A Study of SKB264 Versus Investigator's Choice of Chemotherapy in Subjects With Unresectable Locally Advanced, Relapsed, or Metastatic HR+/HER2- Breast Cancer Who Have Previously Failed Endocrine Therapy

Inclusion Criteria:

1. Aged ≥ 18 and ≤ 75 years at the time of signing the ICF, male or female;

2. Histologically and/or cytologically confirmed HR+/HER2- BC based on pathologicalreports from the most recent biopsy or other pathological specimens;

3. Subjects must have radiologically documented disease progression during or after themost recent treatment prior to enrollment;

4. No prior systemic chemotherapy for locally advanced, relapsed, or metastatic stages.Subjects who previously received adjuvant/neoadjuvant chemotherapy and progressed >6months after completion of the last chemotherapy treatment will be allowed for studyinclusion;

5. The investigator assessed that the patient could not continue to benefit fromendocrine therapy and was suitable for receiving first-line chemotherapy;

6. Able to provide recently newly obtained or archival tumor tissue sections at orafter diagnosis of relapsed or metastatic tumor within the recent prior torandomization;

7. At least one measurable lesion per RECIST v1.1；

8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with noworsening within 2 weeks prior to randomization;

9. Life expectancy of ≥ 12 weeks;

10. Suitable to receive one of the chemotherapy regimens listed in the investigator'schoice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine) as assessed by theinvestigator;

11. Adequate organ and bone marrow function;

12. Having recovered from all toxicities due to prior treatment;

13. Use of effective medical contraception during study treatment and for 6 months afterthe end of dosing for female subjects of childbearing potential and male subjectswith partners of childbearing potential;

14. Willingness to participate in the study, sign the ICF, and comply with theprotocol-specified visits and relevant procedures.

Exclusion Criteria:

1. Subjects with locally advanced (Stage IIIc) breast cancer suitable for curativetherapy at study enrollment;

2. Other malignancies (except those tumors cured by local treatment, such as basal cellcarcinoma of skin, squamous cell carcinoma of skin, carcinoma in situ of the cervix)within 3 years prior to randomization;

3. Central nervous system (CNS) metastases (including parenchymal brain metastases ormetastases to meninges) or cancerous meningitis;

4. Presence of any serious cardiovascular and cerebrovascular diseases orcardiovascular and cerebrovascular risk factors;

5. History of (noninfectious) interstitial lung disease (ILD)/noninfectious pneumonitisrequiring steroid therapy and current ILD/noninfectious pneumonitis, or suspectedILD/noninfectious pneumonitis at screening that cannot be excluded by imaging;

6. Clinically serious lung injuries caused by lung diseases;

7. Serious infection within 4 weeks prior to randomization, including but not limitedto complications requiring hospitalization, sepsis, or severe pneumonia; activeinfection requiring systemic anti-infective therapy within 2 weeks prior torandomization;

8. Documented severe dry eye syndrome, severe meibomian gland dysfunction and/orblepharitis, or history of severe corneal disorders that prevent/delay cornealhealing;

9. History of esophagogastric varices, severe ulcers, gastric perforation,gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinalbleeding within 6 months prior to randomization;

10. Active hepatitis B (hepatitis B surface antigen positive and HBV-DNA ≥ 500 IU/mL orabove the ULN, whichever is higher) or hepatitis C (hepatitis C antibody positiveand HCV-RNA above the ULN);

11. Positive result of human immunodeficiency virus (HIV) test or history of acquiredimmunodeficiency syndrome (AIDS); known active syphilis infection;

12. 12 Known hypersensitivity to SKB264 or investigator's choice chemotherapy or any ofits excipients, including but not limited to polysorbate-20, or history of severehypersensitivity reaction to other monoclonal antibodies;

13. Known history of allogeneic organ transplantation and allogeneic hematopoietic stemcell transplantation.

14. Pregnant or lactating women;

15. Prior TROP2-targeted therapy or any treatment containing chemotherapeutic agentstargeting topoisomerase I (including antibody-drug conjugates [ADCs]);

16. Live vaccines within 4 weeks prior to randomization or scheduled to receive livevaccines during study treatment;

17. Receipt of the following therapies prior to randomization: a)Major surgery within 4weeks prior or expected major surgery during the study; b)Radiation therapy within 2weeks prior (extensive radiation therapy including radiopharmaceuticals within 4weeks prior); c)Any immunotherapy, biological therapy, or other investigationaldrugs within 4 weeks or 5 half-lives of prior drug use (whichever is shorter) (bisphosphonates or RANK-L inhibitors for bone metastases are permitted prior torandomization); or traditional Chinese medicine with approved anti-tumorindications, small molecule targeted therapy, or endocrine therapy within 2 weeksprior.

18. Rapid deterioration of the condition, e.g., significant changes in performancestatus, etc., during the screening process.