Phase IIa Open‑Label Study of Increased‑Frequency VCN‑01 Dosing Combined with nab‑Paclitaxel/Gemcitabine in Newly Diagnosed Metastatic Pancreatic Adenocarcinoma

Trial ID: 2026-525566-21-00
Protocol: P-VCNA-004
Sponsor: Theriva Biologics S.L.

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Diseases & Conditions

Adenocarcinoma pancreas

Objectives

The primary objective is to assess the safety and tolerability of VCN-01 administered every 56 days for three doses in combination with nab‑paclitaxel/gemcitabine in adults with newly diagnosed metastatic pancreatic adenocarcinoma. A secondary primary aim is to characterize the pharmacodynamic profile of VCN-01 by quantifying viral genome levels in peripheral blood. Secondary objectives include:

Determination of the objective response rate according to RECIST 1.1.
Determination of the progression‑free survival according to RECIST 1.1.
Determination of the duration of response.
Estimation of overall survival at 12‑month and 18‑month landmarks.
Evaluation of the disease control rate (stable disease + partial/complete response).
Assessment of changes in serum neutralizing anti‑adenovirus antibodies.
Assessment of changes in the tumor marker CA 19‑9.

Participants

The trial enrolled adult patients (≥18 years) of both sexes with histologically confirmed metastatic pancreatic adenocarcinoma that was treatment‑naïve for the standard gemcitabine/nab‑paclitaxel regimen. Eligible participants were required to have at least one measurable lesion according to RECIST 1.1, an ECOG performance status of 0 or 1, and adequate baseline hematologic, hepatic, renal, and cardiac function as defined by specific laboratory thresholds and left ventricular ejection fraction ≥50 %. Selection was based on these clinical and laboratory criteria, and enrollment required written informed consent and willingness to follow the study treatment schedule. General health status at enrollment was therefore limited to individuals with preserved organ function and good functional capacity; no specific dietary or physical‑activity requirements were stipulated. The sponsor did not provide information on the total number of participants enrolled.

Plans and Procedures

The study is a phase IIa, single‑arm, single‑center, open‑label, proof‑of‑concept trial evaluating VCN‑01 administered intravenously at a dose of 1 × 10^13 vector genomes per mL in combination with standard gemcitabine/nab‑paclitaxel in adult patients with newly diagnosed metastatic pancreatic adenocarcinoma. Participants undergo an initial screening visit to confirm eligibility, including histologic confirmation, measurable disease per RECIST 1.1, ECOG performance status 0‑1, and adequate hematologic, hepatic, renal, and cardiac function. Eligible subjects receive the first VCN‑01 infusion on day 1 together with the first GnP cycle; subsequent VCN‑01 infusions are scheduled on days 57 and 113, each followed by standard GnP cycles every 28 days. Study visits are conducted at baseline, prior to each VCN‑01 dose, every 28 days for safety laboratory assessments, and at weeks 4, 8, 12 and every 8 weeks thereafter for radiologic tumor assessments, viral genome pharmacodynamic sampling, and measurement of anti‑adenovirus antibodies and CA 19‑9. The end‑of‑study visit occurs 30 days after the third VCN‑01 dose or earlier if discontinuation criteria are met. Participant involvement therefore spans approximately 5–6 months from first infusion to end‑of‑study assessment. Early termination may be triggered by Grade ≥ 3 treatment‑related adverse events, disease progression per RECIST 1.1, withdrawal of consent, or investigator determination that continuation is not feasible.

Treatment

The investigational product VCN-01 is supplied as a concentrate for solution for infusion and consists of a genetically modified human adenovirus encoding human PH20 hyaluronidase. The formulation is administered by intravenous infusion at a concentration of 1 × 10¹³ vector genomes (vg) per milliliter. Dosing is scheduled every 56 days, with a total of three planned administrations during the study period.

The concomitant chemotherapy regimen comprises nab‑Paclitaxel combined with Gemcitabine, referred to as nab-Paclitaxel/Gemcitabine (GnP). This standard‑of‑care regimen is given according to the approved dosing schedule for metastatic pancreatic cancer, typically on a 28‑day cycle with nab‑Paclitaxel administered on days 1 and 8 and Gemcitabine on days 1, 8, and 15.

All study treatments are recorded in the case report form, and infusion times are documented to ensure adherence to the prescribed schedule. Participants are monitored for dose compliance through infusion logs, pharmacy dispensing records, and periodic assessment of viral genome levels in peripheral blood to evaluate pharmacodynamic exposure.

Efficacy

Efficacy will be evaluated using several secondary endpoints, including the proportion of participants achieving a partial or complete response as defined by RECIST 1.1, progression‑free survival, duration of response, overall survival at one‑year and 18‑months, disease control rate, and changes in serum levels of neutralizing anti‑adenovirus antibodies and the tumor marker CA 19‑9.

Responses will be assessed by radiologic imaging interpreted according to RECIST 1.1 criteria. Survival endpoints will be calculated from the date of the first VCN‑01 dose to the relevant event (progression, death, or response loss). Serum biomarkers will be measured with validated immunoassays at predefined study visits. The proportion of participants meeting the response definitions will be reported as the Objective response rate (ORR) and disease control rate.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Written informed consent obtained prior to initiating any study-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) de novo and who have not received any previous treatment for their pancreatic cancer for which the established therapy is gemcitabine/nab-paclitaxel (clinical SoC).
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 study treatment regimen, including prophylactic medications, and study 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.

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Exclusion Criteria

Unwillingness to complete the study 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) Patients with HIV with undetectable viral load are eligible to participate.
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 study due to concerns over safety or potential non-compliance with clinical study 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 IMP.
Treatment with an adenovirus type-5 (Ad5)-based COVID-vaccine in the last 12 weeks before the administration of IMP.
Treatment with another investigational agent within five of that investigational agent’s half-lives prior to the randomization.
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 study drugs or any of the study drug excipients.
Subjects, for whom first line treatment options other than the combination gemcitabine/nab-paclitaxel are recommended by the investigator.