Combining anti-PD-L1 immune checkpoint inhibitor durvalumab with TLR-3 agonist rintatolimod in patients with metastatic pancreatic ductal adenocarcinoma for therapy efficacy. DURIPANC Study

Phase 1

Recruiting

Conditions: Metastatic pancreatic cancer
MedDRA version: 27.0Level: LLTClassification code: 10033605Term: Pancreatic cancer metastatic Class: 10029104
Therapeutic area: Diseases [C] - Neoplasms [C04]
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: CTIS2024-514597-42-00

Lead Sponsor: Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 43

Inclusion Criteria

Histologically or cytologically (Bethesda 5 or 6) confirmed metastatic pancreatic cancer, as indicated by a definite cytology/histology report., 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., 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.

Exclusion Criteria

Child-Pugh Classification grade B/C., Prior randomisation 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 (non-interventional) 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. oPatients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. oPatients 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., Current treatment with immunotherapeutic drugs., 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., 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 infe