Phase Ib/II Clinical Study of Adebrelimab in Combination With Decitabine, Albumin-bound Paclitaxel, and Gemcitabine for the First-line Treatment of Metastatic Pancreatic Cancer

Inclusion Criteria:

1. Age 18-75 years old, male or female; 2. Histologically or cytologically confirmeddiagnosis of pancreatic cancer (originating from the pancreatic ductal epithelium),with clinical records showing metastatic pancreatic cancer (stage IV according tothe AJCC 8th edition TNM staging of pancreatic cancer); 3. Have not received anyanti-tumor therapy (including chemotherapy, targeted, immunotherapy, etc.); 4. Musthave at least one measurable lesion as a target lesion (according to RECIST v1.1criteria); the target lesion should not have received localized treatment such asradiotherapy (lesions located within the area of previous radiotherapy may also beselected as target lesions if progression is confirmed to have occurred and meetsRECIST1.1 criteria); 5. ECOG: 0 to 1; 6. Expected survival ≥ 3 months; 7. Good majororgan function, i.e., the following criteria are met (in the absence of receivingany blood components, cell growth factors within 14 days prior to randomization):

2. Neutrophils ≥1.5109/L; platelets ≥80109/L; hemoglobin ≥9g/dl; serum albumin ≥3g/dl;

3. Total bilirubin ≤ 1.5 times the upper limit of normal value (biliary obstructionallows biliary drainage); ALT and AST ≤ 3 times the upper limit of normal value (forpatients with hepatic metastases, it can be relaxed to ≤ 5 times the upper limit ofnormal value);

4. Serum creatinine ≤1.5 times the upper limit of normal value, creatinine clearance ≥50ml/min;

5. INR ≤1.5 times the upper limit of normal value and APTT ≤1.5 times the upper limitof normal value (for the use of a stable dose of anticoagulation therapy, such aslow molecular heparin or warfarin, and the INR is within the expected therapeuticrange of anticoagulants can be screened);

6. Electrocardiogram: QTcF ≤450ms (men), ≤470ms (women);

7. Cardiac ultrasound: LVEF (left ventricular ejection fraction) ≥50%; 8. Women ofchildbearing potential must have had a negative blood pregnancy test within 3 daysprior to randomization and be willing to use an appropriate method of contraceptionduring the trial and for 6 months after completion of treatment. For men, thisshould be surgical sterilization or agreement to use an appropriate method ofcontraception for the duration of the study and for 3 months after completion oftreatment; 9. Subjects voluntarily enroll in this study by signing an informedconsent form.

Exclusion Criteria:

1. patients with pancreatic cancer originating from non-pancreatic ductal epithelium,including pancreatic neuroendocrine carcinoma, pancreatic follicular cell carcinoma,pancreatoblastoma, and solid-pseudopapillary tumors;

2. patients with known central nervous system metastases;

3. severe gastrointestinal dysfunction (with bleeding, obstruction; inflammationgreater than grade 2; diarrhea greater than grade 1);

4. the presence of third interstitial fluid (e.g., massive pleural fluid) that couldnot be stabilized (without interventional therapy after drain removal) except forascites within 2 weeks before randomization;

5. Patients with clinically symptomatic ascites who require puncture or drainage or whohave received ascites drainage within the previous 3 months (except for imaging thatshows only a small amount of ascites that is manageable but not accompanied byclinical symptoms);

6. current concomitant interstitial pneumonia or interstitial lung disease, or a priorhistory of interstitial pneumonia or interstitial lung disease requiring hormonaltherapy, or other pulmonary fibrosis that may interfere with the determination andmanagement of immune-related pulmonary toxicity, mechanized pneumonia (e.g.,occlusive bronchiectasis), pneumoconiosis, drug-associated pneumonitis, idiopathicpneumonitis, or active pneumonia or severely impaired pulmonary function asdemonstrated by chest CT at the Screening Period Subjects; active tuberculosis;

7. the presence of active autoimmune disease or a history of autoimmune disease withpotential for relapse [including, but not limited to, autoimmune hepatitis,interstitial pneumonitis, uveitis, enteritis, pituitary gland inflammation,vasculitis, nephritis, hyperthyroidism, and hypothyroidism (subjects who can becontrolled by hormone replacement therapy only are eligible for enrollment)];subjects who have a skin disease that does not require systemic treatment such asvitiligo, psoriasis, alopecia that Controlled type I diabetes mellitus receivinginsulin therapy or asthma that has completely resolved in childhood and does notrequire any intervention in adulthood may be enrolled;

8. known peripheral neuropathy (CTCAE ≥ grade 3);

9. a serious infection (CTCAE > grade 2) within 4 weeks prior to randomization, such assevere pneumonia, bacteremia, or complications of infection requiringhospitalization; signs and symptoms of infection requiring intravenous antibiotictherapy (except for prophylactic use of antibiotics) within 2 weeks prior torandomization;

10. received any of the following treatments: 1) Immunosuppressive or systemic hormonetherapy for immunosuppression within 2 weeks prior to randomization (dose >10 mg/dayprednisone or other equipotent hormone); 2) Radiation therapy within 2 weeks priorto randomization; 3) Major surgery (e.g., open thoracic surgery, open abdominalsurgery, etc.) within 4 weeks prior to randomization; 4) Received any other clinicalstudy medication within 4 weeks prior to randomization, unless it was anobservational (non-interventional) clinical study or an interventional clinicalstudy follow-up.

11. abnormal coagulation, bleeding tendency or undergoing thrombolytic or anticoagulanttherapy. Prophylactic use of low-dose aspirin (≤100mg/day), low molecular heparin (enoxaparin 40mg/day and other low molecular heparin at its equivalent dose) isallowed;

12. patients with cardiac clinical conditions or diseases that are not well controlled,such as (1) NYHA class 2 or higher heart failure, (2) unstable angina pectoris, (3)myocardial infarction within 6 months, and (4) clinically significantsupraventricular or ventricular arrhythmias that require treatment or intervention;

13. malignancy other than pancreatic cancer within 5 years prior to randomization, withthe exception of adequately treated carcinoma in situ of the cervix, basal cell orsquamous epithelial cell carcinoma of the skin;

14. known hypersensitivity to PD-L1, albumin paclitaxel, gemcitabine, decitabine, andany of the components of the above products;

15. known to have acquired immunodeficiency syndrome (AIDS) or HIV test positive, activesyphilis infection;

16. previous history of definite neurological or psychiatric disorders, includingepilepsy or dementia;

17. Subjects who, in the judgment of the investigator, have other factors that may causethem to be forced to terminate the study midway, such as non-compliance with theprotocol, other serious illnesses (including psychiatric illnesses) that requirecomorbid treatment, grossly abnormal values of clinically significant laboratorytests, familial or social factors that may affect the safety of the subject or thecollection of trial data.