MET overexpression

P2, N=52, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

P1, N=48, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

Encouragingly, several MET TKIs such as capmatinib, tepotinib, and savolitinib have been approved for the treatment of MET exon 14 skipping mutations. On 14 May 2025, the U.S. Food and Drug Administration granted accelerated approval to telisotuzumab vedotin-tllv for adult patients with locally advanced or metastatic non-squamous NSCLC whose tumors exhibit high c-Met protein overexpression and who have already received prior systemic therapy. In this review, we summarize the structure and physiological role of the MET receptor, the molecular mechanisms underlying aberrant MET activation, its contribution to acquired resistance against targeted therapies, and emerging strategies for effectively targeting MET alterations in NSCLC.

P2, N=47, Active, not recruiting, AstraZeneca | Trial completion date: Aug 2025 --> Jan 2027 | Trial primary completion date: Aug 2025 --> Jan 2027

The targets evaluated have potential drugs currently under trial phase. This may help to define the subgroup for use of targeted therapy in NSCLC-SCC and in designing new treatment protocols.

Treatment-related adverse events of grade 3 or higher occurred in 2 patients (8.7%) in cohort 1 and 12 patients (57.1%) in cohort 2. Osimertinib plus savolitinib showed promising antitumor activity and manageable safety.

Our study reveals that HNK reduced the proliferation and stemness of PC cells via suppressing the c-Met overexpression. These findings provide a potential therapeutic method for PC, offering new hope for improving patients' outcomes.

MET-altered NSCLC is a challenging and heterogeneous molecular subset, and our knowledge is rapidly evolving. Work is ongoing to define the spectrum of actionable mutations, to develop standardized and clinically meaningful biomarker-driven identification of these alterations, and to determine the most effective treatment approaches, with the goal of expanding the treatment landscape and improving outcomes for a subset of patients with limited treatment options.

P2, N=60, Not yet recruiting, Jonsson Comprehensive Cancer Center

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.

In conclusion, the strategy of using the interface residues has been successfully explored for the discovery of new c-Met binders. [68Ga]Ga-SMIC-1014 shows a high tumor imaging performance and potential as a c-Met-targeted diagnostic probe.

scRNA-seq identifies cell populations within the epithelial component that contribute to the malignant transformation and differentiation of the sarcomatoid component. They are characterized by an intermediate EMT state with ECM remodeling signature, suggesting their potential as novel therapeutic targets for PPC.