EGFR wild-type

It received its first approval under accelerated approval in August 2025 in the USA following positive results from the Beamion LUNG-1 phase Ia/Ib trial in patients with previously treated HER2-mutant non-small cell lung cancer (NSCLC). This article summarizes the milestones in the development of zongertinib leading to this first approval for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have HER2 tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.

Findings will be disseminated through peer-reviewed journals, scientific meetings, public forums and guideline updates. Clinicaltrial.gov: NCT07042724.

Moreover, we further explored the potential of PD-1/PD-L1 as a predictive biomarker for EGFR mutations by conducting a systematic and multidimensional analysis, aiming to refine therapeutic decision-making and facilitate personalized treatment strategies for EGFR-mutated NSCLC. Additionally, we also discussed the novel strategies that could alleviate the EGFR-TKIs resistance in NSCLC base on PD-1/PD-L1 immune inhibitors, shedding light on challenges facing future research.

The prevalence and prognostic significance of STAS varied by driver mutation status, suggesting that the clinical interpretation of STAS may depend on the molecular context.

Compound 19 was the most potent inhibitor of WT EGFR (3.0 nM) observed, more potent than the EGFR WT inhibitor Erlotinib (5.9 nM). Compounds 48 and 49 demonstrated better activity for the double-mutant EGFR (3.0 & 2.0 nM, respectively) than Osimertinib (12.8 nM)...Kinetic evaluation of 48 (propenamide moiety) vs 49 (acrylamide electrophile) confirms kinact/Ki values consistent with a covalent mode of action for the latter, but not the former. 2009 Elsevier Ltd.

Additionally, wt-EGFR and pAKTSer473 protein complex formation in A549 cells was disrupted with an AKT inhibitor (MK2206), resulting in enhanced cytotoxicity in vitro. Our study demonstrates that EGFR-TKI response in wt-EGFR cells is dictated by BRG1 status. These findings propose screening of wt-EGFR NSCLC patients for BRG1 status for identifying individuals likely to benefit from EGFR-TKI therapy versus patients who will benefit from AKT inhibitor treatment.

P1/2, N=252, Recruiting, AbbVie | N=132 --> 252

P1/2, N=40, Terminated, Ascentage Pharma Group Inc. | N=104 --> 40 | Recruiting --> Terminated; Company Strategy

Inhibiting the Src pathway with dasatinib reversed this pro-migratory effect, markedly reducing their migration persistence. These insights refine our understanding of GBM infiltration and highlight Src inhibition as a promising strategy in EGFRvIII-positive tumors.

In phase Ib studies, TV-t combined with osimertinib achieved a 50% ORR and 7.4-month PFS, while TV-t with nivolumab, the median PFS was 7.2 months, but ORR was low (7.4%). TV-t demonstrated promising efficacy and tolerability in patients, highlighting its clinical potential. However, further studies are needed to confirm its survival advantage, the durability of response, and safety profile, and to establish its long-term value and support its integration into routine clinical practice.

The sequential regimen involved: (1) SBRT (24 Gy/3 fractions); (2) oral probiotics (6 g/day); (3) nab-paclitaxel (200 mg); and (4) anti-PD-1 antibody over six 21-day cycles...Baseline CLR and LDH are independent prognostic biomarkers for PD-L1-negative NSCLC patients receiving BRICS, reflecting systemic inflammation that may limit efficacy. These markers could optimize patient stratification and guide personalized therapy.

Four compounds 11h-11k showed potency comparable with or better than the positive control Erlotinib and exemplary selectivity towards normal cells...Apoptotic effect of 14h was investigated using annexin V-FITC/PI dual staining assay in which 14h was found to trigger apoptotic pathways effectively with a significantly higher proportion of cells undergoing both early and late apoptotic events, underscoring its potential as a therapeutic agent targeting programmed cell death. Western blot analysis of 14h indicates that it primarily impairs EGFR phosphorylation, supporting its potential as a targeted modulator of EGFR signalling.