Tepotinib

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.

• 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.ICD-10: C34.90

• None. None.contraindicated

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. If an alteration is not detected in a plasma specimen, re-evaluate the feasibility of biopsy for tumor tissue testing. An FDA-approved test for detection of MET exon 14 skipping alterations in NSCLC for selecting patients for treatment with TEPMETKO is not available. 2.2 Recommended Dosage The recommended dosage of TEPMETKO is 450 mg orally once daily with food [see Clinical Pharmacology (12.3) ] until disease progression or unacceptable toxicity. Instruct patients to take their dose of TEPMETKO at approximately the same time every day and to swallow tablets whole. Do not chew, crush or split tablets. Patients who have difficulty swallowing solids can disperse tablets in water [see Dosage and Administration (2.3) ]. Advise patients not to make up a missed dose within 8 hours of the next scheduled dose. If vomiting occurs after taking a dose of TEPMETKO, advise patients to take the next dose at the scheduled time.

Interstitial Lung Disease (ILD)/Pneumonitis : Immediately withhold TEPMETKO in patients with suspected ILD/pneumonitis. Permanently discontinue TEPMETKO in patients diagnosed with ILD/pneumonitis of any severity. ( 2.4 , 5.1 ) Hepatotoxicity : Monitor liver function tests. Withhold, dose reduce, or permanently discontinue TEPMETKO based on severity. ( 5.2 ) Pancreatic Toxicity : Monitor amylase and lipase. Withhold, dose reduce, or permanently discontinue TEPMETKO based on severity. ( 5.3 ) Embryo-fetal toxicity : TEPMETKO can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception. ( 5.4 , 8.1 , 8.3 ) 5.1 Interstitial Lung Disease (ILD)/Pneumonitis ILD/pneumonitis, which can be fatal, occurred in patients treated with TEPMETKO [see Adverse Reactions (6.1) ]. ILD/pneumonitis occurred in 2% patients treated with TEPMETKO, with one patient experiencing a Grade 3 or higher event; this event resulted in death. Five patients (1%) discontinued TEPMETKO due to ILD/pneumonitis. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold TEPMETKO in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified [see Dosage and Administration (2.4) ]. 5.2 Hepatotoxicity Hepatotoxicity occurred in patients treated with TEPMETKO [see Adverse Reactions (6.1) ] . Increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST) occurred in 18% of patients treated with TEPMETKO.

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. The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased albumin, decreased sodium, increased gamma-glutamyltransferase, increased amylase, increased lipase, increased ALT, increased AST, and decreased hemoglobin. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact EMD Serono at 1-800-283-8088 ext. 5563 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to TEPMETKO in 506 patients with solid tumors enrolled in five open-label, single-arm studies receiving TEPMETKO as single agent at a dose of 450 mg once daily. This included 313 patients with NSCLC positive for MET ex14 skipping alterations, who received TEPMETKO in VISION.

Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings in animal studies and the mechanism of action [see Clinical Pharmacology (12.1) ], TEPMETKO can cause fetal harm when administered to a pregnant woman. There are no available data on the use of TEPMETKO in pregnant women. Oral administration of tepotinib to pregnant rabbits during the period of organogenesis resulted in malformations (teratogenicity) and anomalies at maternal exposures less than the human exposure based on area under the curve (AUC) at the 450 mg daily clinical dose (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal development studies, pregnant rabbits received oral doses of 0.5, 5, 25, 50, 150, or 450 mg/kg tepotinib hydrochloride hydrate daily during organogenesis. Severe maternal toxicity occurred at the 450 mg/kg dose (approximately 0.75 times the human exposure at the 450 mg clinical dose). At 150 mg/kg (approximately 0.5 times the human exposure by AUC at the 450 mg clinical dose), two animals aborted and one animal died prematurely; mean fetal body weight was also decreased.

Metabolism

The pharmacokinetics of tepotinib were evaluated in patients with cancer administered 450 mg once daily unless otherwise specified. Tepotinib exposure (AUC 0-12h and C max ) increases dose-proportionally over the dose range of 27 mg (0.06 times the recommended daily dosage) to 450 mg.

• Feb 3, 2021NDANDA214096Emd Serono Inc

1. 1Death10218%
2. 2Diarrhoea559.6%
3. 3Oedema529.1%
4. 4Oedema Peripheral529.1%
5. 5Fatigue508.8%
6. 6Renal Impairment508.8%
7. 7Off Label Use468.1%
8. 8Nausea427.4%
9. 9Disease Progression356.1%
10. 10Peripheral Swelling305.3%
11. 11Decreased Appetite254.4%
12. 12Blood Creatinine Increased213.7%
13. 13Dyspnoea183.2%
14. 14Constipation162.8%
15. 15Interstitial Lung Disease162.8%

The 10 most recently updated of 29 ClinicalTrials.gov registrations naming Tepotinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of Tepotinib and Ivonescimab in People With Non-Small Cell Lung Cancer
  Recruiting · Phase 1 · Interventional · 16 enrolled · Memorial Sloan Kettering Cancer Center
  NCT07619339updated 2026-06-11
• Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has a MET Exon 14 Skipping Gene Change (An Expanded Lung-MAP Treatment Trial)
  Recruiting · Phase 2 · Interventional · 56 enrolled · SWOG Cancer Research Network
  NCT06031688updated 2026-05-05
• POTENT - Tepotinib in Combination With Pembrolizumab in NSCLC
  Active not recruiting · Phase 1 · Interventional · 19 enrolled · Institute of Cancer Research, United Kingdom
  NCT05782361updated 2026-04-24
• Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)
  Active not recruiting · Phase 2 · Interventional · 337 enrolled · EMD Serono Research & Development Institute, Inc.
  NCT02864992updated 2026-04-13
• PhI/II Study of Amivantamab and Tepotinib Combo in MET-altered Non-small Cell Lung Cancer
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 3 enrolled · M.D. Anderson Cancer Center
  NCT06083857updated 2026-03-11
• A Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2)
  Active not recruiting · Phase 2 · Interventional · 140 enrolled · EMD Serono Research & Development Institute, Inc.
  NCT03940703updated 2026-02-27
• Lazertinib & Tepotinib for EGFR Mutant NSCLC in MET Overexpressed or Amplified Who Progressed After Lazertinib Treatment
  Recruiting · Phase 2 · Interventional · 47 enrolled · Samsung Medical Center
  NCT06106802updated 2026-02-23
• Tepotinib vs Standard Treatment in Patients With Advanced MET Exon 14 Mutated Non-Small Cell Lung Cancer Previously Treated
  Recruiting · Phase 3 · Interventional · 133 enrolled · Intergroupe Francophone de Cancerologie Thoracique
  NCT06908993updated 2025-12-17
• Tepotinib Hepatic Impairment Trial
  Completed · Phase 1 · Interventional · 18 enrolled · EMD Serono Research & Development Institute, Inc.
  NCT03546608updated 2024-08-12
• The Finnish National Study to Facilitate Patient Access to Targeted Anti-cancer Drugs
  Recruiting · Phase 2 · Interventional · 250 enrolled · Helsinki University Central Hospital
  NCT05159245updated 2024-07-15

Frequently asked questions

How does Tepotinib work?

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.

What is Tepotinib used for?

According to FDA labeling, Tepotinib carries indications including: 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Tepotinib?

Tepotinib is classified as Cellular-mesenchymal-epithelial transition factor (c-MET) kinase inhibitors, Other protein kinase inhibitors, Kinase Inhibitor, Kinase Inhibitors, Mesenchymal Epithelial Transition Inhibitors, P-Glycoprotein Inhibitors.

What are the brand names for Tepotinib?

Tepotinib is marketed under brand names including Tepmetko.

What are the contraindications for Tepotinib?

Tepotinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.