Overview

This trial is a registrational Phase III, randomized, open-label, multicenter study designed to compare the efficacy and safety of BL-B01D1 in combination with a PD-1 monoclonal antibody versus nab-paclitaxel in combination with a PD-1 monoclonal antibody in patients with PD-L1-positive, previously untreated, inoperable locally advanced or recurrent metastatic triple-negative breast cancer.

Eligibility

Inclusion Criteria:

1. Voluntarily sign the informed consent form and agree to comply with the protocol requirements;
2. Female patients aged 18 to 75 years;
3. Expected survival time ≥ 3 months;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
5. Pathologically confirmed recurrent or metastatic triple-negative breast cancer;
6. Confirmed PD-L1 expression positivity by central laboratory testing;
7. No prior systemic anti-tumor therapy in the advanced/recurrent or metastatic setting;
8. Agree to provide archived tumor tissue specimens (surgical specimens) or fresh tissue samples from primary or metastatic lesions obtained within 3 years;
9. Must have at least one measurable lesion as defined by RECIST v1.1;
10. Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
11. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥ 50%;
12. Organ function levels must meet the protocol-specified requirements;
13. Urine protein ≤ 1+ or \< 1000 mg/24 h;
14. For premenopausal women of childbearing potential, a pregnancy test (serum) must be performed within 7 days before starting treatment, and pregnancy must be ruled out; patients must not be lactating. All enrolled patients (regardless of sex) must use adequate barrier contraception throughout the entire treatment period and for 7 months after the end of treatment.

Exclusion Criteria:

1. Received surgery, radical radiotherapy, or immunotherapy within 4 weeks before the first dose;
2. Prior exposure to ADC drugs with topoisomerase I inhibitor payload;
3. Prior treatment with other T-cell receptor-targeting agents (excluding PD-1/PD-L1);
4. Use of immunomodulators within 14 days before the first study drug dose;
5. History of severe cardiac or cerebrovascular disease;
6. Receiving chronic systemic corticosteroids at \>10 mg/day prednisone before the first dose;
7. Active autoimmune or inflammatory disease;
8. Any thrombotic event within 6 months before randomization;
9. Prolonged QTc, complete left bundle branch block, or similar;
10. Active malignancy diagnosed within 3 years before randomization;
11. Hypertension uncontrolled by two antihypertensives;
12. Poorly controlled diabetes/hyperglycemia;
13. History of steroid-treated ILD/interstitial pneumonitis;
14. Concurrent lung disease causing clinically significant respiratory impairment;
15. Active CNS metastases;
16. Severe infection within 4 weeks before randomization;
17. Massive or symptomatic serosal effusion;
18. Severe non-healing wound, ulcer, or fracture within 4 weeks before consent;
19. Clinically significant bleeding or bleeding tendency within 4 weeks before consent;
20. Inflammatory bowel disease, extensive bowel resection, immune enteritis, bowel obstruction, or chronic diarrhea;
21. Allergy or contraindication to the study drug;
22. History of autologous/allogeneic stem cell transplantation;
23. HIV antibody positive, active HBV, or active HCV;
24. History of severe neurological or psychiatric illness;
25. Received or planning to receive live vaccine within 28 days before randomization;
26. Other conditions rendering the patient unsuitable per investigator's judgment.