Trastuzumab Deruxtecan Plus ivonescImab for Hormone Receptor-positive HER2 Negative Advanced Breast Cancer Study

Inclusion Criteria: 1. Age ≥ 18 years, any gender. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 3. Histologically or cytologically confirmed Hormone Receptor-positive (HR+) and Human Epidermal Growth Factor Receptor 2 (HER2)-low or HER2-ultralow breast cancer, with evidence of locally recurrent or metastatic disease that is not amenable to curative-intent surgery or radiation therapy. * HR positivity is defined as Estrogen Receptor (ER) positive (≥1% positive cells) and/or Progesterone Receptor (PR) positive (≥1% positive cells). * HER2-low or HER2-ultralow expression is defined as HER2 (0 with staining), HER2 (1+), or HER2 (2+) by immunohistochemistry (IHC) with a negative in-situ hybridization (ISH) result. * Fulfillment of these criteria from any single pathological assessment is sufficient for eligibility. 4. Life expectancy of ≥ 3 months. 5. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). 6. History of recurrence or disease progression after prior treatment with a CDK4/6 inhibitor (including in the adjuvant setting). Patients have received a maximum of one line of chemotherapy for recurrent or metastatic disease. Recurrence or disease progression during or within 6 months after completion of neoadjuvant/adjuvant intravenous chemotherapy is counted as one line of therapy. 7. Patients with Central Nervous System (CNS) metastases are eligible. Ventriculoperitoneal shunt to relieve intracranial pressure or use of mannitol, corticosteroids, or anticonvulsants is permitted prior to the first dose. However, the dose of such medications must be stable for at least 1 week without an increase, and neurological symptoms must be stable without worsening for at least 1 week. (Priority will be given to the enrollment of patients with CNS metastases.) 8. Availability of an adequate tumor tissue sample for retrospective analysis of PD-L1 status. 9. Adequate organ function, defined as follows: * Hematology: Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; Platelets (PLT) ≥ 75 × 10⁹/L; Hemoglobin (Hb) ≥ 90 g/L (transfusion or medical support to meet this level is permitted). * Hepatic and Renal Function: Total Bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 × ULN (≤ 5.0 × ULN in the presence of liver metastases); Blood Urea Nitrogen (BUN) or Serum Creatinine (Cr) ≤ 1.5 × ULN, or Creatinine Clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula). * Coagulation: Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN; Prothrombin Time (PT) ≤ 1.5 × ULN. * Cardiac: QT interval corrected by Fridericia's formula (QTcF) \< 470 ms for females and \< 450 ms for males on a 12-lead electrocardiogram (ECG); Left Ventricular Ejection Fraction (LVEF) ≥ 50% by echocardiogram. 10. Voluntary participation in the study with signed informed consent, and willingness to comply with study procedures and follow-up. Exclusion Criteria: 1. Confirmed leptomeningeal metastases by Magnetic Resonance Imaging (MRI) or lumbar puncture. 2. Prior treatment with anti-PD-1/PD-L1 or anti-VEGF agents, unless both of the following conditions are met: (1) The patient did not experience disease progression during treatment with the anti-PD-1/PD-L1 or anti-VEGF agent; and (2) The time from the last dose of the anti-PD-1/PD-L1 or anti-VEGF agent to the time of recurrence or disease progression is ≥ 3 months. 3. Presence of third-space fluid accumulation (e.g., massive pleural or peritoneal effusion) that cannot be controlled by drainage or other methods. 4. Receipt of whole-brain radiotherapy, chemotherapy, targeted biologic therapy, immunotherapy, surgery, or endocrine therapy within 2 weeks prior to the first dose of study drug. Bone-modifying agents for the treatment of bone metastases or prevention of osteoporosis are permitted. 5. Prior treatment with trastuzumab deruxtecan or any antibody-drug conjugate (ADC) containing a topoisomerase inhibitor. 6. Participation in another interventional drug clinical trial within 2 weeks prior to enrollment. Participation in non-interventional studies is allowed. 7. Major surgery or significant trauma within 4 weeks prior to randomization, or anticipation of the need for major surgery during the study. 8. Concurrent receipt of any other anti-cancer therapy. 9. History of other malignancies within the past 5 years, except for curatively treated cervical carcinoma in situ, cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, and papillary thyroid carcinoma. 10. History of any of the following cardiac conditions: (1) Myocardial infarction; (2) Congestive heart failure; (3) Any other cardiac condition judged by the investigator to be unsuitable for study participation. 11. Known history of hypersensitivity to any component of the study drugs. 12. History of immunodeficiency, including positive test for Human Immunodeficiency Virus (HIV), other acquired or congenital immunodeficiency diseases, or a history of organ transplantation. 13. Active hepatitis (Hepatitis B defined as HBsAg positive and HBV DNA ≥ 1000 IU/mL; Hepatitis C defined as HCV antibody positive and HCV RNA \> upper limit of normal). 14. History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. 15. Clinically significant pulmonary-specific comorbidities, including but not limited to any underlying pulmonary disease (e.g., pulmonary embolism within 3 months prior to the study, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.). 16. Uncontrolled infection requiring systemic antibiotic, antiviral, or antifungal therapy. 17. Clear history of neurological or psychiatric disorders, including epilepsy or dementia. 18. Pregnant or breastfeeding women; women of childbearing potential with a positive pregnancy test at baseline or who are unwilling to use effective contraceptive measures throughout the study period. 19. Presence of any concomitant disease that, in the investigator's judgment, could seriously compromise patient safety or interfere with completion of the study (including, but not limited to, uncontrolled severe hypertension, uncontrolled severe diabetes, active infection, etc.). 20. Any other condition for which the investigator considers the patient unsuitable for participation in this study.