MET (MET proto-oncogene, receptor tyrosine kinase)

Here, we report a novel chemical series discovered through iterative core enumeration and decoration guided by free energy perturbation calculations. Type-III inhibitor 20 demonstrated potent activity against both WT and c-MET with the D1228V resistance mutation with promising physicochemical properties, laying the foundation for the development of brain-penetrant therapies targeting c-MET-driven cancers.

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.

Concurrent palliative RT and amivantamab appears feasible and well tolerated. Further validation is warranted.

Collectively, the present findings show anticancer activity of STL in CRC cells, with computational predictions suggesting possible HGFR involvement and favorable pharmacokinetic properties. These results provide initial evidence supporting further investigation and position STL as a potent agent against CRC.

However, novel dual inhibitors may have a resistance problem due to unknown mutations, and heterodimerization. Despite these disadvantages, the coherent results on dual kinase inhibitors indicate that there are still chances to obtain promising therapeutic approaches.

P2, N=152, Not yet recruiting, The Third Xiangya Hospital of Central South University

We retrospectively analyzed 40 patients with R/M HNSCC treated with nivolumab or pembrolizumab monotherapy, evaluating clinical data, laboratory parameters, PD-L1 expression, tumor-infiltrating T cells, and peripheral immune features. Notably, c-Met-derived peptide stimulation induced significantly higher IFN-γ production in responders, indicating the presence of circulating tumor antigen-reactive T cells. These findings suggest that tumor antigen-reactive T cells, together with a favorable systemic immune profile, are associated with clinical benefit from PD-1 blockade, and that peripheral blood-based peptide-reactive T-cell assays may provide a practical approach for biomarker development in R/M HNSCC.

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.

P3, N=412, Active, not recruiting, Hutchison Medipharma Limited | Trial completion date: Aug 2026 --> May 2028 | Trial primary completion date: Aug 2026 --> May 2028

These results indicate c-Met protein overexpression can be assessed before or after treatment since most patients maintain consistent c-Met status. As targeted therapies may elevate c-Met overexpression over time, retesting may be necessary in those with an oncogenic driver alteration initially diagnosed as c-Met negative.

P1/2, N=67, Recruiting, D3 Bio (Wuxi) Co., Ltd | Active, not recruiting --> Recruiting | Trial completion date: Apr 2028 --> Aug 2028 | Trial primary completion date: Apr 2028 --> Aug 2028