Tabrecta (capmatinib)

P2, N=66, Recruiting, SWOG Cancer Research Network | Trial completion date: May 2027 --> Jun 2028 | Trial primary completion date: May 2026 --> Jun 2027

P=N/A, N=44, Recruiting, Novartis Pharmaceuticals | N=250 --> 44

P1/2, N=1000, Recruiting, Oslo University Hospital HF | N=6000 --> 1000

We review the characteristics of MET-altered pediatric high-grade glioma using the Open Pediatric Brain Tumor Atlas (Open PBTA) and published series, which suggests that MET fusions may be enriched in RIGs. Our two cases highlight the promising CNS penetration and on-target activity of capmatinib in MET-altered glioma; however, the development of rapid resistance emphasizes the pressing need to develop combination and/or new therapies for RIG.

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.