EGFR T790M

P2, N=36, Active, not recruiting, Shandong Cancer Hospital and Institute

The results suggest that carmofur and B13 are promising alternatives for therapeutic targets in drug-resistant lung cancer cells.

P1/2, N=32, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028

In a small-sample-size test, the ESEA system achieved 100% sensitivity and specificity in pleural effusion samples (n=5) and a 100% ctDNA detection rate in patients with extracranial lesions and disease progression (n=6). These results highlight its potential as a cost-effective, highly sensitive, and robust platform for dynamic, real-time companion diagnostics, as well as non-invasive monitoring of treatment response and tumor evolution.

T790M-positive samples showed clearly higher measured DNA concentration values after hybridization (5.9-7.4 ng/µL; mean = 6.7 ± 0.6 ng/µL), whereas negative and control samples remained low (1.7-2.3 ng/µL), confirming the analytical specificity and reproducibility of the developed system.This platform offers a rapid, cost-effective, and portable approach for mutation detection without requiring complex instrumentation. The CNT-Fe3O4-probe nanoplatform demonstrates promising potential for future translation into liquid biopsy applications and personalized therapeutic monitoring in NSCLC.

This study represents the latest investigation of resistance mechanisms to afatinib in NSCLC patients with nonclassical mutations. The mechanism of resistance to EGFR-TKI in this study was discovered different from that of patients with classical mutations.

P1, N=36, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Feb 2027 | Trial primary completion date: Jun 2026 --> Feb 2027

Exploiting these vulnerabilities, Unesbulin (PTC596), a tubulin-binding agent with BMI1 inhibitory activity, triggers mitotic catastrophe, mechanistically induces apoptosis in vitro and drives regression of resistant xenografts in vivo. Our findings establish BMI1 as a key mediator of Osimertinib resistance and aggressiveness, uncovering a mutation-context-dependent mitotic vulnerability that can be therapeutically exploited, providing a rationale for targeting BMI1 and mitotic abnormalities to overcome resistance in T790M/L858R backgrounds.

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.

We present an AI-based approach to TCR design with broad utility for efforts to engineer TCRs and for the development of new cell therapies. Artificial intelligence-based approach enables the directed engineering of functional TCRs with enhanced features that target cancer neoantigens.

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.