Capmatinib

Capmatinib : Mechanism of Action, Uses & Safety

✅ What is Capmatinib?

Capmatinib is a targeted kinase inhibitor used for treating metastatic non-small cell lung cancer (NSCLC) in patients with tumors that exhibit a MET exon 14 skipping mutation. This mutation causes overactivation of the MET (mesenchymal-epithelial transition) receptor tyrosine kinase, contributing to uncontrolled cancer cell growth.

Brand names: Capmaxen®, Tabrecta®
Drug class: MET inhibitor / Tyrosine kinase inhibitor (TKI)

⚙️ Mechanism of Action

Capmatinib works by selectively inhibiting the c-MET receptor tyrosine kinase, including both wild-type and mutant forms associated with exon 14 skipping. Here’s how it works:

  1. MET exon 14 skipping mutations result in the loss of a regulatory domain of the c-MET protein.

  2. This leads to constitutive (uncontrolled) MET signaling, driving cancer cell survival and proliferation.

  3. Capmatinib:

    • Blocks MET phosphorylation triggered by its natural ligand hepatocyte growth factor (HGF).

    • Prevents activation of downstream signaling pathways such as PI3K/AKT, RAS/MAPK, and STAT.

    • Inhibits the proliferation, invasion, and survival of MET-dependent tumor cells.

Preclinical models have shown significant tumor regression in NSCLC xenografts with MET exon 14 mutations or MET amplification.

💊 Indications

Capmatinib is indicated for:

  • Adults with metastatic NSCLC harboring MET exon 14 skipping mutations, as detected by an FDA- or EMA-approved test.

🧬 Targeted Patient Population

  • Patients with advanced or metastatic NSCLC who test positive for METex14 alterations.

  • Especially useful in cases where other therapies fail or are not well tolerated.

⚠️ Warnings and Precautions

Adverse Effect Details
Interstitial Lung Disease (ILD)/Pneumonitis May be fatal. Discontinue if ILD is suspected. Monitor for cough, fever, dyspnea.
Photosensitivity Capmatinib may cause phototoxicity. Advise patients to use sunscreen and avoid tanning.
Hepatotoxicity Monitor liver function tests. May require dose adjustment or discontinuation.
Embryo-Fetal Toxicity May cause fetal harm. Use effective contraception during and after treatment.

📊 Clinical Pharmacology

Parameter Description
Absorption Rapid oral absorption
Metabolism Primarily via CYP3A4 and aldehyde oxidase
Elimination Feces (78%), urine (22%)
Half-life ~6.5 hours
Protein binding ~96%

🌐 Regulatory Status

  • FDA approval (US): Yes, for MET exon 14-mutated NSCLC.

  • EMA approval (EU):

    • Positive opinion granted by CHMP on April 22, 2022.

    • EU approval: September 2022 under the trade name Tabrecta® by Novartis Europharm Ltd.

📢 Patient Counseling Points

  • Avoid sun exposure: Use broad-spectrum sunscreen (SPF ≥30), wear protective clothing.

  • Report symptoms like shortness of breath, persistent cough, or fever immediately.

  • Avoid pregnancy during treatment and for 1 week after the final dose.

  • Inform healthcare providers about any liver issues or use of CYP3A4 modulators.

🧾 Summary

For metastatic non-small cell lung cancer, capmatinib is a targeted MET inhibitor. Examine its brands, side effects, dosage, and mechanism. EmergencyDrug.com offers quick delivery.