Surufatinib in Combination With Iparomlimab and Tuvonralimab Injection and AG Chemotherapy for Neoadjuvant Therapy of HRPC or BRPC

Inclusion Criteria:

* Have fully understood this study and voluntarily signed the informed consent form.
* Aged between 18 and 75 years inclusive, of any gender.
* Patients with high-risk resectable or borderline resectable pancreatic adenocarcinoma confirmed by histopathology or cytology. (The definition of borderline resectable pancreatic pancreatic cancer refers to the NCCN Guidelines 2026 (Version 1). High-risk resectable disease is defined as meeting all three of the following criteria:

  ① The tumor does not abut the portal vein-superior mesenteric vein (PV-SMV), or abuts the PV-SMV for \<180° with intact venous contour.

  ② The tumor does not abut arteries (celiac trunk, superior mesenteric artery, or common hepatic artery).

  ③ CA19-9 ≥ 500 U/mL or maximum diameter of primary tumor \> 3.0 cm.
* Have at least one measurable lesion per RECIST 1.1.
* No pathogenic BRCA1/2 or PALB2 mutations, or unknown BRCA1/2 and PALB2 mutation status.
* No prior systemic anti-tumor therapy or locoregional radiotherapy.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Expected survival ≥ 24 weeks.
* Absence of contraindications to surgery.
* Laboratory hematology parameters (without blood transfusion within the preceding 14 days):

  ① Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelets ≥ 100 × 10⁹/L; hemoglobin ≥ 9 g/dL.

  ② Liver function: AST and ALT ≤ 2.5 × upper limit of normal (ULN); total bilirubin ≤ 1.5 × ULN. For patients with liver metastases, AST and ALT ≤ 5 × ULN.

  ③ Renal function: serum creatinine ≤ 1.5 × ULN; creatinine clearance (CCr) ≥ 60 mL/min.

  ④ Coagulation parameters: international normalized ratio (INR) ≤ 1.5 × ULN; prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
* Male and female patients of reproductive potential agree to use effective contraceptive methods throughout the study period and for 6 months after the last study drug administration, such as dual-barrier contraception, condoms, oral or injectable contraceptives, intrauterine devices, etc. All female patients will be considered of reproductive potential unless they have natural menopause, induced menopause, or sterilization procedures (e.g., hysterectomy, bilateral adnexectomy, ovarian radiation, etc.).

Exclusion Criteria:

* Patients with distant metastasis.
* Patients who have received blood transfusion, blood products or hematopoietic growth factors (such as albumin and granulocyte colony-stimulating factor \[G-CSF\]) within 14 days prior to enrollment.
* Patients who have undergone any surgery or invasive treatment/procedure within 4 weeks prior to enrollment (except venous catheterization, puncture and drainage, etc.).
* Known hypersensitivity to any study drug.
* Uncontrolled hypertension defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg.
* Patients with any disease or condition affecting drug absorption, or patients unable to receive oral surufatinib.
* Patients with active gastrointestinal diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding from unresected tumors, or other conditions judged by the investigator to carry risks of gastrointestinal bleeding or perforation.
* Uncontrolled malignant ascites (defined as ascites that cannot be controlled by diuretics or paracentesis as assessed by the investigator).
* Patients with evidence or history of obvious bleeding tendency within 3 months prior to enrollment (bleeding \>30 mL within 3 months, hematemesis, melena, hematochezia), hemoptysis (fresh blood \>5 mL within 4 weeks), or thromboembolic events within 10 months (including stroke and/or transient ischemic attack \[TIA\]).
* Clinically significant electrolyte abnormalities as judged by the investigator.
* Significant clinically relevant cardiovascular diseases, including but not limited to: acute myocardial infarction, severe/unstable angina or coronary artery bypass grafting within 6 months prior to enrollment; New York Heart Association (NYHA) class \>2 congestive heart failure; ventricular arrhythmias requiring pharmacological treatment; left ventricular ejection fraction (LVEF) \<50%.
* History of other malignancies within the past 5 years, except for radically resected basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
* Active or uncontrolled severe infections:

  ①Known human immunodeficiency virus (HIV) infection;

  ②Known history of clinically significant liver disease, including viral hepatitis. ③Known hepatitis B virus (HBV) carriers must be excluded if there is active HBV infection, i.e., positive HBV DNA (\>1×10⁴ copies/mL or \>2000 IU/mL); Known hepatitis C virus (HCV) infection with positive HCV RNA (\>1×10³ copies/mL), or other hepatitis, liver cirrhosis.
* Pregnant females (positive pregnancy test prior to study drug administration) or lactating females.
* The investigator judges that the subject has any clinical or laboratory abnormality or other conditions rendering the subject unsuitable for participation in this clinical study.
* Urinalysis showing urine protein ≥2+, with 24-hour urinary protein quantification \>1.0 g.
* Patients with active autoimmune or inflammatory diseases requiring systemic therapy within the previous 2 years (i.e., disease-modifying agents, glucocorticoids or immunosuppressive agents); or diseases treated with long-term systemic hormones or any other immunosuppressive drugs (excluding inhaled corticosteroids).
* Patients with hypothyroidism/adrenal or pituitary insufficiency who only require stable hormone replacement therapy, as well as patients with type 1 diabetes mellitus with stable disease managed solely by insulin replacement, are eligible for enrollment.
* History of (non-infectious) pneumonia requiring steroid treatment; past or current history of interstitial lung disease, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, pulmonary fibrosis or other lung diseases resulting in severely impaired pulmonary function; or active pulmonary infection at present.
* Receipt of any live or attenuated live vaccine within 4 weeks before the first study drug administration, or planned administration of such vaccines during the study period.