Tabrecta (capmatinib)

Splice site mutations around or within exon 14 of MET (METex14+) are rare, but are one of the common actionable driver mutations in elderly patients with non-small cell lung cancer (NSCLC). On June 30, 2025, vebreltinib has been approved for NSCLC with MET amplification while combination of savoltinib and osimertinib has been approved for EGFR+ post EGFR TKINSCLC with MET amplification post EGFR TKI based on the SACHI trial (NCT05015608). We discuss the current unmet clinical need (need to develop Type II MET TKI to overcome acquired resistance MET mutations at D1228 and Y1230) and future optimal treatment approaches.

All these molecular and biological effects were inhibited by trametinib, a MEK inhibitor, which was potentiated by combination with capmatinib, a MET inhibitor. Thus, we report an original and powerful strategy to uncover key regulators, including transcription factors that have not been widely described in METex14Del signaling, such as SMAD3. These factors are activated by specific signaling pathways and could provide a novel therapeutic strategy involving a combination of receptor and signaling inhibitors.

P1/2, N=57, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2026 --> May 2028

Although these targeted therapies show potential to overcome resistance and improve patient outcomes, challenges remain due to the complex regulation of EMP. Future directions focus on refining combination strategies and advancing personalized approaches to enhance efficacy across multiple cancer types.

In vitro and in vivo experiments confirm that Fe-MOF/Cap is able to significantly inhibit the lung metastasis of HCC after iRFA by inhibiting the c-MET/STAT3/VEGF pathway. Fe-MOF/Cap provides a potentially promising strategy for HCC immunotherapy and anti-metastasis after iRFA, with favorable clinical prospects.

HIF-1α and FOSL1 played crucial roles in driving the proliferation, invasion, and migration of cholangiocarcinoma cells within the tumor microenvironment, orchestrated by CAFs. Furthermore, this study has provided theoretical support for the application of the HA receptor HRH2 inhibitor, Cimetidine, and the HGF receptor cellular mesenchymal-epithelial transition factor (c-MET) inhibitor, Capmatinib, in biliary tract tumors.

Our study identifies PTEN deficiency and ERBB2/ERBB3-mediated reactivation as key resistance mechanisms to MET inhibition in MET-amplified HCC. The findings support biomarker-informed combination strategies and underscore the importance of stratifying patients based on MET amplification status.

P4, N=50, Completed, Novartis Pharmaceuticals | Recruiting --> Completed

P2, N=29, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P1, N=105, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2025 --> Mar 2026 | Trial primary completion date: Oct 2025 --> Mar 2026

Furthermore, capmatinib and tepotinib demonstrate extraordinary efficacy for patients with NSCLC and MET exon 14 (METex14) skipping mutation, and the combination of capmatinib and gefitinib in particular can achieve remarkable therapeutic effects in patients with EGFR-mutated, MET-dysregulated (amplified/overexpressing) NSCLC. The administration of capmatinib can help mitigate potential food-intake and drug-drug interactions in clinical settings. This facilitates the optimization of long-term medication schedules, enhancing the clinical efficacy of the treatment.