A Study of BL-M07D1, BL-M07D1+Pertuzumab and BL-M07D1+Pertuzumab+Docetaxel in Patients With Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer

Inclusion criteria

• Sign the informed consent form voluntarily and follow the protocol requirements;
• Gender is not limited;
• Age ≥18 years old and ≤75 years old;
• Expected survival time for 3 months or more;
• Patients with histologically and/or cytologically confirmed unresectable locally advanced or metastatic HER2-positive breast cancer;
• Consent to provide archived tumor tissue samples or fresh tissue samples from the primary or metastatic lesions;
• At least one measurable lesion meeting the RECIST v1.1 definition was required;
• Physical condition score ECOG 0 or 1 ;
• The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
• No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
• No blood transfusion, no colony-stimulating factor, and no albumin are allowed within 14 days before the first use of the study drug, and the organ function level must meet the requirements;
• Blood coagulation function: international standardization ratio (INR) 1.5 or less, and the part activated clotting time (APTT) live enzymes acuities were 1.5 x ULN;
• Urinary protein ≤2+ or ≤1000mg/24h;
• Fertile female subjects, or male subjects with fertile partners, must use highly effective contraception from 7 days before the first dose until 7 months after the end of the dose. Female subjects of childbearing potential had to have a negative serum pregnancy test within 7 days before the first dose.

Exclusion criteria

• Received chemotherapy with mitomycin C and nitrosourea within 6 weeks before the first dose, received surgery within 4 weeks before the first dose, and received endocrine therapy within 2 weeks before the first dose;
• Patients with locally advanced or metastatic disease who have received previous systemic therapy;
• Had received prior ADC drug therapy with camptothecin derivative as toxin;
• Screening within the first half of the serious heart, cerebrovascular disease;
• Complicated with pulmonary diseases leading to severe impairment of lung function;
• A history of ILD/interstitial pneumonia requiring steroid therapy, current ILD/interstitial pneumonia, or suspected ILD;
• QT prolongation, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
• Other primary malignancies diagnosed within 5 years before the first dose;
• Poorly controlled hypertension;
• Patients with active central nervous system metastases;
• Need treatment intervention of unstable thrombotic events, except infusion related thrombosis;
• Patients with a history of allergy to recombinant humanized antibodies or to any excipients of the trial drug;
• Had received more than the following cumulative doses of anthracyclines;
• Systemic corticosteroids or immunosuppressive agents were required within 2 weeks before study dosing;
• Patients with massive or symptomatic effusions or poorly controlled effusions;
• Severe systemic infection within 4 weeks before screening;
• Active autoimmune and inflammatory diseases;
• Human immunodeficiency virus antibody positive, active hepatitis B virus infection or hepatitis C virus infection;
• Previous history of allogeneic stem cell, bone marrow or organ transplantation;
• A history of severe neurological or psychiatric illness;
• Pregnancy or lactation women;
• Patients who were deemed by the investigator to be ineligible for participation in the study.