Intra-Tumoral Mitazalimab with Irreversible Electroporation for the Treatment of Locally Advanced Pancreas Cancer

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. Multiple guidelines defining locally advanced PDAC have been developed, including the MD Anderson definition, the National Comprehensive Cancer Network (NCCN) definition, as well as the criteria developed during the Consensus Conference sponsored by the American Hepato-Pancreato-Biliary Association, Society of Surgical Oncology, and Society for Surgery of the Alimentary Tract. Locally advanced PDAC cases will be identified per the definition developed by the Alliance for Clinical Trials in Oncology. 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
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Absolute neutrophil count (ANC) ≥ 5 x 10^9/L
• Platelets ≥ 100 x 10^9/L
• Hemoglobin ≥ 9 g/dL
• Serum creatinine (sCr) ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (Ccr) ≥ 40 mL/min (as calculated by modified Cockcroft-Gault formula)
• Serum total bilirubin ≤ 1.5 x ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x ULN
• A minimum of 4 months of fluorouracil, irinotecan, leucovorin calcium, oxaliplatin (FOLFIRINOX)-based systemic chemotherapy
• High quality imaging triphasic CT scan contrast-enhanced dynamic magnetic resonance imaging (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. If tumor is not PET-avid on pre-chemotherapy PET imaging, no further PET imaging is recommended. If tumor is PET-avid on pre-chemotherapy imaging (or no PET imaging was performed prior to chemotherapy), post-treatment surveillance imaging should ideally include PET imaging
• Tumor amenable to “in situ” (complete) ablation with maximum primary tumor dimension ≤ 4.0 cm to align with current practices
• 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°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