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Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors
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 carri...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401714/ https://www.ncbi.nlm.nih.gov/pubmed/32328660 http://dx.doi.org/10.1093/jjco/hyaa042 |
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author | Shitara, Kohei Yamazaki, Kentaro Tsushima, Takahiro Naito, Tateaki Matsubara, Nobuaki Watanabe, Morihiro Sarholz, Barbara Johne, Andreas Doi, Toshihiko |
author_facet | Shitara, Kohei Yamazaki, Kentaro Tsushima, Takahiro Naito, Tateaki Matsubara, Nobuaki Watanabe, Morihiro Sarholz, Barbara Johne, Andreas Doi, Toshihiko |
author_sort | Shitara, Kohei |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7401714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-74017142020-08-06 Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors Shitara, Kohei Yamazaki, Kentaro Tsushima, Takahiro Naito, Tateaki Matsubara, Nobuaki Watanabe, Morihiro Sarholz, Barbara Johne, Andreas Doi, Toshihiko Jpn J Clin Oncol Original Article 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. Oxford University Press 2020-04-24 /pmc/articles/PMC7401714/ /pubmed/32328660 http://dx.doi.org/10.1093/jjco/hyaa042 Text en © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Article Shitara, Kohei Yamazaki, Kentaro Tsushima, Takahiro Naito, Tateaki Matsubara, Nobuaki Watanabe, Morihiro Sarholz, Barbara Johne, Andreas Doi, Toshihiko Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors |
title | Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors |
title_full | Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors |
title_fullStr | Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors |
title_full_unstemmed | Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors |
title_short | Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors |
title_sort | phase i trial of the met inhibitor tepotinib in japanese patients with solid tumors |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401714/ https://www.ncbi.nlm.nih.gov/pubmed/32328660 http://dx.doi.org/10.1093/jjco/hyaa042 |
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