Preliminary results from an ongoing phase 1 study of LB2102, a dnTGFBR2-armored DLL3-targeted autologous CAR-T cell therapy, in patients with relapsed or refractory SCLC or LCNEC.

Abstract

8012 Background: Delta-like ligand 3 (DLL3) is a promising target for small cell lung cancer (SCLC) and other neuroendocrine tumors. We present results from an ongoing dose-escalation study of LB2102, an autologous CAR-T cell therapy engineered to target DLL3 and armored with a TGF-β receptor blockade to overcome the immunosuppressive tumor microenvironment. Methods: This open-label, multicenter, phase 1 study evaluates LB2102 in patients with SCLC or large cell neuroendocrine carcinoma (LCNEC), relapsed or refractory to ≥1 prior line of therapy (LOT). Dose escalation follows an i3+3 design, with dose levels (DL) of 0.3, 1.0, 2.0, 4.0, 8.0, 12.0, and 16.0x10 6 CAR+ T cells/kg. Subjects received a single infusion of LB2102 after standard lymphodepletion (LD). The primary objectives are to assess safety and tolerability, and to determine the recommended phase 2 dose. Results: As of 05-JAN-2026, 20 subjects received LB2102 (DL1–DL5, n = 3 each; DL6 was skipped based on data; DL7, n = 5). Seventeen subjects had SCLC and 3 LCNEC; 13 (65%) had a history of brain metastases. Median age was 56.5 yrs (range 20–73 yrs) with median 1 prior LOT (range 1–7); 95% received bridging therapy between apheresis and LB2102. The most-common grade ≥ 3 LB2102-related adverse events (TRAEs) were hematologic and co-attributed to LD. Four subjects (20%) had cytokine-release syndrome (CRS; 3 Grade 1 and 1 Grade 2); all resolved. Two subjects developed ICANS (1 Grade 1 and 1 Grade 3); both resolved. There were no dose-limiting toxicities (DLTs) or TEAE-related deaths. Other grade ≥ 3 non-hematologic LB2102-related TEAEs were dyspnea, prolonged QT, and hypoxia (all n = 1 at DL7). Of 17 response-evaluable subjects, best overall responses per RECIST1.1 criteria were 3 partial responses (PR, one each at DL3, DL4, and DL7) and 10 stable diseases (SD, at DLs 2–7), for an objective response rate (ORR) of 3/17 (18%) and a disease control rate (DCR) of 13/17 (76%). Median DOR among patients with a PR was 208 days. CAR-T expansion in peripheral blood (measured by qPCR) was observed at DL3 (N = 3), DL4 (N = 3), DL5 (N = 3), and DL7 (N = 5; 1 patient excluded due to incomplete PK profile): median C max was 694, 581, 527, and 2851 copies/µg gDNA; median T max was 15, 15, 6, and 6 days, respectively. Patients with partial responses had relatively higher PK exposure (median C max ) compared to the PK exposure of patients with stable diseases and progressive diseases. Median tumor expression of DLL3 at baseline was 97% (n = 16, range 45%–100%) and at Day 29 post-infusion was 90% (n = 8, range 55%–100%). Conclusions: LB2102 demonstrated consistent CAR-T expansion and encouraging anti-tumor activity at doses ≥ 2x10 6 CAR+T cells/kg (ORR 27% and DCR 91%). LB2102 was well tolerated with no DLTs and manageable CRS and ICANs. Clinical trial information: NCT05680922 .