What Is Capmatinib (Tabrecta)? FDA Approval History

• FDA-approved: Yes (first approval: May 6, 2020)
• Active ingredient: Capmatinib
• Brand name: Tabrecta
• Administration: Tablet (200 and 150 mg formulations available)
• Class: MET kinase inhibitor
• Category: Targeted agent
• Manufacturer: Novartis
• Distribution in Turkey: Novartis
• Approved cancer indication: Non-small cell lung cancer (MET exon 14-mutant)

Capmatinib's Mechanism of Action

• Capmatinib is a signal transduction inhibitor that targets an enzyme called MET kinase.
• MET is a receptor that activates processes promoting cell growth and proliferation.
• A specific MET gene mutation (METex14) occurs in non-small cell lung cancer (NSCLC).
• This mutation increases MET activity, allowing cancer cells to grow and proliferate uncontrollably.
• Capmatinib works by stopping the growth and proliferation of cancer cells carrying this MET mutation.

FDA Approval Timeline for Capmatinib

• May 6, 2020: FDA Approves Tabrecta (Capmatinib) for Non-Small Cell Lung Cancer (NSCLC) With a METex14 Mutation

Capmatinib Licensing and Reimbursement in Turkey

Tabrecta, containing capmatinib, has not yet been licensed by Turkey's Ministry of Health or included in reimbursement by SGK (Social Security Institution). It can be obtained through the overseas medicines unit. 

Absorption

Capmatinib is rapidly and extensively absorbed when taken orally (by mouth). Food does not significantly affect absorption.

Distribution

Capmatinib binds to human plasma proteins by up to 96%.

Metabolism and Elimination

Capmatinib is primarily metabolized by the liver enzyme CYP3A4, with additional metabolism through CYP2C9 and CYP2D6. It is mainly excreted in feces (69%), with less renal elimination (23%).

Dose Range

The recommended dose is 400 mg (two 200 mg tablets) twice daily. The starting dose is therefore 2 tablets of 200 mg in the morning and 2 tablets of 200 mg in the evening, totaling 800 mg/day. It may be taken with or without food.

The dose may be reduced depending on side effects:

Permanently discontinue capmatinib in patients unable to tolerate 200 mg orally twice daily.

Drug Interactions

• Drugs such as ketoconazole, itraconazole, erythromycin, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole can slow capmatinib metabolism, increasing drug levels and potentially increasing toxicity.
• Phenytoin, carbamazepine, rifampin, phenobarbital and other inducers of hepatic microsomal CYP3A4 enzymes, such as St. John's Wort, can increase capmatinib metabolism. This may lower effective drug levels and potentially reduce efficacy.

Precautions

• No dose reduction is required in mild, moderate or severe hepatic impairment.
• No dose reduction is needed in mild to moderate renal impairment.
• It has not been studied in patients with severe renal impairment or end-stage renal disease.
• Patients should be monitored for new lung symptoms because capmatinib can cause interstitial lung disease and pneumonia.
• Liver function tests should be performed every 2 weeks during the first 3 months and then monthly as clinically needed.
• Avoid sun exposure during capmatinib treatment and use sunscreen and protective clothing.
• Capmatinib can harm a fetus when given during pregnancy. Women of reproductive potential should use effective contraception during treatment and for at least one week after the last dose.
• Breastfeeding should be avoided during capmatinib treatment.

Side Effects

Side effects during capmatinib treatment are listed below from most to least common: