LB2102 (DLL3-targeted, dnTGFBR2-armored autologous CAR-T) shows early signals in R/R SCLC/LCNEC with manageable CRS/ICANS

LB2102 is an autologous DLL3-directed CAR-T cell therapy armored with a dominant-negative TGF-β receptor 2 (dnTGFBR2) to blunt TGF-β–mediated immunosuppression, evaluated in an open-label, multicenter Phase 1 i3+3 dose-escalation study in relapsed/refractory SCLC or LCNEC after ≥1 prior line (NCT05680922). As of January 5, 2026, 20 patients were treated (17 SCLC/3 LCNEC; 65% with prior brain metastases; median 1 prior LOT, range 1–7; 95% received bridging); among 17 response-evaluable patients, ORR was 18% (3/17 PR) with DCR 76% (13/17), median DOR for PRs 208 days, and the abstract highlights ORR 27% and DCR 91% at doses ≥2×10^6 CAR+T/kg—numerically in the ballpark of (or below) typical single-agent 2L benchmarks like lurbinectedin (35% ORR; DCR ~67%) and generally above chemo-refractory topotecan expectations (10% ORR in some series). Safety looked CAR-T–familiar but relatively contained in this small dataset: CRS in 20% (all Grade 1–2) and ICANS in 2 patients (1 Grade 3), with no DLTs or TEAE-related deaths; most Grade ≥3 TRAEs were hematologic and co-attributed to lymphodepletion, with isolated Grade ≥3 dyspnea/prolonged QT/hypoxia (each n=1 at the highest reported dose level).