Inclusion Criteria:
* Voluntary Participation Willingly participate in the clinical study; fully comprehend the study details and sign the Informed Consent Form (ICF); commit to and demonstrate capacity to complete all trial procedures.
* Age and Gender Any gender; age ≥18 and ≤75 years at the time of ICF signing.
* Diagnosis Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC).
* Prior Therapy \*No prior systemic antitumor therapy for metastatic PDAC.
\*Exception: Patients who received one cycle of chemotherapy (nab-paclitaxel + gemcitabine) as initial treatment for newly diagnosed PDAC may enroll.
\*Prior neoadjuvant/adjuvant therapy is permitted if completed \>6 months before enrollment, and treatment-related adverse events (AEs) have recovered to NCI-CTCAE ≤ Grade 1 (alopecia excluded).
* Measurable Disease At least one measurable lesion per RECIST v1.1, assessed by the investigator. Target lesions must not be exclusively bone metastases.
* HER2 Status \*HER2-positive defined by ASCO/CAP gastric cancer HER2 testing guidelines: IHC 3+ (primary or metastatic lesion), or IHC 2+ with ISH/FISH-positive confirmation.
\*Note: ≤15 patients with IHC 2+/FISH-positive status may enroll.
* Performance Status ECOG performance status 0 or 1 within 7 days prior to first dose.
* Life Expectancy Expected survival ≥3 months.
* Hepatitis B \*HBsAg-negative and HBcAb-negative. \*If HBsAg-positive or HBcAb-positive, HBV-DNA must be \<2500 copies/mL or 500 IU/mL (or within institutional normal range).
* Hepatitis C \*HCV antibody-negative.
* If HCV antibody-positive, HCV-RNA must be negative.
* Exclusion: Co-infection of HBV and HCV (HBsAg/HBcAb-positive and HCV antibody-positive).
* HIV Status HIV antibody-negative.
* Organ Function
Adequate organ function within 14 days before first dose (without transfusion, albumin, thrombopoietin, or CSF support):
\*Hematology: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L Platelets ≥100 × 10⁹/L Hemoglobin ≥90 g/L
\*Liver: Total bilirubin ≤1.5 × ULN AST/ALT ≤2.5 × ULN (≤5 × ULN if liver metastases present) Alkaline phosphatase ≤5.0 × ULN Albumin ≥25 g/L
\*Renal: Creatinine clearance ≥50 mL/min (Cockcroft-Gault formula)
\*Coagulation: INR ≤1.5 × ULN APTT ≤1.5 × ULN PT ≤1.5 × ULN
* Contraception
* Females of childbearing potential: Negative serum pregnancy test within 7 days before first dose.
* All participants: Use of ≥1 medically approved contraceptive method (e.g., IUD, oral contraceptives, barrier devices) during treatment and for ≥7 months after last dose.
Exclusion Criteria:
* Other Malignancies
History of other malignancies within 2 years prior to first dose, except:
Curatively treated localized tumors (e.g., basal cell carcinoma, squamous cell carcinoma of skin, superficial bladder cancer, carcinoma in situ of prostate/cervix/breast/thyroid).
* Prior Anthracycline Exposure
Cumulative doxorubicin dose \> 360 mg/m² (or equivalent):
Equivalent agents: Epirubicin \>720 mg/m², mitoxantrone \>120 mg/m², idarubicin \>90 mg/m², or liposomal doxorubicin \>360 mg/m² doxorubicin-equivalent.
If multiple anthracyclines were used, the total cumulative dose must not exceed 360 mg/m² doxorubicin-equivalent.
* Prior HER2-Targeted Therapy Any previous HER2-targeted treatment (e.g., trastuzumab, pertuzumab).
* Active Gastrointestinal Bleeding
≥ Grade 2 toxicity per NCI-CTCAE v5.0.
* CNS Involvement Central nervous system (CNS) metastases and/or leptomeningeal metastases.
* Cardiovascular Events
History within 6 months prior to first dose:
Cerebrovascular accident, myocardial infarction, unstable angina, or poorly controlled arrhythmias.
QTc interval ≥450 ms (males) or ≥470 ms (females) (Fridericia formula).
* Cardiac Dysfunction NYHA Class III-IV heart failure or left ventricular ejection fraction (LVEF) \< 55% by echocardiography.
* Pulmonary/Infectious Conditions Interstitial lung disease (current or history). Active infection requiring systemic therapy or active tuberculosis.
* Recent Live Vaccines Administration of live attenuated vaccines within 28 days prior to first dose (exception: inactivated influenza or COVID-19 vaccines).
* Major Surgery Within 28 days prior to first dose.
* Radiotherapy Curative radiotherapy within 28 days prior to first dose.
* Concurrent Clinical Trials Current participation in other interventional studies or use of investigational drugs/devices within 28 days prior to first dose.
* Hypersensitivity Known severe allergy to monoclonal antibodies or excipients of the study drugs.
* Substance Abuse History of illicit drug use or psychiatric medication abuse.
* Pregnancy/Lactation Pregnant or breastfeeding women.
* Other Exclusionary Factors
Any condition deemed by the investigator to:
Compromise patient safety or data integrity. Require concomitant treatment for severe comorbidities (including psychiatric disorders).
Exhibit critically abnormal laboratory values. Pose significant social/familial impediments to study completion.
