This is a phase Ib, open-label study to evaluate safety and efficacy of NRT6008 in combination with standard-of-care chemotherapy in patients with unresectable Locally Advanced Pancreatic Carcinoma (LAPC).

The efficacy and safety of Yttrium-90 carbon microspheres in patientswith unresectable LAPC remain unknown. This trial is a prospective, multicenter,open-label, single-arm phase I trial designed to evaluate the safety and efficacyof NRT6008 injection.The primary objective is to evaluate the safety of NRT6008 Injection. While the secondary objectives include the assessments of the preliminary efficacy. In addition, the changes of tumor biomarkers and the improvement of cancer pain status of participants after administration will also be evaluated.

Inclusion Criteria:

1. Aged ≥18 and ≤85 years of age and able to understand and sign the informed consent form (ICF).

2. Histopathological or cytologically confirmed diagnosis of ductal adenocarcinoma of the pancreas.

3. Deemed by the Investigator to have unresectable locally advanced pancreatic cancer.

4. Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1.

5. Life expectancy of at least 3 months in the opinion of the Investigator.

6. Must have only one measurable target radiologically confirmed lesion in the pancreas according to RECIST 1.1, with the longest diameter of ≤ 6 cm and the shortest diameter of ≥ 2 cm (based on baseline imaging).

7. Adequate organ and marrow function as defined by the following criteria:

   1. Renal function: Blood creatinine ≤ 1.5 × the upper limit of normal (ULN), or eGFR ≥ 60 mL/min [by a clinically validated calculator such as Modification of diet in renal disease (MDRD) formula];

   2. Liver function: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3×ULN; serum total bilirubin ≤ 1.5×ULN*

      *For study participants with recent biliary obstruction treated by drainage (e.g. stent), serum total bilirubin of > 1.5×ULN will be accepted for study entry provided that serial levels demonstrate clear improvement. In addition, chemotherapy should not be commenced until serum bilirubin is ≤ 1.5×ULN.

   3. Bone marrow function (without transfusion or treatment with granulocyte-colony stimulating factor (G-CSF), human thrombopoietin (TPO), or TPO receptor agonists (TPO-RAs) within 14 days before signing the ICF: Neutrophil count ≥ 1.5×10^9/L, haemoglobin ≥ 90 g/L, platelets≥ 100×10^9/L;

   4. Coagulation function: International normalised ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.

8. Women of childbearing potential (WOCBP) must have a negative serum beta-human chorionic gonadotropin (β-hCG) test and must not be breastfeeding. WOCBP are defined as those who are not surgically sterile or post-menopausal. Female participants will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause.

9. WOCBP and male participants must agree to use a highly effective method of contraception after signing the ICF, during the study, and for 12 months after administration of NRT6008.

10. Male participants who are able to father a child must agree to avoid impregnating a partner and to adhere to a highly effective method of contraception during the study and for 12 months after the administration of NRT6008. All male participants must agree to not donate sperm during the study and for at least 12 months after NRT6008 administration.

Exclusion Criteria:

1. Allergic to the investigational device NRT6008 Injection or any of its components.
2. Participants who are deemed by the Investigator to be clinically inappropriate for treatment with either standard-of-care chemotherapy regimen (Regimen group A or Regimen group B).
3. Prior anti-tumour therapy for pancreatic carcinoma, including but not limited to chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.
4. Contraindications to anaesthesia.
5. Participants who have any other known, active malignancy, except for treated cervical intraepithelial neoplasia, or nonmelanoma skin cancer in the past 5 years. Participants with a history of malignancies of low recurrence potential who have received curative-intent therapy may be approved on a case-by-case basis in discussion with the study Sponsor, if it is determined not to put the participant at an increased risk of adverse device effects and/or interfere with the integrity of study outcome.
6. Presence or suspicion of distant metastasis, including non-regional lymph nodes, on imaging.
7. Pregnant or lactating women.
8. The participant is considered by the Investigator to be at an unacceptably high risk for the EUS-FNI procedure, or the procedure is deemed technically infeasible based on clinical judgment.
9. Radiation injury to the stomach, duodenum, or peritoneum, and/or other conditions that put the participant at an increased risk of intervention-related toxicities such as certain types of prior abdominal surgery that significantly alters the upper abdomen anatomy, by Investigator judgment.
10. Presence of uncontrolled or unstable chronic medical conditions despite appropriate treatment (e.g., hypertension, diabetes mellitus), or any medical condition that, in the Investigator's judgment, would compromise participant safety or study participation, or interfere with the integrity of study outcomes.
11. History of acute pancreatitis, severe gastrointestinal haemorrhage, a severe cardio- or cerebrovascular event (including but not limited to stroke, unstable angina pectoris) within 6 months before the first dose of chemotherapy regimen, or presence of an active infection requiring systemic treatment within 2 weeks prior to first dose of chemotherapy regimen.
12. Participation in any other clinical study within 1 month before the first dose of the chemotherapy regimen.
13. Positive status for human immunodeficiency virus (HIV).
14. For participants positive for HBsAg and/or HBcAb, hepatitis B virus (HBV) DNA must be undetectable or <500 IU/mL to be eligible. Antiviral therapy must be maintained throughout the study period, where clinically applicable.
15. Participants who are positive for hepatitis C virus (HCV) antibody must have undetectable HCV RNA to be eligible for enrolment.
16. Patients with syphilis infection or active tuberculosis.
17. Any medical condition which, in the opinion of the Investigator, places the participant at an unacceptable high risk for toxicities or limit participant ability to complete study procedure(s).