Abstract CT162: Analysis of tumor and biomarker responses in the VIRAGE Trial, a randomized Phase IIb, open-label, study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC)

Abstract Background: VCN-01 (zabilugene almadenorepvec) is an oncolytic adenovirus expressing hyaluronidase to degrade tumor stroma, facilitate chemotherapy penetration and stimulate tumor immunity, which is being developed for different cancer indications. The randomized, open-label, Phase 2b VIRAGE trial tested the efficacy and safety of 2 intravenous (IV) doses of VCN-01 combined with standard of care (SoC) gemcitabine/nab-paclitaxel (GA) in mPDAC. Methods: Chemonaïve mPDAC patients were randomized 1:1 to receive SoC doses of GA on days 1, 8 and 15 of repeated 28-day cycles (Arm I) or 2 separate IV doses of VCN-01 (1x1013 vp/dose) 1 week prior to cycles 1 and 4 of GA (Arm II). Primary endpoints were overall survival (OS) and safety. Secondary objectives included progression free survival (PFS), objective response rates (ORR), duration of response (DoR) and Ca19.9 changes. VCN-01 genomes in blood and serum levels of neutralizing anti-adenovirus antibodies (anti-Ad-NAb’s) were also analyzed. Results: 96 patients in the trial received at least 1 dose of GA or VCN-01+GA (48 patients in each arm). Median OS was 10.8 vs. 8.6 months for Arm II and Arm I, respectively (HR 0.57, 95% CI 0.34-0.96; P=0.055) and PFS was 7.0 vs. 4.6 months (HR 0.55, 95% CI 0.34-0.88; P=0.011). OS benefits with VCN-01+GA vs. GA alone were consistent across different subgroups, including patients aged over 70 years, presence of hepatic metastases, or patients with >2 metastatic sites. Compared to patients in Arm I who started cycle 4 of GA, patients in Arm II who received 2 VCN-01 doses and started cycle 4 of GA showed greater improvement in OS (14.8 vs 11.6 months; HR 0.44; 95% CI 0.21-0.92; P=0.046) and PFS (11.2 vs 7.4 months; HR 0.48; 95% CI 0.25-0.91; P=0.017). ORR was 39.6% vs. 31.3% (P=0.314), and more patients had target tumor shrinkage with VCN-01 + GA than GA (84.1% vs. 69.8%; P=0.13). DoR was longer for VCN-01+GA (11.2 vs 5.4 months; HR 0.22; 95% CI 0.08 - 0.62; P=0.004) and 8 of 19 patients in this group achieved late objective responses after the second VCN-01 dose (>4 months after randomization). Ca19.9 levels declined more markedly in Arm II, with a median reduction of -61.0% versus -64.9% in Arm I vs. Arm II by cycle 3, and a further decrease to -16.7% vs -86.3% by cycle 9, following the second VCN-01 dose. No correlation between baseline levels of anti-Ad-NAbs and OS or PFS were observed. The peak of viral genome levels in blood was similar between the first and the second dose of VCN-01. Conclusions: Compared to patients in Arm I (GA), mPDAC patients in Arm II (VCN-01+GA) showed improved OS and PFS and later and more durable responses. Patients that received a second VCN-01 dose+GA showed a further delayed disease progression and extended patient survival compared to patients that received equivalent cycles of GA. Citation Format: Rocio Garcia-Carbonero, Roberto Pazo, Teresa Macarulla, Berta Laquente, Alana Nguyen, Carmen Guillén-Ponce, Andres J. Muñoz, Edward J. Kim, Mireya Cazorla, Tara Seery, Miriam Lobo de Mena, Chris Nevala-Plagemann, Vivek R. Sharma, Eva Martinez de Castro, Charles Le, Ana Mato-Berciano, Luis A. Rojas, Carmen Blasco, Manel Cascallo, Manuel Hidalgo. Analysis of tumor and biomarker responses in the VIRAGE Trial, a randomized Phase IIb, open-label, study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT162.