HER2-positive Breast Cancer
Conditions
Keywords
Breast Cancer, HER2-positive, Neoadjuvant therapy, Trastuzumab rezetecan
Brief 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.
Interventions
DRUGTHP Regimen (Taxane + Trastuzumab + Pertuzumab)
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.
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (tpCR) Rate | Perioperative | Proportion of patients achieving pathologic complete response (tpCR), defined as the absence of invasive carcinoma in both the breast primary lesion and axillary lymph nodes (ypT0/is ypN0) after neoadjuvant therapy and surgery. Ductal carcinoma in situ (DCIS) is allowed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 24 weeks | Proportion of patients achieving complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST version 1.1 criteria. |
| Event-Free Survival (EFS) | From study enrollment up to 3 years after the last patient is enrolled | Time from study enrollment to the first occurrence of invasive disease recurrence (local, regional, or distant), death from any cause, or contralateral invasive breast cancer. |
| Overall Survival (OS) | From study enrollment up to 5 years after the last patient is enrolled | Time from study enrollment to death from any cause. |
| 3-Year Invasive Disease-Free Survival (iDFS) Rate | 3 years after study enrollment | Proportion of patients alive and free from invasive breast cancer recurrence (local, regional, or distant) or contralateral invasive breast cancer at 3 years after study enrollment. |
Countries
China
Contacts
CONTACTHao Zhou
STUDY_CHAIRZhaoji Guo
The First Affiliated Hospital of Soochow University
Outcome results
None listed