SHR-A1811 Versus Investigator's Chemotherapy in Recurrent/Metastatic Breast Cancer Clinical Trial

Study Overview
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Brief Summary
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The aim of this study was to evaluate whether the progression-free survival of SHR-A1811 was superior to investigator-selected chemotherapy in patients with HER2-low recurrent/metastatic breast cancer. To evaluate whether SHR-A1811 is superior to investigator-selected chemotherapy in patients with HER2-low recurrent/metastatic breast cancer.

Official Title
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A Randomized, Open, Parallel-controlled, Multicenter Phase III Trial of SHR-A1811 Versus Investigator Chemotherapy in HER2-low Expressing Recurrent/Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: SHR-A1811
* Drug: Capecitabine/Eribulin/Gemcitabine/Paclitaxel/Nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested). HR-positive breast cancer with at least one endocrine therapy and disease progression was judged by the investigator to no longer benefit from endocrine therapy. Has been treated with 0 to 1 prior lines of chemotherapy in the metastatic setting. Has documented radiologic progression (during or after most recent treatment). Has at least 1 protocol-defined measurable lesion. Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions. Fertile women (WOCBP) subjects agreed to use highly effective contraception and not to breastfeed from the time of study screening until 7 months after receiving the last study medication; a fertile woman must have a negative serum pregnancy test result within 7 days prior to the first treatment. Exclusion Criteria: Has known active central nervous system (CNS) metastases. Subjects with previously treated brain metastases may participate provided they are stable. A history of human immunodeficiency virus (HIV) infection is known, or has an active autoimmune disease. History of interstitial lung disease or pneumonia requiring oral or intravenous steroids. Has moderate or severe cardiovascular disease. Active HBV(hepatitis B) or HCV (Hepatitis C virus)-infected subjects. Any other malignancies within 5 years except for those with negligible risk of metastasis or death.

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
Interventional Model Description: Parallel model, randomized at a 1:1 ratio
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-A1811<br> | Drug: SHR-A1811<br>* SHR-A1811 is a lyophilized powder for injection intravenously. Administered according to label, as one option for Physician's Choice.<br>|
| Active Comparator: Physician's Choice<br>Capecitabine/Eribulin/Gemcitabine/Paclitaxel/Nab-paclitaxel | Drug: Capecitabine/Eribulin/Gemcitabine/Paclitaxel/Nab-paclitaxel<br>* Administered according to label, as one option for Physician's Choice (determined before randomization).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) Based on Blind Independent Video Review Committee (BIRC) |  | within approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Time from the date of randomization to the date of death for any cause. If there is no death reported for a participant before the data cutoff for OS analysis, OS will be censored at the last contact date at which the participant is known to be alive. | within approximately 3 years | 
| Objective Response Rate (ORR) | Percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR), confirmed by a second assessment. | within approximately 2 years | 
| Duration of Response (DoR) | DoR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death. | within approximately 2 years | 
| Clinical Benefit Rate (CBR) | CBR is defined as complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1. | within approximately 2 years |