MET amplification

P2, N=33, Completed, University Health Network, Toronto | N=50 --> 33 | Recruiting --> Completed

P1, N=41, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Sep 2026

MGMT methylation was significantly more prevalent in elderly GBM patients and favorably influenced prognosis. No NGS-derived genetic alterations reached statistical significance between age groups after Fisher's exact test and multiple testing correction. Larger multicenter studies are needed to validate these exploratory findings.

The temporal relationship between molecular and radiologic findings observed here suggests potential value for earlier detection of disease activity, although whether such lead time translates into improved clinical outcomes requires prospective validation. The findings support prospective evaluation of this approach, including the ongoing TROPHY trial investigating this therapeutic approach.

P1/2, N=16, Recruiting, Misty Shields | Not yet recruiting --> Recruiting | Initiation date: May 2026 --> Aug 2026

This study represents the latest investigation of resistance mechanisms to afatinib in NSCLC patients with nonclassical mutations. The mechanism of resistance to EGFR-TKI in this study was discovered different from that of patients with classical mutations.

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.

This case underscores dynamic clonal evolution in advanced NSCLC: the initial L747S/L858R clone showed Osimertinib sensitivity, while subsequent resistance revealed a distinct profile (distinct TP53 mutation, MET amplification, high PD-L1/TMB) that explained the durable response to Pembrolizumab. These findings provide crucial evidence for sequential therapy strategies in compound EGFR mutations. Our findings also highlight the utility of Next Generation Sequencing (NGS) in identifying targetable resistance mechanisms, enabling prolonged survival in patients with compound EGFR mutations and offering valuable insights for clinical decision-making.

P2, N=66, Recruiting, SWOG Cancer Research Network | Trial completion date: May 2027 --> Jun 2028 | Trial primary completion date: May 2026 --> Jun 2027

Savolitinib monotherapy showed encouraging antitumor activities and a tolerable safety profile in heavily treated, later-line METamp G/GEJ cancers, supporting further investigation in randomized controlled trials. ClinicalTrials.gov identifier: NCT04923932 .

P3, N=216, Completed, Hutchison Medipharma Limited | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Aug 2025 | Trial primary completion date: Dec 2025 --> Aug 2025

Molecular docking simulations revealed that the evaluated compounds adopt a linear binding mode within the c-MET active site, in contrast to the U-shaped binding pattern characteristic of class Ib c-MET inhibitors. Overall, the newly developed isatin-1,2,4-triazine hybrids exhibited potent anticancer activity, highlighting their potential as promising lead structures for future anticancer drug development.