- Class: Targeted therapy – MET tyrosine kinase inhibitor (TKI)
- Mechanism of action:
- Selectively inhibits MET receptor tyrosine kinase (including MET exon 14 skipping mutations and MET amplification).
- Blocks downstream signaling pathways (RAS–MAPK, PI3K–AKT, STAT3) → inhibits tumor cell growth, survival, and metastasis.
Indications (FDA-approved)
- Non–small cell lung cancer (NSCLC) with MET exon 14 skipping mutation (detected by FDA-approved test), in adults.
- Studied in other solid tumors with MET dysregulation (ongoing).
Dosing
- 400 mg orally twice daily (with or without food).
- Continue until disease progression or unacceptable toxicity.
Dose adjustments:
- Hepatic impairment: Avoid in severe (Child-Pugh C).
- Renal impairment: No adjustment for mild/moderate; limited data in severe.
- Drug interactions: Substrate of CYP3A4 and P-gp → avoid strong inducers/inhibitors.
Adverse Effects
Common (≥20%):
- Peripheral edema
- Nausea, vomiting, decreased appetite
- Fatigue
- Increased creatinine (due to inhibition of tubular secretion, not always true renal injury)
Serious:
- Interstitial lung disease (ILD)/pneumonitis
- Hepatotoxicity (↑ ALT/AST)
- Photosensitivity
- Rare: pancreatitis
Monitoring
- Baseline and periodic LFTs (ALT, AST, bilirubin)
- Monitor for pulmonary symptoms (cough, dyspnea, fever → ILD suspicion)
- Monitor for edema and renal function
- Dermatologic counseling for photosensitivity
Key Clinical Points
- Only for patients with MET exon 14 skipping mutation (identified via NGS or FDA-approved assay).
- Avoid strong CYP3A inducers/inhibitors (may ↓ or ↑ capmatinib levels).
- Oral agent, convenient vs IV chemotherapy.
- FDA approval (2020) was based on the GEOMETRY mono-1 trial, showing ORR ~68% in treatment-naïve NSCLC with MET exon 14 skipping.