257P Phase I clinical trial of ragistomig (ABL503/TJ-L14B: PD-L1 × 4-1BB bispecific antibody) Q6W dosing balances favorable safety and sustained efficacy through extended immunologic memory and reinvigoration of CD8+ T cells

Background: ANV600 is a novel PD-1-targeted, IL-2R/ agonist designed to selectively activate PD-1 + CD8 + T cells with pre-exhausted, cytotoxic phenotype.By binding to a unique epitope distinct from checkpoint inhibitors, ANV600 aims to reinvigorate tumor antigen-experienced CD8 + T cells within the tumor microenvironment, while limiting IL-2 related toxicities and potentiating the response in checkpoint-refractory tumors.Methods: EXPAND-1 (NCT06470763) is a global, multicenter, open-label, first-inhuman phase I/II trial enrolling patients with advanced solid tumors.ANV600 is administered as monotherapy Q2W or in a dose intensification regimen or in combination with 200 mg pembrolizumab Q3W.Phase I uses a BOIN design to determine the MTD and/or RP2D, evaluating safety, PK, PD and preliminary anti-tumor activity.Phase II will explore efficacy and safety of ANV600 in tumor-specific expansion cohorts.The study is ongoing (data cut-off 17 September 2025).Results: 52 patients have been treated: 28 with monotherapy Q2W (10 -150 g/kg), 8 with an "intensified" dosing regimen monotherapy (Q1W 4, then Q2W; 60/90 g/kg 4, then 120 g/kg maintenance) and 16 patients with ANV600/pembrolizumab combination therapy (10-90 g/kg Q2W + 200 g pembrolizumab Q3W).ANV600 was generally well tolerated.Most treatment related adverse events were pyrexia, transient and self-limiting liver enzyme elevations, and low-grade (G2) cytokine release syndrome.Pharmacodynamics analyses demonstrate selective targeting of PD-1-expressing cells, with preferential induction of proliferation of PD-1 + CD8 + T cells compared to PD-1 -CD8 + T cells.ANV600 leads to a preferential expansion of CD8 + T and NK cells with negligible Treg activation, supporting its IL-2R-targeted mechanism.Conclusions: ANV600 demonstrates a favorable safety profile and selective immunomodulatory activity, supporting its potential as a novel immunotherapy for advanced solid tumors.Updated safety, efficacy and translational data will be presented.