EGFR L858R

P2, N=32, Recruiting, Nanfang Hospital, Southern Medical University

P1/2, N=67, Recruiting, D3 Bio (Wuxi) Co., Ltd | Active, not recruiting --> Recruiting | Trial completion date: Apr 2028 --> Aug 2028 | Trial primary completion date: Apr 2028 --> Aug 2028

Our study demonstrated that both afatinib and osimertinib as first-line treatments offer favorable median OS in patients with advanced EGFR-mutant NSCLC. In addition, we recommend that patients receiving afatinib as first-line therapy undergo sequential osimertinib treatment, regardless of their T790M mutation status.

P2, N=277, Active, not recruiting, Daiichi Sankyo | Trial completion date: Jul 2026 --> Jan 2027

This case underscores dynamic clonal evolution in advanced NSCLC: the initial L747S/L858R clone showed Osimertinib sensitivity, while subsequent resistance revealed a distinct profile (distinct TP53 mutation, MET amplification, high PD-L1/TMB) that explained the durable response to Pembrolizumab. These findings provide crucial evidence for sequential therapy strategies in compound EGFR mutations. Our findings also highlight the utility of Next Generation Sequencing (NGS) in identifying targetable resistance mechanisms, enabling prolonged survival in patients with compound EGFR mutations and offering valuable insights for clinical decision-making.

This study suggests that common molecular alterations in lung cancer exhibit prognostic value within specific stages, and notably, TP53, KRAS and ALK alterations hold the potential to modify the current staging system. These findings provide a valuable reference for the forthcoming 10th Edition TNM staging system.

Notably, the mean duration of disease progression following EGFR-TKI initiation did not differ significantly between patients with EGFR exon 21 p.L858R mutation and those with EGFR 19-Del. Our study reveals the heterogeneity of compound EGFR mutations, and characterizes the spectrum of acquired resistance mutations to EGFR TKIs.

P2, N=50, Not yet recruiting, Taipei Medical University Hospital

She was initially treated with icotinib for an EGFR exon 21 L858R mutation but the disease progressed after 4 months. CONCLUSIONS As a single case with multiple confounders, this study generates hypotheses but does not confirm efficacy. Further investigation is required to validate high-dose furmonertinib for NSCLC with EGFR exon 14 missense mutations.

Furthermore, the engineered InCasRD system enabled mapping of RNA mutations, such as the EGFR L858R and ovarian tumor domain (OTUD) single-nucleotide variant (SNV, 23439980 G>T), in tumor tissue sections, thereby facilitating clear tumor boundary delineation. Collectively, InCasRD is a powerful, one-step tool for in situ RNA analysis with potential for diagnosis and precision medicine.

P2, N=60, Not yet recruiting, Peking University Cancer Hospital & Institute

P=N/A, N=3400, Not yet recruiting, AstraZeneca