EGFR exon 19 deletion

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

Overall survival analysis showed no consistent prognostic disadvantage for CO, except in EGFR-KRAS co-mutant NSCLC. These findings further refine the ME landscape of BRAF, KRAS, and EGFR variants, offering a variant-level reference to support mutation-informed precision oncology.

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

Using tumor necrosis factor-α to activate this pathway, we observed enhanced internalization of cetuximab-monomethyl auristatin E and increased cytotoxicity in vitro. Notably, we also found that cisplatin, the backbone of lung cancer chemotherapy, induces a similar noncanonical endocytic response, further supporting the physiological relevance of this pathway. Collectively, our results highlight noncanonical endocytosis as a tractable mechanism to enhance the intracellular delivery and antitumor activity of EGFR-targeted ADCs. This mechanistic insight provides a foundation for developing improved platforms and combination regimens capable of overcoming resistance in NSCLC.

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.

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.

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

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

P2, N=68, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jul 2026 --> Mar 2027

Consistently, afatinib treatment resulted in marked tumor shrinkage and suppression of EGFR signaling in the established mDEL OsiR #1/#3 in vivo. These findings establish secondary Egfr V804F/EGFR V802F as an on-target osimertinib resistance mechanism, providing a preclinical rationale for evaluating afatinib in biomarker-selected patients harboring this alteration.