The FDA has granted Fast Track designation to VCN-01, when administered with gemcitabine and nab-paclitaxel, for the treatment of patients with metastatic pancreatic adenocarcinoma. This decision aims to expedite the development and review of the drug, addressing the urgent need for new treatment options for this aggressive cancer.
The combination therapy is currently being investigated in the phase 2b VIRAGE trial (NCT05673811), a multinational study evaluating the safety and efficacy of intravenous VCN-01 in conjunction with standard-of-care chemotherapy (gemcitabine and nab-paclitaxel) as a first-line treatment for patients with pancreatic ductal adenocarcinoma (PDAC).
VCN-01: Mechanism of Action and Clinical Development
VCN-01 is an oncolytic adenovirus designed to selectively replicate within tumor cells and disrupt the tumor stroma, a physical and immunosuppressive barrier to cancer treatment. This mechanism allows VCN-01 to exert multiple antitumor effects, including direct lysis of tumor cells, improved access for co-administered chemotherapy, and increased tumor immunogenicity, potentially enhancing the patient's immune response and the effectiveness of immunotherapy.
Systemic administration of VCN-01 enables targeting of both the primary tumor and metastases. The agent has been administered to over 80 patients across various clinical trials, including the ongoing VIRAGE study in PDAC. Other tumor types studied include head and neck squamous cell carcinoma (in combination with immune checkpoint inhibitors), ovarian cancer (plus CAR-T cell therapy), colorectal cancer, and retinoblastoma (via intravitreal injection).
VIRAGE Trial Details
The VIRAGE trial is an open-label, randomized, controlled study. Eligible patients must have histologically or cytologically confirmed, treatment-naive, metastatic PDAC with at least one measurable lesion, a minimum life expectancy of 5 months, an ECOG performance status of 0 or 1, and adequate baseline organ function.
The treatment regimen involves nab-paclitaxel administered on days 1, 8, and 15 of each 28-day cycle, followed by gemcitabine on the same days. VCN-01 is administered as a single intravenous infusion on day 1 of the first cycle and on day 1 of the fourth cycle, 7 days prior to the chemotherapy cycles.
The primary endpoints of the trial are overall survival and safety/tolerability. Secondary endpoints include progression-free survival, objective response rate, and measures of biodistribution, VCN-01 replication, and immune response.
Significance of Fast Track Designation
"The FDA’s decision to grant fast track designation to VCN-01 highlights the urgent need for new treatment options for PDAC, which accounts for the fourth highest cause of cancer-associated deaths in the United States and Europe," stated Steven A. Shallcross, chief executive officer of Theriva Biologics. The Fast Track designation is expected to expedite the review process and build upon the clinical data supporting VCN-01’s therapeutic potential in combination with chemotherapy or immunotherapy.
