EGFR wild-type

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.

P1, N=167, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | N=403 --> 167

This first comprehensive analysis of PD-L1 prevalence in patients with NSCLC in Jordan demonstrates a relatively high prevalence of both PD-L1 positivity (≥1%) and high expression (≥50%) compared with reported data from other regions. Distinct molecular associations were observed, with higher PD-L1 expression in ALK-rearranged and EGFR wild-type tumors. These findings underscore the need for prospective and multicenter studies to further identify the biologic and clinical implications of PD-L1 expression in Jordanian patients with NSCLC.

Dynamic changes in serum VEGF levels were associated with treatment response; however, these findings should be interpreted with caution due to the retrospective design and absence of a control group. Further well-designed prospective controlled studies are warranted to validate these observations.

Compounds JRC-2 and JRC-6 exhibited potent antiproliferative effects against MCF-7 breast cancer cells, with IC50 values of 4.59 ± 0.23 µM and 4.01 ± 0.14 µM, respectively, outperforming erlotinib (IC50 = 9.39 ± 0.16 µM). Notably, JRC-6 displayed microtubule-stabilising activity comparable to that of paclitaxel and induced ROS generation, mitochondrial membrane depolarisation, and G2/M phase cell cycle arrest. Molecular docking and molecular dynamics simulations confirmed stable binding of compounds at the EGFR ATP-binding site and the tubulin taxol-binding site.

NGS-based liquid biopsy identified actionable and resistance-associated mutations in 25% of advanced NSCLC patients in this Turkish Black Sea cohort. Total cfDNA concentration correlated with metastatic burden. The detection of KRAS G12C and EGFR T790M variants supports the complementary clinical utility of multi-gene plasma ctDNA panels alongside tissue genotyping in personalized treatment decisions, although confirmation in larger prospective cohorts with paired tissue analysis is warranted.