Trastuzumab Rezetecan Neoadjuvant Therapy in THP-Insensitive HER2-Positive Early Breast Cancer
An Interventional, Multicenter Study of Trastuzumab Rezetecan as Neoadjuvant Therapy in Patients With THP-Insensitive HER2-Positive Early Breast Cancer
The First Affiliated Hospital of Soochow University
124 participants
Mar 24, 2026
INTERVENTIONAL
Conditions
Summary
This study is a response-adapted, multicenter, interventional trial enrolling patients with HER2-positive early or locally advanced breast cancer. All enrolled patients will first receive 2 cycles of standard neoadjuvant THP regimen, consisting of a taxane, trastuzumab, and pertuzumab. After the initial 2-cycle treatment, tumor response will be evaluated by radiologic imaging and patient-derived organoid (PDO) drug sensitivity testing. Patients with an inadequate response to THP are defined as those with \<50% tumor size reduction on imaging, or failure to reach the PDO sensitivity threshold (\<80% tumor cell killing for HER2+/HR- tumors; \<60% for HER2+/HR+ tumors). These non-responders will switch to receive 4 cycles of trastuzumab rezetecan (SHR-A1811), a novel HER2-targeted antibody-drug conjugate (ADC). Patients with a favorable response (≥50% tumor reduction or meeting the PDO threshold) will continue with an additional 4 cycles of THP. The primary objective is to evaluate the pathologic complete response (pCR) rate in THP non-responders after switching to trastuzumab rezetecan. Secondary objectives include objective response rate (ORR), event-free survival (EFS), overall survival (OS), 3-year invasive disease-free survival (iDFS), and safety profiles of both treatment strategies. Outcomes in patients who continue THP will be described for exploratory purposes. A total of 124 patients will be enrolled. This response-adapted, individualized strategy aims to provide an effective option for HER2-positive breast cancer patients with an inadequate early response to conventional THP neoadjuvant therapy.
Eligibility
Inclusion Criteria18
- 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.
- 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).
- At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
- No prior chemotherapy, immunotherapy, endocrine therapy, radical surgery, or radiotherapy for breast cancer.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Ability to understand and provide written informed consent.
- 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
- 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.
- All required baseline laboratory and radiologic examinations completed prior to neoadjuvant therapy.
- No dysphagia.
- Availability of complete clinical data.
Exclusion Criteria10
- Male breast cancer or inflammatory breast cancer.
- Metastatic breast cancer (Stage IV).
- 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.
- Receipt of any other concurrent anti-cancer therapy or participation in another clinical trial.
- Presence of severe non-malignant disease that would compromise patient compliance or place the patient at unacceptable risk.
- Major surgical procedure within 4 weeks prior to initiation of study treatment, or anticipated need for major surgery during the study period.
- 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).
- History of hypersensitivity or contraindication to any component of the study drugs.
- 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.
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Interventions
Neoadjuvant combination therapy consisting of a taxane, trastuzumab, and pertuzumab. Administered as initial treatment to all patients, and continued for responders.
HER2-targeted antibody-drug conjugate (ADC). Administered to patients with inadequate response to initial THP therapy.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07647263