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 (8Suppl): Abstract nr CT162.