EGFR wild-type

P3, N=698, Active, not recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: May 2026 --> Dec 2026 | Trial primary completion date: May 2026 --> Dec 2026

Patients in cluster 1 may benefit from anti-nucleotide repair therapies such as platinum therapy, radiotherapy, targeting of fibroblasts, and targeting of NTRK3, while patients in cluster 2 may benefit from immunotherapy, antiangiogenic therapy, targeting of lipid metabolism, and targeting of EGFR. This study may offer novel insights into improving the overall prognosis of patients with LUAD by leveraging molecular subtype-based precision therapy, as demonstrated by recent advancements in the identification of prognostic biomarkers and therapeutic targets.

The study underscores the importance of integrating NGS-based molecular testing with PD-L1 evaluation for personalised management of NSCLC. Distinct patterns of PD-L1 expression across molecular subtypes, particularly lower in EGFR-mutated tumours and higher in KRAS-mutated tumours, underscore the need for tailored therapeutic strategies and informed sequencing of targeted therapies and immunotherapies.

EGFR testing prior to surgery may help guide surgical decision-making when it comes to selecting lobar versus sub-lobar resections.

P1, N=4, Not yet recruiting, AstraZeneca AB

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.

First-line treatment with the tyrosine kinase inhibitor afatinib was associated with improved OS compared with that of patients treated with erotinib or gefitinib. In addition, combination therapy with the angiogenesis inhibitor bevacizumab had a positive impact on OS...These findings highlight the importance of molecular profiling and individualized treatment strategies in optimizing OS for patients with advanced lung adenocarcinoma. Furthermore, the validated machine learning models may serve as useful tools for risk stratification and personalized prognostic assessment to support clinical decision-making.

P1, N=36, Recruiting, Beijing Biotech

The median PFS was generally consistent with that of the control arm in the LAURA trial. Increased pneumonitis risk necessitates close monitoring in patients with EGFR-mutant unresectable stage III NSCLC.

A novel EGFR mSig that captures the transcriptional footprint of EGFR activation revealed a subset of EGFR WT LUADs with "mt-like" features. mSig refines LUAD taxonomy beyond mutation-only pie-chart models by incorporating lineage and co-mutation context. Lineage-directed stratification with co-alteration identifies clinically relevant groups across EGFR and RAS states and highlights new treatment opportunities for patients currently considered "oncogene-negative.".

P2, N=36, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting | Trial completion date: Jul 2025 --> Aug 2026

The study highlights a pro-metastatic ELANE + neutrophil subpopulation, with RELB acting as its primary transcriptional regulator. The RELB signature may serve as a biomarker for prognosis and treatment response prediction, indicating a potential target for precision treatment in EGFR wildtype LUAD.