FDA Grants Fast Track Designation to VCN-01 in Metastatic Pancreatic Cancer

The FDA has granted fast track designation to VCN-01 in combination with gemcitabine and nab-paclitaxel (Abraxane) for the treatment of patients with metastatic pancreatic adenocarcinoma, according to a press release.¹

Treatment with intravenous VCN-01 is being explored in the ongoing, multinational phase 2b VIRAGE trial (NCT05673811) in combination with standard-of-care chemotherapy consisting of gemcitabine and nab-paclitaxel in the first line for patients with pancreatic ductal adenocarcinoma (PDAC).

Notably, in June 2023, orphan drug designation was granted to VCN-01 by the FDA for the treatment of patients with PDAC.²

“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,” Steven A. Shallcross, chief executive officer of Theriva Biologics, stated in the press release.¹ “VIRAGE, our phase 2b trial evaluating VCN-01 in metastatic PDAC continues to progress, with enrollment expected to complete in the third quarter of 2024.”

Tumors originating from the ductal cells of the pancreas or from the endocrine cells of the pancreas are the 2 main histological types that make up pancreatic cancer. PDAC represents over 90% of all pancreatic tumors and these tumors can develop in either the head or the body and tail of the pancreas which often spreads to the liver and peritoneum.

Additionally, pancreatic cancer is usually diagnosed at an advanced stage, making surgical resection and potential curative treatment unfeasible. It is estimated that only 10% of cases are resectable at diagnosis, whereas 30% to 40% are identified at a locally advanced and unresectable stage and 50% to 60% are diagnosed with distant metastases.

The systemicall administered oncolytic adenovirus, VCN-01, is designed to selectively and aggressively replicate within tumor cells and break down the tumor stroma, which acts as a significant physical and immunosuppressive barrier to cancer treatment. This mechanism of action allows the agent to achieve multiple antitumor effects by selectively infecting and lysing tumor cells; improving the access and effectiveness of co-administered chemotherapy; and increasing tumor immunogenicity, thereby exposing the tumor to the patient’s immune system and co-administered immunotherapy.

Systemic administration allows VCN-01 to target both the primary tumor and metastases.

VCN-01 has been administered to over 80 patients in various clinical trials, including the ongoing VIRAGE study in patients with PDAC. Patients with other tumor types that have been treated with this agent include those with head and neck squamous cell carcinoma in combination with an immune checkpoint inhibitor, ovarian cancer plus CAR-T cell therapy, colorectal cancer, and retinoblastoma via intravitreal injection.

“Fast track designation is an important step that furthers our ability to expedite the review of, and build upon the compelling clinical data that underscores VCN-01’s multiple modes of action and therapeutic potential in combination with chemotherapy or immunotherapy. We will continue to deliver on our mission to advance new therapeutic options for these patients,” Shallcross emphasized in the press release.

Patients are eligible for enrollment in the open-label, randomized, controlled, clinical trial if they present with histologically or cytologically confirmed, treatment-naive, metastatic PDAC and have at least 1 measurable lesion, as well as a minimum life expectancy of 5 months, an ECOG performance status of 0 or 1, and adequate baseline organ function.³

Nab-paclitaxel will be administered on days 1, 8, and 15 of each 28-day cycle, plus gemcitabine after the completion of nab-paclitaxel on days 1, 8, and 15. VCN-01 will be 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 first and fourth cycles of chemotherapy.²

The primary end points are overall survival and safety/tolerability. Other end points include progression-free survival, objective response rate, and measures of biodistribution, VCN-01 replication, and immune response.

References

1. Theriva biologics announces fast track designation granted by the U.S. FDA for VCN-01 for the treatment of metastatic pancreatic cancer. News release. Theriva Biologics. May 23, 2024. Accessed May 23, 2024. https://therivabio.com/press_releases/theriva-biologics-announces-fast-track-designation-granted-by-the-u-s-fda-for-vcn-01-for-the-treatment-of-metastatic-pancreatic-cancer/
2. 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 May 23, 2024. https://therivabio.com/press_releases/theriva-biologics-announces-orphan-drug-designation-granted-by-the-u-s-fda-for-vcn-01-for-the-treatment-of-pancreatic-cancer/
3. Study of nab-paclitaxel and gemcitabine and plus/minus VCN-01 in patients with metastatic pancreatic cancer (VIRAGE). ClinicalTrials.gov. Updated April 19, 2024. Accessed May 23, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05673811