AG Followed by FOLFIRINOX Both Combined With PD-L1 Antibodies as a Conversion Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer.

Pancreatic cancer originating from non-pancreatic ductal epithelium, including pancreatic neuroendocrine carcinoma, pancreatic acinar cell carcinoma, pancreatic blastoma, solid-pseudopapillary tumors patients

Patients with known central nervous system metastasis

Severe gastrointestinal dysfunction (with bleeding, obstruction; grade 2 or higher inflammation; grade 1 or higher diarrhea)

Randomly within the previous 2 weeks, there was third-space effusion (such as large pleural effusion) that could not reach a stable state (after removing the drainage tube, no intervention treatment was required)

Abdominal effusion with clinical symptoms, requiring puncture and drainage, or patients who had undergone abdominal effusion drainage within 3 months previously (excluding those with only imaging showing a small amount of abdominal effusion and controllable, but without clinical symptoms)

Currently accompanied by interstitial pneumonia or interstitial lung disease, or having a history of interstitial pneumonia or interstitial lung disease requiring hormone treatment previously, or other possible pulmonary fibrosis, organizing pneumonia (such as obliterative bronchiolitis), pneumoconiosis, drug-related pneumonia, idiopathic pneumonia or in the screening period, chest CT showing active pneumonia or severely impaired lung function subjects; active tuberculosis

Presence of active autoimmune disease or having a history of autoimmune disease that may recur \[including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism (only subjects with controlled hormone replacement therapy can be enrolled)\], having a skin disease that does not require systemic treatment such as vitiligo, psoriasis, alopecia, receiving insulin treatment for controlled type 1 diabetes or having completely resolved childhood asthma and no need for any intervention after adulthood, eligible for enrollment

Known peripheral neuropathy (CTCAE ≥ 3 grade)

Known dihydroorotate dehydrogenase (low activity) or deficiency

Randomly within the previous 2 weeks, had severe infection (CTCAE \> 2 grade), such as severe pneumonia requiring hospitalization, sepsis, infection complications, etc.; randomly within the previous 2 weeks, had symptoms and signs of infection requiring intravenous antibiotic treatment (except for prophylactic use of antibiotics)

Had received any of the following treatments:

1. Randomly within the previous 2 weeks, the medication used included strong inhibitors/inducers of CYP3A4, CYP2C8 or strong inhibitors of UGT1A1;

2. Randomly within the previous 2 weeks, received immunosuppressants or systemic hormone treatment to achieve immunosuppression purposes (dose \> 10mg/day prednisone or other equivalent efficacy hormones);

3. Randomly within the previous 2 weeks, received radiotherapy;

4. Randomly within the previous 4 weeks, underwent major surgery (such as thoracotomy, laparotomy, etc.);

5. Randomly within the previous 4 weeks, received any other clinical research drug treatment, unless it is an observational (non-interventional) clinical study or follow-up of an interventional clinical study.

Abnormal coagulation function, with bleeding tendency or undergoing thrombolysis or anticoagulation treatment. Allowed to use preventive low-dose aspirin (≤100mg/day) or low-molecular-weight heparin (enoxaparin 40mg/day and other low-molecular-weight heparins at equivalent doses)

Had poor control of clinical symptoms or diseases of the heart, such as: (1) NYHA grade 2 or above heart failure; (2) unstable angina pectoris; (3) having had a myocardial infarction within 6 months; (4) having clinical significance of supraventricular or ventricular arrhythmias and requiring treatment or intervention

Randomly within the previous 5 years had malignant tumors other than pancreatic cancer, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell carcinoma of the skin

Those who are known to be allergic to PD-L1, gemcitabine, albumin paclitaxel, gemcitabine, albumin paclitaxel, irinotecan liposome, other liposome products, oxaliplatin, 5-FU, folic acid calcium, or any of the components in the above products

Those who are known to have acquired immunodeficiency syndrome (AIDS) or have tested positive for HIV, or active syphilis patients

Those who have a clear history of neurological or mental disorders, including epilepsy or dementia

Based on the investigator's judgment, the subjects have other factors that may cause them to be forced to terminate the study prematurely, such as non-compliance with the protocol, having other serious diseases (including mental disorders) that require combined treatment, having severely abnormal laboratory test values with clinical significance, family or social factors, and situations that may affect the safety of the subjects or the collection of trial data.

What this study is about