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Title: Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection.
Authors: Garcia-Carbonero, Rocio
Salazar, Ramon
Duran, Ignacio
Osman-Garcia, Ignacio
Paz-Ares, Luis
Bozada, Juan M
Boni, Valentina
Blanc, Christine
Seymour, Len
Beadle, John
Alvis, Simon
Champion, Brian
Calvo, Emiliano
Fisher, Kerry
metadata.dc.subject.mesh: Adenoviruses, Human
Administration, Intravenous
CD8-Positive T-Lymphocytes
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Carcinoma, Transitional Cell
Colorectal Neoplasms
Combined Modality Therapy
DNA, Viral
Digestive System Surgical Procedures
Lung Neoplasms
Oncolytic Virotherapy
Oncolytic Viruses
Pulmonary Surgical Procedures
Treatment Outcome
Urologic Surgical Procedures
Issue Date: 19-Sep-2017
Abstract: Enadenotucirev (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 ( NCT02053220).
metadata.dc.identifier.doi: 10.1186/s40425-017-0277-7
Appears in Collections:Producción 2020

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