A Multicenter Single-arm Prospective Clinical Study on First-line Treatment of Pancreatic Cancer Liver Metastases With Arterial Infusion Chemotherapy and Embolization Combined With Dual Immune Checkpoint Inhibitors.

\*\*Subjects meeting any of the following criteria will be excluded from this study:\*\*

1. Diagnosis of another malignancy within 5 years prior to the first dose, unless cured (exceptions include radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or carcinoma in situ that has undergone radical resection).

2. Currently participating in an interventional clinical study or having received other investigational drugs or devices within 4 weeks prior to the first dose.

3. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2 agents, or drugs targeting another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).

4. Poor tumor blood supply as observed during selective arterial catheterization and angiography of pancreatic tumors and liver metastases.

5. Systemic treatment with Chinese herbal medicine with anti-tumor indications or immunomodulatory drugs within 2 weeks prior to the first dose.

6. Active autoimmune disease requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) is not considered systemic treatment.

7. Current systemic corticosteroid therapy (excluding nasal sprays, inhalational, or other local corticosteroids) or any other form of immunosuppressive therapy within 7 days prior to the first dose.

* Note:\*\* Physiological doses of corticosteroids (e.g., ≤10 mg/day prednisone or equivalent) are permitted.

8. Known history of allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.

9. Known hypersensitivity to iparomlimab and tuvonralimab or any excipients of the combined chemotherapy drugs used in this study.

10. Insufficient recovery from toxicities and/or complications of prior interventions (i.e., not recovered to ≤ Grade 1 or baseline, excluding fatigue or alopecia) before starting treatment.

11. Known history of human immunodeficiency virus (HIV) infection (i.e., positive for HIV 1/2 antibodies).

12. Untreated active hepatitis B (defined as HBsAg positive with HBV-DNA copy number above the upper limit of normal \[ULN\] at the local laboratory).

* Note:\*\* Subjects with hepatitis B meeting the following criteria may be enrolled:

1. HBV viral load \< 1000 copies/mL (200 IU/mL) prior to the first dose. The subject must receive anti-HBV therapy throughout the study chemotherapy treatment period to prevent viral reactivation.

2. Subjects who are anti-HBc (+), HBsAg (-), anti-HBs (-), and have undetectable HBV viral load do not require prophylactic anti-HBV therapy but require close monitoring for viral reactivation.

13. Active HCV infection (HCV antibody positive with HCV-RNA levels above the lower limit of detection).

14. Administration of a live vaccine within 30 days prior to the first dose (Cycle 1, Day 1).

* Note:\*\* Inactivated seasonal influenza vaccines administered by injection are permitted within 30 days prior to the first dose. However, live attenuated influenza vaccines administered intranasally are not permitted.

15. Pregnant or breastfeeding women.

16. Any severe or uncontrolled systemic disease, such as:

1. Resting ECG showing significant and symptomatic abnormalities in rhythm, conduction, or morphology (e.g., complete left bundle branch block, second-degree or higher heart block, ventricular arrhythmia, or atrial fibrillation).

2. Unstable angina, congestive heart failure, or chronic heart failure of New York Heart Association (NYHA) Class ≥2.

3. Myocardial infarction within 6 months prior to enrollment.

4. Poorly controlled hypertension (systolic blood pressure \>140 mmHg, diastolic blood pressure \>90 mmHg).

5. History of non-infectious pneumonitis requiring corticosteroid treatment within 1 year prior to the first dose, or current clinically active interstitial lung disease.

6. Active pulmonary tuberculosis.

7. Active or uncontrolled infection requiring systemic therapy.

8. Clinically active diverticulitis, abdominal abscess, or gastrointestinal obstruction.

9. Liver diseases such as cirrhosis, decompensated liver disease, or acute or chronic active hepatitis.

10. Poorly controlled diabetes (fasting blood glucose \>10 mmol/L).

11. Urinalysis showing protein ≥++ and confirmed 24-hour urine protein \>1.0 g.

12. Psychiatric disorders that may interfere with treatment compliance.

17. Any medical history, condition, treatment, or laboratory abnormality that, in the investigator's judgment, may interfere with the trial results, prevent the subject from completing the study, or pose other potential risks making the subject unsuitable for participation.

What this study is about