Capmatinib

TABRECTA is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. TABRECTA is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.

Capmatinib is a kinase inhibitor that targets MET, including the mutant variant produced by exon 14 skipping. MET exon 14 skipping results in a protein with a missing regulatory domain that reduces its negative regulation leading to increased downstream MET signaling. Capmatinib inhibited cancer cell growth driven by a mutant MET variant lacking exon 14 at clinically achievable concentrations and demonstrated anti-tumor activity in murine tumor xenograft models derived from human lung tumors with either a mutation leading to MET exon 14 skipping or MET amplification. Capmatinib inhibited the phosphorylation of MET triggered by binding of hepatocyte growth factor or by MET amplification, as well as MET-mediated phosphorylation of downstream signaling proteins and proliferation and survival of MET-dependent cancer cells.

Select patients for treatment with TABRECTA based on presence of a mutation that leads to MET exon 14 skipping. Recommended Dosage: 400 mg orally twice daily with or without food.

None. None.

Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Permanently discontinue TABRECTA in patients with ILD/pneumonitis. Hepatotoxicity: Monitor liver function tests. Withhold, dose reduce, or permanently discontinue TABRECTA based on severity. Pancreatic Toxicity: Monitor amylase and lipase levels. Hypersensitivity Reactions: Withhold or permanently discontinue TABRECTA based on severity. Risk of Photosensitivity: May cause photosensitivity reactions. Advise patients to limit direct ultraviolet exposure. Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

The following clinically significant adverse reactions are described elsewhere in the labeling: ILD/Pneumonitis Hepatotoxicity Pancreatic Toxicity Hypersensitivity reactions The most common adverse reactions (≥ 20%) are edema, nausea, musculoskeletal pain, fatigue, vomiting, dyspnea, cough, and decreased appetite.

Strong and Moderate CYP3A Inducers: Avoid concomitant use. Effect of Other Drugs on TABRECTA Strong CYP3A Inhibitors Coadministration of TABRECTA with a strong CYP3A inhibitor increased capmatinib exposure, which may increase the incidence and severity of adverse reactions of TABRECTA. Closely monitor patients for adverse reactions during coadministration of TABRECTA with strong CYP3A inhibitors. Strong and Moderate CYP3A Inducers Coadministration of TABRECTA with a strong CYP3A inducer decreased capmatinib exposure. Coadministration of TABRECTA with a moderate CYP3A inducer may also decrease capmatinib exposure. Decreases in capmatinib exposure may decrease TABRECTA anti-tumor activity. Avoid coadministration of TABRECTA with strong and moderate CYP3A inducers.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Storage Dispense in the original package with the desiccant cartridge. Protect from moisture.