A Phase III, Active-Controlled Study of SHR-A1811 Versus Trastuzumab Emtansine (T-DM1) in HER2-Positive Primary Breast Cancer Participants With Residual Invasive Disease Following Neoadjuvant Therapy

Study Overview
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Brief Summary
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This study aims to Active-Controlled Study of SHR-A1811 Versus Trastuzumab Emtansine (T-DM1) in HER2-Positive Primary Breast Cancer Participants with Residual Invasive Disease Following Neoadjuvant Therapy，This study will examine SHR-A1811versus trastuzumab emtansine (T-DM1) in patients with HER2-positive primary breast cancer who have residual invasive disease in breast or axillary lymph nodes after neoadjuvant therapy.The primary objective is to compare invasive disease-free survival (IDFS) between SHR-A1811 and T-DM1 treatment arms in this population. The key secondary objective of the study is to evaluate disease-free survival (DFS), overall survival (OS) and distant recurrence-free interval (DRFI).

Official Title
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A Phase III, Multicenter, Randomized, Open-Label, Active-Controlled Study of SHR-A1811 Versus Trastuzumab Emtansine (T-DM1) in HER2-Positive Primary Breast Cancer Participants With Residual Invasive Disease Following Neoadjuvant Therapy

Conditions
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HER2-Positive Primary Breast Cancer Participants With Residual Invasive Disease Following Neoadjuvant Therapy

Intervention / Treatment
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* Drug: SHR-A1811
* Drug: Trastuzumab Emtansine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The age is 18-75 years old (including both ends), and female HER2 positive invasive breast cancer Confirmed by pathological examination Clinical Stage before Neoadjuvant Therapy was T1-4, N0-3, M0 (excluding T1N0). Residual invasive cancer confirmed by pathological examination after radical surgery must meet one of the following two conditions: If the clinical stage before neoadjuvant therapy is cT4N0-3M0 or cT1-3N2-3M0, there is residual invasive cancer in the primary breast lesion and/or ipsilateral axillary lymph nodes after surgery. If the clinical stage before neoadjuvant therapy was cT1-3N0-1M0 (except T1N0), there was residual invasive cancer in the ipsilateral axillary lymph nodes after surgery. Previous neoadjuvant therapy must meet all of the following conditions: Neoadjuvant chemotherapy: At least 6 treatment cycles, including no less than 9 weeks of taxane-based chemotherapy (anthracycline-containing chemotherapy allowed). Neoadjuvant anti-HER2 targeted therapy: No less than 9 weeks of targeted therapy including trastuzumab must be completed. Have received radical surgery for breast cancer: The interval from the completion of radical surgery to the first random medication should be at least 3 weeks and no more than 12 weeks. Hormone receptor (HR) status was confirmed by postoperative pathologic examination. HR positive is defined as positive for the estrogen receptor (ER) or progesterone receptor (PR), and HR negative is defined as negative for both ER and PR. The ECOG score is 0 or 1 Heart function is good Agree to birth control Exclusion Criteria: Stage IV metastatic breast cancer Evidence of recurrent breast cancer, including local recurrence, regional recurrence and distant metastasis . In the past 5 years, patients suffered from other malignant tumors, excluding cured basal cell carcinoma of skin andcervical carcinoma in situ,. Previously received systemic anti-HER2-ADC drug therapy, including but not limited to trastuzumab emtansine (T-DM1), Trastuzumab Deruxtecan (T-DXd), etc. Previous dosage requirements for anthracycline exposure meet one of the following conditions: Doxorubicin or anthracyclines with similar exposure equivalent > 240mg/m2; Epirubicin or liposomal doxorubicin hydrochloride > 480mg/m2. History of cardiovascular diseases with clinical significance, such as severe/unstable angina pectoris, symptomatic congestive heart failure (NYHA ≥ Ⅱ), supraventricular or ventricular arrhythmia with clinical significance and requiring treatment or intervention, and myocardial infarction within 6 months. Subjects with known or suspected interstitial pneumonia. Known hereditary or acquired bleeding and thrombosis tendency. History of active hepatitis B, hepatitis C or liver cirrhosis. There were other serious physical or mental diseases or abnormal laboratory examinations that may increase the risk of participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-A1811<br> | Drug: SHR-A1811<br>* Lyophilized powder injection, 100mg / bottle, intravenous drip<br>|
| Active Comparator: Trastuzumab Emtansine (T-DM1)<br> | Drug: Trastuzumab Emtansine<br>* Lyophilized powder injection, 160mg / bottle, 100mg / bottle, intravenous drip<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive disease-free survival (IDFS) |  | Randomization until the disease progressed, up to approximately 77 months postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) |  | Randomization until the disease progressed, up to approximately 77 months postdose | 
| Overall survival(OS) |  | Randomization until death from any cause, up to approximately 101 months postdose. | 
| Distant recurrence-free interval (DRFI) |  | Randomization until distant recurrence or death from any cause, up to approximately 101 months postdose. | 
| Safety endpointPercentage of Adverse Events in Participants |  | Baseline up to approximately 101 months postdose |