CompletedPhase IIIInterventional

Disitamab vedotin with pembrolizumab vs chemotherapy in previously untreated urothelial cancer expressing HER2

Advanced bladder cancer that has spread or cannot be removed by surgery is difficult to treat. Standard chemotherapy often only works for a limited time. This Phase 3 trial compares a new combination of two targeted medicines against standard chemotherapy in adults who have not yet had treatment for advanced disease. The new treatment pairs disitamab vedotin, a drug that targets a protein on cancer cells called HER2, with pembrolizumab, an immunotherapy that helps the immune system fight cancer. Participants will be randomly chosen to receive either this new combination or standard chemotherapy given through a drip into a vein. Doctors will closely check each patient's health with regular scans and blood tests. The aim is to find out if the new treatment can shrink tumours, keep the cancer under control for longer, and improve survival with manageable side effects.

At a glance

Status

Completed

Phase

Phase III

Sponsor

Seagen Inc.

Enrolment target

700

Start

31 Aug 2024

Estimated completion

30 Sep 2026

Previously untreated locally advanced or metastatic urothelial carcinoma that expresses HER2 (IHC 1+ and greater)

What is this study about?

Urothelial cancer is the most common form of bladder cancer, starting in the cells that line the urinary system. When this cancer spreads to other organs or grows too deep to be removed with surgery, it is described as advanced or metastatic. At this stage, standard treatment usually relies on chemotherapy. While chemotherapy can help, the cancer often starts growing again, so better and longer-lasting treatments are urgently needed.

This trial is looking at a new targeted approach. Some bladder cancers produce a specific protein called HER2 on the surface of their cells. Researchers have developed a drug called disitamab vedotin that tracks down this HER2 protein and delivers medicine directly into the cancer cell. In this study, it is combined with pembrolizumab, an established immunotherapy drug that trains the body's own immune system to spot and attack cancer cells.

The main purpose of this study is to compare this new two-drug combination directly against the current standard platinum-based chemotherapy used in the UK. By comparing the two groups, doctors hope to learn whether this targeted approach can help people live longer, better lives with fewer or more manageable side effects.

Key takeaways

Tests a new targeted combination (disitamab vedotin and pembrolizumab) against standard chemotherapy.
For adults with previously untreated, advanced bladder cancer that tests positive for the HER2 protein.
Participants are randomly assigned to receive either the new combination or standard treatment.
All medicines are given through a drip into a vein during hospital visits.
Participation is entirely voluntary, with close health monitoring throughout.

Who may be eligible?

This trial is open to adults aged 18 and over who have advanced or metastatic bladder cancer that cannot be cured by surgery. To be eligible, you must not have received treatment for this stage of your cancer yet, and tests on your tumour must show that it produces the HER2 protein.

Because cancer therapies are strong, your general health needs to be well enough to take part safely. You will need blood and urine tests to make sure your kidneys, liver, and bone marrow are working within safe limits.

This study is not suitable for people who are pregnant or breastfeeding. If there is a chance you could become pregnant or father a child, you will need to agree to use reliable forms of contraception during the trial and for several months after finishing treatment.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I am aged 18 or older.
I have been diagnosed with advanced or metastatic bladder cancer that cannot be removed by surgery.
I have not yet received treatment for my advanced cancer.
My tumour has tested positive for the HER2 protein (or can be tested for it).
My kidneys, liver, and blood counts are working well enough for treatment.

Answer every question to see your result.

What does participation involve?

If you join the trial, a computer will randomly place you into one of two treatment groups. In Group A, you will receive disitamab vedotin through a drip into your vein once every two weeks, and pembrolizumab once every six weeks. In Group B, you will receive standard chemotherapy drips in cycles across several weeks, followed by standard maintenance therapy if appropriate.

You will visit the clinic regularly for treatment and health checks. These visits will include physical examinations, blood tests, heart checks (ECGs), and imaging scans (such as CT or MRI scans) to see how the cancer is responding. The trial will run for several years, and you will continue your assigned treatment for as long as it helps you and the side effects remain acceptable. Afterwards, the team will keep in touch to check on your long-term wellbeing.

Potential risks and benefits

Taking part may give you access to a promising new combination of treatments before it is widely available, alongside very close monitoring by cancer specialists. However, there is no guarantee that the new combination will work better than standard chemotherapy. All cancer medicines carry a risk of side effects, which may include tiredness, nausea, nerve tingling, or immune-related symptoms. Your care team will watch you carefully and treat any side effects promptly. Taking part is completely your choice, and you can leave the study at any time without your ordinary NHS care being affected.

Locations (6)

Beatson West of Scotland Cancer Centre
City only
Glasgow, Scotland
St. Bartholomews Hospital
City only
London, England
Guys Hospital
City only
London, England
Charing Cross Hospital
Approximate
London, England
Royal Devon and Exeter Hospital
City only
Exeter, England
Weston Park Hospital
Unverified
Sheffield, England

Common questions

What is HER2 and how do I know if my tumour has it?

HER2 is a protein found on the surface of some cells. In cancer, having higher levels of HER2 can make tumours grow faster, but it also provides a target for new medicines. A doctor can check for HER2 by testing a small sample of tumour tissue that was taken during a previous biopsy or surgery.

Can I choose which treatment I receive?

No. A computer randomly decides whether you receive the new drug combination or the standard chemotherapy. This process makes sure the results of the study are fair and unbiased.

Will taking part cost me anything?

No, the trial medicines and any additional tests required for the study are provided free of charge. You may also be able to get help with travel expenses to and from hospital visits.

What happens if my cancer gets worse during the trial?

Your doctor will do regular scans. If your cancer grows or if the treatment is no longer safe for you, the trial treatment will stop, and your medical team will discuss other care and treatment options with you.

Can I stop taking part if I change my mind?

Yes, you are free to leave the trial at any point, for any reason. Choosing to leave will not affect your relationship with your healthcare team or the standard of care you receive.

How to find out more

Marcel Koopman

eu-regulatory@seagen.com +3 (0)120 238 2497 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.