VCN-01 Receives FDA Orphan Drug Designation in Pancreatic Cancer

Investigators previously evaluated VCN-01 plus nab-paclitaxel and gemcitabine among patients with advanced solid tumors in a multi-center, open-label phase 1 trial (NCT02045602).

The FDA has granted orphan drug designation to VCN-01, a selective stroma-degrading oncolytic adenovirus, for the treatment of patients with pancreatic cancer, according to a press release from Theriva Biologics, Inc.¹

Investigators are assessing the agent in combination with gemcitabine and nab-paclitaxel (Abraxane) in the frontline setting for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) in the phase 2b VIRAGE trial (NCT05673811). The FDA previously granted orphan drug designation to VCN-01 as a treatment for patients with retinoblastoma.

“The FDA’s decision to grant orphan drug designation to VCN-01 highlights the urgent need for new treatment options for patients with PDAC, which has one of the lowest survival rates among all cancers,” Steven A. Shallcross, chief executive officer at Theriva Biologics, said in the press release. “The growing clinical data that underscore VCN-01’s multiple modes of action, and the compelling clinical outcomes observed in phase 1 studies of VCN-01 in combination with chemotherapy or immunotherapy in patients with PDAC and other solid tumors, give us confidence that VCN-01 has the potential to address this unmet medical need.”

Developers designed VCN-01 to undergo aggressive replication within tumor cells, thus degrading the tumor stroma that acts as a physical and immunosuppressive barrier to cancer treatment. It is hypothesized that VCN-01 enables tumor lysis through this mechanism, enhancing the access and perfusion of chemotherapy agents, increasing tumor immunogenicity, and exposing the tumor to the patient’s immune system and any immunotherapy agents. Moreover, the adenovirus is designed to target both the primary tumor and metastases.

Investigators previously evaluated VCN-01 plus nab-paclitaxel and gemcitabine among patients with advanced solid tumors in a multi-center, open-label phase 1 trial (NCT02045602).² According to a preliminary analysis of clinical activity in part 3 of the trial, treatment with 1.0 x 101³ viral particles per patient of VCN-01 produced an overall response rate of 83%, a median progression-free survival (PFS) of 6.3 months, and a median overall survival (OS) of 20.8 months. Investigators observed no dose-limiting toxicities in part 3, and the most common treatment-emergent adverse effects included fever (93%), vomiting (21%), asthenia (21%), nausea (21%), and alanine aminotransferase increase (21%).

In the open-label, controlled, multi-center, randomized VIRAGE study, investigators will assess VCN-01 as a treatment for up to 92 adult patients with newly diagnosed metastatic PDAC across 25 sites in the United States and Europe. In the comparator arm, patients will receive 125 mg/m2 of nab-paclitaxel as a 30-to-40-minute intravenous infusion, as well as 1000 mg/m2 of gemcitabine intravenously over 30 minutes, on days 1, 8, and 15 of each 28-day cycle. In the experimental arm, patients will receive VCN-01 as a single intravenous dose of 1 x 101³ viral particles per patient on day 1 of the first and fourth cycles, in addition to gemcitabine at the same dose as the comparator regimen and nab-paclitaxel.

The primary end points of the VIRAGE study are OS and safety. Secondary end points include PFS, disease control rate, and duration of response.

Patients 18 years and older with histologically or cytologically confirmed metastatic PDAC who have not received prior systemic treatment are eligible for enrollment on the trial. Additional eligibility criteria include the presence of at least 1 measurable lesion per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and a life expectancy of at least 5 months.

References

1. Theriva Biologics announces orphan drug designation granted by the U.S. FDA for VCN-01 for the treatment of pancreatic cancer. News release. Theriva Biologics, Inc. June 27, 2023. Accessed June 30, 2023. https://rb.gy/aanj7
2. Garcia-Carbonero R, Bazan-Peregrino M, Gil-Martín M, et al. Phase I, multicenter, open-label study of intravenous VCN-01 oncolytic adenovirus with or without nab-paclitaxel plus gemcitabine in patients with advanced solid tumors. J Immunother Cancer. 2022;10(3):e003255. doi:10.1136/jitc-2021-003255