VCN-01 Plus SOC Improves Survival, Is Safe in Metastatic PDAC

The addition of zabilugene almadenorepvec (VCN-01) to standard-of-care (SOC) gemcitabine plus nab-paclitaxel (Abraxane) improved overall survival (OS), progression-free survival (PFS), and duration of response (DOR) compared with SOC for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who did not receive no prior systemic therapy, according to data shared at the 2025 ESMO Congress.

Results from the multicenter, open-label, randomized phase 2b VIRAGE trial (NCT05673811) 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, confirm 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 2 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 2 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 (95% CI, 10.6-NE) vs 11.6 months (95% CI, 8.6-12.8) in the SOC-alone arm (HR, 0.44; 95% CI, 0.21-0.92; P = .046).

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 (95% CI, 7.3-16.6) vs 7.4 months (95% CI, 5.7-8.4) in patients receiving SOC alone (HR, 0.48; 95% CI, 0.25-0.91; P = .017).

Median OS in the modified intent-to-treat (mITT) population was 10.6 months (95% CI, 6.6-14.8) vs 8.6 months (95% CI, 6.9-11.6) in the VCN-01 and SOC arms, respectively, with an HR of 0.69 (95% CI, 0.42-1.12; P = .196). The full analysis set (FAS) population yielded a median OS of 10.8 months (95% CI, 7.4-15.8) vs 8.6 months (95% CI, 6.9-11.6), respectively, with an HR of 0.5 (95% CI, 0.34-0.96; P = .055).

Patients receiving VCN-01 had a median DOR of 11.2 months (95% CI, 7.4-NE) vs 5.4 months (95% CI, 2.06-6.8) in the SOC arm (HR, 0.22; 95% CI, 0.08-0.62; P = .0035).

The VCN-01 arm had an overall response rate (ORR) ORR of 39.6% with 1 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 (P = .314). 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 genomes levels indicated persistent replication and confirmed the bioactivity of the second dose despite the presence of neutralizing antibodies,” Gracia-Carbonero reported in her presentation.

How Safe Was VCN-01 in This Patient Population?

All serious treatment-related adverse events (TRAEs), of which there were 13, were resolved. The most common grade 3 or higher TRAEs were transaminase increase (15.1%), flu-like symptoms (13.2%), and drug-induced liver injury (3.8%). TRAEs decreased with the second dose, with only 1 patient experiencing a grade 3 or higher TRAE (asthenia/fatigue) compared with 27 in the first dose.

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

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

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

The systemic treatment brings VCN-01 to the primary tumor as well as 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 nab-paclitaxel days 1, 8, and 15 of 28-day cycles, or SOC with 2 doses of IV VCN-01 (1x10¹³ vp) 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 had an ECOG status of 0 or 1. Stratification factors included geographical area (US vs EU) and ECOG status (0 vs 1). OS was analyzed after 57 total deaths.

Reference

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.