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Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors
PURPOSE: Patritumab (U3-1287) is a human epidermal growth factor receptor-3 (HER3)-targeted antibody that blocks ligand-associated activation of HER3. This open-label, phase 1 and dose-finding study (ClinicalTrials.jp Identifier: JapicCTI-101262) aimed to assess the safety, pharmacokinetics, inciden...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931937/ https://www.ncbi.nlm.nih.gov/pubmed/24442032 http://dx.doi.org/10.1007/s00280-014-2375-2 |
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author | Wakui, Hiroshi Yamamoto, Noboru Nakamichi, Shinji Tamura, Yousuke Nokihara, Hiroshi Yamada, Yasuhide Tamura, Tomohide |
author_facet | Wakui, Hiroshi Yamamoto, Noboru Nakamichi, Shinji Tamura, Yousuke Nokihara, Hiroshi Yamada, Yasuhide Tamura, Tomohide |
author_sort | Wakui, Hiroshi |
collection | PubMed |
description | PURPOSE: Patritumab (U3-1287) is a human epidermal growth factor receptor-3 (HER3)-targeted antibody that blocks ligand-associated activation of HER3. This open-label, phase 1 and dose-finding study (ClinicalTrials.jp Identifier: JapicCTI-101262) aimed to assess the safety, pharmacokinetics, incidence of anti-patritumab antibody, recommended dose for subsequent clinical studies, preliminary efficacy, and patritumab-related biomarkers in Japanese patients with advanced solid tumors. METHODS: Patients received patritumab 9 or 18 mg/kg intravenously every 3 weeks until disease progression or intolerable toxicity occurred. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Dose-limiting toxicities (DLTs) were evaluated from the initial dose to Cycle 1 Day 21. Tumor response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). RESULTS: Nine patients received patritumab 9 mg/kg (n = 3) or 18 mg/kg (n = 6). Five patients were male, all patients had Eastern Cooperative Oncology Group performance status (PS) ≤ 1, and median (range) age of 67 (50–69) years. No DLTs were reported. Patritumab-related AEs reported in ≥2 patients were ALT increase (three patients), thrombocytopenia, diarrhea, stomatitis, cheilitis, rash maculo-papular and AST increase (two each). Pharmacokinetics profile was similar to the preceding US phase 1 study. Soluble HER3 concentration in serum unexpectedly increased in all patients. These changes did not correlate with clinical response. Four patients had a best response of stable disease. All patients tested had negative for anti-patritumab antibody formation. CONCLUSIONS: Patritumab was well tolerated up to 18 mg/kg without DLTs in Japanese patients with advanced solid tumors. Soluble HER3 increased in all patients. |
format | Online Article Text |
id | pubmed-3931937 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-39319372014-02-28 Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors Wakui, Hiroshi Yamamoto, Noboru Nakamichi, Shinji Tamura, Yousuke Nokihara, Hiroshi Yamada, Yasuhide Tamura, Tomohide Cancer Chemother Pharmacol Original Article PURPOSE: Patritumab (U3-1287) is a human epidermal growth factor receptor-3 (HER3)-targeted antibody that blocks ligand-associated activation of HER3. This open-label, phase 1 and dose-finding study (ClinicalTrials.jp Identifier: JapicCTI-101262) aimed to assess the safety, pharmacokinetics, incidence of anti-patritumab antibody, recommended dose for subsequent clinical studies, preliminary efficacy, and patritumab-related biomarkers in Japanese patients with advanced solid tumors. METHODS: Patients received patritumab 9 or 18 mg/kg intravenously every 3 weeks until disease progression or intolerable toxicity occurred. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Dose-limiting toxicities (DLTs) were evaluated from the initial dose to Cycle 1 Day 21. Tumor response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). RESULTS: Nine patients received patritumab 9 mg/kg (n = 3) or 18 mg/kg (n = 6). Five patients were male, all patients had Eastern Cooperative Oncology Group performance status (PS) ≤ 1, and median (range) age of 67 (50–69) years. No DLTs were reported. Patritumab-related AEs reported in ≥2 patients were ALT increase (three patients), thrombocytopenia, diarrhea, stomatitis, cheilitis, rash maculo-papular and AST increase (two each). Pharmacokinetics profile was similar to the preceding US phase 1 study. Soluble HER3 concentration in serum unexpectedly increased in all patients. These changes did not correlate with clinical response. Four patients had a best response of stable disease. All patients tested had negative for anti-patritumab antibody formation. CONCLUSIONS: Patritumab was well tolerated up to 18 mg/kg without DLTs in Japanese patients with advanced solid tumors. Soluble HER3 increased in all patients. Springer Berlin Heidelberg 2014-01-18 2014 /pmc/articles/PMC3931937/ /pubmed/24442032 http://dx.doi.org/10.1007/s00280-014-2375-2 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/2.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Article Wakui, Hiroshi Yamamoto, Noboru Nakamichi, Shinji Tamura, Yousuke Nokihara, Hiroshi Yamada, Yasuhide Tamura, Tomohide Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors |
title | Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors |
title_full | Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors |
title_fullStr | Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors |
title_full_unstemmed | Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors |
title_short | Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors |
title_sort | phase 1 and dose-finding study of patritumab (u3-1287), a human monoclonal antibody targeting her3, in japanese patients with advanced solid tumors |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931937/ https://www.ncbi.nlm.nih.gov/pubmed/24442032 http://dx.doi.org/10.1007/s00280-014-2375-2 |
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