eligibility_summary
Patients with locally advanced (IIIB/IIIC) or metastatic (IV) NSCLC not amenable to radical surgery/radiotherapy, histologically/cytologically confirmed, no prior systemic therapy, PD-L1 TPS ≥1%, ≥1 measurable lesion (RECIST 1.1), ECOG 0–1, life expectancy ≥12 weeks, adequate organ/bone marrow. Exclude: active second cancer, significant CV disease, pneumonitis/ILD, recent systemic infection, active HBV/HCV, HIV/AIDS/syphilis, allergy to SKB264/pembrolizumab, prior ICIs/TROP2/topo I drugs, recent major surgery, pregnancy/lactation.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 3, randomized study in first-line PD-L1+ locally advanced/metastatic NSCLC comparing SKB264 + pembrolizumab vs pembrolizumab alone. Interventions and mechanisms: 1) SKB264: a TROP2-targeting antibody–drug conjugate (ADC). The anti-TROP2 monoclonal antibody binds TROP2 on tumor cells, is internalized, and releases a cleavable topoisomerase I inhibitor payload, causing DNA damage/replication stress and tumor cell death (with potential bystander effect). 2) Pembrolizumab: an anti–PD-1 immune-checkpoint inhibitor (humanized IgG4 mAb) that blocks PD-1 on T cells to restore antitumor immunity. Cells/pathways targeted: TROP2-expressing epithelial tumor cells, DNA topoisomerase I–mediated replication, PD-1/PD-L1 axis on T cells/tumor, enhancing cytotoxic T-cell activity in the tumor microenvironment.