Activity and bioavailability of tepotinib for leptomeningeal metastasis of NSCLC with MET exon 14 skipping mutation

Cancer Commun (Lond). 2021 Jan;41(1):83-87. doi: 10.1002/cac2.12124. Epub 2021 Jan 2.


Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene (MET) exon 14 skipping mutation. However, its bioavailability in the cerebrospinal fluid (CSF) in humans has not been fully elucidated. Moreover, information about the efficacy of tepotinib in patients with leptomeningeal metastasis is limited. Here, we present the case of a 56-year-old man who was diagnosed with lung adenocarcinoma with MET exon 14 skipping mutation. He was urgently hospitalized due to leptomeningeal metastasis. We administered tepotinib 500 mg/day as the second-line therapy and observed improvement in leptomeningeal metastasis and performance status. The tepotinib concentrations reached 1,648 ng/mL in the plasma and 30.6 ng/mL in the CSF, with a penetration rate (CSF/plasma) of 1.83%. These demonstrate tepotinib could achieve a high rate of central nervous system transition and could be effective against leptomeningeal metastasis.

Keywords: IC50; MET exon 14 skipping mutation; cerebrospinal fluid; leptomeningeal metastasis; non-small cell lung carcinoma; performance status; pharmacokinetics; tepotinib.

Publication types

  • Case Reports

MeSH terms

  • Biological Availability
  • Exons / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Male
  • Middle Aged
  • Mutation
  • Piperidines
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism
  • Pyridazines
  • Pyrimidines


  • MAS1 protein, human
  • Piperidines
  • Proto-Oncogene Mas
  • Pyridazines
  • Pyrimidines
  • tepotinib
  • Proto-Oncogene Proteins c-met