Trastuzumab Rezetecan Neoadjuvant Therapy for HER2-Positive Breast Cancer

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 response-adapted, multicenter phase 2 trial for adults with HER2-positive early or locally advanced breast cancer. Participants receive two cycles of standard THP therapy (taxane, trastuzumab, and pertuzumab) before tumor response is assessed with imaging and patient-derived organoid testing. Non-responders (less than 50% tumor shrink or not meeting PDO sensitivity thresholds) switch to four cycles of trastuzumab rezetecan, while responders continue with four more cycles of THP. The primary aim is to evaluate the effectiveness of the adaptive strategy to guide subsequent therapy based on early response and PDO results. Interventions include THP and SHR-A1811 (trastuzumab rezetecan).

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 1.Age ≥18 years. For premenopausal and perimenopausal patients, a negative pregnancy test is required, and the patient must agree to use effective contraception during treatment.
* 2.Pathologically confirmed invasive breast cancer, stage II-III according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system, with HER2-positive disease defined as: immunohistochemistry (IHC) 3+; or IHC 2+ with confirmed HER2 gene amplification by fluorescence in situ hybridization (FISH).
* 3.At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
* 4.No prior chemotherapy, immunotherapy, endocrine therapy, radical surgery, or radiotherapy for breast cancer.
* 5.Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* 6.Ability to understand and provide written informed consent.
* 7.Adequate organ function as evidenced by the following laboratory values:
* Hemoglobin ≥90 g/L
* White blood cell count ≥3.5×10⁹/L
* Platelet count ≥100×10⁹/L
* Neutrophil count ≥1.5×10⁹/L
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3× upper limit of normal (ULN)
* Total bilirubin ≤1.5×ULN
* Serum creatinine ≤1.5×ULN
* 8.No evidence of myocardial ischemia on electrocardiogram (ECG); New York Heart Association (NYHA) functional class I; left ventricular ejection fraction (LVEF) ≥55% on echocardiogram; cardiac biomarkers (cardiac troponin I \[cTnI\] and B-type natriuretic peptide \[BNP\]) within normal limits.
* 9.All required baseline laboratory and radiologic examinations completed prior to neoadjuvant therapy.
* 10.No dysphagia.
* 11.Availability of complete clinical data.

Exclusion Criteria:

* 1.Male breast cancer or inflammatory breast cancer.
* 2.Metastatic breast cancer (Stage IV).
* 3.Presence of other concurrent malignancies or history of malignancy other than breast cancer within the past 5 years, except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
* 4.Receipt of any other concurrent anti-cancer therapy or participation in another clinical trial.
* 5.Presence of severe non-malignant disease that would compromise patient compliance or place the patient at unacceptable risk.
* 6.Major surgical procedure within 4 weeks prior to initiation of study treatment, or anticipated need for major surgery during the study period.
* 7.Receipt of radiotherapy, chemotherapy, molecular targeted therapy, endocrine therapy, or major breast surgery for breast cancer within 4 weeks prior to study treatment; current or prior use of HER2-targeted monoclonal antibodies, HER2-targeted antibody-drug conjugates (ADCs), or tyrosine kinase inhibitors (TKIs).
* 8.History of hypersensitivity or contraindication to any component of the study drugs.
* 9.Poorly controlled cardiac symptoms or diseases, including: New York Heart Association (NYHA) Class II or higher heart failure; unstable angina; myocardial infarction within 1 year; clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.

Dementia, intellectual disability, or any psychiatric disorder that impairs the ability to understand the informed consent form.

Where it's running

• The First Affiliated Hospital of Soochow University
  Suzhou, Jiangsu, China Recruiting

Study contacts

• Study coordinator: Hao Zhou
• Email: dlou515@163.com
• Phone: +8613862097709

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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.