Intensified HER2-targeted treatment for people with a suboptimal response to initial dual HER2 therapy and chemotherapy

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a prospective, response-guided phase II trial in which all eligible patients first receive a defined course of neoadjuvant dual HER2-targeted therapy combined with chemotherapy. Tumor response is assessed after the initial phase using standardized clinical and radiologic criteria. Patients with an adequate response continue the initial regimen, while those with a suboptimal response are escalated to an intensified investigational neoadjuvant strategy using either trastuzumab-rezetecan plus pertuzumab or a pyrotinib-containing multi-agent regimen with chemotherapy and HER2-directed therapy. The adaptive approach aims to improve pathologic response rates while avoiding unnecessary toxicity for early responders.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Age ≥18 and ≤75 years.
2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
3. Primary tumor size \>1 cm.
4. Histologically confirmed invasive breast cancer, clinically staged as:

   * Stage I (T1cN0M0)
   * Stage II (T1cN1M0, T2N0-1M0 or T3N0M0)
   * Stage III (T2N2-3M0, T3N1-3M0, or T4N0-3M0)
5. HER2-positive status: IHC 3+ or IHC 2+ with positive ISH.
6. Adequate major organ function:

   1. Hematology (no transfusion or hematopoietic growth factors, e.g., G-CSF, within 14 days):

      * Hemoglobin ≥100 g/L
      * Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L
      * Platelet count ≥100 × 10⁹/L
   2. Biochemistry:

      * Total bilirubin ≤1.5 × ULN
      * ALT and AST ≤1.5 × ULN; ALP ≤2.5 × ULN
      * BUN and creatinine ≤1.5 × ULN
   3. Cardiac function: LVEF ≥55% by echocardiography
7. Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment and agree to use effective contraception during the study and for 8 weeks after the last dose.
8. Voluntary written informed consent and willingness to comply with study procedures and follow-up.

Exclusion Criteria:

1. Prior anti-tumor therapy for breast cancer, including chemotherapy, radiotherapy, targeted therapy, or endocrine therapy.
2. Concurrent administration of any other anti-tumor treatment.
3. Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer.
4. Breast cancer not confirmed histologically.
5. History of other malignancy within the past 5 years, except successfully treated cervical carcinoma in situ.
6. Severe dysfunction of major organs (heart, liver, kidney).
7. Conditions affecting oral drug administration or absorption, e.g., inability to swallow, chronic diarrhea, or intestinal obstruction.
8. Participation in another investigational drug trial within 4 weeks prior to enrollment.
9. Known hypersensitivity to study drug components; history of immunodeficiency (HIV positive, active HCV, active hepatitis B, other congenital/acquired immunodeficiency) or prior organ transplantation.
10. History of clinically significant cardiac disease, including:

    1. Arrhythmia requiring medication
    2. Myocardial infarction
    3. Heart failure
    4. Other cardiac conditions deemed unsuitable for study participation by the investigator
11. Pregnant or breastfeeding women, or women of childbearing potential who test positive at baseline or are unwilling to use effective contraception throughout the study.
12. Any condition that, in the investigator's judgment, poses serious risk to patient safety or may interfere with study completion (e.g., uncontrolled severe hypertension, uncontrolled diabetes, active infection).
13. History of neurological or psychiatric disorders (e.g., epilepsy or dementia) or any other condition the investigator considers incompatible with study participation.

Where it's running

• 2nd Affiliated Hospital, School of Medicine, Zhejiang University
  Hangzhou, China Recruiting

Study contacts

• Study coordinator: Yiding Chen
• Email: ydchen@zju.edu.cn
• Phone: 15868131018

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Neoadjuvant Pyrotinib-to-pertuzumab for HER2-positive early breast cancer

  This trial tests whether a two-step neoadjuvant plan with Pyrotinib plus Trastuzumab and Docetaxel followed by Pertuzumab plus Trastuzumab and Docetaxel works better than four cycles of Pertuzumab plus Trastuzumab and Docetaxel in women with HER2-positive early- to locally advanced breast cancer.

  Recruiting Phase 3 Shanghai Jiao Tong University School of Medicine · Shanghai · NCT07797218

• Pre-surgery trastuzumab deruxtecan (SHR-A1811) plus pertuzumab for HER2-positive breast cancer

  This trial tests giving trastuzumab deruxtecan (SHR-A1811) with pertuzumab before surgery to see if it helps women with stage II–III HER2-positive breast cancer achieve a complete response.

  Recruiting Phase 2 Shanghai Jiao Tong University School of Medicine · Shanghai, Shanghai Municipality · NCT07393425

• Using blood ctDNA to compare two pre-surgery HER2-positive breast cancer regimens

  We will test whether two different pre-surgery drug combinations clear tumor DNA from the blood better in people with HER2-positive early breast cancer.

  Recruiting Phase 2 Shanghai Jiao Tong University School of Medicine · Shanghai · NCT07335081

• Neoadjuvant therapy for HER2-positive early breast cancer

  This study is testing if a new drug called trastuzumab-deruxtecan can work better than standard chemotherapy for people with early HER2-positive breast cancer to see if it helps them respond better to treatment.

  Recruiting at 40 sites Phase 2 Women's Cancer Study Group GmbH · Baden-Baden, Baden-Wurttemberg and 43 other locations · NCT05704829

• Combination treatment for HR+/HER2+ breast cancer

  This study is testing a new combination treatment for patients with stage II-III HR+/HER2+ breast cancer to see if it works better than the standard treatment before surgery.

  Recruiting Phase 2 Shengjing Hospital · Shenyang, Liaoning · NCT05638594

• Combining Pyrotinib and ARX788 for treating HER2-positive breast cancer

  This study is testing a new combination of two drugs, pyrotinib and ARX788, to see if it can help women with stage II-III HER2-positive breast cancer who haven't responded well to other treatments.

  Recruiting Phase 2 Shengjing Hospital · Shenyang, Liaoning · NCT04983121

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.