A multicenter, phase II trial of GC1118, a novel anti-EGFR antibody, for recurrent glioblastoma patients with EGFR amplification
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Cancer medicine - 12(2023), 15 vom: 16. Aug., Seite 15788-15796 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Choi, Seung Won [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.09.2023 Date Revised 02.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/cam4.6213 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360376681 |
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| 100 | 1 | |a Choi, Seung Won |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A multicenter, phase II trial of GC1118, a novel anti-EGFR antibody, for recurrent glioblastoma patients with EGFR amplification |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 01.09.2023 | ||
| 500 | |a Date Revised 02.09.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a EGFR | |
| 650 | 4 | |a glioblastoma | |
| 650 | 4 | |a immune response | |
| 650 | 4 | |a monoclonal antibody | |
| 650 | 7 | |a GC1118 |2 NLM | |
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| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 700 | 1 | |a Jung, Hyun Ae |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Hee-Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Tae Min |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Chul-Kee |e verfasserin |4 aut | |
| 700 | 1 | |a Nam, Do-Hyun |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Se-Hoon |e verfasserin |4 aut | |
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