FDA Grants Orphan Drug Designation to VCN-01 for Pancreatic Cancer

Steven A. Shallcross

The FDA has granted an orphan drug designation to VCN-01, a systemic, selective, stroma-degrading oncolytic adenovirus for the treatment of patients with pancreatic cancer.¹

The agent is being studied as frontline therapy in combination with chemotherapy in the global phase 2b VIRAGE trial (NCT05673811) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC).²

“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 of Theriva Biologics, said in a press release.¹

“Efforts to improve upon the standard of care treatment have largely stalled, despite the growing incidence of PDAC, and the need for novel therapies in this indication is acute. 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.”

Previously, the FDA granted an orphan drug designation to VCN-01 for the treatment of patients with retinoblastoma.

VCN-01 was designed to replicate within tumor cells and degrade the tumor stroma, breaking down the physical and immunosuppressive barrier to cancer treatment. Through its mechanism of action, VCN-01 can infect and lysis primary and metastatic tumor cells, improve the activity of chemotherapy, and increase tumor immunogenicity.

In a prior phase 1 trial (NCT02045602), VCN-01 was evaluated as a single agent and in combination with gemcitabine and nab-paclitaxel (Abraxane) in patients with advanced solid tumors.

No dose-limiting toxicity was reported, and the recommended phase 2 dose was 1 × 10¹³ vp/patient. Among patients with pancreatic adenocarcinoma who received the combination (n = 22), the overall response rate (ORR) was 50%. Moreover, VCN-01 viral genomes were detected in five of six tumor tissue biopsies on day 8. Increased levels of interferon-γ, soluble lymphocyte activation gene-3, interleukin-6 (IL-6), and IL-10 were also detected after VCN-01 administration.³

To be eligible for enrollment in the open label, randomized, controlled, multicenter VIRAGE trial, patients must have histologically or cytologically confirmed, treatment naïve, metastatic PDAC; at least 1 measurable lesion; minimum life expectancy of 5 months; ECOG performance status of 0 or 1; and adequate baseline organ function.²

The study is expected to enroll up to 92 patients at up to 25 sites across the United States and Europe.

In both arms, patients will receive nab-paclitaxel over 30- to 40-minute intravenous (IV) infusions at a rate of 125 mg/m² on day 1, 8, and 15 of each 28-day cycle, plus gemcitabine over 30-minute IV infusions at a rate of 1,000 mg/m² after the completion of nab-paclitaxel on day 1, 8, and 15.

VCN-01 will be administered as a single IV infusion at dose 1 x 10¹³ vp/patient, over a period of 10 minutes on day 1 of the first cycle and on day 1 of the fourth cycle, seven days prior to the first and fourth cycles of chemotherapy, respectively.

Primary end points of the trial include overall survival, safety, and tolerability. Secondary end points include progression-free survival, ORR, disease control rate, duration of response, measures of biodistribution, VCN-01 replication, and immune response.

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. June 27, 2023. Accessed June 28, 2023. https://www.globenewswire.com/news-release/2023/06/27/2695780/0/en/Theriva-Biologics-Announces-Orphan-Drug-Designation-Granted-by-the-U-S-FDA-for-VCN-01-for-the-Treatment-of-Pancreatic-Cancer.html
2. Study of nab-paclitaxel and gemcitabine and plus/minus VCN-01 in patients with metastatic pancreatic cancer (VIRAGE). ClinicalTrials.gov. Updated June 27, 2023. Accessed June 28, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05673811
3. Garcia-Carbonero R, Bazan-Peregrino M, Gil-Martin 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