capmatinib — Drug Monograph

Brand names: Tabrecta

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Capmatinib is a highly selective, potent, orally bioavailable MET (mesenchymal-epithelial transition factor, also known as hepatocyte growth factor receptor/HGFR) tyrosine kinase inhibitor. It binds in the ATP-binding pocket of MET, blocking ligand-independent (e.g., MET exon 14 skipping mutation, which eliminates the regulatory ubiquitin-binding site in the juxtamembrane domain and impairs receptor degradation) and ligand-dependent (HGF-driven) MET autophosphorylation and activation. Capmatinib thereby suppresses downstream RAS/MAPK, PI3K/AKT/mTOR, and STAT3 signaling that drives…

FDA Indications

• Metastatic NSCLC in adults whose tumors harbor a MET exon 14 skipping mutation (METex14), as detected by an FDA-approved test — accelerated approval May 2020 (GEOMETRY mono-1 trial)

Common Side Effects

• Peripheral edema (>50%)
• Nausea
• Fatigue
• Vomiting
• Elevated creatinine (decreased eGFR)
• Decreased appetite
• Dyspnea
• Back pain
• Elevated ALT/AST
• Photosensitivity

Clinical Pearl

Capmatinib was the first MET inhibitor to receive FDA approval for METex14-skipping NSCLC, and the GEOMETRY mono-1 trial demonstrated a particularly high overall response rate (~68%) in treatment-naive patients with this mutation, suggesting it is especially valuable in the first-line setting. An important pharmacokinetic nuance: capmatinib inhibits OCT2 and MATE1/2 transporters, resulting in elevated serum creatinine that does not reflect true renal injury in most patients — clinicians should…

Related Therapies & Mechanisms

• Afatinib (Gilotrif) — Tyrosine Kinase Inhibitor · NSCLC
• Alectinib (Alecensa) — Tyrosine Kinase Inhibitor · NSCLC
• Dabrafenib (Tafinlar) — Tyrosine Kinase Inhibitor · NSCLC
• Erlotinib (Tarceva) — Tyrosine Kinase Inhibitor · NSCLC