Tabrecta (capmatinib)

Collectively, these findings suggest that MUC3A P258S acts as a potential candidate biomarker of CML progression and influences therapeutic response, highlighting Capmatinib and related inhibitors as candidates for drug repurposing in hematological malignancies. To our knowledge, this is the first report implicating MUC3A in leukemia biology, extending its role beyond epithelial cancers.

P3, N=603, Completed, Institut National de la Santé Et de la Recherche Médicale, France | Active, not recruiting --> Completed

Serial cell lines from a patient with EGFR L858R and MET amplification (PE5345), after resistance to osimertinib and capmatinib through gradual escalation of drug exposure in vitro (PE5345 os/cp R) and after clinical resistance to osimertinib and capmatinib (PE5867), were propagated...Osimertinib plus trametinib reversed resistance. PE5345 os/cp R overexpressed EGFR, which was inhibited by afatinib...Amivantamab induced significant ADCC against both MET-amplified EGFR TKI-resistant cancer and resistant cells after dual EGFR/MET inhibition. Understanding resistance mechanisms may provide clues for subsequent therapy.

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.

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

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.

He received capmatinib (800 mg/day) and denosumab, with SBRT to vertebral metastases and later to the primary lung tumor. Temporary suspension of capmatinib during SBRT, along with careful monitoring, optimized tolerability, and outcomes. This case supports the feasibility and potential synergy of precision multimodal therapy in MET-driven oligometastatic NSCLC, highlighting the need for further prospective studies.

P1, N=105, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2026 --> Oct 2026 | Trial primary completion date: Mar 2026 --> Oct 2026

Off-label combination therapy to treat targeted therapy resistance in advanced NSCLC is feasible in routine clinical practice. Additional real-world evidence is needed to clarify best practices with this emerging approach.

Moreover, the combination of the ALK inhibitor alectinib with the MET inhibitor capmatinib and/or the integrin inhibitor cilengitide was more effective than single-agent treatment in suppressing tumor growth in allografted mice. The findings illustrate a previously unappreciated complex nature of concurrent paracrine and juxtacrine mechanisms of CAF-driven resistance that may inform the development of more effective therapeutic approaches.