EGFR mutation

P1, N=16, Recruiting, Memorial Sloan Kettering Cancer Center

We report a 72-year-old man with stage IV squamous NSCLC harboring an EGFR mutation and PD-L1 tumor proportion score of 90% who developed persistent fever shortly after first exposure to ivonescimab combined with nab-paclitaxel and carboplatin. His prior treatments included concurrent chemoradiotherapy, osimertinib, the investigational EGFR inhibitor BH-30643, afatinib, and recent gamma knife for cerebellar metastases plus palliative radiotherapy for bone metastases...Symptoms improved with corticosteroids, tocilizumab, and desmopressin, consistent with probable arginine vasopressin deficiency (AVP-D), possibly secondary to hypophysitis-though pituitary metastasis cannot be ruled out without biopsy...Advanced age, EGFR-mutant/PD-L1-high tumor biology, recent radiotherapy, and Parkinsonism may have contributed to the inflammatory environment, though none can be proven causal in a single case and each deserves prospective study. Early recognition of persistent steroid-responsive fever, serial IL-6 monitoring, thorough endocrine workup, and timely IL-6 blockade are critical.

Targeting the HHLA2-KIR3DL3 axis, particularly in combination with EGFR tyrosine kinase inhibitors, may provide a rational precision immunotherapy strategy for EGFR-mutant lung cancer. Further mechanistic and translational studies are warranted to fully define its therapeutic value.

We report a 59-year-old female non-smoker with stage IV EGFR Leu858Arg-mutated lung adenocarcinoma who sequentially received first-line osimertinib (~9 months), second-line osimertinib plus savolitinib for MET amplification (~20 months), third-line platinum-based chemotherapy with local ablative therapy for oligo-progression, and fourth-line docetaxel. This case illustrates that an acquired BRAF fusion may emerge as a potentially targetable bypass alteration in EGFR-mutated MET-amplified NSCLC after progression on combined EGFR-MET inhibition and that the combination of a first-generation EGFR-TKI and a MEK inhibitor can be associated with prolonged systemic disease control. The findings are hypothesis-generating and support the value of CGP at sequential progression points to guide mechanism-based therapy in oncogene-driven NSCLC.

ACT was not significantly associated with improved RFS for stage IA LUADmp patients postoperatively. This study was registered at ClinicalTrials.gov: NCT03351842.

P3, N=412, Active, not recruiting, Hutchison Medipharma Limited | Trial completion date: Aug 2026 --> May 2028 | Trial primary completion date: Aug 2026 --> May 2028

Our findings offer initial insights into the features of CSF-enriched eccDNAs across LUAD subtypes with varying pathogenic mechanisms, emphasizing their potential as diagnostic and prognostic indicators for LUAD.

Our study reveals the genomic and transcriptomic evolution of LBBC recurrence, suggesting that most drivers are established in the primary tumor. Acquired mutations or alterations warrant further investigation as potential therapeutic targets and MATH scores may represent a candidate biomarker associated with LBBC recurrence.

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

This study delineates an epigenetic-transcriptional regulatory network that drives nodule malignancy. Our findings provide a robust theoretical foundation and a high-performance liquid biopsy tool for the precise, noninvasive diagnosis of pulmonary nodules.

These results indicate c-Met protein overexpression can be assessed before or after treatment since most patients maintain consistent c-Met status. As targeted therapies may elevate c-Met overexpression over time, retesting may be necessary in those with an oncogenic driver alteration initially diagnosed as c-Met negative.

Higher levels of serum VEGF121 were associated with lower EGFR-TKI efficacy and poorer prognosis in patients with EGFR-mutated NSCLC.