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Neoadjuvant Study of Trastuzumab, Pertuzumab and Zongertinib Without Chemotherapy in Patients with Stage II‑IIIA HER2‑Positive Breast Cancer

InvestigationalNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study focuses on women with breast cancer that is classified as HER2-positive and measured as stage II-IIIA. Instead of traditional chemotherapy, the treatment plan combines three medicines: trastuzumab, pertuzumab and the oral drug zongertinib, which is given as a film‑coated tablet.

The purpose of the study is to evaluate the safety of this neoadjuvant (pre‑surgery) regimen without chemotherapy. Participants will receive the three medicines for a set period before surgery, followed by routine monitoring for side effects and disease status, and will continue to be followed after the last dose to assess overall health outcomes.

The research process

The trial runs in 8 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Enrollment Confirmation

    You are officially entered into the study after signing the consent form and confirming eligibility.

    At this point you will receive a study identification number and be scheduled for baseline assessments.

  2. Step 2

    Baseline Assessments

    A series of medical evaluations is performed, including a physical examination, blood tests, and imaging studies to document the size and location of the breast tumor.

    Your tumor is confirmed to be HER2‑positive, which means it has high levels of the human epidermal growth factor receptor 2 protein.

  3. Step 3

    Start of Treatment

    You receive the first dose of trastuzumab and pertuzumab by intravenous infusion according to the study schedule.

    You begin taking zongertinib 60 mg as a film‑coated tablet taken by mouth each day.

  4. Step 4

    Ongoing Treatment

    You continue to receive trastuzumab and pertuzumab by intravenous infusion at the intervals specified by the study protocol.

    You take one 60 mg tablet of zongertinib orally every day for the duration of the neoadjuvant phase.

  5. Step 5

    Monitoring Visits

    Regular clinic visits are scheduled to check for any side effects, called adverse events, and to perform blood tests and imaging to evaluate tumor response.

    During each visit the study team records the severity of any adverse events and may adjust treatment if necessary.

  6. Step 6

    Surgery

    After completing the neoadjuvant treatment period, you undergo surgery to remove the remaining tumor tissue.

    Pathological analysis of the removed tissue determines whether a complete response was achieved.

  7. Step 7

    Post‑Treatment Follow‑Up

    You continue to be monitored for at least 30 days after the last dose of study medication to capture any late‑appearing adverse events.

    During this period, additional clinic visits and assessments may be performed as directed by the study protocol.

  8. Step 8

    Study Completion

    All required data are collected, and your participation in the study is formally concluded.

    You receive a summary of the study findings that pertain to your care.

Who can join the trial?

11 criteria

  • Provide a signed written informed consent, which means you agree in writing after understanding the study.
  • Have recent lab test results (taken within the last 4 weeks) showing you meet the study’s safety standards.
  • If you are a woman who could become pregnant, you must be ready to use two highly effective birth‑control methods that together have less than a 1% chance of failure each year, and continue using them during the study and for 7 months after the last dose.
  • Have a diagnosis of primary invasive breast cancer, confirmed by a tissue test that shows cancer cells have spread into surrounding breast tissue.
  • Have cancer that is classified as Stage II to Stage IIIA based on the TNM staging system (tumor size and spread), meaning the main tumor is larger than 2 cm on a special MRI scan (DCE‑MRI) or there is involvement of nearby lymph nodes confirmed by a needle test (FNA) or tissue examination.
  • Show uniform HER2 over‑expression on the initial biopsy, described as IHC 3+ (a lab test that stains the protein very strongly) and have a confirmatory test called in situ hybridization that proves extra copies of the HER2 gene.
  • Have known levels of the hormone receptors estrogen and progesterone on the cancer cells; if both are less than 10% of cells, the tumor is considered hormone‑receptor negative.
  • Have a WHO performance status of 0 or 1, meaning you are fully active or limited in physically strenuous activity but able to do light work.
  • Be 18 years of age or older.
  • Have a left‑ventricular ejection fraction (LVEF) of at least 50% as measured by an ultrasound of the heart (echocardiography) or a nuclear scan (MUGA), indicating normal heart function.
  • Be eligible for neoadjuvant treatment, which means receiving therapy before any planned surgery.

Who cannot join the trial?

19 criteria

  • Having inflammatory breast cancer or tumors classified as cT4 (large tumor) or cN3 (extensive lymph‑node involvement).
  • Having important problems with heart rhythm, the way electrical signals travel, or the shape of a resting heart test (electrocardiogram or ECG).
  • Having chronic hepatitis B (a liver virus) that is active and not already on medication that suppresses the virus.
  • Having a past hepatitis C infection (another liver virus) and either currently receiving cure‑focused antiviral treatment or still having the virus detectable in the blood.
  • Having HIV infection and any of the following: a low immune‑cell count (CD4+ count below 350 cells/µL), a high amount of virus in the blood (viral load above 400 copies/µL), not taking HIV medicines, taking them for less than 4 weeks, or having a serious AIDS‑related infection in the past year.
  • Having ongoing or past non‑infectious lung disease that causes scarring or inflammation (interstitial lung disease or pneumonitis).
  • Having serious stomach or intestine problems that could stop you from swallowing or absorbing the medication, such as severe nausea, vomiting, Crohn’s disease, ulcerative colitis, chronic diarrhea, or poor nutrient absorption (malabsorption).
  • Having an active infection that needs treatment affecting the whole body and puts you at higher risk.
  • Having very severe liver disease (classified as Child‑Pugh C, a scoring system for liver function).
  • Being allergic to any of the study medications or their ingredients, or having a medical reason they cannot be used (contraindication).
  • Having a condition that makes an MRI scan unsafe or impossible to evaluate.
  • Having hidden breast cancer that cannot be seen on imaging (stage cT0).
  • Having cancer in both breasts at the same time.
  • Being pregnant or currently breastfeeding (you must stop nursing before joining).
  • Having another cancer now or in the past unless it was treated without chemotherapy and it has been more than five years.
  • Having mixed HER2 status (HER2 heterogeneity) in the tumor sample taken before treatment.
  • Having mental‑health, family, social, or travel issues that could prevent you from following the study plan.
  • Having heart conditions such as uncontrolled high blood pressure, severe heart failure (NYHA class III or IV), unstable chest pain (unstable angina), poorly controlled irregular heartbeat (arrhythmia), a heart attack, stroke, or a lung blood clot (pulmonary embolism) within the past six months.
  • Any other significant heart rhythm or electrical test (ECG) problems seen by the doctor.
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Investigated drugs

  • Trastuzumab

    is a targeted medicine that attaches to a protein called HER2 on the surface of some breast cancer cells. By binding to HER2, it helps the immune system recognize and destroy those cancer cells and also blocks signals that make the tumor grow. In this study, trastuzumab is given before surgery to try to shrink the tumor without using chemotherapy.

  • Pertuzumab

    works together with trastuzumab. It also targets the HER2 protein but binds to a different part of it. This double‑targeting approach can more effectively block the growth signals that the cancer cells use. Like trastuzumab, pertuzumab is given before surgery as part of a chemotherapy‑free plan to shrink the tumor.

  • Zongertinib

    is a newer oral medicine that blocks a specific enzyme inside cancer cells called a tyrosine kinase. By inhibiting this enzyme, zongertinib helps stop the cells from multiplying and can make them die. In the trial, it is taken as a pill and added to trastuzumab and pertuzumab to see if this combination can treat HER2‑positive breast cancer without the need for traditional chemotherapy.

What is already known about the treatment

  • Zongertinib

    This medication is taken as an oral film‑coated tablet. It is an experimental drug that is still being studied in clinical trials and is not yet approved for general use. Zongertinib is being tested for HER2‑positive breast cancer and works by blocking the HER2 protein’s activity inside cancer cells. It belongs to the class of HER2 tyrosine‑kinase inhibitors, a type of targeted therapy.

  • Trastuzumab

    This drug is given by intravenous infusion into a vein. It is an approved monoclonal antibody that has been used for many years to treat HER2‑positive breast cancer. Trastuzumab attaches to the HER2 protein on the surface of cancer cells and helps the immune system destroy those cells. It is classified as a targeted therapy monoclonal antibody.

  • Pertuzumab

    This medication is also administered by intravenous infusion. It is an approved monoclonal antibody used together with trastuzumab for HER2‑positive breast cancer. Pertuzumab binds to a different part of the HER2 protein, preventing it from pairing with other proteins and thus stopping cancer growth signals. It belongs to the same class of targeted therapy monoclonal antibodies.

Investigated diseases

HER2-positive breast cancer - HER2-positive breast cancer is a form of breast cancer in which tumor cells produce excess HER2 protein, driving rapid cell growth. It typically begins as a lump in the breast and can enlarge or involve nearby lymph nodes. In stage II–IIIA, the tumor is larger or has spread to a few regional lymph nodes but has not yet reached distant organs. Without treatment, the cancer can continue to grow and may eventually spread beyond the breast and regional nodes. The disease course is marked by progressive enlargement of the primary tumor and increasing nodal involvement.
Trial detailsLast updated 11 Oct 2026
Age18+ yearsPhasePhase ITrial ID2026-526214-93-00Estimated enrolment30 patientsSponsorHet Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

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