IBI354 With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer

Participants are eligible to be included in the study only if they meet all of the following criteria: 1. Have signed the informed consent form (ICF) and are able to comply with the follow-up visits and related procedures required in the protocol. 2. Male or female participants: ≥18 years of age 3. Pathologically confirmed breast cancer: 1. Unresectable, locally advanced or metastatic breast cancer, i.e. participants who cannot be treated with curative intent and confirmed HER2-positive (HER2 IHC 3+ or HER2 ISH+) on specimens taken after confirmed locally advanced or metastatic disease by central testing. 2. Documented history of hormone receptor (HR)-positive (defined as estrogen receptor \[ER\] and/or progesterone receptor \[PgR\] positive \[ER or PgR ≥1%\]) or HR-negative after local testing in the metastatic setting according to ASCO/CAP guidelines. If a participant has more than one ER/PgR result after metastatic disease, the most recent result will be used. 4. No prior chemotherapy or HER2-targeted therapy for unresectable, locally advanced or metastatic breast cancer (first-line endocrine therapy is allowed for patients with metastatic breast cancer). Participants who have received chemotherapy or HER2-directed therapy in the neoadjuvant or adjuvant therapies and have a DFI of \>6 months from completion of systemic chemotherapy or HER2-targeted therapy to advanced or metastatic diagnosis are eligible. 5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1. 6. Evidence of radiographic or objective disease progression on or after the last systemic therapy prior to starting study treatment. 7. Have a life expectancy of ≥12 weeks at screening. 8. At least 1 measurable lesion as defined per RECIST v1.1 that has not been previously irradiated. Must be ≥ 10 mm in long axis (except for lymph nodes, which must be ≥ 15 mm in short axis) when accurately measured at baseline by CT or MRI (preferably with intravenous contrast) and the lesion is suitable for repeated accurate measurement. 9. Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days prior to randomization. 10. Adequate organ and bone marrow function. Laboratory test values within 7 days prior to the first dose of the investigational product meet the following requirements in (if the laboratory tests during the screening period do not meet the following requirements, only one retest is allowed during the screening period): 1. Hemoglobin (HGB) ≥ 90 g/L (transfusion of red blood cells or erythropoietin are not allowed within 1 week prior to the screening assessment, and participants requiring ongoing transfusion or growth factor support to maintain hemoglobin ≥ 90 g/L are not eligible). 2. Absolute neutrophil count (ANC) ≥ 1.5 × 109 /L or within the normal range (G-CSF is not allowed within 1 week prior to the screening assessment). 3. Platelet (PLT) ≥ 90 × 109 /L (transfusion with platelets or thrombopoietin is not allowed within 1 week prior to screening assessment, participants requiring thrombopoietic growth factors to maintain adequate platelet count are not eligible). 4. Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN) in the absence of liver metastasis; TBIL \< 3 × ULN in the presence of Gilbert syndrome (unconjugated hyperbilirubinemia) or liver metastasis. 5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN (\<5×ULN for participants with liver metastases). 6. Serum albumin ≥ 25 g/L. 7. Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 60 mL/min ( calculated using the Cockcroft-Gault formula ); if urinalysis indicates that the urine protein is \< 2+, participants with urine protein ≥ 2+ from urinalysis at baseline should undergo a 24-hour urine collection and have a 24-hour urine protein quantitation \< 1 g (if both methods are used, a 24-hour urine protein quantitation will be used to determine participant eligibility). Cockcroft/Gault formula: Female: CrCl = (140 - Age) × Weight (kg) × 0.85 72 × serum creatinine (mg/dL) Male: CrCl = (140 - years) × weight (kg) × 1.00 72 × serum creatinine (mg/dL) 8. International normalized ratio (INR) ≤ 1.5 × ULN, and prothrombin time (PT) or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. 11. Participants with evidence of postmenopausal status or negative serum pregnancy test (Sexually active, WOCBP with a non-sterilized male partner) must have a negative serum pregnancy test at the screening visit. WOCBP are women who are not surgically sterile (i.e., have undergone bilateral salpingectomy, bilateral oophorectomy, or total hysterectomy) or are not postmenopausal. 12. Female participants of childbearing potential or male participants with partners of childbearing potential must take effective contraceptive measures during the entire course of the trial and 6 months after the treatment Participants should not be included in the study if they meet any of the following criteria: 1. Prior treatment with antibody-drug conjugates containing camptothecin or its derivatives (topoisomerase I inhibitors). 2. Uncontrolled or significant cardiovascular and cerebrovascular diseases, including any of the following: 1. History of myocardial infarction or symptomatic congestive heart failure (New York Heart Association \[NYHA\] class II to IV) or uncontrolled myocarditis within 6 months before randomization. Participants with troponin levels above the ULN at screening (as specified by the manufacturer) and without any myocardial infarction-related symptoms should have a cardiology consultation before randomization to rule out myocardial infarction. 2. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) despite of standard treatment. 3. History of any arterial thromboembolic events within 6 months prior to randomization, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack. 4. History of deep vein thrombosis, pulmonary embolism, or any other serious thromboembolic events within 3 months prior to randomization (thrombosis or catheter-derived thrombosis of caused by implanted venous ports, or superficial vein thrombosis, intermuscular vein thrombosis are not considered serious thromboembolisms). 5. History of arrhythmia (polymorphic premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, ventricular fibrillation, torsades de pointes) that is symptomatic or requires treatment (CTCAE 5.0 Grade 3), atrial fibrillation that is symptomatic or uncontrolled despite treatment, or asymptomatic sustained ventricular tachycardia. Participants whose atrial fibrillation is controlled by medication or whose arrhythmia is controlled by a pacemaker will be allowed to be enrolled in the study. 6. Fridericia-corrected QT interval (QTcF) \>480 msec. If QTcF is \> 480 ms in 1 ECG during the screening period, 3 consecutive ECGs should be performed and the mean QTcF should be calculated. If QTcF is still \> 480 ms, the participant will not be enrolled. 7. History of QT prolongation associated with other drugs that require discontinuation, or any current concomitant medication known to prolong QT interval leading to Torsade de Pointes. 8. Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in first-degree relatives under 40 years old. 3. Non-infectious pneumonitis that requires corticosteroid treatment, or other clinically significant lung diseases such as a history of interstitial lung disease (ILD)/non-infectious pneumonitis, current ILD/non-infectious pneumonitis, or uncontrolled lung diseases (e.g., pulmonary fibrosis, severe radiation pneumonitis, and acute lung injury) or suspected ILD/non-infectious pneumonitis cannot be ruled out by imaging at screening. 4. Have a lung-specific intercurrent clinically significant illness including, but not limited to, any u