Design and rationale of DOMISOL, a first-in-human Phase I/II study of DT-7012 (NCT06819735) in advanced solid tumors

Background: CCR8 has recently emerged as a promising target in the treatment of solid tumors. DT-7012, a novel anti-CCR8 monoclonal antibody, distinguishes itself from competitors through its binding properties and optimized effector functions. These characteristics suggest that DT-7012 has the potential to effectively modulate the tumor microenvironment and improve clinical outcomes. Based on its differentiated mechanism, DT-7012 has advanced into first-in-human evaluation. Objectives: To describe the design and scientific rationale of the ongoing Phase I/II trial (NCT06819735) assessing the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of DT-7012 in patients with advanced solid tumors. Methods: This multicenter and open-label DOMISOL study comprises a dose-escalation phase followed by indication-specific expansion cohorts. Adaptive Bayesian dose-escalation will identify the recommended Phase II dose (RP2D) based on safety, pharmacokinetics, and biomarker readouts (CCR8 + Treg depletion, cytokine modulation). Expansion cohorts will evaluate antitumor activity as monotherapy and in combination with anti-PD-1 therapy. Paired tumor biopsies and peripheral blood analyses will enable translational assessment of immune modulation. Results: The trial is actively enrolling across multiple centers. The design incorporates real-time translational endpoints and stringent safety monitoring to optimize dose selection and patient benefit. Preclinical data predict a favorable therapeutic window and synergy with checkpoint blockade. Conclusions: This Phase I/II study is designed to rigorously characterize DT-7012's safety profile and biological activity in patients with solid tumors. The integration of adaptive design and translational biomarkers aims to accelerate clinical validation of this novel CCR8-depleting antibody.