Safety and Efficacy of NRT6008 in Patients with Unresectable Locally Advanced Pancreatic Cancer (LAPC)

Inclusion Criteria:

1. Aged ≥18 years and ≤80 years, able to comprehend and sign an informed consent form;

2. Diagnosed with pancreatic adenocarcinoma confirmed histologically or cytologically;

3. Evaluated as unresectable LAPC by the investigator, or having contraindications tosurgery, or refusing surgical resection (only patients with non-regional lymph nodemetastasis are eligible);

4. ECOG performance status score ≤1;

5. Expected survival ≥3 months;

6. According to RECIST v1.1 criteria, there is only one measurable lesion in thepancreas confirmed by imaging, and the lesion has the shortest axis diameter ≥2.0cm, the longest axis diameter ≤6.0 cm (based on baseline imaging);

7. Adequate normal organ and marrow function as defined below: (1) Renal function:serum creatinine ≤1.5×ULN, or creatinine clearance ≥60 mL/min (calculated by theCockcroft-Gault formula); (2) Liver function: aspartate aminotransferase (AST) oralanine aminotransferase (ALT) ≤3×ULN; serum total bilirubin ≤1.5×ULN; (3) Bonemarrow function [[no blood transfusion or granulocyte colony-stimulating factor (G-CSF), human thrombopoietin (TPO), or TPO receptor agonist treatment within 14days prior to signing informed consent]: neutrophils ≥1.5×10^9/L, hemoglobin ≥90g/L, platelets ≥100×10^9/L; (4) Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN, and activated partial thromboplastin time (APTT) ≤1.5×ULN;

8. Female and male participants of reproductive age must voluntarily agree to practicestrict and effective contraception after signing the informed consent form, duringthe study period, and within 12 months after administration of the investigationaldrug. Males are prohibited from donating sperm during this period. Femaleparticipants of reproductive age must have a negative pregnancy test result duringthe screening period and within 24 hours before administration of theinvestigational drug.

Exclusion Criteria:

1. Allergic to the investigational drug NRT6008 injection itself or any of itscomponents;

2. Contraindications to any of the three optional systemic chemotherapy regimens inthis study judged by investigators;

3. Previous anti-tumor treatments for pancreatic cancer, including but not limited tochemotherapy, radiotherapy, targeted therapy, immunotherapy, etc. Except fordiscontinuation of traditional chinese medicine or herbal medicine for at least 7days prior to the screening period;

4. Contraindications to anesthesia;

5. History of any other malignant tumors within 5 years before receivinginvestigational drug treatment, except for cases of cured non-melanoma skin cancer,cervical carcinoma in situ, or basal cell carcinoma of the skin, Stage I Grade 1endometrial carcinoma, or thyroid cancer;

6. Presence or suspected presence of distant metastases according to imaging;

7. Pregnant or lactating females;

8. Participants assessed by the investigators to be at high risk or had difficulty inoperation for EUS-FNI procedures;

9. Evidence of radiographic invasion into stomach, duodenum or peritoneum;

10. Participants with chronic diseases that are actively treated but not wellcontrolled, such as primary hypertension, diabetes, etc.;

11. Within 6 months prior to the the first administration of chemotherapy, occurrence ofacute pancreatitis, severe gastrointestinal bleeding, severe cardiovascular diseases (including but not limited to stroke, unstable angina), or occurrence of acuteinfections requiring systemic treatment within 2 weeks before the screening period;

12. Participated in other interventional clinical trials within 1 month prior to thefirst administration of chemotherapy;

13. Positive for human immunodeficiency virus (HIV) antibodies;

14. Positive for hepatitis B virus (HBV) surface antigen (HBsAg) and/or hepatitis B coreantibody (HBcAb), HBV DNA testing required, participants with HBV-DNA levels belowthe lower limit of the reference range or < 500 IU/mL will be eligible for inclusionin this study (use of antiviral drugs during the study period is required);

15. Positive for hepatitis C virus (HCV) antibodies, HCV RNA testing required,participants with negative HCV RNA results will be eligible for inclusion in thisstudy;

16. Participants with syphilis infection or active tuberculosis;

17. Other reasons deemed unsuitable for participation in this trial by theinvestigators.