A Study of More Frequent Dosing of VCN-01 Combined With Standard Chemotherapy in Patients With Newly Diagnosed Metastatic Pancreatic Cancer

Inclusion criteria

• Written informed consent obtained prior to initiating any trial-specific procedures or assessments.
• Male or female patients aged 18 years or over.
• Patients with histologically or cytologically confirmed pancreatic adenocarcinoma that is metastatic (stage IV) at diagnosis and who have not received any treatment for their pancreatic cancer.
• Patients must be able to receive their first dose of VCN-01 ≤6 weeks after their metastatic pancreatic cancer diagnosis.
• Patients must have at least one measurable tumor lesion that can be imaged for assessments according to RECIST 1.1.
• ECOG performance status of 0 or 1 at enrollment.
• Must be willing to comply with the trial intervention, including prophylactic medications, and procedures.
• Adequate baseline organ function (hematologic, liver, renal) within the 7 days prior to enrollment:

Hematology:

• Leukocytes ≥3.0x103 mcL
• Absolute neutrophil count ≥1.5x10⁹/L
• Hemoglobin ≥9 g/dL
• Platelets ≥100x10⁹/L

Coagulation:

• Prothrombin time or international normalized ratio ≤1x upper limit of normal (ULN)
• Activated partial thromboplastin time ≤1.2xULN

Hepatic:

• Total bilirubin ≤1.5xULN
• ALT and AST ≤2.5xULN (<5xULN is acceptable if liver metastases are present)

Renal:

• Serum creatinine ≤1.5xULN; or,
• If serum creatinine >1.5xULN, an estimated creatinine clearance >50 mL/min using the Cockcroft and Gault formula

Nutritional:

• Serum Albumin ≥30 g/L

• Adequate left ventricular ejection fraction (LVEF) ≥ 50% measured by ECHO or MUGA and QT interval corrected by Fridericia (QTcF) assessment ≤ 450 ms for men or ≤ 470 ms for women.

Exclusion criteria

• Unwillingness to complete the trial procedures for geographic, psychiatric, or social reasons.
• Patient has previously received treatment for their metastatic pancreatic cancer with surgery, radiotherapy, chemotherapy or investigational therapy; except that:
• Palliative radiotherapy for pain is permitted;
• Placement of a biliary stent/tube is permitted.
• Patients who, in the opinion of the investigator, have symptoms or signs suggesting clinically unacceptable deterioration during the Screening Period.
• Active infection or other serious illness or autoimmune disease at the moment of enrollment. Active infection includes:

• Tuberculosis (TB; clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice.
• Patients with past or resolved TB are eligible to participate.

• Hepatitis B Virus (HBV; positive HBV surface antigen [HBsAg] result).
• HBV carriers (patients positive for HBsAg without an active infection) are not eligible to participate;
• Patients requiring antiviral medicines for HBV prophylaxis or treatment are not eligible to participate;
• Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible to participate provided that blood HBV DNA is negative at enrollment.

• Hepatitis C Virus (HCV; positive HCV Ribonucleic acid [RNA]).
• Patients requiring antiviral medicines for HCV prophylaxis or treatment are not eligible to participate;
• Patients positive for HCV antibody are eligible to participate (only if polymerase chain reaction is negative for HCV RNA).

• Human immunodeficiency virus (positive HIV 1/2 antibodies)

Active infection or other serious illness or autoimmune disease at the moment of enrollment. Active infection includes:

• Tuberculosis (TB; clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice.

• Patients with past or resolved TB are eligible to participate.
• Hepatitis B Virus (HBV; positive HBV surface antigen [HBsAg] result).

• HBV carriers (patients positive for HBsAg without an active infection) are not eligible to participate;
• Patients requiring antiviral medicines for HBV prophylaxis or treatment are not eligible to participate;
• Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible to participate provided that blood HBV DNA is negative at enrollment.
• Hepatitis C Virus (HCV; positive HCV Ribonucleic acid [RNA]).

• Patients requiring antiviral medicines for HCV prophylaxis or treatment are not eligible to participate;
• Patients positive for HCV antibody are eligible to participate (only if polymerase chain reaction is negative for HCV RNA).
• Human immunodeficiency virus (positive HIV 1/2 antibodies)

• Known chronic liver disease (e.g. liver cirrhosis, liver fibrosis, chronic hepatitis); except that:
• Patients with fatty liver disease are eligible to participate if their liver transaminases meet inclusion criterion 8.
• Concurrent malignant hematologic or solid disease; except that:
• Patients with a prior history of cancer are eligible to participate if they are in complete remission from their prior cancer for at least 3 years.
• Patients with Li Fraumeni syndrome or with previously known retinoblastoma protein pathway germline deficiency.
• Patients with untreated brain metastases and/or leptomeningeal carcinomatosis with progressive symptoms despite corticosteroid coverage; except that:
• Patients with brain metastases with stable symptoms are eligible to participate.
• Patients with previous pneumonitis or interstitial lung disease.
• Patients with pre-existing sensory neuropathy >G1
• Clinical evidence of deep vein thrombosis, pulmonary embolism or arterial thromboembolic event during the Screening Period.
• Patients with superficial vein thrombosis are eligible to participate.
• Patients with uncontrolled coagulopathy.
• Any other condition, disease, metabolic dysfunction (e.g., uncontrolled diabetes mellitus), active or uncontrolled infection/inflammation, physical examination finding, mental state or clinical laboratory finding that would contraindicate participation in the clinical trial due to concerns over safety or potential non-compliance with clinical trial procedures.
• A female patient, who is pregnant or lactating.
• Female patients of reproductive potential must agree to use a highly effective method of birth control. Male patients must agree to use condoms.
• Treatment with live attenuated vaccines in the last 3 weeks before the administration of the IMP.
• Treatment with an adenovirus type-5 (Ad5)-based COVID-vaccine in the last 12 weeks before the administration of the IMP.
• Treatment with another investigational agent within five of that investigational agent's half-lives prior to the administration of the IMP.
• Chronic immunosuppressive therapy; except that:
• Inhaled corticosteroids are permitted;
• Oral or IV corticosteroids with a dose lower than 10 mg prednisone or equivalent/day are permitted;
• Dexamethasone up to a maximum dose of 1 mg/day is permitted.
• Known allergy or hypersensitivity to any of the trial-specific interventions or any of their excipients.
• Subjects, for whom first line treatment options other than the combination nab-paclitaxel/gemcitabine are recommended by the investigator.