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Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression
BACKGROUND: This Phase 1b/2 study evaluated tepotinib, a highly selective MET inhibitor, in US/European patients with sorafenib pretreated advanced hepatocellular carcinoma (aHCC) with MET overexpression. METHODS: Eligible adults had aHCC, progression after ≥4 weeks of sorafenib, and, for Phase 2 on...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292404/ https://www.ncbi.nlm.nih.gov/pubmed/33824476 http://dx.doi.org/10.1038/s41416-021-01334-9 |
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author | Decaens, Thomas Barone, Carlo Assenat, Eric Wermke, Martin Fasolo, Angelica Merle, Philippe Blanc, Jean-Frédéric Grando, Véronique Iacobellis, Angelo Villa, Erica Trojan, Joerg Straub, Josef Bruns, Rolf Berghoff, Karin Scheele, Juergen Raymond, Eric Faivre, Sandrine |
author_facet | Decaens, Thomas Barone, Carlo Assenat, Eric Wermke, Martin Fasolo, Angelica Merle, Philippe Blanc, Jean-Frédéric Grando, Véronique Iacobellis, Angelo Villa, Erica Trojan, Joerg Straub, Josef Bruns, Rolf Berghoff, Karin Scheele, Juergen Raymond, Eric Faivre, Sandrine |
author_sort | Decaens, Thomas |
collection | PubMed |
description | BACKGROUND: This Phase 1b/2 study evaluated tepotinib, a highly selective MET inhibitor, in US/European patients with sorafenib pretreated advanced hepatocellular carcinoma (aHCC) with MET overexpression. METHODS: Eligible adults had aHCC, progression after ≥4 weeks of sorafenib, and, for Phase 2 only, MET overexpression. Tepotinib was administered once daily at 300 or 500 mg in Phase 1b (‘3 + 3’ design), and at the recommended Phase 2 dose (RP2D) in Phase 2. Primary endpoints were dose-liming toxicities (DLTs; Phase 1b) and 12-week investigator-assessed progression-free survival (PFS; Phase 2). RESULTS: In Phase 1b (n = 17), no DLTs occurred and the RP2D was confirmed as 500 mg. In Phase 2 (n = 49), the primary endpoint was met: 12-week PFS was 63.3% (90% CI: 50.5–74.7), which was significantly greater than the predefined null hypothesis of ≤15% (one-sided binomial exact test: P < 0.0001). Median time to progression was 4 months. In Phase 2, 28.6% of patients had treatment-related Grade ≥3 adverse events, including peripheral oedema and lipase increase (both 6.1%). CONCLUSIONS: Tepotinib was generally well tolerated and the RP2D (500 mg) showed promising efficacy and, therefore, a positive benefit–risk balance in sorafenib pretreated aHCC with MET overexpression. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02115373. |
format | Online Article Text |
id | pubmed-8292404 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-82924042021-07-23 Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression Decaens, Thomas Barone, Carlo Assenat, Eric Wermke, Martin Fasolo, Angelica Merle, Philippe Blanc, Jean-Frédéric Grando, Véronique Iacobellis, Angelo Villa, Erica Trojan, Joerg Straub, Josef Bruns, Rolf Berghoff, Karin Scheele, Juergen Raymond, Eric Faivre, Sandrine Br J Cancer Article BACKGROUND: This Phase 1b/2 study evaluated tepotinib, a highly selective MET inhibitor, in US/European patients with sorafenib pretreated advanced hepatocellular carcinoma (aHCC) with MET overexpression. METHODS: Eligible adults had aHCC, progression after ≥4 weeks of sorafenib, and, for Phase 2 only, MET overexpression. Tepotinib was administered once daily at 300 or 500 mg in Phase 1b (‘3 + 3’ design), and at the recommended Phase 2 dose (RP2D) in Phase 2. Primary endpoints were dose-liming toxicities (DLTs; Phase 1b) and 12-week investigator-assessed progression-free survival (PFS; Phase 2). RESULTS: In Phase 1b (n = 17), no DLTs occurred and the RP2D was confirmed as 500 mg. In Phase 2 (n = 49), the primary endpoint was met: 12-week PFS was 63.3% (90% CI: 50.5–74.7), which was significantly greater than the predefined null hypothesis of ≤15% (one-sided binomial exact test: P < 0.0001). Median time to progression was 4 months. In Phase 2, 28.6% of patients had treatment-related Grade ≥3 adverse events, including peripheral oedema and lipase increase (both 6.1%). CONCLUSIONS: Tepotinib was generally well tolerated and the RP2D (500 mg) showed promising efficacy and, therefore, a positive benefit–risk balance in sorafenib pretreated aHCC with MET overexpression. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02115373. Nature Publishing Group UK 2021-04-06 2021-07-20 /pmc/articles/PMC8292404/ /pubmed/33824476 http://dx.doi.org/10.1038/s41416-021-01334-9 Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Decaens, Thomas Barone, Carlo Assenat, Eric Wermke, Martin Fasolo, Angelica Merle, Philippe Blanc, Jean-Frédéric Grando, Véronique Iacobellis, Angelo Villa, Erica Trojan, Joerg Straub, Josef Bruns, Rolf Berghoff, Karin Scheele, Juergen Raymond, Eric Faivre, Sandrine Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression |
title | Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression |
title_full | Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression |
title_fullStr | Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression |
title_full_unstemmed | Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression |
title_short | Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression |
title_sort | phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with met overexpression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292404/ https://www.ncbi.nlm.nih.gov/pubmed/33824476 http://dx.doi.org/10.1038/s41416-021-01334-9 |
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