Tepotinib
Overview
Tepotinib is a targeted small‑molecule tyrosine kinase inhibitor that selectively inhibits the mesenchymal‑epithelial transition (MET) receptor tyrosine kinase, including oncogenic variants caused by exon 14 skipping alterations. By blocking MET phosphorylation and downstream signalling pathways involved in tumour growth and survival, tepotinib reduces proliferation and induces apoptosis in MET‑dependent cancer cells. It is administered orally as a once‑daily tablet and is used in adult patients with metastatic non‑small cell lung cancer (NSCLC) whose tumours harbour MET exon 14 skipping mutations, a specific genetic alteration that drives oncogenesis. Tepotinib’s mechanism and oral dosing make it an important option in precision oncology, particularly for patients whose tumours have acquired this actionable mutation and who may not benefit sufficiently from conventional cytotoxic therapies.
Background and Date of Approval
Tepotinib was first approved for medical use in Japan in March 2020 for adult patients with advanced or unresectable NSCLC harbouring MET exon 14 skipping alterations. The United States Food and Drug Administration granted accelerated approval for tepotinib on February 3, 2021, for adult patients with metastatic NSCLC with MET exon 14 skipping alterations based on clinical response data from the pivotal VISION trial, and later converted this to traditional approval on February 15, 2024, following additional follow‑up data confirming durability of response. Tepotinib subsequently received marketing authorisation in the European Union in February 2022 for similar indications, reflecting regulatory recognition of its therapeutic value in this molecularly defined cancer population.
Uses
Tepotinib is indicated for the treatment of adult patients with metastatic non‑small cell lung cancer whose tumours have documented MET exon 14 skipping alterations, as detected by an appropriate diagnostic test. It is used when the disease is advanced, including in patients who have received prior systemic therapy or are ineligible for platinum‑based chemotherapy, and clinical decisions are guided by molecular profiling and multidisciplinary oncologic assessment.
Administration
Tepotinib is administered orally, typically at a recommended dose of 450 milligrams once daily with food, to be taken continuously until disease progression or unacceptable toxicity. Dose modifications, including reductions or temporary treatment interruptions, may be necessary based on individual patient tolerance, adverse effect profile, and organ function parameters. Regular clinical evaluation during treatment ensures appropriate management of side effects and optimisation of therapeutic benefit.
Side Effects
Frequently observed side effects with tepotinib therapy include peripheral oedema, nausea, fatigue, diarrhoea, musculoskeletal pain, dyspnoea, decreased appetite, and rash. The severity and incidence of these effects vary among patients, and most are manageable under clinical supervision through supportive care and dose adjustments as needed.
Warnings
Serious adverse events associated with tepotinib may include interstitial lung disease or pneumonitis, hepatotoxicity with potential liver injury, and embryo‑fetal toxicity if exposure occurs during pregnancy. Hypersensitivity reactions and severe gastrointestinal symptoms can occur, and treatment should be interrupted or discontinued if life‑threatening toxicity develops. Tepotinib should be avoided in pregnancy due to potential harm to the developing fetus, and effective contraception is advised during treatment and for a defined period after the last dose.
Precautions
Baseline assessments, including liver function tests, should be performed prior to initiating tepotinib and monitored periodically during therapy due to the risk of hepatotoxicity. Caution is warranted in patients with pre‑existing lung disease, hepatic impairment, or risk factors for pulmonary toxicity. Tepotinib is metabolised via hepatic pathways, and concomitant use of strong enzyme inducers or inhibitors may alter its exposure; clinicians should evaluate other medications for potential interactions. Live vaccines should generally be avoided during treatment given potential alterations in immune response.
Expert Tips
Patient selection for tepotinib should be based on confirmed molecular diagnosis of MET exon 14 skipping alterations and a clear understanding of prior treatment history. Clinicians should counsel patients on the importance of adherence to once‑daily oral dosing with food, recognition of early symptoms of serious toxicity, and the necessity of regular clinical follow‑up. Pharmacists play a crucial role in reviewing concomitant medications for interaction potential, advising on side effect management strategies, and reinforcing pregnancy prevention measures for patients of child‑bearing potential. Coordination with molecular pathology and oncology teams ensures appropriate use within precision medicine frameworks.