Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors

Jpn J Clin Oncol. 2020 Aug 4;50(8):859-866. doi: 10.1093/jjco/hyaa042.


Objectives: Tepotinib (MSC2156119J) is an oral, potent and highly selective small molecule mesenchymal-epithelial transition factor (MET) inhibitor for which the recommended Phase II dose of 500 mg once daily has been defined, based on the first-in-man trial conducted in the USA and Europe. We carried out a multicenter Phase I trial with a classic `3 + 3' design to determine the recommended Phase II dose in Japanese patients with solid tumors (NCT01832506).

Methods: Patients aged ≥20 years with advanced solid tumors (refractory to standard therapy or for whom no effective standard therapy was available) received tepotinib at 215, 300 or 500 mg once daily in a 21-day cycle. Occurrence of dose-limiting toxicities during cycle 1 was used to determine the maximum tolerated dose. Efficacy, safety and pharmacokinetics were also evaluated to support the dose assessment.

Results: Twelve patients were treated. Tepotinib was generally well tolerated with no observed dose-limiting toxicities; treatment-related adverse events were mainly grades 1-2. The tolerability profile of tepotinib was similar to that observed in non-Japanese populations. Pharmacokinetics in Japanese and Western patients was comparable. One patient with gastric cancer and one patient with urachal cancer had stable disease of ≥12 weeks in duration. The observed safety profile and pharmacokinetics are comparable with those in patients from the USA and Europe, and the recommended Phase II dose of tepotinib in Japanese patients was confirmed as 500 mg once daily.

Conclusions: These results, including initial signals of antitumor activity, support further development of tepotinib in Japanese patients with cancer.

Keywords: GI-stomach-Med; clinical trials; molecular diagnosis.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Asian People*
  • Biomarkers, Tumor / blood
  • Female
  • Humans
  • Japan
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • Piperidines / adverse effects
  • Piperidines / pharmacokinetics
  • Piperidines / pharmacology
  • Piperidines / therapeutic use*
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / metabolism
  • Pyridazines / adverse effects
  • Pyridazines / pharmacokinetics
  • Pyridazines / pharmacology
  • Pyridazines / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyridazines
  • Pyrimidines
  • tepotinib
  • MET protein, human
  • Proto-Oncogene Proteins c-met

Associated data