EGFR wild-type

A biopsy-level reflex workflow enables feasible, tissue-efficient concurrent molecular and immune profiling in advanced NSCLC. Integration of TPS, CPS, TIL assessment, and EGFR testing within a reflex workflow demonstrates the feasibility of coordinated immuno-molecular profiling from limited biopsy tissue in advanced NSCLC.

Teliso-V monotherapy 1.9 mg/kg elicited durable responses, irrespective of the type of previous therapy received, and maintained a manageable safety profile in patients with c-Met protein overexpressing EGFR wild-type, nonsquamous NSCLC. NCT03539536.

CTNNB1 mutations in NSCLC are associated with older age at diagnosis, lower PD-L1 expression and potentially favorable survival outcomes, particularly when appearing alongside EGFR mutations.

The addition of bevacizumab to chemoimmunotherapy was associated with improved survival in ns-NSCLC specifically in patients with LMs. These hypothesis-generating findings suggest that the benefit may stem from disruption of VEGF-A-driven immunosuppressive signaling in the liver, but require prospective confirmation.

Free energy of binding calculations using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method supported these findings, with D4 showing the most favourable interaction, dominated by Van Der Waals and electrostatic contributions from key catalytic amino acid. Our research, with further experimental validation, could be helpful to support that certain MET inhibitors, especially D4, are promising competitive inhibitors of EGFRwt, offering potential for the development of new therapeutic strategies targeting EGFRwt-driven cancers.

Therapeutic progress in this population has accelerated over the past several years, first with trastuzumab deruxtecan and more recently with selective HER2 tyrosine kinase inhibitors (TKIs). Zongertinib demonstrates that selective HER2 inhibition can achieve durable responses in HER2 -mutant NSCLC with a favorable safety profile. However, optimal treatment sequencing, resistance mechanisms, and biomarker-guided patient selection remain to be defined.

P3, N=1051, Active, not recruiting, AstraZeneca | Trial primary completion date: Jun 2026 --> Sep 2026

Patients with EGFR-mutant LUSC or LUAS had shorter overall survival on first-line osimertinib compared with those with EGFR-mutant LUAD...Combined EGFR and MET inhibition suppressed tumor growth in patient-derived xenograft models of LUSC transformation. Together, these findings highlight Rb pathway inactivation as a promoter of LUSC transformation in EGFR-mutant lung cancer and identify MET signaling as a therapeutic vulnerability that may suppress plasticity in this setting and extend response to targeted therapy.

Several alterations associated with cystic GBM, including CDK4 and KDR, are targets of small-molecule inhibitors. Further research is required to explore the diagnostic and therapeutic implications of this association.

In this cohort of surgically resected NSCLC, preoperative corrected serum calcium and smoking exposure were more closely associated with tumor metabolic activity than with specific molecular alterations. These findings suggest that simple clinical and biochemical parameters may provide complementary information, although their utility for discriminating individual molecular subgroups appears limited.

P2, N=120, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital | Initiation date: Jan 2026 --> Jun 2026

A 55-year-old female with HER2-mutant non-small cell lung cancer (NSCLC) was treated with zongertinib as second-line therapy following chemo-immunotherapy with pembrolizumab. Serial chest radiographs confirmed significant tumor shrinkage in the left lung, achieving a partial response without recurrence of severe scAEs. A cautious dose-escalation strategy can allow for the continuation of zongertinib even after severe EM-like eruptions, preserving a potent treatment option.