PANFIRE-3 Trial: Assessing Safety and Efficacy of Irreversible Electroporation (IRE) + Nivolumab + CpG for Metastatic Pancreatic Cancer

Inclusion Criteria:

* Radiological and histopathologically proven stage IV pancreatic cancer (according to the AJCC staging system for pancreatic cancer);
* Primary oligometastatic disease, defined as at least 1 hepatic metastasis but occurrence of other metastases is not necessarily restricted to the liver, maximum of metastases is to be determined on a case by case basis by the multidisciplinary tumor board.
* Primary tumor is in situ.
* A minimum of 4 cycles of FOLFIRINOX chemotherapy is required but with the explicit aim to strive for completion of 8 cycles of FOLFIRINOX before study inclusion, with at least stable disease on CTscan.
* Age ≥ 18 years.
* World Health Organisation scale (WHO) performance status 0 - 2;
* Adequate bile drainage in case of biliary obstruction.

Exclusion Criteria:

* Trans-mucosal tumor invasion into surrounding duodenum or stomach;
* Active epilepsy (last convulsion \< 5 years);
* History of cardiac disease:

  * Congestive heart failure \> NYHA Class 2
  * Active coronary artery disease (defined as myocardial infarction within 6 months prior to screening);
  * Ventricular cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker (beta blockers for antihypertensive regimen are permitted; atrial fibrillation is not contra-indicated);
* Known hypersensitivity to any oligodeoxynucleotides.
* Compromised liver function defined as warning signs of portal hypertension, INR \> 1,5 without use of anticoagulants, bilirubin \> x 1.5 Upper limit of normal range (ULN) ASAT \>3.0 x ULN, ALAT \>3.0 x ULN.
* Compromised kidney function defined as eGFR \<30 ml/min (using the Cockcroft Gault formula);
* Active autoimmune disease requiring disease-modifying therapy at the time of screening: i.e. \> 10 mg prednisolone per day or equivalent to this regimen.
* Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen;
* Uncontrolled infections (\> grade 2 NCI-CTC version 3.0); requiring antibiotics
* Pregnant or breast-feeding subjects; Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment;
* Immunotherapy prior to the procedure for the treatment of cancer;
* Previous surgical therapy for pancreatic cancer;
* Second primary malignancy with median 5 year OS \< 90%, this excludes adequately treated cancers like: non-melanoma skin cancer, in situ carcinoma of the cervix uteri, superficial bladder cancer or other malignancies treated previously without signs of recurrence.
* Allergy to contrast agent.
* Allergy to PET tracers 18F-FDG and 18F-BMS-986192 Zr-89-Nivolumab
* Any implanted stimulation device;
* Portal vein or VMS stenosis \> 70% (relative contra-indication)
* Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study.