Overview
11 DESCRIPTION Tepotinib is a kinase inhibitor. TEPMETKO (tepotinib) tablets for oral use are formulated with tepotinib hydrochloride hydrate. The chemical name for tepotinib hydrochloride hydrate is 3-{1-[(3-{5-[(1-methylpiperidin-4-yl)methoxy]pyrimidin-2-yl}phenyl)methyl]-6-oxo-1,6-dihydropyridazin-3-yl}benzonitrile hydrochloride hydrate.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tepotinib is a kinase inhibitor that targets MET, including variants with exon 14 skipping alterations. Tepotinib inhibits hepatocyte growth factor (HGF)-dependent and -independent MET phosphorylation and MET-dependent downstream signaling pathways. Tepotinib also inhibited melatonin 2 and imidazoline 1 receptors at clinically achievable concentrations. In vitro, tepotinib inhibited tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent tumor cells. In mice implanted with tumor cell lines with oncogenic activation of MET, including MET ex14 skipping alterations, tepotinib inhibited tumor growth, led to sustained inhibition of MET phosphorylation, and, in one model, decreased the formation of metastases. 12.
Indications
- 1 INDICATIONS AND USAGE TEPMETKO is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition ( MET ) exon 14 skipping alterations. TEPMETKO is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition ( MET ) exon 14 skipping alterations. ( 1 )
Common Doses
- 450 mg
- 30 mL
- 225 mg
Dosage
2 DOSAGE AND ADMINISTRATION Select patients for treatment with TEPMETKO on the presence of MET ex14 skipping. ( 2.1 , 14 ) Recommended dosage : 450 mg orally once daily with food until disease progression or unacceptable toxicity. ( 2.2 ) 2.1 Patient Selection for METex14 Skipping Alterations Select patients for treatment with TEPMETKO based on the presence of MET exon 14 skipping alterations in plasma or tumor specimens. Testing for the presence of MET exon 14 skipping alterations in plasma specimens is recommended only in patients for whom a tumor biopsy cannot be obtained.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are described in greater detail elsewhere in the labeling: Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Pancreatic Toxicity [see Warnings and Precautions (5.3) ] Most common adverse reactions (≥ 20%) were edema, nausea, fatigue, musculoskeletal pain, diarrhea, dyspnea, decreased appetite, and rash.
Interactions
- 7 DRUG INTERACTIONS Certain P-gp substrates : Avoid coadministration of TEPMETKO with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. ( 7.1 ) 7.1 Effects of TEPMETKO on Other Drugs Certain P-gp Substrates Tepotinib is a P-gp inhibitor. Concomitant use of TEPMETKO increases the concentration of P-gp substrates [see Clinical Pharmacology (12.3) ], which may increase the incidence and severity of adverse reactions of these substrates.