Experimental combo therapy targets Hard-to-Treat pancreatic cancer

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study * Histologically/cytologically-confirmed pancreatic ductal adenocarcinoma (PDAC) * Persons, aged \> 18 years of age, as PDAC is extremely rare in pediatric populations. * Locally advanced disease that is not amenable to surgical resection. Locally advanced PDAC cases will be identified per the definition developed by the Alliance for Clinical Trials in Oncology\[53\]. Per this definition, locally advanced PDAC is defined as presence of any one or more of the following on CT: * Occlusion of the superior mesenteric vein (SMV) and/or portal vein (PV) that is not amenable to resection and venous reconstruction * Interface between tumor and hepatic artery that is not amenable to resection and reconstruction * Interface between the tumor and superior mesenteric artery (SMA) measuring \> 180º of the circumference of the vessel wall * Interface between the tumor and celiac axis measuring \> 180º of the circumference of the vessel wall that is not amenable to resection * ECOG Performance Status of 0-2 * Have adequate organ function per criteria below: * Absolute neutrophil count (ANC) ≥ 1.5x109/L * Platelets ≥ 100x109/L * Hemoglobin ≥9 g/dL * Serum creatinine ≤1.5 x ULN OR creatinine clearance ≥40 mL/min (as calculated by Modified Cockcroft-Gault formula) * Serum total bilirubin ≤ 1.5 X ULN * AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN * A minimum of 4 months of one of the chemotherapy regimens preferred by the NCCN for good performance status patients (currently modified FOLFIRINOX, gemcitabine + albumin-bound paclitaxel, or NALIRIFOX) * High quality imaging triphasic CT scan contrast-enhanced dynamic MRI of abdomen and either contrast-enhanced or non-contrast CT of chest and pelvis that demonstrate no evidence of metastatic disease within 30 days of enrollment * FDG-PET imaging (skullbase-midthigh) at any timepoint between diagnosis and study intervention to determine whether tumor is PET-avid and evaluate for extra-pancreatic metastatic disease, as suggested by NCCN guidelines for high-risk patients. * Tumor amenable to "in situ" (complete) ablation with maximum primary tumor dimension \< 4.0 cm * For participants able to become pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method until the study intervention and for an additional 1 month after the study intervention. * For participants able to cause a pregnancy: use of condoms or other methods to ensure effective contraception with partner for 1 month after study intervention. Exclusion Criteria: * Pregnancy or lactation * Known allergic reactions to components of the mitazalimab solution (L-Histidine, trehalose, or polysorbate 20) * Fever \> 38 degrees C within 14 days of study intervention * Treatment with another investigational drug or other intervention within 30 days of enrollment * Prior treatment with a CD40 antibody * History of severe auto-immune disease * The presence of metal fiducials or embolization coils within the tumor. * Prior receipt of radiation therapy to the pancreas * The presence of implanted metallic cardiac stimulation devices within the chest * Uncontrolled cardiac arrhythmias that prevent synchronization of pulse delivery with the refractory period of the cardiac cycle * Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed topical corticosteroids (doses \> 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks (14 days) before study treatment administration. Physiologic doses of corticosteroids (≤ 10 mg/day of prednisone or its equivalent) or short pulses of corticosteroids (≤ 3 days) may be permitted. * Any medical condition that precludes major abdominal surgery under general anesthesia * Presence of distant metastatic disease (including positive peritoneal cytology) on staging laparoscopy and/or exploratory laparotomy at any timepoint.