Tepmetko (tepotinib)

The incremental cost-effectiveness ratio (ICER) of Capmatinib treatment vs. Tepotinib treatment was calculated at 60,977.28 USD/QALY. Tepotinib was not cost-effective compared to Capmatinib as the second-line treatment for advanced or metastatic NSCLC patients with MET exon 14 skipping mutations in China.

The therapeutic strategy involved an immediate switch from rivaroxaban to therapeutic low-molecular-weight heparin (LMWH) and the initiation of dual targeted therapy with selpercatinib and tepotinib. Upon diagnosis of NBTE, a rapid oncologic work-up is warranted, as ongoing tumor progression is highly likely. This case questions the appropriateness of direct oral anticoagulants in patients with NBTE and active, progressive malignancy.

Notably, one patient with acquired MET amplification achieved a renewed partial response to the combination of sotorasib and tepotinib after progression on sotorasib monotherapy. Our findings support rebiopsy at progression on sotorasib. Further prospective trials are warranted to validate MET amplification as a resistance mechanism and to define optimal therapeutic thresholds for combined KRAS and MET inhibition.

Although the tumour relapsed 4 months postoperatively, treatment with tepotinib resulted in a favourable response and subsequent pembrolizumab therapy achieved a durable response. This case suggests that patients with sarcomatoid carcinoma, which is generally associated with a poor prognosis, may experience improved outcomes with the use of molecular targeted therapies and immune checkpoint inhibitors.

P2, N=47, Recruiting, Samsung Medical Center | Not yet recruiting --> Recruiting

Tepotinib was resumed at a reduced dose without further renal deterioration, resulting in a partial tumour response. This case highlights the feasibility of tepotinib therapy in carefully selected patients with ESRD and underscores the clinical utility of incorporating complementary renal biomarkers, cystatin C, for guiding treatment decisions and avoiding unnecessary treatment discontinuation.

RWE confirms the effectiveness and safety of multiple recently approved oncology drugs reinforcing the external validity of RCTs.

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