Different Targeted Antibody-drug Conjugates For HER2 Ultra-low or No Expression Advanced Breast Cancer（GALAXY）

Study Overview
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Brief Summary
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This is a phaseⅠb/Ⅱ, open-label, two-arm parallel study evaluating the efficacy and safety of different targeted antibody-drug conjugates for HER2 ultra-low or no expression advanced breast cancer

Official Title
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Different Targeted Antibody-drug Conjugates for HER2 Ultra-low or no Expression Advanced Breast Cancer: a Phase Ⅰb/Ⅱ Study（GALAXY）

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: SHR-A1811
* Drug: TROP2 ADC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECOG Performance Status of 0 or 1 Pathologically documented breast cancer that: is advanced or metastatic is histologically confirmed to be HER2 IHC 0 (ISH- or untested) was never previously HER2-positive (IHC 3+ or ISH+) At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1. Disease progression on at least 1 previous line of chemotherapy for recurrent/metastatic breast cancer. Subjects with HER2-negative and hormone-receptor positive tumors must have progressed after at least 1 line of endocrine therapy with or without CDK4/6 inhibitor. Has protocol-defined adequate organ and bone marrow function. Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: Has previously been treated with any anti-HER2 therapy. Known prior severe hypersensitivity to investigational product or any component in its formulation and other monoclonal antibodies. Any major surgery, radiotherapy, chemotherapy, immunotherapy or molecular targeted therapy, biotherapy or other drug clinical trial within 4 weeks; received endocrine therapy within 2 weeks before the first study drug administration. History of other malignancy than breast cancer within 5 years prior to screening (except for cured skin basal cell carcinoma and cervical carcinoma in situ). Meningeal metastasis or active brain parenchymal metastasis. Any concurrent use of immunosuppressant or systemic corticosteroid treatment to achieve immunosuppression purpose (dose of > 10mg/day prednisone or equivalent), and still in use within 2 weeks before the first study drug administration. Has uncontrolled intercurrent illness or significant cardiovascular disease. History of clinically significant lung diseases. History of immunodeficiency, including HIV positive. Known active hepatitis B virus or hepatitis C virus infection. Has any medical history or condition that per protocol or in the opinion of the investigator is inappropriate for 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: HER2 ADC<br>Patients diagnosed with HER2 ultra-low or no expression are recruited | Drug: SHR-A1811<br>* HER2 ADC<br>|
| Experimental: Experimental: TROP2 ADC<br>Patients diagnosed with HER2 ultra-low or no expression are recruited. | Drug: TROP2 ADC<br>* TROP2 ADC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of adverse events (AEs)- Phase 1 | Occurrence of AEs in Phase 1 graded according to CTCAE v5.0 | Up to follow-up period, approximately 24 months | 
| Objective Response Rate (ORR)- Phase 2 | The proportion of patients who have a CR or PR, as determined by the Investigator at local site per RECIST 1.1. | Until progression, assessed up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS | Time to progression as assessed by the Investigator at local site per RECIST 1.1, or death due to any cause. | Until progression, assessed up to approximately 24 months | 
| Overall Survival (OS) | time to death due to any cause | Until death, assessed up to approximately 24 months | 
| Duration of Response (DoR) | Time from the date of first documented response until the date of documented progression or death in the absence of disease progression. | Until progression, assessed up to approximately 24 months | 
| Disease Control Rate (DCR) | The proportion of patients who have a CR or PR or SD, as determined by the Investigator at local site per RECIST 1.1. | Baseline through end of study, assessed up to 24 months | 
| Clinical Benefit Rate (CBR) | The percentage of subjects with CR, PR and SD≥24 weeks，as determined by the Investigator at local site per RECIST 1.1. | Until progression or death, assessed up to approximately 24 months | 
| Exploratory analyses | HER2-PET was done at baseline to further explore the clinical utility of HER2-PET for HER2 detection | Baseline until disease progression or loss of clinical benefit, assessed up to 24 months | 
| Safety | Occurrence of Adverse Events(AEs) graded according to CTCAE v5.0 | Up to follow-up period, approximately 24 months |