SMP-656 for HER2-Positive Advanced Breast Cancer

Inclusion Criteria: 1. Voluntarily participate in this clinical trial, understand and comply with study procedures, and provide written informed consent voluntarily. 2. Female patients aged ≥ 18 years at the time of signing the informed consent form. 3. Patients with histologically or cytologically confirmed unresectable HER2-positive locally advanced or metastatic breast cancer, regardless of hormone receptor (HR) status. 4. HER2-positive status confirmed by testing at the study center or an accredited laboratory, where HER2 positivity is defined as IHC 3+, or IHC 2+ with positive fluorescence in situ hybridization (FISH+) results. 5. Patients with HER2-positive locally advanced or metastatic breast cancer who have received prior treatment with one TOP inhibitor ADC targeting HER2 (e.g., DS-8201 and other ADCs with topoisomerase inhibitor payloads), and have experienced disease progression. 1\) Endocrine monotherapy is excluded from the abovementioned standard therapy lines; 2) Disease recurrence occurring within 12 months following neoadjuvant or adjuvant chemotherapy will be regarded as progression after first-line standard therapy; 6. Have at least one measurable target lesion per the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) . 7\. ECOG performance status 0-1. 8. Expected survival ≥ 3 months. 9. Bone marrow, hepatic, renal and coagulation function shall be deemed adequate based on laboratory tests performed within 7 days prior to the first dose of the investigational product. Blood transfusion or growth factor supportive therapy is prohibited within 14 days before the first administration of the investigational product： * Bone marrow function: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelet count (PLT) ≥ 80 × 10⁹/L; hemoglobin (Hb) ≥ 90 g/L; * Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); total serum bilirubin (TBIL) ≤ 1.5 × ULN, with the following exceptions; * For participants with confirmed liver metastases: AST and/or ALT ≤ 5 × ULN; * For participants diagnosed with Gilbert's syndrome: TBIL ≤ 3 × ULN; * Serum albumin ≥ 30 g/L; * Renal function: Creatinine clearance (CrCL) ≥ 50 mL/min (calculated via the Cockcroft-Gault formula), OR serum creatinine ≤ 1.5 × ULN; * Coagulation function: International Normalized Ratio (INR) ≤ 1.5 × ULN, and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. 10\. Women of childbearing potential (WOCBP) must agree to use highly effective contraception or maintain abstinence from the time of informed consent signature through 6 months after the last administration of the investigational product；For WOCBP, serum pregnancy testing performed within 7 days prior to the first dose of the investigational product must yield a negative result. Exclusion Criteria: 1. Patients with inflammatory breast cancer. 2. Have received eribulin in prior lines of therapy. 3. Have received prior treatment with an ADC with a tubulin inhibitor payload for recurrent or metastatic disease following prior treatment with an ADC with a topoisomerase inhibitor payload. 4. Prior anti-tumor therapy consisting of utidelone or vinca alkaloids as the last regimen. 5. Patients with a known history of severe hypersensitivity to inetetamab, SMP-656, or any of their excipients. 6. Patients with meningeal metastases. 7. Patients with active central nervous system (CNS) metastases are excluded, with the following exception: symptomatic CNS metastases limited to supratentorial region and/or cerebellum (i.e., no midbrain, pons, medulla oblongata or spinal cord metastases) that have received local therapy, with neurological symptoms stabilized for at least 2 weeks prior to the first dose of investigational product, and no requirement for steroid therapy or receiving prednisone ≤10 mg/day (or equivalent corticosteroids). 8. Patients diagnosed with any other malignancy (other than the study tumor type) within 5 years prior to the first dose of the investigational product, except curatively treated localized malignancies such as basal cell carcinoma of the skin. 9. History of interstitial lung disease (ILD) requiring corticosteroid intervention; current or suspected ILD; or has evidence of clinically significant active pneumonia at screening; or has active radiation pneumonitis requiring ongoing medical therapy; or has other severe pulmonary disease impairing respiratory function. 10. Patients with a clinically significant history of cardiovascular disease, including but not limited to： (1) Left ventricular ejection fraction (LVEF) \< 50%; congestive heart failure with New York Heart Association (NYHA) functional class \> 2; (2) Have experienced myocardial infarction, unstable angina, severe pericardial disease or severe myocardial disease within the previous 6 months; (3) Presence of cardiac valve regurgitation or stenosis requiring therapeutic intervention; (4) Any supraventricular or ventricular arrhythmia requiring treatment or intervention; poorly controlled malignant arrhythmias despite medication; complete left bundle branch block, second-degree or third-degree atrioventricular block; (5) QTc interval \> 470 ms at screening (for female participants), or known family history of long QT syndrome; (6) Uncontrolled hypertension (defined as systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg despite antihypertensive medication, or prior history of hypertensive crisis or hypertensive encephalopathy). 11. History of arterial or venous thromboembolic events within 6 months prior to the first dose of the investigational product, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism. 12. Participants with uncontrollable pleural effusion, pericardial effusion or ascites as judged by the Investigator, which requires repeated drainage once every two weeks or more frequently. Participants with indwelling pleural catheters are permitt