VCN-01 with Standard Care Boosts Survival, Shows Safety in PDAC

Adding VCN-01 (zabilugene almadenorepvec) to standard-of-care (SOC) gemcitabine plus Abraxane (nab-paclitaxel) led to improved overall survival (OS), progression-free survival (PFS), and duration of response (DOR) compared with SOC alone in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who had not received previous systemic therapy, according to findings presented at the 2025 ESMO Congress.

Results from the multicenter, open-label, randomized phase 2b VIRAGE trial presented by Rocio Garcia-Carbonero, MD, head of the GI and NET oncology unit of Hospital Universitario 12 de Octubre’s oncology department in Madrid, Spain, confirmed that the trial met its primary end points of OS and safety along with secondary end points of PFS, response rates, DOR, and biomarker Ca19.9.

“Survival benefit was greater among patients who received two VCN-01 doses and with longer follow-up,” explained Garcia-Carbonero in her presentation. “These encouraging data support further evaluation of this combination in a larger, blinded, randomized trial with additional VCN-01 doses.”

How Effective Was VCN-01 in Metastatic PDAC?

A preplanned subgroup analysis of all patients who started the fourth cycle of SOC (which, for patients in the experimental arm, included two doses of VCN-01) revealed that risk of death was reduced by 56% for patients who received VCN-01 and SOC compared with SOC alone, with an improved OS of 14.8 months versus 11.6 months in the SOC-alone arm.

Likewise, the subgroup analysis showed the addition of VCN-01 led to a 52% reduction in the risk of disease progression or death compared with the SOC arm. Patients receiving VCN-01 demonstrated a PFS of 11.2 months versus 7.4 months in patients receiving SOC alone.

Median OS in the modified intent-to-treat (mITT) population was 10.6 months versus 8.6 months in the VCN-01 and SOC arms, respectively. The full analysis set (FAS) population yielded a median OS of 10.8 months versus 8.6 months, respectively.

Patients receiving VCN-01 had a median DOR of 11.2 months versus 5.4 months in the SOC arm.

The VCN-01 arm had an overall response rate (ORR) of 39.6% with one complete response, 18 partial responses, 18 patients with stable disease, and 11 patients with progressive disease. The SOC-alone arm yielded a 31.3% ORR with no complete responses, 15 partial responses, 19 patients with stable disease, and 14 patients with progressive disease. Disease control rates (DCR) were 77.1% and 70.8% for experimental and SOC arms, respectively.

Additional biologic data confirmed the efficacy of VCN-01.

“Sustained VCN-01 genome levels indicated persistent replication and confirmed the bioactivity of the second dose despite the presence of neutralizing antibodies,” Garcia-Carbonero reported in her presentation.

How Safe Was VCN-01 in This Patient Population?

All serious treatment-related side effects, of which there were 13, were resolved. The most common grade 3 or higher side effects were transaminase increase (15.1%), flu-like symptoms (13.2%), and drug-induced liver injury (3.8%). Side effects decreased with the second dose, with only one patient experiencing a grade 3 or higher side effect (asthenia/fatigue) compared with 27 in the first dose.

Two patients died of treatment-emergent side effects, but neither were related to VCN-01 or SOC. The VCN-01 arm had greater incidence of grade 3 or higher neutropenia (33.9% versus 14.6%), increased transaminase (20.8% versus 10.4%), and increased GGT (7.5% versus 0%), among other side effects.

VCN-01: What Is It, and How Was It Dosed?

VCN-01 is an oncolytic adenovirus that multiplies in cancer cells with a dysfunctional RB1 pathway, according to Garcia-Carbonero. VCN-01 expresses hyaluronidase (PH2) and degrades tumor stroma, enhancing chemotherapy efficacy and anticancer immune response.

The systemic treatment delivers VCN-01 to the primary tumor and metastases while de-targeting the liver. It is designed to target tumor cells while leaving healthy tissue intact, making “cold” tumors “hot” and priming them for immunotherapy.

Patients in the VIRAGE trial were randomized 1:1 to receive either SOC, which entails 125 mg/m2 of IV gemcitabine with 1000 mg/m2 of IV Abraxane on days 1, 8, and 15 of 28-day cycles, or SOC with two doses of IV VCN-01 a week before cycles 1 and 4 of SOC therapy. Each arm contained 46 patients.

Patients eligible for VIRAGE had histologically or cytologically confirmed newly diagnosed mPDAC with no prior systemic therapy and an ECOG status of 0 or 1. Stratification factors included geographical area (US versus EU) and ECOG status (0 versus 1). OS was analyzed after 57 total deaths.

Reference

1. Cid RAP, Mercade TM, Laquente B, et al. VIRAGE trial: Randomized phase IIb, open-label, study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 2216MO.