Inclusion Criteria:
* Voluntary participation with signed written informed consent, good compliance, and willingness to adhere to follow-up visits.
* Age ≥ 18 years, male or female.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 and life expectancy ≥ 3 months.
* Histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic adenocarcinoma.
* Must have received prior first-line (1L) systemic therapy. Prior neoadjuvant or adjuvant chemotherapy is allowed if the last treatment was administered \> 6 months before disease recurrence/progression.
* No prior exposure to irinotecan or oxaliplatin.
* At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
* Adequate major organ function, defined as follows:
Hematology: Hemoglobin ≥ 90 g/L (no transfusion within 14 days); Absolute Neutrophil Count ≥ 1.5 × 10⁹/L; Platelets ≥ 75 × 10⁹/L.
Biochemistry: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 3 × ULN (or ≤ 5 × ULN in the presence of liver metastases); Serum creatinine ≤ 1 × ULN with calculated creatinine clearance \> 50 mL/min (Cockcroft-Gault formula).
Coagulation: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN (or within therapeutic range for patients on stable anticoagulation).
Thyroid: Normal TSH, or abnormal TSH with normal FT3/FT4 (e.g., controlled hypothyroidism).
Cardiac: QTc interval (Fridericia's formula) ≤ 450 ms for males and ≤ 470 ms for females.
\- Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose and agree to use effective contraception during the study and for 6 months after the last dose. Male participants with female partners of childbearing potential must agree to use effective contraception during the study and for 6 months after the last dose.
Exclusion Criteria:
* Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibodies, or any other agents specifically targeting T-cell co-stimulation or immune checkpoint pathways.
* Prior treatment with bevacizumab or other anti-angiogenic agents. Radiological evidence of major vascular tumor invasion or high risk of fatal hemorrhage; active gastrointestinal bleeding, persistent bleeding disorders, or coagulopathy.
* Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy, immunotherapy, or molecular targeted therapy within 4 weeks prior to the first dose (bisphosphonates for bone metastases are allowed).
* Uncontrolled central nervous system (CNS) metastases (i.e., symptomatic or requiring corticosteroids or mannitol for symptom control).
* Clinically significant or uncontrolled cardiac disease within 6 months prior to the first dose, including congestive heart failure, angina pectoris, myocardial infarction, or ventricular arrhythmias.
* Persistent toxicities from prior therapy ≥ Grade 1 (per NCI-CTCAE v5.0), including Grade 1 peripheral neuropathy. Exceptions: alopecia or conditions deemed not exclusionary by the investigator (with clear documentation).
* Other active malignancy within 5 years prior to the first dose, except for adequately treated basal cell carcinoma of the skin or cervical carcinoma in situ.
* Active autoimmune disease requiring systemic treatment within 2 years prior to the first dose. Exceptions: vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis requiring only hormone replacement therapy.
* History of immediate hypersensitivity reactions, eczema, or asthma not controlled by topical corticosteroids.
* History of drug-induced interstitial lung disease (ILD), pneumonitis, obstructive pulmonary disease severely affecting lung function, or symptomatic bronchospasm.
* Severe infection (\> CTCAE Grade 2) requiring antibiotic therapy within 14 days prior to the first dose (e.g., severe pneumonia, bacteremia, infectious complications requiring hospitalization).
* Receipt of live-attenuated vaccine within 4 weeks prior to the first dose, or planned vaccination during the study period.
* Known human immunodeficiency virus (HIV) infection, history of allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation.
* History of allergy or hypersensitivity to any component or excipient of the investigational drugs.
* Any other condition deemed by the investigator to be unsuitable for participation in the study.
