AuthorisedPhase I and Phase II (Integrated)- OtherInterventional

Neoadjuvant trastuzumab, pertuzumab and zongertinib without chemotherapy in HER2-positive breast cancer: the TRAIN-5 study

The TRAIN-5 study is looking at a new way to treat HER2-positive breast cancer before surgery. Standard care usually involves targeted medicines combined with chemotherapy. While chemotherapy can be effective, it often causes difficult side effects such as nausea, hair loss, and extreme tiredness. This trial explores whether combining two established targeted drugs (trastuzumab and pertuzumab) with a new targeted medicine called zongertinib (60 mg) can treat the cancer without needing standard chemotherapy. The main goal is to test the safety of this combination and track any side effects. Doctors will also check how well the treatment shrinks the tumour before surgery, whether any cancer remains afterwards, and how patients fare in the long term. The aim is to find kinder, effective treatments for adults diagnosed with early HER2-positive breast cancer.

At a glance

Status

Authorised

Phase

Phase I and Phase II (Integrated)- Other

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Enrolment target

Start

08 Oct 2026

Breast cancer

What is this study about?

Breast cancer cells sometimes have high levels of a protein called HER2 on their surface. This is known as HER2-positive breast cancer. The HER2 protein acts like an accelerator pedal, telling the cancer cells to grow and divide. Standard treatment before surgery usually involves targeted medicines to block HER2, given alongside strong chemotherapy drugs. Although this approach works well, chemotherapy affects healthy cells too and can cause unpleasant side effects.

The TRAIN-5 clinical trial is testing a chemotherapy-free option. It combines two approved targeted drugs (trastuzumab and pertuzumab) with a new targeted drug called zongertinib. Zongertinib is designed to attach specifically to the abnormal HER2 proteins and shut down their growth signals. Researchers hope that combining these three targeted medicines will attack the tumour powerfully enough that patients will not need chemotherapy at all.

Treatment given before surgery is called 'neoadjuvant' therapy. Its purpose is to shrink the tumour so it is easier to remove during an operation. In this trial, doctors want to find out whether the tumour can be cleared completely by the time of surgery, a result known as a complete response. They will also measure how long patients stay free from cancer after treatment.

Because this is an early-phase trial, safety is the top priority. The study team will closely monitor all participants to understand the side effects of zongertinib and determine how well the body tolerates this triple-drug combination.

Key takeaways

Tests a chemotherapy-free treatment for HER2-positive breast cancer before surgery.
Combines a new targeted tablet (zongertinib) with two existing targeted drugs.
Open to adults aged 18 and over who have not yet had surgery for their breast cancer.
Aims to find out if targeted medicines alone are safe and effective at shrinking tumours.
Joining is entirely your choice, and you can withdraw at any time without losing standard care.

Who may be eligible?

This study is open to adults aged 18 and over who have been diagnosed with HER2-positive breast cancer that has not spread to distant parts of the body. Both women and men may be considered. Participants must be preparing to have surgery as part of their planned cancer care.

You may not be able to take part if your tumour is not HER2-positive, if your cancer has already spread to other organs, or if you have already started chemotherapy or targeted therapy for this cancer. People with certain serious medical conditions, such as significant heart, kidney, or liver problems, may also be excluded for safety reasons.

Your hospital breast care team will run detailed tests, including heart scans, blood tests, and tumour biopsies, to confirm whether your cancer has the right markers and whether this trial is safe and appropriate for you.

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 HER2-positive breast cancer.
My cancer has not spread to distant parts of my body.
I have not yet started treatment or had surgery for this breast cancer.
I am able to attend regular hospital visits for scans and check-ups.

Answer every question to see your result.

What does participation involve?

If you take part, you will receive treatment before your breast cancer surgery. Zongertinib is taken as a daily tablet by mouth, while trastuzumab and pertuzumab are usually given as drips into a vein or as injections under the skin at the hospital every few weeks. You will need to visit the hospital regularly for blood tests, heart checks, and scans to monitor your health and see how your tumour is responding. After finishing the course of medication, you will have your planned breast surgery. Doctors will examine the tissue removed during the operation to check how much cancer remains. You will then have follow-up visits, including close safety monitoring for at least 30 days after your last trial dose, followed by regular check-ups over several years to monitor your long-term recovery.

Potential risks and benefits

A potential benefit is receiving a targeted treatment that could shrink your tumour without the harsh side effects of traditional chemotherapy. You will also receive very close medical care and monitoring from cancer specialists. However, there are risks. Zongertinib is a new medicine, so it may cause unexpected side effects or common problems such as diarrhoea, sickness, skin rash, or liver changes. There is also a risk that the cancer might not shrink as effectively as it would with standard chemotherapy. Taking part is completely voluntary. You can choose to leave the trial at any point, and your standard NHS cancer care will continue without being affected.

Locations (1)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

—
Unverified
Netherlands

Common questions

What does HER2-positive mean?

It means your cancer cells have extra copies of the HER2 protein, which makes the cancer grow. Targeted medicines can latch onto these proteins to stop the cells growing.

Why is the trial trying to avoid chemotherapy?

Chemotherapy can cause harsh side effects like hair loss and severe fatigue. Doctors want to see if targeted medicines alone can clear the tumour with fewer side effects.

Will I still need breast surgery?

Yes. The trial medicines are given before surgery to shrink the tumour, but surgery is still a planned part of your treatment to remove any remaining cancer.

What happens if the tumour does not shrink?

Your medical team will monitor you closely with regular scans. If the tumour is not responding, they will stop the trial treatment and switch you to standard NHS therapies.

Do I have to pay to take part in this trial?

No. In the UK, clinical trial medications and study-related tests are provided free of charge through the hospital.