EGFR wild-type

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.

Secondary endpoints include duration of response, progression-free survival, disease control, occurrence of treatment-emergent adverse events, and health-related quality of life. Recruitment is ongoing in 13 countries globally.Clinical trial registration http://www.clinicaltrials.gov identifier is NCT06581432.

P3, N=686, Not yet recruiting, CSPC Megalith Biopharmaceutical Co.,Ltd.

P=N/A, N=80, Completed, The Netherlands Cancer Institute | Recruiting --> Completed | Trial completion date: Dec 2024 --> Jan 2026

Non-responders to durvalumab and supraclavicular nodal involvement were significant predictors of brain metastasis in NSCLC treated with CCRT followed by durvalumab. These findings support risk-adapted CNS surveillance strategies in high-risk patients.

Treatment was then switched to the ALK inhibitor alectinib, and the patient again achieved a partial response. This case suggests that chemotherapy may enrich ALK fusion-positive tumour cell clones through selective pressure. These findings highlight the clinical importance of repeated genetic testing after disease progression and provide new insights for post-resistance treatment strategies.

Recently developed agents such as amivantamab and mobocertinib have improved response rates, yet challenges related to tolerability, CNS penetration, and durability of benefit persist. Early-phase clinical trials, including the WU-KONG series, have reported promising clinical efficacy, including objective response rates ranging from 44-60% in previously treated patients and meaningful activity in treatment-naïve cohorts. The tolerability profile of the drug seems manageable, with diarrhea, rash, and stomatitis among the most commonly observed adverse events; these, however, tend to be milder compared with other agents targeting EGFR Ex20ins.

IDH mutant gliomas and IDHwt GBM express different progenitor cell markers. THY1 is highly expressed in IDH mutant gliomas.

P2, N=321, Active, not recruiting, Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

In this large real-world cohort of advanced NSCLC patients treated with EGFR-TKI, female sex, stage IIIb (vs. stage IV) disease, adenocarcinoma histology, EGFR exon 19 deletion, and the use of EGFR-TKI as first-line therapy were independently associated with longer DoT and/or OS. These factors may help identify patients more likely to derive durable benefit from EGFR-TKIs and support risk stratification and treatment optimization in EGFR-mutant NSCLC.

Zongertinib is the first oral TKI approved for HER2-mutant NSCLC and will provide patients with a convenient, tolerable and effective treatment option in an area of significant unmet need. Next steps include its potential transition to a first-line setting, identification of additional indications, and development of novel combination regimens.