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

• DOI: 10.1136/jitc-2021-003255
• Publication Date: 2022-03-25T16:34:46Z
• Authors: Rocio Garcia-Carb...; Miriam Bazan-Pere...; Marta Gil-Martín; Rafael Álvarez; Teresa Macarulla; Maria C Riesco-Ma...; Helena Verdaguer; Carmen Guillén-Ponce; Martí Farrera-Sal; Rafael Moreno; Ana Mato-Berciano; Maria Victoria Ma...; Silvia Torres-Manjon; Marcel Costa; Natalia del Pozo; Jaime Martínez de...; Francisco X Real; Noemí Vidal; Gabriel Capella; Ramon Alemany; Emma Blasi; Carmen Blasco; Manel Cascalló; Ramon Salazar
• Keywords: Pharmacodynamics; Oncolytic adenovirus

VCN-01 is an oncolytic adenovirus (Ad5 based) designed to replicate in cancer cells with dysfunctional RB1 pathway, express hyaluronidase enhance virus intratumoral spread and facilitate chemotherapy immune extravasation into the tumor. This phase I clinical trial was aimed find maximum tolerated dose/recommended II dose (RP2D) dose-limiting toxicity (DLT) of intravenous delivery replication-competent patients advanced cancer.Part I: refractory solid tumors received one single VCN-01. Parts III: pancreatic adenocarcinoma (only cycle 1) nab-paclitaxel plus gemcitabine (VCN-concurrent on day 1 Part II, 7 days before III). Patients were required have anti-Ad5 neutralizing antibody (NAbs) titers lower than 1/350 dilution. Pharmacokinetic pharmacodynamic analyses performed.26% initially screened excluded based high NAbs levels. Sixteen 12 enrolled respectively: RP2D 1×1013 viral particles (vp)/patient (Part I), 3.3×1012 vp/patient II). Fourteen included there no DLTs vp/patient. Observed grade 4 aspartate aminotransferase increase patient I, vp), febrile neutropenia 5 thrombocytopenia enterocolitis another vp). In overall response rate 50% II) genomes detected tumor tissue five out six biopsies (day 8). A second plasmatic peak increased serum levels suggested replication after injection all patients. Increased biomarkers (interferon-γ, soluble lymphocyte activation gene-3, interleukin (IL)-6, IL-10) found administration.Treatment feasible has acceptable safety. Encouraging biological activity observed when administered combination adenocarcinoma.NCT02045602.