MET overexpression

P2, N=367, Active, not recruiting, AstraZeneca | Trial completion date: May 2025 --> Dec 2026

SP44R, SP44Z, LBP4-C-MET, and 811B7F4 performed reliably, although D1C2 was less consistent for clinical score 3+. Clinical score 2+/3+ or H score ≥150 is associated with high diagnostic consistency, supporting multiple validated IHC assays for c-Met evaluation in lung adenocarcinoma.

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.