A Study of More Frequent Dosing of VCN-01 Combined With Standard Chemotherapy in Patients With Newly Diagnosed Metastatic Pancreatic Cancer (VIRAGE2)

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.