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Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection.

dc.contributor.authorGarcia-Carbonero, Rocio
dc.contributor.authorSalazar, Ramon
dc.contributor.authorDuran, Ignacio
dc.contributor.authorOsman-Garcia, Ignacio
dc.contributor.authorPaz-Ares, Luis
dc.contributor.authorBozada, Juan M
dc.contributor.authorBoni, Valentina
dc.contributor.authorBlanc, Christine
dc.contributor.authorSeymour, Len
dc.contributor.authorBeadle, John
dc.contributor.authorAlvis, Simon
dc.contributor.authorChampion, Brian
dc.contributor.authorCalvo, Emiliano
dc.contributor.authorFisher, Kerry
dc.contributor.funderPsiOxus Limited
dc.contributor.funderPsiOxus Limited
dc.date.accessioned2023-01-25T09:52:17Z
dc.date.available2023-01-25T09:52:17Z
dc.date.issued2017-09-19
dc.description.abstractEnadenotucirev (formerly ColoAd1) is a tumor-selective chimeric adenovirus with demonstrated preclinical activity. This phase 1 Mechanism of Action study assessed intravenous (IV) delivery of enadenotucirev in patients with resectable colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), urothelial cell cancer (UCC), and renal cell cancer (RCC) with a comparator intratumoral (IT) dosed CRC patient cohort. Seventeen patients scheduled for primary tumor resection were enrolled. IT injection of enadenotucirev (CRC only) was administered as a single dose (≤ 3 × 1011 viral particles [vp]) on day 1, followed by resection during days 8-15. IV infusion of enadenotucirev was administered by three separate doses (1 × 1012 vp) on days 1, 3, and 5, followed by resection during days 8-15 (CRC) or days 10-25 (NSCLC, UCC, and RCC). Enadenotucirev activity was measured using immunohistochemical staining of nuclear viral hexon and quantitative polymerase chain reaction for viral genomic DNA. Delivery of enadenotucirev was observed in most tumor samples following IV infusion, with little or no demonstrable activity in normal tissue. This virus delivery (by both IV and IT dosing) was accompanied by high local CD8+ cell infiltration in 80% of tested tumor samples, suggesting a potential enadenotucirev-driven immune response. Both methods of enadenotucirev delivery were well tolerated, with no treatment-associated serious adverse events. This study provides key delivery and feasibility data to support the use of IV infusion of enadenotucirev, or therapeutic transgene-bearing derivatives of it, in clinical trials across a range of epithelial tumors, including the ongoing combination study of enadenotucirev with the checkpoint inhibitor nivolumab. It also provides insights into the potential immune-stimulating properties of enadenotucirev. This MOA study was a phase 1, multicenter, non-randomized, open-label study to investigate the administration of enadenotucirev in a preoperative setting (ClinicalTrials.gov: NCT02053220).
dc.description.versionSi
dc.identifier.citationGarcia-Carbonero R, Salazar R, Duran I, Osman-Garcia I, Paz-Ares L, Bozada JM, et al. Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection. J Immunother Cancer. 2017 Sep 19;5(1):71.
dc.identifier.doi10.1186/s40425-017-0277-7
dc.identifier.essn2051-1426
dc.identifier.pmcPMC5604344
dc.identifier.pmid28923104
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604344/pdf
dc.identifier.unpaywallURLhttps://doi.org/10.1186/s40425-017-0277-7
dc.identifier.urihttp://hdl.handle.net/10668/11588
dc.issue.number1
dc.journal.titleJournal for immunotherapy of cancer
dc.journal.titleabbreviationJ Immunother Cancer
dc.language.isoen
dc.organizationInstituto de Biomedicina de Sevilla-IBIS
dc.organizationHospital Universitario Virgen del Rocío
dc.page.number13
dc.provenanceRealizada la curación de contenido 26/06/2025.
dc.publisherBMJ Group
dc.pubmedtypeClinical Trial, Phase I
dc.pubmedtypeJournal Article
dc.pubmedtypeMulticenter Study
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.publisherversionhttps://jitc.bmj.com/lookup/pmidlookup?view=long&pmid=28923104
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAdenoviruses, Human
dc.subjectCarcinoma, Non-Small-Cell Lung
dc.subjectColorectal Neoplasms
dc.subjectDigestive System Surgical Procedures
dc.subjectOncolytic Virotherapy
dc.subjectTreatment Outcome
dc.subject.decsNeoplasias
dc.subject.decsNivolumab
dc.subject.decsInmunidad
dc.subject.decsCognición
dc.subject.decsNeoplasias pulmonares
dc.subject.decsAdenoviridae
dc.subject.decsNeoplasias colorrectales
dc.subject.decsVirión
dc.subject.decsInyecciones
dc.subject.meshAdministration, Intravenous
dc.subject.meshCD8-Positive T-Lymphocytes
dc.subject.meshCarcinoma, Renal Cell
dc.subject.meshCarcinoma, Transitional Cell
dc.subject.meshCombined Modality Therapy
dc.subject.meshDNA, Viral
dc.subject.meshHumans
dc.subject.meshLung Neoplasms
dc.subject.meshOncolytic Viruses
dc.subject.meshPulmonary Surgical Procedures
dc.subject.meshUrologic Surgical Procedures
dc.titlePhase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number5
dspace.entity.typePublication

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