophageal junction) 
  • have cancer that has spread to another part of the body (advanced cancer) or that doctors can’t remove by surgery
  • have cancer that has many the HER2 receptor (HER2 positive cancer)
  • have a tissue sample that the trial team can access to test for HER2 
  • have an area of cancer the doctor can measure
  • are willing to have a test that shows your heart works well enough. The doctor will arrange this test and tell you the results. 
  • 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 treatment and for a while after if there is any chance you or your partner could become pregnant
  • 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 treatment for your cancer spread. You might be able to join if you had treatment for cancer along as it was finished at least 6 months before the diagnosis of your cancer spread. 
  • spinal cord compression Open a glossary item that is causing symptoms, has not been treated or needs treatment to control it
  • cancer spread to the brain or spinal cord that is causing symptoms, has not been treated or needs treatment to control it. You might be able to join if you have had treatment. Your doctor can tell you about this.
  • ongoing side effects from previous treatment apart from hair loss and mild or moderate side effects that might not get any worse. Your doctor will talk to you about this. 
  • other cancers in the past 3 years. This is apart from successfully treated non melanoma skin cancer Open a glossary item, an in situ carcinoma Open a glossary item and a solid cancer Open a glossary item treated with the aim to cure. 

Medical conditions

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

  • a very low level of an enzyme called dihydropyrimidine dehydrogenase (DPD deficiency Open a glossary item)
  • severe nerve damage or hearing loss
  • had a heart attack within 6 months of going into a treatment group (randomisation Open a glossary item) or another heart problem Open a glossary item that could affect you taking part 
  • an autoimmune disease Open a glossary item or a disease that causes inflammation apart from certain ones. Your doctor will know which ones these are.
  • a lung problem that isn’t caused by an infection that affects the tissue of the lung or another lung problem Open a glossary item that could affect you taking part
  • an infection that needs treatment with medication through a drip (intravenous infusion Open a glossary item)
  • HIV, hepatitis B, hepatitis C or another disease that affects how well the immune system Open a glossary item works
  • fluid around the abdomen, heart or on the lungs that needs treatment
  • had a organ transplant
  • a problem with how well your digestive system Open a glossary item absorbs food or medications 

Other

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

  • are sensitive or allergic to the treatments used or any of their ingredients
  • have a live vaccine Open a glossary item within 30 days of starting treatment. You shouldn’t have a live vaccine within 30 days after stopping treatment. The COVID-19 vaccines aren’t live so you can have those. 
  • are pregnant or breastfeeding
     

Trial design

This is an international phase 1/2 trial. The trial team need 334 people to join with 10 from the UK.

There are 2 parts to the trial. In the 1st part the team found the best dose of trastuzumab deruxtecan to give with the standard care for this cancer. This part is ongoing but not open in the UK. 

Part 2 is a randomised trial. A computer puts you into 1 of 4 treatment groups. Neither you nor your doctor can choose which group you are in. The groups are:

  • trastuzumab deruxtecan - closed
  • trastuzumab deruxtecan with chemotherapy - closed
  • trastuzumab deruxtecan, chemotherapy and pembrolizumab
  • trastuzumab and pembrolizumab

Trastuzumab deruxtecan 
You have trastuzumab deruxtecan as a drip into a vein. You have it once every 3 weeks. This is a cycle of treatment Open a glossary item. 

You have the first cycle over 90 minutes. This is in case you have a reaction to trastuzumab deruxtecan. If you don’t have a reaction you can then have it over 30 minutes for the rest of the treatments. 

Trastuzumab deruxtecan with chemotherapy 
You have trastuzumab deruxtecan as above. 

The chemotherapy you have is:

•    fluorouracil (5FU) or 
•     capecitabine 

Your doctor will talk to you about the chemotherapy and decided which is the best for you. 

You might  have 5FU continuously for 5 days once every 3 weeks. Each 3 weeks is a cycle of treatment. You can have 5FU either as a drip into a vein. For this you stay in hospital for the treatment. You might be able to have it through a syringe driver Open a glossary item. For this you won’t need to stay in hospital.

Capecitabine is a tablet. You take it every day for 2 weeks and then not take it for a week. This is a cycle of treatment. 

Your doctor tells you how many capecitabine tablets to take. You take them within 30 minutes after a meal.

Your doctor decides which chemotherapy to give you. 

Trastuzumab deruxtecan, chemotherapy and pembrolizmab
You have pembrolizumab as a drip into a vein. You have it once every 3 weeks. Each 3 weeks is a cycle of treatment. You have it over an hour. 

You have trastuzumab deruxtecan as above. 

The chemotherapy is the same as above. Your doctor decides which chemotherapy to give you. 

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

Trastuzumab deruxtecan and pembrolizumab

You have these the same way as above. 

Samples for research
You give blood samples for research during the trial. When they can the team will take these when you have your routine bloods taken. 

They ask for a piece of tissue from a previous tissue sample (biopsy Open a glossary item) when you join the trial. This is to test for HER2. They will also ask for another optional biopsy if your cancer gets worse. 

Researchers will use these samples to:

  • look for substances (biomarkers Open a glossary item) that might show how well treatment is working
  • find out what happens to the drugs in the body and what affect they have on the body
  • look for small pieces of cancer DNA (ctDNA Open a glossary item) 
  • find out more about these cancers
     

Hospital visits

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

  • a physical examination Open a glossary item
  • blood tests
  • eye examination
  • urine test
  • breathing tests (lung function tests Open a glossary item)
  • CT scan or an MRI scan
  • bone scan if your doctor thinks the cancer may have spread to the bones
  • heart trace (ECG Open a glossary item)
  • heart scan (ECHO  Open a glossary itemor MUGA Open a glossary item)

During treatment you see the doctor once a week for 3 weeks and then once every 3 weeks until your cancer gets worse.

This is to see how you are and for blood tests. 

You see the doctor when you finish treatment for similar tests you had at the start. You then see the doctor a month after and then at:

  • 2 months
  • 3 months
  • 6 months
  • 8 months
  • 10 months
  • 1 year 
  • then every 6 months

You only have ongoing scans after treatment if your cancer hasn’t got any worse during treatment. You have a scan:

  • every 6 weeks for the first 48 weeks
  • then every 12 weeks until your cancer starts to grow again 
     

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. 
The most common side effects of trastuzumab deruxtecan are:

Trastuzumab 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 issues
  • fever

 

Pembrolizumab can affect the immune system. It may cause inflammation in different parts of the body. This can cause serious side effects. They could happen during treatment, or some months after treatment has finished. Rarely, these side effects could be life threatening.

We have information about pembrolizumab and its side effects. 
 
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. 

We have information on:

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.

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Questions to ask your doctor about clinical trials
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Chief Investigator

Dr Starling

Supported by

AstraZeneca
Daiichi Sankyo

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

Freephone 0808 800 4040

Last review date

CRUK internal database number:

17685

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

Last reviewed:

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