Trispecific DLL3 T-Cell Engager ZG006 Delivers 67% ORR in Post-PD-1 Small-Cell Lung Cancer

ZG006 is a bispecific antibody that bridges CD3+ T cells to two DLL3 epitopes. In a Phase 2 dose-expansion study (NCT06283719) involving 40 heavily pretreated small-cell lung cancer (SCLC) patients (≥2 prior lines of therapy; 73% previously treated with anti–PD-(L)1 agents), 27 evaluable patients demonstrated an overall RECIST ORR of 66.7% and a DCR of 92.6%. The ORR increased from 54% at 10 mg administered every two weeks (Q2W) to 79% at 30 mg, with responses observed in 71% of tumors expressing low or medium levels of DLL3. Cytokine release syndrome (CRS) and fever were common (48% and 58%, respectively), but grade ≥3 TRAEs were infrequent (13%, including one grade 3 CRS). No treatment-related discontinuations or deaths occurred.