A Study Comparing BL-M07D1 With T-DM1 in Patients With Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer

Inclusion criteria

• Voluntarily sign the informed consent and follow the requirements of the protocol;
• No gender limit;
• Age ≥18 years old and ≤75 years old at the time of signing the informed consent;
• expected survival time ≥3 months;
• Patients with histologically or cytologically confirmed, unresectable, locally advanced or metastatic HER2-positive breast cancer;
• Provide the latest tumor tissues to the central laboratory for HER2 and HR detection;
• Must have at least one measurable target lesion that meets the RECIST v1.1 definition;
• ECOG 0 or 1;
• Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
• No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
• Blood transfusion is not allowed within 14 days before the first use of the study drug, and no cell growth factor is allowed;
• Coagulation function: international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT)≤1.5×ULN;
• Urine protein ≤2+ or < 1000mg/24h;
• For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the initiation of treatment, serum pregnancy must be negative, and must be non-lactating; All enrolled patients (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 7 months after the end of treatment.

Exclusion criteria

• Received chemotherapy with mitomycin C and nitrosourea within 6 weeks before the first dose, received surgery, chemotherapy, immunotherapy, etc. Within 4 weeks before the first dose, received endocrine therapy, palliative radiotherapy, and anti-tumor therapy approved by NMPA within 2 weeks before the first dose;
• Previous use of HER2-ADC in the metastatic background;
• Prior treatment with an ADC drug containing a camptothecin derivative (topoisomerase I inhibitor) as a toxin;
• The history of severe cardiovascular and cerebrovascular diseases in the past six months was screened;
• Complicated with pulmonary diseases leading to severe impairment of lung function;
• History of ILD/interstitial pneumonia, current ILD/interstitial pneumonia, or suspected ILD/interstitial pneumonia; According to CTCAE v5.0 was defined as ≥ grade 3 pulmonary disease and ≥ grade 2 radiation pneumonitis;
• 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 (systolic blood pressure &gt; 150 mmHg or diastolic blood pressure &gt; 100 mmHg);
• Patients with active central nervous system metastases;
• Patients with a history of allergy to recombinant humanized antibody or to any of the excipents of BL-M07D1;
• Patients with known hypersensitivity or delayed hypersensitivity to certain components of T-DM1 or similar drugs, or known contraindications to T-DM1;
• History of autologous or allogeneic stem cell transplantation or organ transplantation;
• Anthracycline-equivalent cumulative dose of adriamycin > 360 mg/m2;
• Human immunodeficiency virus antibody positive, active hepatitis B virus infection, cirrhosis, or hepatitis C virus infection;
• Serious infection within 4 weeks before the first dose of study drug; There was active pulmonary inflammation at the time of screening;
• Patients with massive or symptomatic effusions or poorly controlled effusions;
• Receiving active antiinflammatory drugs or any form of immunosuppressive therapy before randomization;
• A history of severe neurological or psychiatric illness;
• Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
• Intestinal obstruction, Crohn's disease, ulcerative colitis or chronic diarrhea;
• Subjects who are scheduled to receive live vaccine or receive live vaccine within 28 days before the first dose;
• Patients who were deemed by the investigator to be ineligible for the study.