A phase IIa, single-arm, single-center, open label, proof-of-concept trial evaluating increased frequency dosing of VCN-01 (zabilugene almadenorepvec) in combination with nab-Paclitaxel/Gemcitabine (GnP) in Patients with Newly-Diagnosed Metastatic Pancreatic Cancer (VIRAGE2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Theriva Biologics S.L.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-06-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Theriva Biologics S.L.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Safety

• To evaluate the safety and tolerability of VCN-01 administered every 56 days, with three planned doses, combined with GnP treatment in the participant Population.
• To evaluate the pharmacodynamic of VCN-01 through the analysis of its viral genome levels in blood.

Secondary objectives 7

1. • To determine the objective response rate (ORR) in the participant Population according to RECIST Version 1.1 guidelines. •
2. • To determine the progression free survival (PFS) in the Participant Population according to RECIST Version 1.1.
3. • To determine the duration of response (DoR) in the Participant Population
4. • To determine the overall survival (OS) at one-year and 18-month landmarks.
5. • To evaluate the disease control rate (DCR) (defined as stable disease + partial response + complete response) in the participant population.
6. • To evaluate changes in serum levels of neutralizing anti-adenovirusantibodies (Anti-Ad-NAbs).
7. • To assess changes in tumor marker carbohydrate antigen 19.9 (CA 19-9) in the participant Population.

Conditions and MedDRA coding

metastatic pancreatic adecarcinoma

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Theriva Biologics S.L.

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Written informed consent obtained prior to initiating any study-specific procedures or assessments.
2. Male or female patients aged 18 years or over.
3. 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).
4. Patients must have at least one measurable tumor lesion that can be imaged for assessments according to RECIST 1.1.
5. ECOG performance status of 0 or 1 at enrollment.
6. Must be willing to comply with the study treatment regimen, including prophylactic medications, and study procedures.
7. 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
8. 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 20

1. Unwillingness to complete the study procedures for geographic, psychiatric, or social reasons.
2. 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.
3. Patients who, in the opinion of the investigator, have symptoms or signs suggesting clinically unacceptable deterioration during the Screening Period.
4. 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.
5. 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.
6. 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.
7. Patients with Li Fraumeni syndrome or with previously known retinoblastoma protein pathway germline deficiency.
8. 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.
9. Patients with previous pneumonitis or interstitial lung disease.
10. Patients with pre-existing sensory neuropathy >G1
11. 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.
12. Patients with uncontrolled coagulopathy.
13. 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.
14. 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.
15. Treatment with live attenuated vaccines in the last 3 weeks before the administration of IMP.
16. Treatment with an adenovirus type-5 (Ad5)-based COVID-vaccine in the last 12 weeks before the administration of IMP.
17. Treatment with another investigational agent within five of that investigational agent’s half-lives prior to the randomization.
18. 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.
19. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
20. Subjects, for whom first line treatment options other than the combination gemcitabine/nab-paclitaxel are recommended by the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. • Safety and tolerability of the administration regimen of VCN-01 administered every 56 days, with three planned doses, combined with SoC GnP cycles.
2. • Pharmacodynamics of VCN-01 following intravenous administration and characterization of the pharmacokinetic profile across the three planned doses.

Secondary endpoints 7

1. • Proportion of participants who have a partial or complete response confirmed by RECIST 1.1 to the combination therapy (Objective response rate (ORR)).
2. • Progression Free Survival (PFS), defined as the time from the first VCN-01 dose until radiologically confirmed progressive disease (according to RECIST version 1.1) or death by any cause.
3. • Duration of response (DoR) defined as the time from the first partial response or complete response until radiologically confirmed progressive disease (according to RECIST version 1.1) or death by any cause.
4. • Landmark one-year and 18-months Overall survival (OS)
5. • Disease control rate (DCR), defined as the proportion of participants whose best response is either stable disease or partial response or complete response (according to RECIST version 1.1).
6. • Changes in serum levels of neutralizing anti-adenovirus antibodies (Anti-Ad-NAbs)
7. • Changes in serum levels of tumor marker CA 19-9.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Theriva Biologics S.L.

Sponsor organisation

Theriva Biologics S.L.

Address

Torrent De Can Ninou 5-6, Llevant Industrial Llevant Industrial

City

Parets Del Valles

Postcode

08150

Country

Spain

Scientific contact point

Organisation

Theriva Biologics S.L.

Contact name

Manel

Public contact point

Organisation

Theriva Biologics S.L.

Contact name

Manel

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications