A Study of SHR-A1811 as Neoadjuvant Treatment for Patients With HR-Positive, Low HER2 Expression Breast Cancer

Study Overview
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Brief Summary
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HR-positive breast cancers accounts for about 50% to 60% of all breast cancer patients. Neoadjuvant Chemotherapy is the core treatment mode for this type of breast cancer, and endocrine therapy can be used in some low-risk patients. However, the pathological complete response (pCR) rate obtained is low. HER2 is an important prognostic indicator and therapeutic target for breast cancer. Nearly 60% of HR-positive breast cancers have low expression of HER2, and antibody-drug conjugates (ADC) targeting HER2 may achieve better efficacy in this subtype.

Detailed Description
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This prospective, single-arm study is being conducted to evaluate the efficacy and safety of SHR-A1811 for early-stage or locally advanced breast cancer patients with HR-Positive, Low HER2 Expression. Subjects will receive the neoadjuvant therapy of SHR-A1811 for eight cycles, and then undergo surgery within 4 weeks after neoadjuvant therapy. The follow-up visit will last for at least 5 years.

Official Title
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Phase II Study of SHR-A1811 as Neoadjuvant Treatment for Patients With HR-Positive, Low HER2 Expression Breast Cancer

Conditions
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HER2 Low Breast Carcinoma

Intervention / Treatment
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* Drug: SHR-A1811 for injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 to 70 years old (inclusive); Treatment-naive patients with clinically confirmed T2-T3, any nodal status and M0; HR-positive, HER2 low expression, the expression of Ki-67 exceed 14% invasive breast cancer confirmed by histology or cytology; ECOG performance status of 0-1; Normal organ and bone marrow function; Patients of childbearing age must consent to use highly effective contraception for 7 months from the start of study screening until the last study medication and agree not to breastfeeding; Patients voluntarily joined the study and signed informed consent; Exclusion Criteria: Patients have evidence of metastatic breast cancer, or inflammatory breast cancer; Patients previously received antineoplastic therapy or radiotherapy for any malignancy, excluding cured malignancies such as cervical carcinoma in situ, basal cell carcinoma, or squamous carcinoma; Patients received any other anti-tumor therapy at the same time, including endocrine therapy, bisphosphonates or immunotherapy; Patients have major surgical procedures unrelated to breast cancer within 4 weeks before the first medication, or not fully recovered from surgical procedures; Clinically significant pulmonary or cardiovascular disease; Failure to swallow, chronic diarrhea, intestinal obstruction, or presence of other factors affecting drug administration and absorption; Known to be allergic to any study drug or any of its excipients; History of immunodeficiency, including HIV-positive, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation; Pregnant and lactating women; Patients with serious concomitant diseases or other comorbidities that will interfere with the planned treatment, or any other condition that is not suitable for participation assessed by investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-A1811<br>SHR-A1811 group | Drug: SHR-A1811 for injection<br>* SHR-A1811 for injection<br>* Other names: SHR-A1811 group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Tumours (RECIST) v1.1 | Objective Response Rate (ORR) according to Response Evaluation Criteria in Solid | During 24 weeks of the neoadjuvant treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | Evaluate the nature, incidence and severity of SHR-A1811 adverse events according to CTCAE 5.0 | from consent to 28 days after last dose | 
| Residual cancer burden (RCB) | Residual cancer burden (RCB) | At the time of surgery | 
| Pathological complete response | pCR: ypT0/is ypN0 | At the time of surgery | 
| Event-free survival (EFS) | EFS was defined as the time from randomization to any of the following events: disease progression during neoadjuvant therapy, local or distant recurrence, second primary malignancy (breast or other cancer), or death from any cause | 5 years | 
| Disease-free survival (DFS) | Disease-free Survival, From the date of surgery to the first local, regional, contralateral or distant recurrence, and death from any cause | 5 years |