EGFR T790M

In a PC-9Del19/T790M/C797S xenograft model, 6g achieved significant dose-dependent tumor growth inhibition (TGI: 47.3% at 5 mg/kg; 64.2% at 10 mg/kg), markedly surpassing Osimertinib (TGI: 16.07% at 10 mg/kg), with no observed significant toxicity. These results establish 6g as a promising fourth-generation EGFR-TKI candidate with potent activity, favorable pharmacokinetics, and a high safety profile, offering a potential therapeutic strategy against Osimertinib resistance driven by the C797S mutation.

P2, N=60, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

P2, N=35, Not yet recruiting, Shanghai Junshi Bioscience Co., Ltd.

P3, N=345, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2025 --> Jun 2026

P2, N=173, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2026 --> Apr 2027 | Trial primary completion date: Apr 2026 --> Apr 2027

Orthogonal validation via amplicon sequencing confirmed the reference values with high concordance to dPCR. These findings provide evidence that nDNA-based RMs can serve as a biologically representative and reliable standard for validating assays at low VAFs, expanding to large-scale RM production and interlaboratory evaluation.

P2, N=46, Completed, Sun Yat-sen University | Recruiting --> Completed | N=30 --> 46

FGTKIs have altered the therapeutic concept for mutant NSCLC patients and offered unprecedented efficacy and durability compared to earlier-generation inhibitors.

P2, N=27, Active, not recruiting, University of California, San Francisco | Trial completion date: Oct 2026 --> Sep 2027

Molecular docking, molecular dynamics simulations, and MM-GBSA analyses supported stable binding of the active compounds within the catalytic sites of the investigated enzymes. Overall, these findings identify compounds 1, 9, 12, and 13 as promising multi-target anticancer leads warranting further optimization and development.

Among the tested compounds, Tetrandrine, Dauricine, and Olmutinib exhibited robust binding affinities across both wild-type and mutant EGFR configurations, highlighting their potential as effective inhibitors. The integrated approach of combining molecular docking using CB-dock2, ADMET profiling, and Lipinski's rule of five provides a robust framework for preliminary drug candidate screening, potentially accelerating the development of more precise and effective EGFR-targeted therapies. The findings contribute to the growing body of research exploring alternative and more nuanced strategies for inhibiting EGFR-driven oncogenic mechanisms, highlighting the importance of computational methods in identifying novel molecular targets with improved specificity and reduced side effects.

A focused translational approach that combines structural insights with innovative therapeutic strategies is urgently needed to achieve lasting clinical benefits in EGFR-driven cancers.