Phase 1 study of META 10-19, an IL-10-expressing, anti-CD19 CAR T cell product in patients with high-risk DLBCL.

2552 Background: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of B cell lymphoma. However, limited duration of remission remains a significant challenge. We designed a metabolically armored anti-CD19 CAR T-cell product (META 10-19) that autocrine interleukin (IL)-10 to enhance antitumor activity, and assess the therapeutic potential in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Methods: This phase 1 study is designed to evaluate the safety and preliminary efficacy of META 10-19 in relapsed/refractory DLBCL patients aged 3–70 years old. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded by ASTCT criteria, and other adverse events (AEs) were evaluated according to CTCAE 5.0. Tumor response was assessed by investigators using Lugano 2014 criteria and IPCG criteria. Results: From December 2022 to December 2024, 14 patients with a median age of 54.5 years have been enrolled and received META 10-19 infusion at doses ranging from (0.002–0.1) ×10 6 cells/kg, following a standard lymphodepletion regimen (30 mg/m 2 /day Flu ×3 days, 300 mg/m 2 /day Cy ×3 days). All patients had relapsed/refractory disease, with high-risk features including primary refractory (n = 9), nodal and extranodal involvement (n = 6), CNS lymphoma (n = 5), and bulky disease (n = 2). The most frequent Grade 3–4 AEs comprised neutropenia (100%, 14/14), thrombocytopenia (85.7%, 12/14), and anemia (71.4%, 10/14). CRS was predominantly manifesting as low-grade events (Grade 1–2, n = 13; Grade 3, n = 1). ICANS developed in 2 patients (14.3%) with primary CNS disease, manifesting as transient seizures and classified as Grade 3. At 3 months post-infusion, the overall response rate was 100%, including 13 patients (92.9%) achieved complete response (CR), and 1 patient achieved partial response. As of December 1, 2025, with a median follow-up of 23.3 months (range, 5.6–33.4), 9 patients maintained CR for over 1 year, 4 for over 2 years, and the earliest infused patient remains in remission at 33.4 months. The median progression-free survival (PFS) and overall survival (OS) have not yet been reached, while the 12-month PFS rate and 12-month OS rate were 71.4% and 92.9% , respectively. Conclusions: This first-in-human trial of META 10-19, an IL-10 expressing, anti-CD19 CAR T-cell product, for the treatment of relapsed/refractory DLBCL has exhibited manageable safety profile and durable efficacy at ultra-low doses in patients with high-risk features. Studies evaluating larger cohorts and longer follow-up are ongoing. Clinical trial information: NCT05715606 .