A Study of MRG002 in the Treatment of Patients With HER2-positive Unresectable Locally Advanced or Metastatic Breast Cancer

The primary objective of Phase II is to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of MRG002 in patients with HER2-positive, unresectable locally advanced or metastatic breast cancer. The primary objective of Phase III is to evaluate the efficacy and safety of MRG002 versus Trastuzumab Emtansine (T-DM1) in patients with HER2-positive unresectable locally advanced or metastatic breast cancer who have been previously treated with trastuzumab (or a biosimilar) and an anti-HER2 tyrosine kinase inhibitor (anti-HER2-TKI) and have progressed on or after the most recent therapy.


Eligibility Criteria:
Inclusion Criteria:

* 1. Aged 18 to 75 (including 18 and 75)，both genders;

  2. Expected survival time ≥ 6 months;

  3. The score of ECOG for performance status is 0 or 1;

  4. Patients with histologically and/or cytologically confirmed HER2-positive invasive breast cancer, including unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (MBC);

  5. Phase II: patients with advanced or metastatic disease who have previously failed trastuzumab (containing trastuzumab biosimilar) ± pertuzumab and taxane, or progressed within 12 months after neoadjuvant or adjuvant therapy (using trastuzumab (containing trastuzumab biosimilar) ± pertuzumab and taxane regimen); patients who have failed TKI and/or HER2-targeted ADCs can also be included. Phase III: patients who have received 1 or 2 prior lines of anti-HER2 therapy for locally advanced or recurrent/metastatic breast cancer (in the case of (neo) adjuvant therapy, such (neo) adjuvant therapy also counts as one line of anti-HER2 therapy if relapse occurs within 12 months of (neo) adjuvant therapy); have received prior treatment with trastuzumab (containing a trastuzumab biosimilar) and anti-HER2-TKI; have not received prior treatment with ADCs;

  6. Patients must have imaging evidence of tumor progression during or after the most recent treatment confirmed by the investigator and have at least one measurable lesion baseline according to RECIST 1.1;

  7. Organ functions must meet the basic requirements;

  8. Reproductive male and female patients of childbearing age shall be willing to take effective contraceptive measures from the date of signing the ICF to 6 months after the last dose. Women of childbearing potential must have a negative pregnancy test within 7 days before the first dose.

Exclusion Criteria:

* 1. History of other primary malignancies;

  2. Received investigational drugs from other clinical trials, any anti-tumor drugs, or radiotherapy within 4 weeks prior to the first dose/randomization; or use of endocrine therapy for breast cancer within 7 days prior to the first dose/randomization, or have current requirement of endocrine therapy; or have received strong CYP3A4 inhibitors or inducers within 2 weeks prior to the first dose/randomization, or have current requirement of CYP3A4 inhibitors or inducers; cumulative doxorubicin up to 450 mg/m2 or equivalent prior to the first dose/randomization; or had major surgery within 4 weeks prior to the first dose/randomization without full recovery or planned surgery within 12 weeks after study treatment;

  3. Presence of central nervous system (CNS) metastasis;

  4. The pleural or peritoneal effusion with combined clinical symptoms, which seriously endangers the life safety of the subjects or urgently needs clinical treatment. Or the pericardial effusion with combined clinical symptoms;

  5. Any severe or uncontrolled systemic disease, uncontrolled heart disease, uncontrolled diabetes, and active bleeding signs judged by the investigator;

  6. Evidence of active infection, including hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection, active bacteria infection requiring systematic anti-infective therapy, infection caused by other viruses, fungi, rickettsia or parasites;

  7. History of hypersensitivity to any component of MRG002 or history of hypersensitivity of ≥ Grade 3 to trastuzumab injection;

  8. Subjects with active autoimmune disease or a history of autoimmune disease are receiving immunosuppressive agents or systemic hormone therapy, and are still receiving within 2 weeks prior to enrollment/randomization;

  9. History of interstitial pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc;

  10. Other conditions inappropriate for participation in this study, as deemed by the investigator;

  11. Presence of peripheral neuropathy \> Grade 1;

  12. History of cirrhosis (decompensated cirrhosis Child-Pugh class B, C).