Overview

This trial is a registrational Phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-B01D1 in patients with unresectable locally advanced, recurrent, or metastatic HR+/HER2- breast cancer after failure of prior endocrine therapy.

Eligibility

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements;
2. No gender restrictions;
3. Age ≥ 18 years;
4. Expected survival time ≥ 3 months;
5. Patients with unresectable locally advanced, recurrent, or metastatic HR+ HER2- breast cancer;
6. Trial participants have not received systemic chemotherapy;
7. Trial participants have progressed after at least one line of endocrine therapy, etc.;
8. Documented radiographic disease progression prior to enrollment;
9. Agree to provide archived tumor tissue specimens or fresh tissue samples from the primary or metastatic lesion within 3 years;
10. Must have at least one measurable lesion as defined by RECIST v1.1;
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
12. Toxicity from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
13. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥ 50%;
14. Must meet required organ function levels;
15. Urinary protein ≤ 2+ or \< 1000 mg/24h;
16. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, with a negative serum pregnancy result, and they must not be breastfeeding; all enrolled patients (regardless of gender) must use adequate barrier contraception throughout the treatment period and for 6 months after treatment ends.

Exclusion Criteria:

1. Previously treated with ADC drugs that use topoisomerase I inhibitors as the toxin or target EGFR and/or HER3;
2. Use of chemotherapy, biotherapy, immunotherapy, etc., within 4 weeks or 5 half-lives before the first dose;
3. Previous treatment with anthracycline drugs where the equivalent cumulative dose of doxorubicin exceeds 360 mg/m²;
4. History of severe cardiovascular or cerebrovascular diseases;
5. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening;
6. Prolonged QT interval, complete left bundle branch block, etc.;
7. Diagnosis of another malignancy within 3 years before the first dose;
8. Hypertension poorly controlled by two antihypertensive medications;
9. Poorly controlled blood glucose levels;
10. History of ILD requiring steroid therapy, current ILD, or grade ≥2 radiation pneumonitis, etc.;
11. Concurrent pulmonary diseases causing clinically severe respiratory function impairment;
12. Patients with active central nervous system metastases;
13. Presence of large serous cavity effusions or symptomatic serous cavity effusions, etc.;
14. Imaging findings indicating tumor invasion or encasement of the abdomen, chest, etc.;
15. Severe infection within 4 weeks before study randomization;
16. Severe, unhealed wounds, ulcers, or fractures within 4 weeks before signing the informed consent form;
17. Trial participants with clinically significant bleeding or a significant bleeding tendency within 4 weeks prior to signing the informed consent form;
18. History of inflammatory bowel disease, extensive bowel resection, etc.;
19. Patients with a history of allergy to recombinant humanized antibodies or allergy to BL-B01D1 or any of its excipients;
20. History of autologous or allogeneic stem cell transplantation;
21. Positive for human immunodeficiency virus antibodies, active hepatitis B virus infection, or hepatitis C virus infection;
22. Receipt of other unapproved clinical study drugs or treatments within 4 weeks before the first dose;
23. Trial participants planning to receive or having received live vaccines within 28 days before the first dose;
24. Other conditions deemed by the investigator to be unsuitable for participation in this clinical trial due to complications or other reasons.