TILT-123 (Ad5/3-E2F-d24-hTNFα-IRES-hIL2, igrelimogene litadenorepvec) is a chimeric oncolytic adenovirus engineered to selectively replicate in tumor cells and express TNF and IL-2. While oncolytic viruses are commonly administered intratumorally, this approach often restricts practical applicability. Intravenous delivery is less invasive, and offers a more practical alternative, however systemic immune barriers challenge effective tumor targeting. In a cohort of a phase I clinical trial, six patients with advanced solid tumors who had exhausted standard treatments received two intravenous doses of TILT-123 (split-dose), per treatment day across seven cycles. Safety was the primary objective, while efficacy outcomes were exploratory and assessed using PET/CT imaging, and overall survival. Split-dosing was safe, with chills, fever, fatigue, and lymphocyte reduction being the most common treatment-related events. In imaging, the disease control rate was 83.3% according to PET criteria and 33.3% by RECIST 1.1. Median overall survival was 198 days. Split-dosing increased the area under the curve of TILT-123 and amplified systemic cytokine responses. Proteomic analysis of serum and neutralizing antibody profiling indicated that enhanced humoral immune activity was associated with shorter overall survival. Post-treatment biopsies confirmed virus presence and alterations in immune cell composition. These findings support further evaluation of intravenous TILT-123 administration in clinical trials.
Jirovec et al. (Fri,) studied this question.