Including VCN-01 (zabilugene almadenorepvec) to standard-of-care (SOC) gemcitabine plus Abraxane (nab-paclitaxel) led to improved total survival (OS), progression-free survival (PFS), and length of response (DOR) in contrast with SOC alone in sufferers with metastatic pancreatic ductal adenocarcinoma (mPDAC) who had not obtained earlier systemic remedy, in line with findings offered on the
Outcomes from the multicenter, open-label, randomized section 2b VIRAGE trial offered by Rocio Garcia-Carbonero, MD, head of the GI and NET oncology unit of Hospital Universitario 12 de Octubre’s oncology division in Madrid, Spain, confirmed that the trial met its major finish factors of OS and security together with secondary finish factors of PFS, response charges, DOR, and biomarker Ca19.9.
“Survival profit was better amongst sufferers who obtained two VCN-01 doses and with longer follow-up,” defined Garcia-Carbonero in her presentation. “These encouraging knowledge assist additional analysis of this mix in a bigger, blinded, randomized trial with extra VCN-01 doses.”
How Efficient Was VCN-01 in Metastatic PDAC?
A preplanned subgroup evaluation of all sufferers who began the fourth cycle of SOC (which, for sufferers within the experimental arm, included two doses of VCN-01) revealed that danger of loss of life was diminished by 56% for sufferers who obtained VCN-01 and SOC in contrast with SOC alone, with an improved OS of 14.8 months versus 11.6 months within the SOC-alone arm.
Likewise, the subgroup evaluation confirmed the addition of VCN-01 led to a 52% discount within the danger of illness development or loss of life in contrast with the SOC arm. Sufferers receiving VCN-01 demonstrated a PFS of 11.2 months versus 7.4 months in sufferers receiving SOC alone.
Median OS within the modified intent-to-treat (mITT) inhabitants was 10.6 months versus 8.6 months within the VCN-01 and SOC arms, respectively. The total evaluation set (FAS) inhabitants yielded a median OS of 10.8 months versus 8.6 months, respectively.
Sufferers receiving VCN-01 had a median DOR of 11.2 months versus 5.4 months within the SOC arm.
The VCN-01 arm had an total response fee (ORR) of 39.6% with one full response, 18 partial responses, 18 sufferers with secure illness, and 11 sufferers with progressive illness. The SOC-alone arm yielded a 31.3% ORR with no full responses, 15 partial responses, 19 sufferers with secure illness, and 14 sufferers with progressive illness. Illness management charges (DCR) have been 77.1% and 70.8% for experimental and SOC arms, respectively.
Further biologic knowledge confirmed the efficacy of VCN-01.
“Sustained VCN-01 genome ranges indicated persistent replication and confirmed the bioactivity of the second dose regardless of the presence of neutralizing antibodies,” Garcia-Carbonero reported in her presentation.
How Secure Was VCN-01 in This Affected person Inhabitants?
All severe treatment-related unwanted side effects, of which there have been 13, have been resolved. The most typical grade 3 or greater unwanted side effects have been transaminase enhance (15.1%), flu-like signs (13.2%), and drug-induced liver harm (3.8%). Unwanted side effects decreased with the second dose, with just one affected person experiencing a grade 3 or greater aspect impact (asthenia/fatigue) in contrast with 27 within the first dose.
Two sufferers died of treatment-emergent unwanted side effects, however neither have been associated to VCN-01 or SOC. The VCN-01 arm had better incidence of grade 3 or greater neutropenia (33.9% versus 14.6%), elevated transaminase (20.8% versus 10.4%), and elevated GGT (7.5% versus 0%), amongst different unwanted side effects.
VCN-01: What Is It, and How Was It Dosed?
VCN-01 is an oncolytic adenovirus that multiplies in most cancers cells with a dysfunctional RB1 pathway, in line with Garcia-Carbonero. VCN-01 expresses hyaluronidase (PH2) and degrades tumor stroma, enhancing chemotherapy efficacy and anticancer immune response.
The systemic remedy delivers VCN-01 to the first tumor and metastases whereas de-targeting the liver. It’s designed to focus on tumor cells whereas leaving wholesome tissue intact, making “chilly” tumors “scorching” and priming them for immunotherapy.
Sufferers within the VIRAGE trial have been randomized 1:1 to obtain both 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 every week earlier than cycles 1 and 4 of SOC remedy. Every arm contained 46 sufferers.
Sufferers eligible for VIRAGE had histologically or cytologically confirmed newly identified mPDAC with no prior systemic remedy and an ECOG standing of 0 or 1. Stratification elements included geographical space (US versus EU) and ECOG standing (0 versus 1). OS was analyzed after 57 complete deaths.
Reference
- Cid RAP, Mercade TM, Laquente B, et al. VIRAGE trial: Randomized section IIb, open-label, examine of nab-paclitaxel and gemcitabine with/with out intravenous VCN-01 in sufferers with metastatic pancreatic most cancers (mPDAC). Introduced at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Summary 2216MO.
