Theriva Biologics (NYSE American: TOVX) has announced the U.S. Food and Drug Administration's (FDA) guidance on the design of its Phase 3 clinical study for VCN-01 in combination with standard-of-care chemotherapy for the treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). The FDA advised against expanding the ongoing VIRAGE Phase 2b study into Phase 3, recommending instead a standalone Phase 3 study of VCN-01 with gemcitabine/nab-paclitaxel. This guidance is intended to streamline the trial design and facilitate clearer data interpretation.
The FDA's feedback, obtained during a Type D meeting, supports Theriva's proposed Phase 3 design, indicating that the inclusion of additional standard-of-care chemotherapy for PDAC was unnecessary. The meeting also addressed statistical elements for confirmatory clinical studies, including methods for sample size estimation and study populations for data analysis. Theriva Biologics recently completed target enrollment for the multinational VIRAGE Phase 2b clinical study, which evaluates intravenous VCN-01 in combination with gemcitabine/nab-paclitaxel as a first-line therapy for PDAC patients.
VCN-01: Oncolytic Adenovirus Approach
VCN-01 is a systemically administered oncolytic adenovirus designed to selectively replicate within tumor cells and degrade the tumor stroma. This mechanism aims to overcome physical and immunosuppressive barriers to cancer treatment. VCN-01 exerts antitumor effects by selectively infecting and lysing tumor cells, enhancing the access and perfusion of co-administered chemotherapy, and increasing tumor immunogenicity.
Clinical Development and Future Plans
To date, VCN-01 has been administered to 142 patients in company- and investigator-sponsored clinical trials across various cancers, including PDAC, head and neck squamous cell carcinoma, ovarian cancer, colorectal cancer, and retinoblastoma. Following the completion of the VIRAGE study, Theriva plans to request another meeting with the FDA to discuss the details of the proposed confirmatory Phase 3 study protocol.
Management Perspective
"The FDA’s advice on key elements of a potential confirmatory Phase 3 study evaluating VCN-01 plus gemcitabine/nab-paclitaxel as a first-line treatment for metastatic PDAC patients is critical as the VIRAGE study has entered final patient follow-up and we are actively planning the next steps in VCN-01 development," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. "The feedback from the FDA and European regulatory agencies will facilitate the design of a Phase 3 study protocol that is expected to maximize our ability to provide a new therapeutic option to patients suffering this terrible disease."
Pancreatic Cancer Landscape
Pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of all pancreatic tumors. It is often diagnosed in late stages due to the lack of characteristic symptoms in early stages, making surgical resection and curative treatment challenging. Only 10% of cases are resectable at presentation, while 50-60% present with distant metastases.
