Academic Journal
Phase I Trial of Intravenous VCN-01 Oncolytic Adenovirus and Durvalumab in Patients with Head and Neck Metastatic Squamous Cell Carcinoma Refractory to Immunotherapy.
| Τίτλος: | Phase I Trial of Intravenous VCN-01 Oncolytic Adenovirus and Durvalumab in Patients with Head and Neck Metastatic Squamous Cell Carcinoma Refractory to Immunotherapy. |
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| Συγγραφείς: | Jove M; Medical Oncology Department, Institut Catala d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain., Braña I; Vall d´Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Oliva M; Medical Oncology Department, Institut Catala d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain., Hernando-Calvo A; Vall d´Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Erasun C; Medical Oncology Department, Institut Catala d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain., Mato-Berciano A; Theriva Biologics SL, Parets del Vallès, Barcelona, Spain., Maliandi MV; Theriva Biologics SL, Parets del Vallès, Barcelona, Spain., Torres-Manjon S; Cancer Immunotherapy Group, Oncobell and ProCure programs, IDIBELL-Institut Català d'Oncologia, Hospitalet de Llobregat, Barcelona, Spain., Rojas LA; Theriva Biologics SL, Parets del Vallès, Barcelona, Spain., Connelly S; Theriva Biologics Inc, Rockville, Maryland., Bazan-Peregrino M; Theriva Biologics SL, Parets del Vallès, Barcelona, Spain., Moreno R; Cancer Immunotherapy Group, Oncobell and ProCure programs, IDIBELL-Institut Català d'Oncologia, Hospitalet de Llobregat, Barcelona, Spain., Martínez de Villarreal J; Epithelial Carcinogenesis Group, Spanish National Cancer Research Center-CNIO, Madrid, Spain.; CIBERONC, Madrid, Spain., Real FX; Epithelial Carcinogenesis Group, Spanish National Cancer Research Center-CNIO, Madrid, Spain.; CIBERONC, Madrid, Spain.; Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain., Le C; Theriva Biologics Inc, Rockville, Maryland., Nuciforo P; Molecular Oncology Group, VHIO, Barcelona, Spain., Alemany R; Theriva Biologics SL, Parets del Vallès, Barcelona, Spain.; Cancer Immunotherapy Group, Oncobell and ProCure programs, IDIBELL-Institut Català d'Oncologia, Hospitalet de Llobregat, Barcelona, Spain., Capellà G; CIBERONC, Madrid, Spain.; Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL-ONCOBELL, Hospitalet de Llobregat, Barcelona, Spain., Blasco C; Theriva Biologics SL, Parets del Vallès, Barcelona, Spain., Cascalló M; Theriva Biologics SL, Parets del Vallès, Barcelona, Spain., Mesía R; Medical Oncology Department, Institut Catala d'Oncologia, Badalona, B-ARGO group, CARE program, IGTP, Badalona, Spain. |
| Πηγή: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2026 Sep 01; Vol. 32 (17), pp. 3786-3798. |
| Τύπος έκδοσης: | Journal Article; Clinical Trial, Phase I |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Denville, NJ : American Association for Cancer Research, c1995- |
| Ιατρικοί όροι (MeSH): | Antibodies, Monoclonal*/administration & dosage , Antibodies, Monoclonal*/adverse effects , Adenoviridae*/genetics , Oncolytic Virotherapy*/methods , Oncolytic Virotherapy*/adverse effects , Squamous Cell Carcinoma of Head and Neck*/therapy , Squamous Cell Carcinoma of Head and Neck*/pathology , Squamous Cell Carcinoma of Head and Neck*/immunology , Oncolytic Viruses*/genetics , Head and Neck Neoplasms*/therapy , Head and Neck Neoplasms*/pathology , Head and Neck Neoplasms*/immunology, Immunotherapy/methods ; Antineoplastic Agents, Immunological/administration & dosage ; Humans ; Female ; Male ; Middle Aged ; Aged ; Combined Modality Therapy ; Adult |
| Περίληψη: | 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. (©2026 American Association for Cancer Research.) |
| Substance Nomenclature: | 28X28X9OKV (durvalumab) 0 (Antibodies, Monoclonal) 0 (Antineoplastic Agents, Immunological) |
| Entry Date(s): | Date Created: 20260608 Date Completed: 20260901 Latest Revision: 20260910 |
| Update Code: | 20260911 |
| DOI: | 10.1158/1078-0432.CCR-26-0601 |
| PMID: | 42257887 |
| Βάση Δεδομένων: | MEDLINE |
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