This study is a single-arm, multi-center, multi-cohort, prospective clinical study initiated by the investigator.

The indication of this study is: patients with advanced metastatic pancreatic cancer who have progressed after first-line chemotherapy. Eligible patients will be assigned to liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/leucovorin (LV) (nal-IRI/5-FU/LV) combined with benmelstobart and anlotinib ± SBRT.

The total sample size for this study is expected to be 56 subjects.

For patients with advanced metastatic pancreatic cancer who failed first-line treatment, the screening and enrollment will be completed according to the enrollment and exclusion criteria described in the study protocol, and the informed consent form will be signed after full communication. After enrollment, patients will be treated with cohort A) or cohort B), and followed up regularly.

Cohort A: nal-IRI/5-FU/LV + PD-L1 inhibitor + multi-target anti-angiogenic small molecule:

Irinotecan liposome: 50mg/m2 IV D1, D15 LV: 400mg/m2 IV D1, D15 5-FU ：2.4g/m2 CIV 46h D1, D15 bemosubaemab: 1200mg IV Q3W Anlotinib: 12mg po D1-D14 Q3W

Cohort B: nal-IRI/5-FU/LV + PD-L1 inhibitor+ multi-target anti-angiogenic small molecule+SBRT Group:

Irinotecan liposomes: 50mg/m2 IV D1, D15 LV: 400mg/m2 IV D1, D15 5-FU ：2.4g/m2 CIV 46h D1, D15 bemosubaemab: 1200mg IV Q3W Anlotinib: 12mg po D1-D14 Q3W SBRT

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 75 years, ECOG score of ≤2 points, expected survival time ≥ 3 months.
2. Patients with histologically or cytologically confirmed advanced metastatic pancreatic cancer.
3. Imaging suggests distant measurable lesions.
4. Failure of first-line therapy and no use of fluorouracil, irinotecan, or liposomal irinotecan drugs in the first-line therapy.

Patients need to meet the following hematologic indicators e1. Neutrophil count ≥ 1.5×109/L e2. Hemoglobin ≥ 10 g/dL e3. Platelet count ≥ 100×109/L f. Patients need to meet the following biochemical parameters f1. Total bilirubin ≤ 1.5× upper limit of normal (ULN) f2. AST and ALT <1.5×ULN f3. Creatinine clearance ≥ 60ml/min g. Patients of childbearing age need to take appropriate protective measures (contraception or other methods of birth control) before enrollment and during the trial.

H. Has signed an informed consent form. i. Able to follow the study protocol and follow-up process.

Exclusion Criteria:

1. Have received second-line or more anti-tumor therapy in the past.
2. First-line treatment with fluorouracil, irinotecan or liposomal irinotecan, etc.
3. Patient has a prior history of other tumors, unless it is cervical cancer in situ, treated squamous cell carcinoma or bladder epithelial tumors (Ta and TIS) or other malignancies that have received curative therapy (at least more than 5 years prior to enrollment).
4. Patient has an active bacterial or fungal infection (≥ 3rd edition NCI-CTC2 grade).

Patient has HIV, HCV, HBV infection, uncontrolled coronary artery disease or asthma, uncontrolled cerebrovascular disease or other disease deemed non-enrollable by the investigator.

f. Patients with autoimmune diseases or immunodeficiencies who should be treated with immunosuppressive drugs.

g. Pregnant and lactating women. Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.

h. Substance abuse, clinical or psychological, or social factors that compromise informed consent or study conduct.

i. Those who may be allergic to treatment drugs.