MesoPher/Mitazalimab-combination Therapy in Metastatic Pancreatic Disease (REACtiVe-2 Trial)

Inclusion Criteria:

* Metastatic pancreatic cancer as defined by the presence of radiologically suspect metastatic lesions.
* Inclusion ≤ 4 weeks after stopping FOLFIRINOX chemotherapy.
* No more than 1 line of chemotherapy for metastatic disease is allowed. Prior FOLFIRINOX for locally advanced disease if given within 1 year before screening will be counted as first-line treatment. Any FOLFIRINOX given in the curative intent setting if more than a year before screening will not be considered first line therapy.
* An accessible metastatic lesion for histological tissue collection.
* Patients must be at least 18 years old and must be able to give written informed consent.
* WHO performance status 0-1.
* Patients must have normal organ function and adequate bone marrow reserve: absolute neutrophil count \> 1.0 x 109/l, platelet count \> 100 x 109/l, and Hb \> 6.0 mmol/l (as determined during screening). Transfusion in the 2 weeks preceding screening is not allowed.
* Laboratory tests: ASAT/ALAT \<5xULN (upper limit of normal), bilirubine \<1.5xULN, Creatinine value \<1.5xULN, Lactate dehydrogenase value \< ULN and albumin value \> LLN (lower limit of normal).
* Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test just prior to the first study drug administration on Day 1, and must be willing to use an effective contraceptive method (intrauterine devices, hormonal contraceptives, contraceptive pill, implants, transdermal patches, hormonal vaginal devices, infusions with prolonged release) or true abstinence (when this is in line with the preferred and usual lifestyle)\* during the study and for at least 12 months after the last study drug administration.

  \*True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (such as calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
* Men must be willing to use an effective contraceptive method (e.g. condom, vasectomy) during the study and for at least 12 months after the last study drug administration.
* Ability to return to the hospital for adequate follow-up as required by this protocol.
* Written informed consent according to ICH-GCP.

Exclusion Criteria:

* Medical or psychological impediment to probable compliance with the protocol.
* Abdominal ascites.
* Current or previous use of a CD40 antibody and/or anti-tumor vaccinations.
* Current use of steroids (or other immunosuppressive agents). Patients must have had 6 weeks of discontinuation and must stop any such treatment during the time of the study. Prophylactic usage of dexamethasone during chemotherapy is excluded from this 6 weeks interval.
* Prior malignancy except adequately treated basal cell or squamous cell skin cancer, superficial or in-situ cancer of the bladder or other cancer for which the patient has undergone curative intent treatment and has been disease-free for two years.
* Serious concomitant disease, or active infections.
* History of autoimmune disease, organ allografts or active acute or chronic infection, including but not limited to HIV and viral hepatitis.
* Serious intercurrent chronic or acute illness such as pulmonary disease (asthma or COPD), cardiac disease (NYHA class III or IV), hepatic disease or other illness considered by the study coordinator to constitute an unwarranted high risk for the investigational treatment.
* Known allergy to shell fish (may contain keyhole limpet hemocyanin (KLH)).
* Pregnant or lactating women.
* Inadequate vein access to perform leukapheresis.
* Concomitant participation in another clinical intervention trial (except participation in a biobank study).
* An organic brain syndrome or other significant psychiatric abnormality which would compromise the ability to give informed consent, and preclude participation in the full protocol and follow-up.