• Is willing and able to comply with the protocol for the duration of the study,including undergoing treatment and scheduled visits and examinations, including follow-up

• Biopsy-proven locally advanced unresectable or metastatic PDAC

‣ Patients who have undergone prior resection will be excluded unless there is recurrent pancreatic tumor that is amenable to EUS-RFA.

⁃ If biliary metal stent is placed, during procedure of EUS-RFA, indwelling biliary metal stent will be removed during initial EUS-RFA and then replaced with plastic stent.

• Mental capacity to provide informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

• Eastern Cooperative Oncology Group (ECOG) Performance status 0-2

• At least one measurable metastatic lesion on axial imaging per Response Evaluation Criteria in Solid Tumors (RECIST) v1.

• No prior systemic therapy, including chemotherapy or chemoradiation is permitted with the following exceptions:

‣ Prior adjuvant therapy (including chemotherapy and/or radiotherapy) for pancreatic adenocarcinoma is permitted if standard of care neoadjuvant or adjuvant therapy was completed at least 3 months prior to study enrollment. Prior adjuvant therapy may include mFFX, NALIRIFOX, GA or Capecitabine (Xeloda).

⁃ If started on first-line treatment for mPDAC elsewhere (i.e., not at our study site), eligible participants can have undergone 3 months of chemotherapy with stable disease before study entry. Note: Imaging done outside the site will need to be reviewed for a 2nd opinion to confirm stable disease.

• i. For patients who had prior treatment and stable disease up to 3 months and confirmed radiographically by our radiology investigators, then patients can proceed with EUS-RFA within 6-8 weeks of enrollment of study.

• c. Patients who have started chemotherapy within a 3-month timeframe are allowed.

• Absolute neutrophil count (ANC) ≥1 x 109/L

• Platelet count ≥75 x 109/L

• Albumin levels ≥3 g/dL

• Total serum bilirubin \<2× upper limit of normal (ULN) unless secondary to Gilbert's Syndrome

• a. Subjects requiring biliary decompression, biliary stent, or drainage using percutaneous trans-hepatic cholangiogram are allowed (patients with a declining bilirubin status post stent placement are eligible with serum bilirubin ≤2.5 x ULN)

• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤3× ULN, or ≤5× ULN in cases of documented liver involvement

• Serum creatinine clearance must be ≥30 mL/minute either measured or calculated using a standard Cockcroft and Gault formula

• Prior surgery that required general anesthesia or other major surgery as defined by the Investigator must be completed at least 4 weeks before immunotherapy.