NCT07172412

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

An Umbrella Ib/II Phase Study Evaluating the Efficacy and Safety of First-Line Combination Therapy in the Treatment of Extensive-Stage Small Cell Lung Cancer

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 165 (estimated)
• Sponsor: Tianjin Medical University Cancer Institute and Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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).

Detailed description

Patients received specific targeted therapy combined with SOC treatment (etoposide 100 mg/m² on days 1-3 + carboplatin AUC5 on day 1 + immunotherapy on day 1): (1) DLL3 cohort: 1.0 × 10\^9 DLL3-CAR-positive NK cells d5 q6w; (2) XPO1 cohort: Oral selinexor 60 mg biweekly q21d; (3) Anlotinib cohort: Oral anlotinib 12 mg on days 1-14, q21d.

Conditions

• Extensive Stage Lung Small Cell Cancer

Interventions

Type	Name	Description
DRUG	Selinexor	Selinexor 60 mg biw q21d
DRUG	Anlotinib	Anlotinib 12mg d1-14 qd PO
BIOLOGICAL	DLL3 CAR-NK cells	1.0×10\^9 DLL3-CAR-NK+ cells d5 q6w
DRUG	Etoposide + Cisplatin/Carboplatin	Etoposide 100mg/m\^2 d1-3+ cisplatin 75mg/m\^2 d1-3 or Carboplatin AUC5
DRUG	Tislelizumab/Atezolizumab/ Durvalumab/Benmelstobart/Toripalimab/Serplulimab	Use immunotherapy according to the standard immunotherapy-combined-chemotherapy protocol.

Timeline

• Start date: 2025-11-01
• Primary completion: 2027-12-01
• Completion: 2028-12-01
• First posted: 2025-09-15
• Last updated: 2025-09-30

Locations

1 site across 1 country: China