VCN-01 Plus Chemo Improves Survival in Newly Diagnosed Metastatic Pancreatic Cancer

Image Credit: © Sebastian Kaulitzki

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The addition of zabilugene almadenorepvec (VCN-01) to standard-of-care (SOC) gemcitabine and nab-paclitaxel (Abraxane) led to an improvement in overall survival (OS) and progression-free survival (PFS) compared with gemcitabine plus nab-paclitaxel alone in patients with newly diagnosed metastatic pancreatic ductal adenocarcinoma (PDAC), according to data from the phase 2b VIRAGE trial (NCT05673811).¹

Findings announced by Theriva Biologics showed that patients treated with VCN-01 followed by at least 1 dose of gemcitabine plus nab-paclitaxel (n = 48) achieved a median OS of 10.8 months compared with 8.6 months for those given at least 1 dose of gemcitabine plus nab-paclitaxel alone (n = 48; HR, 0.57; 95% CI, 0.34-0.96; P = .0546). Notably, patients treated with at least 2 doses of VCN-01 and 4 or more cycles of chemotherapy (n = 34) experienced a median OS of 14.8 months vs 11.6 months for those who received 4 or more cycles of gemcitabine plus nab-paclitaxel alone (n = 29; HR, 0.44; 95% CI, 0.21-0.92; P = .046).

Furthermore, the median PFS was 7.0 months in the VCN-01 arm vs 4.6 months in the control arm (HR, 0.55; 95% CI, 0.34-0.88; P = .0105). The median duration of response (DOR) was 11.2 months in responders in the VCN-01 arm (n = 19) vs 5.4 months in the control arm (n = 15; HR, 0.22; 95% CI, 0.08-0.62; P = .0035).

“The exciting topline data from the VIRAGE phase 2b trial demonstrate the potential opportunity for VCN-01 to benefit [patients with] metastatic PDAC treated with gemcitabine/nab-paclitaxel SOC chemotherapy.” Steven A. Shallcross, chief executive officer of Theriva Biologics, stated in a news release. “The significantly reduced hazard ratios for survival parameters in the VCN-01 treatment group provide compelling evidence that VCN-01 in combination with gemcitabine/nab-paclitaxel may extend the lives of metastatic PDAC patients. These data, combined with recent advice from the U.S. FDA and the European [Medicines] Agency, are expected to facilitate engagement with industry partners and enable the design of a phase 3 confirmatory trial that, if successful, may deliver an important new therapeutic option for patients suffering this rapidly fatal disease.”

VCN-01 is a systemic oncolytic adenovirus that selectively and aggressively replicates in tumor cells and degrades tumor stroma. The stroma represented a significant physical and immunosuppressive barrier to cancer therapy.

VIRAGE was a multicenter, open-label, randomized trial that enrolled patients at least 18 years of age with histologically or cytologically confirmed stage IV PDAC who had not received prior systemic therapy for pancreatic cancer and were candidates for first-line gemcitabine plus nab-paclitaxel.² Key inclusion criteria comprised at least 1 measurable lesion per RECIST 1.1 criteria, a life expectancy of at least 5 months, an ECOG performance status of 0 or 1, and adequate hematologic, liver, and renal function.

Patients were excluded if they had active infection, other serious illness, or autoimmune disease at screening; received a live attenuated vaccine within 3 weeks or an adenovirus type-5–based COVID-19 vaccine within 12 weeks of enrollment; had known chronic liver disease; or had Li Fraumeni syndrome or a previously known retinoblastoma protein pathway germline deficiency. Investigators excluded patients with untreated brain metastases and/or leptomeningeal carcinomatosis who had progressive symptoms while receiving corticosteroids; however, patients with stable brain metastases were permitted to participate.

Patients were randomly assigned 1:1 to received SOC gemcitabine and nab-paclitaxel with or without VCN-01. In the experimental arm, VCN-01 was given at 1x10¹³ viral particles on day 1 of cycles 1 and 4. Patients in both arms received gemcitabine at 1000 mg/m² plus 125 mg/m² of nab-paclitaxel on days 1, 8, and 15 of each 28-day cycle. Notably, in the experimental arm, chemotherapy was administered on days 8, 15, and 22 in cycles 1 and 4 after VCN-01 was given on day 1.

OS and safety served as the trial’s primary end points. Secondary end points included PFS, overall response rate, disease control rate, 1-year OS and PFS rates, DOR, and changes in CA19.9 tumor marker levels.

The safety profile of VCN-01 was consistent with prior studies.¹ The most common adverse effects (AEs) related to VCN-01 included pyrexia, flu-like illness, vomiting, nausea, and elevated aminotransaminase levels; these AEs were transient and reversible.

References

1. Theriva Biologics announces primary endpoints for efficacy and safety achieved in VIRAGE phase 2b clinical trial of VCN-01 with gemcitabine/nab-paclitaxel in newly-diagnosed metastatic pancreatic cancer patients. News release. Theriva Biologics. May 7, 2025. Accessed May 7, 2025. https://therivabio.com/press_releases/theriva-biologics-announces-primary-endpoints-for-efficacy-and-safety-achieved-in-virage-phase-2b-clinical-trial-of-vcn-01-with-gemcitabine-nab-paclitaxel-in-newly-diagnosed-metastatic-pancre/
2. Study of nab-paclitaxel and gemcitabine and plus/​minus VCN-01 in patients with metastatic pancreatic cancer (VIRAGE). ClinicalTrials.gov. Updated April 16, 2025. Accessed May 7, 2025. https://www.clinicaltrials.gov/study/NCT05673811