Endoscopic Ultrasound Radiofrequency Ablation and Immunotherapy Pembrolizumab for Locally Advanced Unresectable and Metastatic Pancreatic Duct Adenocarcinoma

The purpose of this study is to perform a pilot phase II trial to evaluate the safety and efficacy of combined EUS-RFA, chemotherapy, and systemic immunotherapy (pembrolizumab) for the treatment of locally advanced unresectable and metastatic Pancreatic ductal adenocarcinoma (mPDAC).

Inclusion Criteria: * 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 1. Patients who have undergone prior resection will be excluded unless there is recurrent pancreatic tumor that is amenable to EUS-RFA. 2. 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: 1. 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). 2. 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 clinically stable disease (defined as no evidence of clinical progression) 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 \