A Study of SHR-A1811 Combined With Capecitabine in Treatment of Unresectable or Metastatic Breast Cancer With Low HER2 Expression.

Study Overview
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Brief Summary
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The study is being conducted to evaluate the safety, tolerability， preliminary efficacy, pharmacokinetics, and immunogenicity of SHR-A1811 combined with capecitabine in treatment of unresectable or metastatic breast cancer with low HER2 expression.

Official Title
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An Open-Label, Multi-center Phase Ⅰb/Ⅱ Study of SHR-A1811 Combined With Capecitabine in Treatment of Unresectable or Metastatic Breast Cancer With Low HER2 Expression.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: SHR-A1811 for injection ; capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18 to 75 (inclusive). HER2 low expression unresectable or metastatic breast cancer confirmed by histology or cytology. ECOG score is 0 or 1. An expected survival of ≥ 12 weeks. At least one measurable lesion according to RECIST v1.1 criteria. Women of childbearing potential (WOCBP) subjects must agree 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, had good compliance and willingness to cooperate with the visit and study related procedures. Exclusion Criteria: Have other malignancies within the past 5 years. Presence with uncontrollable third space effusion. Have surgical treatment, radiotherapy, chemotherapy, immunotherapy, molecular targeted therapy, biological therapy or other drug clinical studies within 4 weeks before the first medication. Accepted antibody drug conjugates containing etoisomercan derivative topoisomerase I inhibitor. Clinically significant cardiovascular disorders. Presence of active hepatitis B, hepatitis C, cirrhosis,or serious infected persons requiring antibiotic, antiviral or antifungal control. The toxicity from previous anti-tumor treatment has not recovered to ≤ grade I. Known to be allergic to any study drug or any of its excipients, or to humanized monoclonal antibody products. Failure to swallow, chronic diarrhea, intestinal obstruction, or presence of other factors affecting drug administration and absorption. Presence of other serious physical or mental diseases or laboratory abnormalities.

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
Intervention Model: Single Group Assignment
Interventional Model Description: SHR-A1811 combined with capecitabine
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-A1811 combined with capecitabine<br> | Drug: SHR-A1811 for injection ; capecitabine<br>* SHR-A1811 for injection; Capecitabine tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT（Phase I (dose exploration phase) ） [ Time Frame: 21 days after the first administration of each subject ] |  | 21 days after the first administration of each subject ] | 
| Incidence of AEs（Phase I (dose exploration phase) ） |  | from Day1 to 40 days after last dose | 
| Incidence of SAEs（Phase I (dose exploration phase) ） |  | from Day1 to 40 days after last dose | 
| Objective response rate（Phase II (efficacy expansion phase)） |  | One year after the last subject was enrolled in the group | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response(DoR ) |  | One year after the last subject was enrolled in the group | 
| Progression Free Survival(PFS) |  | One year after the last subject was enrolled in the group | 
| Objective response rate（Phase I (dose exploration phase)） |  | One year after the last subject was enrolled in the group | 
| Incidence of AEs（Phase II (efficacy expansion phase)） |  | from Day1 to 40 days after last dose | 
| Incidence of SAEs（Phase II (efficacy expansion phase)） |  | from Day1 to 40 days after last dose |