Immunotherapy and Irreversible Electroporation (IRE) in the Treatment of Locally Advanced Pancreatic Adenocarcinoma

Inclusion Criteria:

• Age ≥ 18 years at time of signing Informed consent Form

• Diagnosed with clinical stage III pancreatic cancer (per National Comprehensive Cancer Network [NCCN] guidelines)

• Has undergone standard of care (per NCCN guidelines) neoadjuvant/induction base chemotherapy for at least 2 months in duration and demonstrated stable or responsive disease, and completed a wash-out period of at least 21 days prior to study treatment

• Pancreatic tumor is measurable (bi-dimensional tumor measurements per 3-phase CT scan). If preoperative CT cannot provide 2-dimensional size criteria, then intra-operative ultrasound will be used for baseline size criteria

• Is a candidate for irreversible electroporation

• Able to tolerate surgery

• Glomerular filtration rate > 30 mL/min/1.73 m2

• Aspartate aminotransferase/Alanine aminotransferase < 3 times the upper limit of normal (ULN) and total bilirubin < 1.5 ULN

• Absolute neutrophil count ≥1.5 × 10⁹/L, platelet count ≥ 100 × 10⁹/L, and hemoglobin ≥ 9 g/dL

• Stable surgical post-operative course as defined by the operative surgeon (Eastern Cooperative Oncology Group [ECOG]) of 0 or 1

• Women of childbearing potential

  1. Must have a negative serum human chorionic gonadotropin pregnancy test prior to irreversible electroporation
  2. Are using highly effective contraception, are not lactating, and agree not to become pregnant prior to and during the trial treatment period and for 187 days after treatment with the investigational drug

• Men agree not to donate sperm or to father a child during the trial treatment period and for 97 days after treatment with the investigational drug

• Participants on therapeutic anticoagulation are eligible if therapy can be safely held or bridged to achieve an INR < 1.5 per institutional guidelines

• Adverse events from prior therapy must be resolved to Grade ≤ 1 severity.

• Able to comprehend and have signed the Informed Consent Form to participate in the study

Exclusion Criteria:

• Known allergic reaction to shellfish, crabs, crustaceans, or any trial components
• Participating in another clinical trial for the treatment of pancreatic cancer at the time of screening
• Are pregnant or currently breastfeeding
• New York Heart Association Class III or IV heart disease
• Inability to discontinue medications known to prolong the QT interval or induce Torsades de Pointes before study entry, with drug-specific discontinuation timing documented
• Uncontrolled infection requiring antibiotic therapy
• Contraindication to heparin
• Major surgery within 14 days of enrollment
• Prior high dose radiation therapy defined as total dose of > 5400 cGy
• Have a cardiac pacemaker or ICD implanted that cannot be deactivated during IRE procedure
• Clinically significant history of epilepsy or cardiac arrhythmia
• Have nonremovable implants with metal parts within 1cm of the target lesion
• Had a myocardial infarction within 3 months prior to enrollment (informed consent date)
• Actively bleeding, anticoagulated, or have a known or suspected coagulopathy which has not been corrected
• Autoimmune disease and/or medical condition requiring systemic treatment with corticosteroids that cannot be stopped during treatment