tepotinib 

Action and Spectrum

Actions and Spectrum 

The main action of drug is to selectively bind to the MET receptor, preventing its activation by its ligand, hepatocyte growth factor (HGF). By inhibiting MET activation, drug blocks downstream signaling pathways involved in tumor cell proliferation, invasion, and angiogenesis. 

Its spectrum of activity is mainly focused on tumors with MET alterations, offering a targeted therapeutic option for patients with these specific genetic abnormalities. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

All grades 

Decreased hemoglobin (27%) 

Increased ALT (44%) 

Decreased lymphocytes (48%) 

Increased AST (35%) 

Edema (70%) 

Nausea (27%) 

Decreased sodium (31%) 

Increased alkaline phosphatase (50%) 

Fatigue (27%) 

Decreased albumin (76%) 

Increased potassium (25%) 

Diarrhea (26%) 

Increased gamma-glutamyltransferase (24%) 

Musculoskeletal pain (24%) 

Increased creatinine (55%) 

Grade 3 to 4 

Decreased lymphocytes (11%) 

1-10% 

All grades 

Headache (<10%) 

Fever (<10%) 

Pruritus (<10%) 

Dizziness (<10%) 

Rash (<10%) 

ILD/pneumonitis (<10%) 

Grade 3 to 4 

Increased alkaline phosphatase (1.6%) 

Increased gamma-glutamyltransferase (5%) 

Decreased hemoglobin (2%) 

Increased amylase (4.6%) 

Pneumonia (3.9%) 

Decreased sodium (8%) 

Dyspnea (2%) 

Increased ALT (4.1%) 

Musculoskeletal pain (2.4%) 

Increased AST (2.5%) 

Decreased albumin (9%) 

Pleural effusion (5%) 

<1% 

Grade 3 to 4 

Cough (0.4%) 

Abdominal pain (0.8%) 

Increased creatinine (0.4%) 

Diarrhea (0.4%) 

Decreased leukocytes (0.8%) 

Nausea (0.8%) 

Black Box Warning

Black Box Warning:  

None  

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity or allergic reaction: 

If a patient has had an allergic reaction or hypersensitivity to tepotinib in the past, it should not be used again. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: AU TGA pregnancy category D 

US FDA pregnancy category Not Assigned 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

• Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 
• Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

The drug is a small molecule inhibitor of the hepatocyte growth factor (HGF) receptor, commonly referred to as c-MET.  

Pharmacodynamics:  

The drug selectively inhibits the activation of the c-MET receptor, which plays a crucial role in cell growth, survival, and migration. Activation of c-MET signaling can lead to uncontrolled cell proliferation and metastasis in cancer. The drug binds to the ATP-binding site of c-MET and prevents its phosphorylation, thereby inhibiting downstream signaling pathways involved in cancer progression.   

Pharmacokinetics: 

Absorption 

The drug is orally administered as a tablet. It is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations reached within approximately 2 hours after oral administration. 

Distribution 

The drug has a moderate volume of distribution, indicating that it is distributed throughout the body tissues. It is highly bound to plasma proteins (approximately 99.9%), primarily to albumin. 

Metabolism 

The metabolism of the drug take place in the liver through the cytochrome P450 enzyme system, particularly CYP3A4 and CYP2C9. The major circulating metabolite is M5, which is formed by oxidative metabolism of tepotinib.  

Excretion and elimination  

The drug and its metabolites are primarily eliminated via the feces (approximately 67%), while renal excretion accounts for a minor fraction (approximately 9%) of the total dose. The elimination half-life of tepotinib is approximately 40 hours. 

Adminstartion

Administration:  

Dosage: The recommended dosage may vary depending on the individual’s condition. It is essential to follow the prescribed dose exactly as instructed by the healthcare provider. 

Timing: The drug is usually taken once a day, with or without food. The specific time of day for administration may be recommended by the prescribing physician. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tepotinib  

Why do we use tepotinib?   

Treatment of NSCLC with MET exon 14 skipping mutations: The drug has been approved for the treatment of NSCLC patients with MET exon 14 skipping mutations who have progressed on or are not eligible for platinum-based chemotherapy. 

MET-driven cancers: The drug may also have potential in the treatment of other cancers that are driven by aberrant activation of the MET receptor, such as gastric cancer, hepatocellular carcinoma, and breast cancer. 

Combination therapy: The drug is being studied in combination with other targeted therapies or immunotherapies to enhance the treatment outcomes in MET-driven cancers. For example, it is being investigated in combination with anti-PD-1/PD-L1 antibodies in NSCLC patients. 

Research tool: The drug can be used as a research tool in preclinical and clinical studies to understand the biology of MET-driven cancers and to evaluate the effectiveness of targeting the MET pathway.