Study of Irinotecan Liposome Injection-containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma

1. Patients with acinar cell carcinoma, pancreatoblastoma, solid pseudopapillary tumor and pancreatic neuroendocrine tumor;

2. Patients with definitive diagnosis of CNS metastasis;

3. Patients with hepatic encephalopathy at screening;

4. Patients with clinically symptomatic ascites requiring puncture or drainage or who have received ascites drainage within the past 3 months, except for those with only a small amount of ascites on imaging but no clinical symptoms;

5. Uncontrolled third lacunar effusion other than ascites (e.g., large pleural or pericardial effusion) within 4 weeks before the first administration of the test drug;

6. Previous malignancies in the past five years (except radically resected and non-recurring basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder carcinoma, local prostate carcinoma, carcinoma in situ of cervical, or other carcinoma in situ);

7. Patients with partial or complete biliary obstruction who has not relieved by active treatment;

8. History of serious cardiovascular disease, including but not limited to:

1\) Acute myocardial infarction, unstable angina pectoris, coronary angioplasty, stroke, severe pulmonary embolism; 2) New York Heart Association class grade III or IV congestive heart failure or left ventricular ejection fraction (LVEF) \< 50%; 3) Poorly controlled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure≥ 95 mmHg) with optimal treatment; 4) Ventricular arrhythmia; 5) Patients with prolonged QT/QTc interval in baseline electrocardiogram (ECG) (QTcF \> 480 ms, Fridericia formula: QTcF = QT/(RR\^0.33), RR = 60/heart rate); 6) Patients with clinically significant abnormal electrocardiogram (ECG) according to the investigator's assessment.

9.Patients with uncontrolled active bleeding.

10.Patients with known interstitial lung disease;

11.Patients with known peripheral neuropathy (CTCAE grade 3 or 4);

12.Patients with severe lung, liver, kidney, endocrine, immune system, skin or musculoskeletal diseases within 3 months prior to the first dose and who are not suitable for enrollment in the opinion of the investigator;

13.Patients who are at risk of active infection or have active infection that may affect the results of the study (such as severe pneumonia requiring hospitalization, bacteremia, acute bacterial infection, infectious complications, tuberculosis, active HIV infection, etc.) or who, in the judgment of the investigator, are not suitable for participation in this clinical trial. Active hepatitis B virus is defined as HBV DNA≥10\^4 copies or ≥ 2000 IU/mL; active hepatitis C virus or active HIV infection is defined as HCV-RNA positive;

14.Gastrointestinal diseases of clinical significance, such as bleeding, inflammation, obstruction, \>grade 1 diarrhea, malabsorption syndrome, diseases significantly affecting gastrointestinal function, gastric or small bowel resection, etc;

15.Patients with known to have dihydropyrimidine dehydrogenase (low activity) or deficiency;

16.Patients with definite Gilbert syndrome;

17.History of explicit neurological or psychiatric disorders, including epilepsy or dementia;

18.Patients with known alcohol or drug dependence.

19.Patients who have concomitant use of strong CYP3A4 inducers within 2 weeks prior to the first dose, or strong CYP3A4 inhibitors or strong UGT1A1 inhibitors within 1 week prior to the first dose;

20.Patients who have required systemic glucocorticoids (prednisone \>10 mg/day or equivalent dose of the similar drugs) or other immunosuppressive agents within 14 days before the first dose of the study drug. Except for treatment with local, ocular, intra-articular, intranasal, and inhaled glucocorticoids in the absence of active autoimmune disease, short-term preventive treatment with glucocorticoids (e.g., prevention of contrast allergy);

21.Patients who have major organ surgery (except for needle biopsy, central venous catheterization, port-cath, stenting to relieve biliary obstruction, and percutaneous hepatic biliary drainage, cholecystostomy) or selective operation plan were performed within 4 weeks before the first dose of the study drug;

22.Patients with known allergy to irinotecan liposome injection, other liposome products, oxaliplatin, 5-fluorouracil, leucovorin, Nab-paclitaxel, other albumin products, gemcitabine or any of the ingredients in the above products.;

23\. Patients who are not suitable for this study as determined by the investigator.

What this study is about