This is a multicenter, two-arm, exploratory clinical study designed to evaluate the efficacy and safety of a response-guided neoadjuvant treatment strategy in patients with HER2-positive early or locally advanced breast cancer.
Breast cancer is the most common malignancy in women worldwide, and HER2-positive disease accounts for approximately 15-20% of cases and is associated with aggressive tumor biology and a higher risk of recurrence. The introduction of HER2-targeted therapies, including trastuzumab and pertuzumab, has significantly improved patient outcomes. However, a proportion of patients exhibit suboptimal response to standard neoadjuvant therapy, highlighting the need for more effective treatment strategies.
In this study, approximately 100 eligible patients will be enrolled. All patients will initially receive 2 cycles of standard neoadjuvant therapy with trastuzumab, pertuzumab, and chemotherapy (THP or TCbHP). Tumor response will be assessed according to RECIST version 1.1 criteria. Patients with tumor reduction greater than 40% will continue the same regimen for an additional 4 cycles. Patients with tumor reduction of 40% or less will switch to an alternative regimen consisting of SHR-A1811, a novel HER2-targeted antibody-drug conjugate, in combination with pertuzumab for 4 cycles.
SHR-A1811 is an investigational HER2-targeted antibody-drug conjugate designed to deliver a cytotoxic payload directly to tumor cells, potentially overcoming resistance to prior HER2-targeted therapies. Emerging clinical data have demonstrated promising anti-tumor activity and manageable safety in HER2-positive breast cancer.
Clinical data, including baseline characteristics, imaging findings, and pathological markers such as Ki-67, will be collected throughout the study. Efficacy will be evaluated based on imaging assessments according to RECIST 1.1 criteria and pathological response at surgery, while safety will be monitored during treatment.
The primary objective of this study is to explore whether switching to SHR-A1811 in combination with pertuzumab in patients with suboptimal early response can improve pathological complete response (pCR) rates. Secondary objectives include evaluation of safety and tolerability of the treatment strategies.
This study aims to provide evidence for an individualized, response-adapted neoadjuvant treatment approach in HER2-positive breast cancer, and to optimize treatment outcomes for patients with inadequate response to standard therapy.
Age ≥18 and ≤70 years.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
At least one measurable lesion according to RECIST version 1.1.
Prior receipt of any anti-tumor therapy not specified in the study protocol, including but not limited to chemotherapy, radiotherapy, targeted therapy, or endocrine therapy for the current breast cancer.
Concurrent receipt of any other anti-tumor therapy during the study. Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer. Stage IV (metastatic) breast cancer.
History of other malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix.
Severe dysfunction of major organs, including but not limited to cardiac, hepatic, or renal insufficiency.
Sequential
SHR-A1811
DrugSHR-A1811 is a HER2-targeted antibody-drug conjugate administered intravenously in combination with pertuzumab as neoadjuvant therapy.
Pertuzumab
DrugPertuzumab is a monoclonal antibody targeting HER2, administered intravenously as part of dual HER2 blockade.
trastuzumab
DrugTrastuzumab is a HER2-targeted monoclonal antibody administered intravenously as part of standard neoadjuvant therapy.
Chemotherapy
DrugChemotherapy includes taxane-based regimens with or without carboplatin (THP or TCbHP) administered according to institutional standards.
Total Pathological Complete Response (tpCR)
Number of participants achieving total pathological complete response, defined as no residual invasive cancer in both breast and axillary lymph nodes (ypT0/is ypN0) at the time of surgery following completion of neoadjuvant therapy.Metric：Proportion of participants (%)
Objective Response Rate (ORR) per RECIST v1.1
Proportion of participants with a best overall response of complete response (CR) or partial response (PR) according to RECIST version 1.1.
Event-Free Survival (EFS)
Time from treatment initiation to the occurrence of disease progression, local or distant recurrence, or death from any cause.Metric：Time-to-event (months).
Breast Conservation Rate
Proportion of participants who undergo breast-conserving surgery after completion of neoadjuvant therapy.
Number of Participants With Treatment-Related Adverse Events (TRAEs)
Number of participants experiencing treatment-related adverse events, assessed according to CTCAE version 5.0.
Change in Circulating Tumor DNA (ctDNA) Levels
Change in ctDNA levels from baseline to post-treatment timepoints (after 2 cycles and pre-surgery), measured using next-generation sequencing.
Predictive Performance of Multi-modal Biomarker Model for Treatment Response
Evaluation of a predictive model integrating genomic features, clinicopathological characteristics, imaging findings, and laboratory biomarkers to predict pathological response.Metric：Area under the curve (AUC).
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Hebei Medical University Fourth Hospital
Lead sponsor
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Collaborator
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