ROCKVILLE, Md., August 6, 2026
Theriva Biologics announced that the first patient has been dosed in the VIRAGE2 Phase 2a clinical trial, an exploratory study evaluating more frequent repeated dosing of VCN-01 (zabilugene almadenorepvec) in combination with standard-of-care gemcitabine/nab-paclitaxel chemotherapy for patients with first-line metastatic pancreatic ductal adenocarcinoma (PDAC). The trial is designed to refine the optimal dosing regimen for VCN-01 ahead of a potential pivotal Phase 3 clinical trial. Enrollment is expected to conclude in the second half of 2026, while initial pharmacodynamic and safety data are anticipated in Q3 2027. The study follows encouraging findings from the earlier VIRAGE Phase 2b trial, where patients receiving two doses of VCN-01 demonstrated improved overall survival, progression-free survival, and duration of response compared with chemotherapy alone. Feedback from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) supported further investigation of repeated dosing to potentially enhance clinical outcomes.
VIRAGE2 Explores Enhanced Dosing Strategy for VCN-01
The Phase 2a, open-label, single-arm VIRAGE2 study will enroll six evaluable patients with newly diagnosed metastatic PDAC at a single clinical site in Spain. Participants will receive at least three macrocycles of intravenous VCN-01 combined with gemcitabine/nab-paclitaxel chemotherapy, followed by continued standard chemotherapy until disease progression. The primary objective is to determine whether administering at least three VCN-01 doses approximately two months apart remains well tolerated while maintaining favorable pharmacodynamic activity. Primary endpoints include the adverse event profile and VCN-01 viral genome levels in blood, while secondary endpoints evaluate objective response rate, progression-free survival, overall survival, duration of response, and anti-VCN-01 neutralizing antibodies. Although the study is not statistically powered to demonstrate efficacy, its findings will help optimize the dosing schedule for future late-stage clinical development.
VCN-01 Designed to Overcome Tumor Stroma Barriers
VCN-01 (zabilugene almadenorepvec) is an intravenously administered oncolytic adenovirus engineered to selectively replicate within tumor cells while degrading the dense tumor stroma that limits the effectiveness of conventional cancer therapies. By breaking down this protective barrier, VCN-01 aims to improve chemotherapy penetration, increase tumor immunogenicity, and enhance the effectiveness of immunotherapies and other targeted treatments. According to Theriva Biologics, repeated administration may further strengthen these tumor stroma-degrading effects while amplifying the body’s anti-tumor immune response. The company believes this strategy could not only improve outcomes in metastatic pancreatic cancer but also expand the therapeutic potential of VCN-01 when combined with immune checkpoint inhibitors, antibody-drug conjugates, KRAS inhibitors, and other emerging cancer therapies.
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Theriva Advances Oncolytic Virus Platform in High-Unmet-Need Cancers
The first patient dosing in VIRAGE2 marks another important milestone for Theriva Biologics’ clinical-stage oncolytic virus platform. To date, VCN-01 has been administered to 143 patients across company- and investigator-sponsored studies involving pancreatic cancer, colorectal cancer, ovarian cancer, head and neck squamous cell carcinoma, and retinoblastoma. The company continues to expand the evaluation of its proprietary oncolytic adenovirus technology, which is designed to selectively destroy tumors while improving the effectiveness of combination therapies. If the repeated dosing strategy demonstrates favorable safety and pharmacodynamic activity, the results are expected to guide the design of a future pivotal Phase 3 trial in metastatic PDAC, a disease where treatment options remain limited and survival outcomes continue to be poor.
Source:Theriva Biologics, press release
