AuthorisedTherapeutic exploratory (Phase II)Interventional

"H3RAKLES": Tucatinib and trastuzumab in HER3-mutant and HER2-not amplified metastatic breast cancer

The 'H3RAKLES' study is looking into a new treatment approach for metastatic breast cancer, which is cancer that has spread. Specifically, it's for patients whose cancer has a gene change called a HER3 mutation and is not HER2-amplified. The study uses two established medications, Tucatinib and Trastuzumab, given together to see if they can help control the cancer. Researchers are particularly interested in how many patients see their cancer shrink, stay the same for a long time, or even disappear. This will help us understand if this combination is a promising new option for people living with this specific type of breast cancer.

At a glance

Status

Authorised

Phase

Therapeutic exploratory (Phase II)

Sponsor

Institut Curie

Enrolment target

Start

11 Sep 2025

HER3-mutant and HER2-not amplified metastatic breast cancer

What is this study about?

The 'H3RAKLES' study is exploring a new treatment for a specific kind of advanced breast cancer. This is for patients whose breast cancer has spread to other parts of the body, which doctors call 'metastatic'. The treatment focuses on cancers with two key features: a change in a gene called HER3 (a 'HER3 mutation') and not having too much of another protein called HER2 (being 'HER2-not amplified'). These specific features help doctors decide which treatments might work best.

The study combines two medications you might have heard of: Tucatinib (sometimes called TUKYSA) and Trastuzumab (sometimes called Ogivri). Trastuzumab is given as an infusion into a vein, and Tucatinib is a tablet you swallow. Researchers want to understand how well these two medicines work together in people with this particular type of breast cancer. They will be looking at how many patients see their cancer stop growing, shrink, or even disappear for a period of time. This is called the 'clinical benefit rate'.

By carefully studying how these medicines affect the cancer and patients' well-being, the researchers hope to find new and more effective ways to treat this specific form of metastatic breast cancer. This kind of research helps doctors understand which treatments are best for different types of cancer, leading to better care for patients in the future.

Key takeaways

Targets specific HER3-mutant, HER2-not amplified metastatic breast cancer.
Combines two known drugs, Tucatinib and Trastuzumab.
Aims to see how many patients benefit from this new combination.
Involves regular hospital visits, treatments, and health checks.
Patients must be over 18, with metastatic breast cancer.
Could offer access to a potential new treatment approach.

Who may be eligible?

To join this study, you need to be at least 18 years old – there's no upper age limit. The study is open to both men and women.

Crucially, your breast cancer must be 'metastatic', meaning it has spread beyond its original site. Doctors will also need to confirm that your cancer has a specific gene change called a 'HER3 mutation' and that it is 'HER2-not amplified'. These are important details that your doctor can check with special tests.

There will be other health checks and requirements to make sure the study treatment is safe for you and that the results of the study are clear and accurate. Your cancer specialist will discuss all these criteria with you in detail.

Quick self-check

Are you 18 years old or older?
Has your breast cancer spread to other parts of your body?
Have tests shown your cancer has a 'HER3 mutation'?
Have tests shown your cancer is 'HER2-not amplified'?
Are you able to travel to study appointments?
Are you able to take tablets and receive infusions?

This is a guide only — the research team will confirm whether you can take part.

What does participation involve?

If you decide to take part in this study, you will receive two medications: Trastuzumab, which is given into a vein, and Tucatinib, which you will take as tablets. The study team will explain exactly how and when to take these.

You'll have regular hospital visits, where doctors and nurses will check your health, give you the infusions, and ask about any side effects. They'll also perform scans and other tests to see how the cancer is responding to the treatment. You'll also be asked to complete questionnaires about your quality of life. The study involves ongoing treatment and monitoring as long as the treatment is helping you, or until you or your doctor decide it's no longer the best option. Your overall health and well-being will be monitored closely throughout the entire process.

Potential risks and benefits

Participating in a clinical trial offers the potential benefit of accessing new and promising treatments that are not yet widely available. While there's no guarantee the treatment will work for everyone, it could help control your cancer. However, like all medications, the drugs used in this study can have side effects, which range from mild to serious. The study team will monitor you closely for any unwanted effects and provide care. You will be fully informed about these potential risks before deciding to join, and you always have the right to withdraw from the study at any time, for any reason, without it affecting your usual care.

Locations (1)

—
France

Common questions

What does 'metastatic breast cancer' mean?

It means the breast cancer cells have spread from the breast to other parts of the body.

What is a 'HER3 mutation'?

It's a specific change in a gene within your cancer cells that doctors can identify with tests.

What medicines are being tested?

The study is testing a combination of Tucatinib (TUKYSA tablets) and Trastuzumab (Ogivri given via infusion).

Will I know if the treatment is working?

Yes, doctors will regularly do scans and tests to see how your cancer is responding.

Is this a new type of treatment?

The medicines themselves are established, but this study is testing them together for a specific type of breast cancer.