FS-1502 Versus T-DM1 for HER2-Positive Unresectable Locally Advanced or Metastatic Breast Cancer

Inclusion Criteria:Subjects are eligible to be included in the study only if they meet allof the following criteria:

1. Male or female age ≥ 18;
2. Histologically or cytologically confirmed HER2-positive unresectable locally advancedor metastatic breast cancer;
3. Prior treatment with trastuzumabs and taxanes in the adjuvant therapy, neoadjuvanttherapy, or advanced treatment phases;
4. ≥ 1 and ≤ 3 previous lines of therapy against locally advanced or metastatic diseases,if PD occurring during adjuvant therapy/neoadjuvant therapy and within 12 months aftertreatment can be taken as one line of therapy;
5. Tissue samples qualified by the central laboratory for HER2 detection are available,and HER2 is confirmed positive by the pathology test in the central laboratory:Immunohistochemistry (IHC) 3+, or IHC2+ and fluorescence in situ hybridization (FISH)+as the basis for inclusion;
6. ECOG score at 0 or 1;
7. Expected survival ≥ 12 weeks;
8. Adequate organ and bone marrow functions: absolute neutrophil count [ANC] ≥1.0×10^9/L (no use of granulocyte-colony-stimulating factor (G-CSF) within 7 days); hemoglobin (HGB) ≥ 90 g/L (no red blood cell transfusion within 14 days); platelet count (PLT) ≥ 100×10^9/L (no use of platelet-elevating drugs within 7 days, no platelet transfusionwithin 14 days); total serum bilirubin (TSB) ≤ 1.5 × upper limit of normal (ULN) or ≤ 3.0 × ULN for patients with Gilbert syndrome; aspartate aminotransferase (AST) andalanine aminotransferase (ALT) ≤ 2.5×ULN; for patients with liver metastases, AST andALT ≤ 5×ULN; creatinine clearance ≥ 50 mL/min (calculated by Cockroft-Gault formula);blood potassium ≥3.5 mmol/L; albumin ≥ 3 g/dL; left ventricular ejection fraction (LVEF) >50%; urine protein ≤1+ or 24h urine protein quantification <1.0 g;
9. At least one non-intracranial evaluable lesion as assessed by RECIST 1.1;
10. Female patients of childbearing potential must agree to take highly effectivecontraceptive measures or avoid sexual intercourse during and after the study andwithin at least 3 months after the last dose of FS-1502 and within at least 7 monthsafter the last dose of T-DM1. Male patients must agree to avoid sexual intercourse, orthey and/or any female partners of childbearing potential must take a medicallyacceptable and effective contraceptive measure, such as double barrier methods,condoms, oral or injectable contraceptives, intra-uterine devices during and after thestudy and within at least 3 months after the last dose of FS-1502 or within at least 4months after the last dose of T-DM1;
11. Be able to understand and voluntarily sign the written Informed Consent Form (ICF).

Exclusion Criteria: Patients that meet any of the following conditions shall not be included in this clinicalstudy:

1. Patients who have received chemotherapy, small molecule targeted drug therapy,endocrinotherapy，radiotherapy, etc. within 14 days or 5 half-lives (whichever isshorter) before administration or who have received major surgical treatment and tumorimmunotherapy within 4 weeks before administration or who have received large moleculemonoclonal antibody drugs for cancer treatment within 21 days before administration.
2. Patients who have participated in other clinical studies within 4 weeks or 5half-lives of the drug (whichever is shorter) before administration.
3. Patients who have been previously treated with anti-HER2 ADCs for metastatic diseases.
4. Patients with known hypersensitivity or delayed type hypersensitivity to certainingredients of T-DM1 or similar drugs, or with known contraindications for the use ofT-DM1.
5. Patients with pia maters, spinal cords, brainstem and brain parenchymal metastases;such patients are allowed to be enrolled if all of the following conditions are met:
6. Patients who have received local treatment and the lesions are stable for morethan 6 months;
7. Patients who have no clinical symptoms and don't need glucocorticoid therapy orother dehydration treatment, and have a stable dose of an antiepileptic drug, ifapplicable.
8. Patients with a large quantity of clinically uncontrolled pleural effusion,pericardial effusion, or ascites (within 2 weeks prior to the first dose).
9. Unresolved toxic reactions from previous anti-tumor therapy (> NCI-CTCAE 5.0 Grade 1);however, alopecia, neurotoxicity or other toxicity that has converted to chronic andreturned to NCI-CTCAE 5.0 Grade ≤ 2, and does not affect the safety of the patient asassessed by the Investigator are allowed to be enrolled.
10. History of non-infectious interstitial lung disease (ILD) / pneumonia, current ILD /pneumonia, or imaging suggestive of suspected moderate-severe ILD / pneumonia atscreening.
11. Subjects with corneal epithelial lesions (except mild punctate keratopathy), or otherocular diseases that affect the evaluation of ocular toxicity after theinvestigational product administration, or unwilling to stop wearing corneal contactlenses during the study.
12. Patients on medications that prolong the QTc interval (mainly Classes Ia, Ic, IIIanti- arrhythmia medications) or with risk factors for prolonging the QTc interval,such as uncorrectable hypokalemia, inherited long QT syndrome; potential medicationsfor prolonging the QTc interval are presented in Appendix 7.
13. Cardiac function and diseases that meet one of the following conditions:
14. Mean QTc > 450 ms for males and mean QTc > 470 ms for females averaged from 3results of 12-lead ECG measurements using the QTcF formula of the ECG instrumentat the study site during the screening period;
15. New York Heart Association (NYHA) Functional Classification ≥ Class 2 congestiveheart failure;
16. Clinically significant arrhythmia (Grade ≥ 2);
17. History of myocardial infarction or severe arteriovenous thrombotic events within 6 months.
18. Pregnant or breastfeeding women.
19. Known hypersensitivity to any excipients of FS-1502.
20. Active infection requiring systemic therapy.
21. Active hepatitis B (positive for HBV surface antigen and detected with HBV DNA > 1000IU/mL or meeting the diagnostic criteria for active hepatitis B infection at the studysite) or hepatitis C (positive for HCV RNA) and human immunodeficiency viral infection (HIV positive).
22. Any other malignancy diagnosed within 5 years prior to the study, except for earlymalignancies (carcinoma in situ) that have undergone radical treatment, such asadequately treated basal or squamous cell skin cancer or cervical carcinoma in situ.
23. Any other diseases or conditions considered clinically significant by the investigatorthat could affect protocol compliance or affect the patient's ability to sign the ICF.