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A multicenter, phase II trial of GC1118, a novel anti‐EGFR antibody, for recurrent glioblastoma patients with EGFR amplification

BACKGROUND: We evaluated the therapeutic efficacy of GC1118, a novel anti‐epidermal growth factor receptor (EGFR) monoclonal antibody, in recurrent glioblastoma (GBM) patients with EGFR amplification. METHODS: This study was a multicenter, open‐label, single‐arm phase II trial. Recurrent GBM patient...

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Autores principales: Choi, Seung Won, Jung, Hyun Ae, Cho, Hee‐Jin, Kim, Tae Min, Park, Chul‐Kee, Nam, Do‐Hyun, Lee, Se‐Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10469652/
https://www.ncbi.nlm.nih.gov/pubmed/37537946
http://dx.doi.org/10.1002/cam4.6213
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author Choi, Seung Won
Jung, Hyun Ae
Cho, Hee‐Jin
Kim, Tae Min
Park, Chul‐Kee
Nam, Do‐Hyun
Lee, Se‐Hoon
author_facet Choi, Seung Won
Jung, Hyun Ae
Cho, Hee‐Jin
Kim, Tae Min
Park, Chul‐Kee
Nam, Do‐Hyun
Lee, Se‐Hoon
author_sort Choi, Seung Won
collection PubMed
description BACKGROUND: We evaluated the therapeutic efficacy of GC1118, a novel anti‐epidermal growth factor receptor (EGFR) monoclonal antibody, in recurrent glioblastoma (GBM) patients with EGFR amplification. METHODS: This study was a multicenter, open‐label, single‐arm phase II trial. Recurrent GBM patients with EGFR amplification were eligible: EGFR amplification was determined using fluorescence in situ hybridization analysis when a sample had both the EGFR/CEP7 ratio of ≥2 and a tight cluster EGFR signal in ≥10% of recorded cells. GC1118 was administered intravenously at a dose of 4 mg/kg once weekly. The primary endpoint was the 6‐month progression‐free survival rate (PFS6). Next‐generation sequencing was performed to investigate the molecular biomarkers related to the response to GC1118. RESULTS: Between April 2018 and December 2020, 21 patients were enrolled in the study and received GC1118 treatment. Eighteen patients were eligible for efficacy analysis. The PFS6 was 5.6% (95% confidence interval, 0.3%–25.8%, Wilson method). The median progression‐free survival was 1.7 months (range: 28 days–7.2 months) and median overall survival was 5.7 months (range: 2–22.0 months). GC1118 was well tolerated except skin toxicities. Skin rash was the most frequent adverse event and four patients experienced Grade 3 skin‐related toxicity. Genomic analysis revealed that the immune‐related signatures were upregulated in patients with tumor regression. CONCLUSION: This study did not meet the primary endpoint (PFS6); however, we found that immune signatures were significantly upregulated in the tumors with regression upon GC1118 therapy, which signifies the potential of immune‐mediated antitumor efficacy of GC1118.
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spelling pubmed-104696522023-09-01 A multicenter, phase II trial of GC1118, a novel anti‐EGFR antibody, for recurrent glioblastoma patients with EGFR amplification Choi, Seung Won Jung, Hyun Ae Cho, Hee‐Jin Kim, Tae Min Park, Chul‐Kee Nam, Do‐Hyun Lee, Se‐Hoon Cancer Med RESEARCH ARTICLES BACKGROUND: We evaluated the therapeutic efficacy of GC1118, a novel anti‐epidermal growth factor receptor (EGFR) monoclonal antibody, in recurrent glioblastoma (GBM) patients with EGFR amplification. METHODS: This study was a multicenter, open‐label, single‐arm phase II trial. Recurrent GBM patients with EGFR amplification were eligible: EGFR amplification was determined using fluorescence in situ hybridization analysis when a sample had both the EGFR/CEP7 ratio of ≥2 and a tight cluster EGFR signal in ≥10% of recorded cells. GC1118 was administered intravenously at a dose of 4 mg/kg once weekly. The primary endpoint was the 6‐month progression‐free survival rate (PFS6). Next‐generation sequencing was performed to investigate the molecular biomarkers related to the response to GC1118. RESULTS: Between April 2018 and December 2020, 21 patients were enrolled in the study and received GC1118 treatment. Eighteen patients were eligible for efficacy analysis. The PFS6 was 5.6% (95% confidence interval, 0.3%–25.8%, Wilson method). The median progression‐free survival was 1.7 months (range: 28 days–7.2 months) and median overall survival was 5.7 months (range: 2–22.0 months). GC1118 was well tolerated except skin toxicities. Skin rash was the most frequent adverse event and four patients experienced Grade 3 skin‐related toxicity. Genomic analysis revealed that the immune‐related signatures were upregulated in patients with tumor regression. CONCLUSION: This study did not meet the primary endpoint (PFS6); however, we found that immune signatures were significantly upregulated in the tumors with regression upon GC1118 therapy, which signifies the potential of immune‐mediated antitumor efficacy of GC1118. John Wiley and Sons Inc. 2023-08-03 /pmc/articles/PMC10469652/ /pubmed/37537946 http://dx.doi.org/10.1002/cam4.6213 Text en © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle RESEARCH ARTICLES
Choi, Seung Won
Jung, Hyun Ae
Cho, Hee‐Jin
Kim, Tae Min
Park, Chul‐Kee
Nam, Do‐Hyun
Lee, Se‐Hoon
A multicenter, phase II trial of GC1118, a novel anti‐EGFR antibody, for recurrent glioblastoma patients with EGFR amplification
title A multicenter, phase II trial of GC1118, a novel anti‐EGFR antibody, for recurrent glioblastoma patients with EGFR amplification
title_full A multicenter, phase II trial of GC1118, a novel anti‐EGFR antibody, for recurrent glioblastoma patients with EGFR amplification
title_fullStr A multicenter, phase II trial of GC1118, a novel anti‐EGFR antibody, for recurrent glioblastoma patients with EGFR amplification
title_full_unstemmed A multicenter, phase II trial of GC1118, a novel anti‐EGFR antibody, for recurrent glioblastoma patients with EGFR amplification
title_short A multicenter, phase II trial of GC1118, a novel anti‐EGFR antibody, for recurrent glioblastoma patients with EGFR amplification
title_sort multicenter, phase ii trial of gc1118, a novel anti‐egfr antibody, for recurrent glioblastoma patients with egfr amplification
topic RESEARCH ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10469652/
https://www.ncbi.nlm.nih.gov/pubmed/37537946
http://dx.doi.org/10.1002/cam4.6213
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