A Study of MRG002 in Treatment of Advanced HER-2 Positive Breast Cancer Patients

Study Overview
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Brief Summary
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The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG002 in patients with HER2 positive breast cancer with liver metastases.

Official Title
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An Open-label, Multi-center, Single-arm Phase II Clinical Study to Evaluate the Efficacy and Safety of MRG002 in Advanced HER-2 Positive Breast Cancer Patients Previously Treated With Trastuzumab and TKIs (Magic-009)

Conditions
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Breast Cancer With Liver Metastases

Intervention / Treatment
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* Drug: MRG002


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to sign the informed consent form and follow the requirements specified in the protocol. Aged 18 to 75 (including 18 and 75), both genders; Life expectancy ≥ 12 weeks; The score of ECOG for performance status is 0 or 1 Patients with HER2-positive breast cancer confirmed by central laboratory and with evidence of liver metastasis by imaging; Archival or biopsy tumor specimens should be provided (primary or metastatic) for HER2 testing; Patients must have measurable lesions according to the Response Criteria in Solid Tumors (RECISTv1.1); Organ functions must meet the basic requirements. Patients of childbearing potential are willing to take effective contraceptive measures from the time of signing the informed consent form to 6 months after last administration of the study drug. Exclusion Criteria: Previous history of other primary malignancies; Presence of peripheral neuropathy ≥ grade 2 (according to CTCAE V5.0); Previously received antibody-drug conjugates, investigational drugs, anti-tumor vaccines or drugs, endocrine therapy for breast cancer, radiotherapy, CYP3A4 inhibitors or inducers, anthracyclines and other treatments; Central nervous system metastasis and/or neoplastic meningitis; History of decompensated cirrhosis, or liver metastases with a single lesion ≥ 10 cm in longest diameter; Pleural or peritoneal effusion with combined clinical symptoms, which seriously endangers the life safety of subjects or urgently requires clinical treatment; Or pericardial effusion with combined clinical symptoms; Any serious or uncontrolled systemic disease judged by the investigator; Uncontrolled cardiac disease; Evidence of active infection; Pulmonary embolism or deep venous thrombosis within 3 months prior to study treatment; History of interstitial pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary dysfuction, symptomatic bronchospasm, etc.; Patients with active autoimmune disease or a history of autoimmune diseases who are receiving immunosuppressive agents or systemic hormone therapy, and are still using them within 2 weeks prior to enrollment; History of hypersensitivity to any component of MRG002 or known history of hypersensitivity of ≥ Grade 3 to trastuzumab injection; Uncontrolled tumor-related bone pain or urgent spinal cord compression; Other conditions inappropriate for participation in this study, as deemed by the investigator.

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

Sexes Eligible for Study
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All

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: MRG002<br>MRG002 will be administrated via intravenous infusion of 2.6 mg/kg once on Day 1 of every 3 weeks (21-day cycle). | Drug: MRG002<br>* Administrated intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by Independent Review Committee (IRC) | ORR is defined as the proportion of subjects with complete response (CR) and partial response (PR) assessed by IRC according to RECIST v1.1. | Baseline to study completion (up to 12 months） | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by Investigator | ORR is defined as the proportion of subjects with CR and PR assessed by investigator according to RECIST v1.1. | Baseline to study completion (up to 12 months) | 
| Duration of Response (DOR) | DOR is defined as the duration from the initial recording of objective disease response to the first onset of tumor progression, or death of any cause. | Baseline to study completion (up to 12 months) | 
| Clinical Benefit Rate (CBR) | CBR is defined as the proportion of subjects with CR, PR and stable disease (SD) ≥ 6 months after treatment. | Baseline to study completion (up to 12 months) | 
| Time to Response (TTR) | TTR is defined as the time from the start of treatment until the first occurrence of CR or PR by tumor assessment. | Baseline to study completion (up to 12 months) | 
| Disease Control Rate (DCR) | DCR is defined as the proportion of subjects achieving CR, PR, and stable disease (SD) after treatment. | Baseline to study completion (up to 12 months) | 
| Progression Free Survival (PFS) | PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause. | Baseline to study completion (up to 12 months) | 
| Overall Survival (OS) | OS is defined as the duration from the start of treatment to death of any cause. | Baseline to study completion (up to 12 months) | 
| Adverse Events (AEs) | Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug. | Baseline to 30 days after the last dose of study treatment | 
| PK parameters: concentration-time curve | Plot of drug concentration changing with time after drug administration. | Baseline to 14 days after decision to discontinue treatment | 
| Immunogenicity (ADA) | The proportion of patients with positive ADA results. | Baseline to 14 days after decision to discontinue treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRG002, Antibody Drug Conjugate (ADC), HER2