A Study Comparing BL-B01D1 With Chemotherapy of Physician's Choice in Patients With Unresectable Locally Advanced, Recurrent, or Metastatic HR+HER2- Breast Cancer(PANKU-Breast01)

Inclusion criteria

• Voluntarily sign the informed consent and follow the requirements of the protocol;
• No gender limit;
• Age ≥18 years old;
• expected survival time ≥3 months;
• Patients with unresectable locally advanced, recurrent metastatic HR+HER2- breast cancer;
• The subjects had received 1-2 lines of chemotherapy regimens in the unresectable locally advanced recurrence or metastasis stage, and had been treated with endocrine, CDK4/6 inhibitors, and taxanes;
• Documented radiographic disease progression;
• Consent to provide archival tumor tissue samples or fresh tissue samples of primary or metastatic lesions within 3 years;
• Must have at least one measurable lesion according to RECIST v1.1 definition;
• ECOG score 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%;
• No blood transfusion, no use of cell growth factors and/or platelet raising drugs within 14 days before screening, and the organ function level must meet the requirements;
• 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 it must be non-lactating; All enrolled patients (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.

Exclusion criteria

• Prior receipt of an ADC drug with a topoisomerase I inhibitor as a toxin;
• Prior receipt of an ADC or antibody drug targeting EGFR and/or HER3;
• Chemotherapy, biological therapy, immunotherapy, etc., have been used within 4 weeks or 5 half-lives before the first dose, small molecule targeted therapy has been used within 5 days, palliative radiotherapy, modern Chinese medicine preparations approved by NMPA for anti-tumor therapy, etc., have been used within 2 weeks;
• anthracycline equivalent cumulative dose of adriamycin > 360 mg/m2;
• History of severe cardiovascular or cerebrovascular disease;
• Unstable deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring medical intervention within 6 months before screening; Infusion-related thrombosis was excluded;
• QT prolongation, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
• Other malignant tumors diagnosed within 3 years before the first dose;
• Hypertension poorly controlled by two antihypertensive drugs; Patients with poor glycemic control;
• A history of interstitial lung disease (ILD) requiring steroid therapy, current ILD or grade ≥2 radiation pneumonitis, or suspicion of such disease on imaging during screening;
• Complicated pulmonary diseases leading to clinically severe respiratory function impairment;
• Patients with active central nervous system metastases;
• Patients with massive or symptomatic effusions or poorly controlled effusions;
• Imaging examination showed that the tumor had invaded or wrapped around the large blood vessels in the abdomen, chest, neck, and pharynx;
• Severe infection within 4 weeks before randomization; Evidence of pulmonary infection or active pulmonary inflammation within 2 weeks before randomization;
• Was receiving &gt before randomization; Long-term systemic corticosteroid therapy with 10mg/ day prednisone or equivalent anti-inflammatory active drugs or any form of immunosuppressive therapy;
• Severe unhealed wound, ulcer, or fracture within 4 weeks before signing the informed consent;
• Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
• Patients with inflammatory bowel disease, extensive bowel resection history, immune enteritis history, intestinal obstruction or chronic diarrhea;
• Have a history of allergy to recombinant humanized antibodies or to BL-B01D1 and any excipients; A history of autologous or allogeneic stem cell transplantation;
• Human immunodeficiency virus antibody positive, active hepatitis B virus infection or hepatitis C virus infection;
• A history of severe neurological or psychiatric illness;
• Received other unmarketed investigational drug or treatment within 4 weeks before the first dose; A live vaccine dose within 28 days before the planned dose or the first dose;
• Any complications or other circumstances deemed by the investigator to preclude participation in the trial.