Data from Phase I Trial of Intravenous VCN-01 Oncolytic Adenovirus and Durvalumab in Patients with Head and Neck Metastatic Squamous Cell Carcinoma Refractory to Immunotherapy
Year: 2026
Type: other
Abstract: Purpose: Zabilugene almadenorepvec (VCN-01) is a hyaluronidase-expressing oncolytic adenovirus that increases immune checkpoint antibody tumor uptake in mice. VCN-01 was evaluated with durvalumab in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) refractory to anti–programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1). Patients and Methods: Patients received intravenous VCN-01 [3.3E12 viral particles (vp), low dose (LD) or 1.0E13 vp, high dose (HD)] plus durvalumab (1,500 mg/every 4 weeks) concomitantly (VCN-01 + durvalumab on day 1; arm I) or sequentially (VCN-01 on day −14 + durvalumab on day 1; arm II). Six patients were enrolled in arm I LD, 8 in arm II LD, and 6 in arm II HD. Results: Two dose-limiting toxicities occurred in arm I LD, one in arm II LD, and none in arm II HD. Antitumor responses were observed, with arm II HD displaying the longest overall survival (OS) of 17.3 months (8.1–not estimable [NE]), although not statistically significant. Eleven (61.1%) patients were alive >12 months. VCN-01 was detected in blood and tumors, and hyaluronidase expression was confirmed. Changes in tumor immune markers were identified, including increased PD-L1 expression correlating with OS. Transcriptomic and radiomic analyses showed changes in the extracellular matrix and increased tumor perfusion. Conclusions: Sequential VCN-01 plus durvalumab was better tolerated than concomitant treatment. The recommended VCN-01 phase II dose was 1.0E13 vp on the sequential schedule. Encouraging survival was observed in patients after progressing on anti–PD-(L)1 agents. Data support VCN-01 replication associated with increased PD-1, PD-L1, and CD8 tumor expression. Sequential systemic delivery of VCN-01 and anti–PD-L1 therapy may represent an improved treatment for HNSCC.
Authors: Maria Jove, Irene Braña, Marc Oliva, Alberto Hernando-Calvo, Carlos Erasun, Ana Mato-Berciano, Maria Victoria Maliandi, Silvia Torres-Manjon, Luis A. Rojas, Sheila Connelly, Miriam Bazan-Peregrino, Rafael Moreno, Jaime Martínez de Villarreal, Francisco X. Real, Charles Le, Paolo Nuciforo, Ramon Alemany, Gabriel Capellà, Carmen Blasco, Manel Cascalló, Ricard Mesía
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W7204960338