Tepmetko (tepotinib)

This case underscores the potential of early onset ILD with tepotinib, especially in patients with possible pre-existing ILD. Close monitoring and early intervention are essential, and further studies are needed to clarify the risk factors for MET-TKI-induced ILD.

MET-TKIs are effective for NSCLC with the METex14 skipping mutation; however, their efficacy for patients with a poor PS is limited.

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.

Molecular docking revealed high-affinity binding between tepotiniband all six hub targets (Vina scores: -8.0 to -10.6 kcal/mol), providing a structural basis for the postulated mechanistic link to AKI. These findings not only highlight the necessity for enhanced renal monitoring in tepotinib-treated patients but, more broadly, establish the FAERS-NetDock Pipeline as a reusable, generalizable and hypothesis-generating framework for evaluating tyrosine kinase inhibitors (TKIs)-induced nephrotoxicity; this framework is immediately applicable to profiling the safety of other TKIs (e.g. crizotinib, capmatinib, savolitinib, afatinib and osimertinib) and is readily adaptable for de-risking a wider spectrum of targeted therapies.

P2, N=56, Recruiting, SWOG Cancer Research Network | Trial completion date: May 2029 --> May 2028

Multigene testing is underutilized in this population. While many targeted therapies carry a high risk of pneumonitis, sotorasib appeared relatively safe. Despite the risks, identifying and treating actionable oncogenic drivers may improve survival.

P2, N=337, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Oct 2025 --> Apr 2026

Combining targeted therapies with immune checkpoint inhibitors showed promising results in 2 patients with advanced BTC driven by specific genetic mutations. Significant tumor reduction and successful surgeries suggest this approach may improve resectability and outcomes. These cases highlight the potential of personalized treatment guided by genetic profiling. Further research is needed to confirm these findings and explore broader applications for this strategy.

This study conducted a comprehensive evaluation of the real-world safety of Tepotinib. The study validates clinical assertions about Tepotinib's safety profile and identifies its novel signals, and also emphasized early monitoring of treatment. Our findings will better guide the clinical practice of Tepotinib and provide a basis for larger prospective studies in the future.

P2, N=140, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Oct 2025 --> May 2026

Utilising a robust next-generation sequencing platform, we have identified this mutation in 5.3% of cases in our cohort. In the absence of information on MET exon 14 skipping from India, this case series will throw some light on this variation in our subcontinent and highlights the fact that the real-world effectiveness of MET inhibitors like Tepotinib and Capmantinib might be lower than expected.

P3, N=133, Recruiting, Intergroupe Francophone de Cancerologie Thoracique | Not yet recruiting --> Recruiting | Initiation date: Jul 2025 --> Nov 2025