Sequential AG and mFOLFOX Combined With Serplulimab Injection and Bevacizumab Injection in Untreated Advanced Pancreatic Cancer

Exclusion Criteria

• •1. subjects with clear brain metastases on imaging or with meningeal metastases;
• •2. untreated spinal compression fractures not treated by surgery and/or radiotherapy; treated spinal compression fractures require disease stabilization for at least 2 weeks prior to enrollment;
• •3. high risk of gastrointestinal or abdominal bleeding as evaluated by the Investigator;
• •4. uncontrolled cancer pain; narcotic analgesics not at a stable dose at enrollment;
• •5. previous treatment with vascular endothelial growth factor (VEGFR) inhibitors or previous treatment with immune checkpoint inhibitors;
• •6. antitumor treatment with chemotherapy, small molecule inhibitors, immunotherapy (e.g., interleukin, interferon, or thymosin) within 28 days prior to enrollment in this study, and herbal medicine with antitumor indications within 14 days prior to dosing;
• •7. major surgical procedures \[such as transabdominal, transthoracic and other major surgeries; excluding diagnostic puncture such as ultrasonic endoscopy-guided pancreatic fine-needle aspiration biopsy (EUS-FNB), percutaneous hepatic perforation biopsy, peripheral venous catheterization, and biliary stent implantation\] or invasive treatments or operations with incomplete healing of the surgical incision, local anti-tumor treatment such as hepatic artery interventional embolization, hepatic metastasis cryo-ablation, radiofrequency ablation and other local anti-tumor treatments. radiofrequency ablation and other local antitumor therapy;
• •8. have received radical radiotherapy within 3 months prior to study entry; palliative radiotherapy 2 weeks prior to dosing is permitted, and the dose of radiotherapy meets local standards of care for palliative care;
• •9. required systemic corticosteroid (\>10 mg/day prednisone or equivalent of other corticosteroid for ≥7 consecutive days) or immunosuppressive therapy within 14 days prior to enrollment in this study; with the exception of inhaled or locally applied hormones, or physiologic replacement doses of hormone therapy due to adrenal insufficiency; short-term (≤7 days) corticosteroids are allowed for prophylaxis (e.g., contrast allergy) or treatment of Non-autoimmune conditions (eg, delayed hypersensitivity reactions caused by exposure to allergens) ;
• •10. subjects with uncorrectable albumin decline (serum albumin \<3.0 g/dL) 14 days prior to enrollment in this study; and
• •11. a 10% or greater weight loss in comparison to the weight loss at the time of ICF signing within 72 hours prior to enrollment in this study; and
• •12. within 72 hours prior to study entry, the subject's ECOG physical status score increases by ≥1 point compared to the ICF score; 13. within 28 hours prior to study entry, the subject's ECOG physical status score increases by ≥1 point compared to the ICF score; and
• •13. has received a live vaccine (including live attenuated vaccine) within 28 days prior to enrollment in this study;
• •14. previous or current interstitial pneumonia/pneumatosis, unless determined by the investigator to be inactive and not requiring hormonal therapy; and
• •15. pre-existing or current autoimmune disease, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, tuberculosis, Wegener's syndrome (granulomatous disease with polyangiitis), Graves' disease, rheumatoid arthritis, hypopituitarism, uveitis, autoimmune hepatitis, systemic sclerosis ( Scleroderma, etc.), Hashimoto's thyroiditis, autoimmune vasculitis, autoimmune neuropathy (Guillain-Barre syndrome). The following conditions are excluded: type I diabetes mellitus, hypothyroidism stabilized by hormone replacement therapy (including hypothyroidism caused by autoimmune thyroid disease), psoriasis or vitiligo that does not require systemic therapy;
• •16. a combination of other malignancies within the last 5 years, except cured squamous skin cancer, basal cell carcinoma, non-basal invasive bladder cancer, and prostate/cervical/breast cancer in situ;
• •17. hepatic metastases comprising more than 50% of the total liver volume;
• •18. uncontrolled comorbidities, including but not limited to the following
• •1. Active HBV or HCV infection; (Note: HBV DNA and/or HCV RNA testing is required for subjects who are HBsAg positive and/or HCV antibody positive at Screening. Subjects who are negative for HBV DNA ≤500 IU/mL (or ≤2000 copies/mL) and/or HCV RNA are eligible for enrollment; HBsAg-positive subjects are required to have their HBV DNA monitored during the course of treatment);
• •2. Known history of HIV infection or AIDS;
• •3. Active syphilis;
• •4. Active tuberculosis;
• •5. Active or uncontrolled serious infection (≥ CTCAE grade 2 infection);
• •6. Medication-uncontrolled hypertension (defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg;), symptomatic cardiac insufficiency (NYHA II-IV), unstable angina pectoris or myocardial infarction within 6 months, or the presence of a prolonged QTc or risk of torsades de pointes (baseline QTc\>470 msec (women)/450 msec (men) \< Fridericia method correction\>, hypokalemia, long QT syndrome, atrial fibrillation with heart rate \>100 bpm at rest or severe cardiac valvular disease, history of medically significant arrhythmias);
• •19. unrecovered toxicity from prior antitumor therapy to CTCAE ≤ Grade 1 (NCI-CTCAE v5.0), except for baldness (any grade allowed) and peripheral neuropathy (recovery to ≤ Grade 2 required);
• •20. history of prior allogeneic bone marrow or organ transplantation;
• •21. prior history of allergic reaction, hypersensitivity reaction, intolerance to investigational drugs or similar medications; prior significant allergy to drugs or foods or other substances (e.g., severe allergic reaction, immune-mediated hepatotoxicity, immune-mediated thrombocytopenia, or anemia)
• •22. pregnant and/or lactating women;
• •23. other conditions that, in the opinion of the investigator, would affect the safety of or adherence to treatment with the study medication, including alcoholism, drug abuse, other serious illnesses (including psychiatric illnesses) that require comorbid treatment, the presence of serious laboratory test abnormalities, moderate to large amounts of plasmapheresis such as pleural fluid, pericardial effusion, ascites, and other concomitant familial or social factors, which would affect the safety of the patient;