Open-Label, Biomarker-Integrated Umbrella Trial for First-Line Treatment of Extensive-stage Small Cell Lung Cancer

Summary

This is an open-label umbrella study conducted in first treatment ES-SCLC patients, employing a novel umbrella trial design (biomarker-integrated multi-arm trial with a shared ICI+chemotherapy control arm). Eligible patients were assigned to trial arms based on biomarker expression levels. Biomarker subgroups were defined as: (1) High ASCL1/NEUROD1/DLL3 expression: DLL3-CAR-NK cells combined with ICI + etoposide + carboplatin (DLL3 group); (2) Myc overexpression: XPO1 inhibitor selinexor combined with ICI + etoposide + carboplatin (XPO1 group); (3) VIM/AXL high expression group treated with anlotinib combined with ICI + etoposide + carboplatin (anlotinib group).

Timeline

Start

2025-11

Primary completion

2027-12

Completion

2028-12

Publications

• Background Liu Q, Zhang J, Guo C, Wang M, Wang C, Yan Y, Sun L, Wang D, Zhang L, Yu H, Hou L, Wu C, Zhu Y, Jiang G, Zhu H, Zhou Y, Fang S, Zhang T, Hu L, Li J, Liu Y, Zhang H, Zhang B, Ding L, Robles AI, Rodriguez H, Gao D, Ji H, Zhou H, Zhang P. Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies. Cell. 2024 Jan 4;187(1):184-203.e28. doi: 10.1016/j.cell.2023.12.004.
• Background Wang J, Sun T, Meng Z, Wang L, Li M, Chen J, Qin T, Yu J, Zhang M, Bie Z, Dong Z, Jiang X, Lin L, Zhang C, Liu Z, Jiang R, Yang G, Li L, Zhang Y, Huang D. XPO1 inhibition synergizes with PARP1 inhibition in small cell lung cancer by targeting nuclear transport of FOXO3a. Cancer Lett. 2021 Apr 10;503:197-212. doi: 10.1016/j.canlet.2021.01.008. Epub 2021 Jan 23.
• Background Qin T, Wang J, Wang J, Du Q, Wang L, Liu H, Liu W, Li X, Jiang Y, Xu Q, Yu J, Liu H, Wang T, Li M, Huang D. Nuclear to Cytoplasmic Transport Is a Druggable Dependency in HDAC7-driven Small Cell Lung Cancer. Adv Sci (Weinh). 2025 Apr;12(14):e2413445. doi: 10.1002/advs.202413445. Epub 2025 Jan 30.

Drugs

Indications