Combining Anti-PD-L1 Immune Checkpoint Inhibitor Durvalumab With TLR-3 Agonist Rintatolimod in Patients With Metastatic Pancreatic Ductal Adenocarcinoma for Therapy Efficacy

Inclusion Criteria: * Histologically or cytologically (Bethesda 5 or 6) confirmed metastatic pancreatic cancer, as indicated by a definite cytology/histology report. * Stable disease according to RECIST criteria version 1.1 after at least 8 cycles of chemotherapy (FOLFIRINOX). * Inclusion ≤ 6 weeks after stopping FOLFIRINOX. * An accessible metastatic lesion for histological tissue collection. * SIII\<900 (Systemic Immune-Inflammation Index = ((absolute neutrophil count \* platelet count) / absolute lymphocyte count)). * CA 19.9 \<1000kU/L. * Age ≥ 18 years at time of study entry. * Body weight \>30 kg. * WHO performance status of 0-1. * Adequate renal function (eGFR \> 40 ml/min). * Adequate liver tests (bilirubin ≤ 1.5 times normal; ALAT/ASAT ≤ 5 times normal). * Adequate bone marrow function (WBC \> 3.0 x 109/L, platelets \> 75 x 109/L, absolute neutrophil count (ANC) ≥1.0 × 109 /L and hemoglobin \> 5.6 mmol/L. * Effective contraceptive methods. * Patient must have a life expectancy of at least 12 weeks. * Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., European Union Data Privacy Directive) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. Exclusion Criteria: * Child-Pugh Classification grade B/C. * Current treatment with immunotherapeutic drugs. * Previous malignancy (excluding non-melanoma skin cancer, pancreatic neuroendocrine tumor (pNET) \<2cm, and gastrointestinal stromal tumor (GIST) \<2cm), unless no evidence of disease and diagnosed more than 3 years before diagnosis of pancreatic cancer, or with a life expectancy of more than 5 years from date of inclusion. * Malignant ascites or pleural effusion. * Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy. * Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. * An active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or other immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion: A. Patients with vitiligo or alopecia; B. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; C. Any chronic skin condition that does not require systemic therapy; D. Patients without active disease in the last 5 years may be included but only after consultation with the study physician; E. Patients with celiac disease controlled by diet alone. * Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the planned first dose of the study. The following are exceptions to this criterion: 1) Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), 2) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent and 3) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). * Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP. * Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment. * Participation in another clinical study with an investigational product during the last 3 months. * Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study. * Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤28 days prior to the first dose of study drug If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca and the investigator. * Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. * Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. * Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician. * Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. * Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. * Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. * History of allogenic organ transplantation. * Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. * History of leptomeningeal carcinomatosis. * Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry to rule out the presence of brain metastasis. * Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart). * Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Adjust wording as necessary and consider evaluating at screening for studies with known hepatotoxicity or other relevant requirements. * Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice). * Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator.