Theriva Biologics has announced that dosing has begun for US patients in the VIRAGE trial evaluating VCN-01 in combination with standard-of-care chemotherapy as a first-line therapy for patients with metastatic pancreatic ductal adenocarcinoma (PDAC).

The multinational, Phase IIb, randomised, open-label, multicentre, controlled clinical trial (NCT05673811) has four sites open in the US and eight in Spain.

The study remains on track to be fully enrolled in the first quarter of 2024. Dosing in Spain started in January and the first patients have received second doses of VCN-01. The pipeline drug has been well tolerated with a safety profile consistent with prior clinical trials.

About VCN-01

VCN-01 is Theriva’s systemic, selective, stroma-degrading oncolytic adenovirus.

The therapy has been granted Orphan Drug designations from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of pancreatic cancer.

It aggressively replicates in tumour cells to degrade the tumour stroma. This mechanism of action enables multiple antitumour effects; selectively infecting and lysing tumour cells, enabling access and perfusion of co-administered chemotherapy products and increasing tumour immunogenicity, and exposing the tumour to the patient’s immune system and co-administered immunotherapy products.

Theriva CEO Steven Shallcross said: ”Through VIRAGE’s advancement, we aim to demonstrate VCN-01’s ability to address the unmet needs of pancreatic cancer patients by synergistically combining with standard-of-care chemotherapy.

“More broadly, this trial will enable us to determine the feasibility of repeated dosing of VCN-01, which could shift the paradigm for standardised treatment cycles that are well established in cancer chemotherapy and immunotherapy, and thereby lead to improved clinical outcomes for patients with PDAC and other solid cancers.”

About VIRAGE

The VIRAGE trial is expected to enrol 92 participants across 25 sites in the US and Spain. Patients in both the control and treatment arms will receive gemcitabine/nab-paclitaxel standard-of-care chemotherapy over 28-day cycles.

In the treatment arm, patients will also receive intravenous VCN-01 seven days before the first and fourth cycles of gemcitabine/nab-paclitaxel treatment. VCN-01 is also being trialled in retinoblastoma, colorectal cancer, head and neck cancer and brain cancer.

The primary endpoints are overall survival (OS) and VCN-01 safety/tolerability. Secondary endpoints include progression-free survival (PFS), objective response rate (ORR), and measures of biodistribution, VCN-01 replication, and immune response.