This is a prospective, multicenter, single arm clinical study. The main purpose of the study is to evaluate the clinical efficacy and safety of SBRT combined with Nimotuzumab and mono-chemotherapy in the treatment of locally advanced pancreatic cancer (LAPC).

This clinical study is designed as a prospective, multicenter, single arm study to evaluate the clinical efficacy and safety of SBRT combined with nimotuzumab and mono-chemotherapy in the treatment of locally advanced pancreatic cancer (LAPC). All eligible patients will receive SBRT with doses ranging from 35-40 Gy in five fractions, intravenous nimotuzumab 400mg weekly or 600mg on day 1 and 8 of a 21-day cycle, and mono-chemotherapy (Gemcitabine, S-1 or capecitabine) until disease progression, death, unacceptable toxicity, or consent withdrawal. The main endpoint is progression-free survival (PFS).

Inclusion Criteria:

• 1. Age 18-75 years old, gender unlimited;
• 2. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC);
• 3. Locally advanced pancreatic cancer (according to the NCCN criteria), unresectable or surgically declined;
• 4. The maximum diameter of the primary tumor was < 5.0cm;
• 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• 6. No prior radiotherapy (upper abdomen) or tumor systemic therapy;
• 7. Adequate organ and bone marrow function, defined as follows: absolute neutrophil count (ANC)≥1.5×10^9/L; hemoglobin≥9.0 g/dL; platelets≥75×10^9/L; serum total bilirubin (TBIL)≤1.5×ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN); serum creatinine≤1.5×ULN;
• 8. Left ventricular ejection fraction ≥50%;
• 9. Fertile subjects are willing to take contraceptive measures during the study period;
• 10. Woman who are breastfeeding during the study period or within 150 days after the last treatment;
• 11. Survival was expected to be ≥3 months;
• 12.Good compliance and signed informed consent voluntarily.

Exclusion Criteria:

• 1. Tumor invasion of gastrointestinal tract;
• 2. Woman who are pregnant or breastfeeding;
• 3. History of other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) within the past 5 years;
• 4. History of uncontrolled epilepsy, central nervous system disease, or mental disorder, which may influence the signing of informed consent or affect the patient's adherence;
• 5.Serious heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) class II or more, severe congestive heart failure or severe arrhythmia requiring medical intervention, or a history of myocardial infarction within the past 12 months;
• 6. Patients requiring immunosuppressive;
• 7.Accompanied by active infections, or a major hematological, renal, metabolic, gastrointestinal, endocrine, or metabolic disorder determined by the investigator, or other serious uncontrolled concomitant disease;
• 8. Known allergy to prescription or any component of the prescription used in this study;
• 9. Immunodeficiency, including HIV infection or other acquired immunodeficiency, or a history of organ transplantation, or other immune-related disorders requiring medical intervention;
• 10. Patients with acute and chronic tuberculosis infection;
• 11. Received Chinese herbal medicines or immune-modulators for anti-tumor within 2 weeks prior to initial administration;
• 12.History of noninfectious pneumonia requiring glucocorticoid therapy or current interstitial lung disease within 1 year prior to initial administration;
• 13. Received any other form of immunosuppressive therapy within 7 days prior to the initial of study administration;
• 14. Participated in other clinical trials within 4 weeks, or received another investigational drugs or investigational device within 4 weeks prior to the initial administration;
• 15.Other reasons that are not suitable to participate in this study according to the researcher's judgment.