2026-04-29T16:05:23Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/251962025-12-18T13:01:35Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991

00925njm 22002777a 4500 dc García-Carbonero, Rocio author Bazan-Peregrino, Miriam author Gil-Martín, Marta author Álvarez, Rafael author Macarulla, Teresa author Riesco-Martinez, Maria C author Verdaguer, Helena author Guillén-Ponce, Carmen author Farrera-Sal, Martí author Moreno, Rafael author Mato-Berciano, Ana author Maliandi, Maria Victoria author Torres-Manjon, Silvia author Costa, Marcel author Del Pozo, Natalia author Martínez de Villarreal, Jaime author Real Arribas, Francisco author Vidal, Noemí author Capella, Gabriel author Alemany, Ramon author Blasi, Emma author Blasco, Carmen author Cascalló, Manel author Salazar, Ramon author 2022-03 VCN-01 is an oncolytic adenovirus (Ad5 based) designed to replicate in cancer cells with dysfunctional RB1 pathway, express hyaluronidase to enhance virus intratumoral spread and facilitate chemotherapy and immune cells extravasation into the tumor. This phase I clinical trial was aimed to find the maximum tolerated dose/recommended phase II dose (RP2D) and dose-limiting toxicity (DLT) of the intravenous delivery of the replication-competent VCN-01 adenovirus in patients with advanced cancer. Part I: patients with advanced refractory solid tumors received one single dose of VCN-01. Parts II and III: patients with pancreatic adenocarcinoma received VCN-01 (only in cycle 1) and nab-paclitaxel plus gemcitabine (VCN-concurrent on day 1 in Part II, and 7 days before chemotherapy in Part III). Patients were required to have anti-Ad5 neutralizing antibody (NAbs) titers lower than 1/350 dilution. Pharmacokinetic and pharmacodynamic analyses were performed. 26% of the patients initially screened were excluded based on high NAbs levels. Sixteen and 12 patients were enrolled in Part I and II, respectively: RP2D were 1×10 viral particles (vp)/patient (Part I), and 3.3×10 vp/patient (Part II). Fourteen patients were included in Part III: there were no DLTs and the RP2D was 1×10 vp/patient. Observed DLTs were grade 4 aspartate aminotransferase increase in one patient (Part I, 1×10 vp), grade 4 febrile neutropenia in one patient and grade 5 thrombocytopenia plus enterocolitis in another patient (Part II, 1×10 vp). In patients with pancreatic adenocarcinoma overall response rate were 50% (Part II) and 50% (Part III). VCN-01 viral genomes were detected in tumor tissue in five out of six biopsies (day 8). A second viral plasmatic peak and increased hyaluronidase serum levels suggested replication after intravenous injection in all patients. Increased levels of immune biomarkers (interferon-γ, soluble lymphocyte activation gene-3, interleukin (IL)-6, IL-10) were found after VCN-01 administration. Treatment with VCN-01 is feasible and has an acceptable safety. Encouraging biological and clinical activity was observed when administered in combination with nab-paclitaxel plus gemcitabine to patients with pancreatic adenocarcinoma. NCT02045602. J Immunother Cancer . 2022 Mar;10(3):e003255. Journal for Immnunotherapy for cancer 35338084 https://hdl.handle.net/20.500.12105/25196 clinical trials as topic gastrointestinal neoplasms oncolytic virotherapy tumor microenvironment Phase I, multicenter, open-label study of intravenous VCN-01 oncolytic adenovirus with or without nab-paclitaxel plus gemcitabine in patients with advanced solid tumors.