A phase I, open-label, dose-escalation study of CAR001 (mRNA-engineered Nb-CAR.BiTE-γδ T cells) in patients with relapsed or refractory solid tumors.

TPS2674 Background: Solid tumors are characterized by a highly immunosuppressive tumor microenvironment (TME). Key immune checkpoint molecules, such as HLA-G and PD-L1, are frequently expressed and act as barriers that limit the infiltration and efficacy of conventional CAR-T cell therapies. CAR001 is an investigational, allogeneic, mRNA-engineered Nb-CAR.BiTE-γδ T cell therapy. By utilizing the innate homing capabilities of γδ T cells and a dual-targeting mechanism, direct binding of HLA-G by T cells and secreting PD-L1 bispecific T-cell engagers from T cells, CAR001 is designed to overcome TME-mediated resistance. This study evaluates the safety and potential activity of repeat intravenous dosing of CAR001 in patients with advanced solid tumors. Methods: Study Design: This is an ongoing, multicenter, open-label, phase I dose-escalation study utilizing a standard 3+3 design or similar escalation schema. Patient Population: Adults with histologically confirmed refractory or relapsed solid tumors (including, but not limited to, colorectal cancer, glioblastoma, and triple-negative breast cancer) who have exhausted standard of care. Intervention: Patients receive escalating doses of CAR001 via intravenous infusion. The protocol allows for repeat dosing to enhance therapeutic persistence. Objectives: The primary objective is to evaluate the safety and tolerability of CAR001 and to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Secondary objectives include assessing preliminary antitumor activity per iRECIST or RANO criteria, as well as characterizing the pharmacokinetic profile of the Nb-CAR.BiTE-γδ T cells. Safety Monitoring: Adverse events (AEs) are monitored using CTCAE v5.0, with specific focus on dose-limiting toxicities (DLTs), cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Trial Status: This trial is currently active and enrolling patients. As of the submission deadline, dose-escalation cohorts are ongoing. To maintain the integrity of the study and comply with ASCO Trials in Progress guidelines, no formal analysis of clinical endpoints or treatment outcomes is provided. Clinical trial information: NCT06150885 .