What is capmatinib (Touradida) and a detailed introduction to its mechanism of action

Capmatinib (trade name: Tabrecta) is an oral small molecule targeted drug developed by Novartis (Novartis). It is the first approved treatment in the world. Selective MET inhibitor for advanced non-small cell lung cancer (NSCLC) with skipping mutations in METexon 14. In 2020, the US FDA took the lead in approving the drug for marketing, marking that the treatment of MET mutation-related lung cancer has entered a new stage of precision medicine. With the popularity of molecular testing worldwide, capmatinib has gradually become an important treatment option for some lung cancer patients.

The MET gene (mesenchymal-epithelial transition factor) encodes a tyrosine kinase receptor that plays an important role in cell growth, differentiation and migration. Under normal circumstances, the MET signaling pathway is strictly regulated; however, when gene amplification, overexpression, or METex14 jump mutations occur, it will lead to abnormal activation of the pathway and promote the unlimited proliferation and metastasis of tumor cells. Research shows that about 3-4% of non-small cell lung cancer patients have METex14 mutations. Such patients usually have limited response to traditional chemotherapy and immunotherapy. Therefore, the development of drugs targeting MET has become a new treatment breakthrough.

Capmatinib is a highly selective, orally effective METtyrosine kinase inhibitor (TKI). It binds to the MET receptor kinase domain and blocks its autophosphorylation process, thereby inhibiting the activation of downstream signaling pathways (such as PI3K/AKT, RAS/MAPK, etc.), ultimately inhibiting the proliferation, invasion and metastasis of tumor cells. In clinical trials, capmatinib showed a high objective response rate (ORR) and durable therapeutic response in patients with METex14 mutations. This mechanism also explains its significant efficacy in the precise population.

The emergence of capmatinib has brought new hope to some lung cancer patients who previously had limited treatment options. Especially in patients with NSCLC related to METex14 mutations, it shows similar "precision treatment" value to EGFR and ALK inhibitors. At present, the indications of capmatinib are mainly concentrated in lung cancer, but with the deepening of research, its application in other MET-driven solid tumors (such as liver cancer, gastric cancer, etc.) is also being explored. In the future, with the improvement of molecular testing coverage and the accumulation of more clinical data, capmatinib is expected to occupy an even more important position in the field of precision tumor treatment.

Reference link:https://www.drugs.com