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Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results
Despite success in hematologic malignancies, the treatment landscape of chimeric antigen receptor (CAR) T cell therapy for solid tumors remains limited. Claudin18.2 (CLDN18.2)-redirected CAR T cells showed promising efficacy against gastric cancer (GC) in a preclinical study. Here we report the inte...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205778/ https://www.ncbi.nlm.nih.gov/pubmed/35534566 http://dx.doi.org/10.1038/s41591-022-01800-8 |
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author | Qi, Changsong Gong, Jifang Li, Jian Liu, Dan Qin, Yanru Ge, Sai Zhang, Miao Peng, Zhi Zhou, Jun Cao, Yanshuo Zhang, Xiaotian Lu, Zhihao Lu, Ming Yuan, Jiajia Wang, Zhenghang Wang, Yakun Peng, Xiaohui Gao, Huiping Liu, Zhen Wang, Huamao Yuan, Daijing Xiao, Jun Ma, Hong Wang, Wei Li, Zonghai Shen, Lin |
author_facet | Qi, Changsong Gong, Jifang Li, Jian Liu, Dan Qin, Yanru Ge, Sai Zhang, Miao Peng, Zhi Zhou, Jun Cao, Yanshuo Zhang, Xiaotian Lu, Zhihao Lu, Ming Yuan, Jiajia Wang, Zhenghang Wang, Yakun Peng, Xiaohui Gao, Huiping Liu, Zhen Wang, Huamao Yuan, Daijing Xiao, Jun Ma, Hong Wang, Wei Li, Zonghai Shen, Lin |
author_sort | Qi, Changsong |
collection | PubMed |
description | Despite success in hematologic malignancies, the treatment landscape of chimeric antigen receptor (CAR) T cell therapy for solid tumors remains limited. Claudin18.2 (CLDN18.2)-redirected CAR T cells showed promising efficacy against gastric cancer (GC) in a preclinical study. Here we report the interim analysis results of an ongoing, open-label, single-arm, phase 1 clinical trial of CLDN18.2-targeted CAR T cells (CT041) in patients with previously treated, CLDN18.2-positive digestive system cancers (NCT03874897). The primary objective was safety after CT041 infusion; secondary objectives included CT041 efficacy, pharmacokinetics and immunogenicity. We treated 37 patients with one of three CT041 doses: 2.5 × 10(8), 3.75 × 10(8) or 5.0 × 10(8) cells. All patients experienced a grade 3 or higher hematologic toxicity. Grade 1 or 2 cytokine release syndrome (CRS) occurred in 94.6% of patients. No grade 3 or higher CRS or neurotoxicities, treatment-related deaths or dose-limiting toxicities were reported. The overall response rate (ORR) and disease control rate (DCR) reached 48.6% and 73.0%, respectively. The 6-month duration of response rate was 44.8%. In patients with GC, the ORR and DCR reached 57.1% and 75.0%, respectively, and the 6-month overall survival rate was 81.2%. These initial results suggest that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive digestive system cancers, particularly in those with GC. |
format | Online Article Text |
id | pubmed-9205778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-92057782022-06-19 Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results Qi, Changsong Gong, Jifang Li, Jian Liu, Dan Qin, Yanru Ge, Sai Zhang, Miao Peng, Zhi Zhou, Jun Cao, Yanshuo Zhang, Xiaotian Lu, Zhihao Lu, Ming Yuan, Jiajia Wang, Zhenghang Wang, Yakun Peng, Xiaohui Gao, Huiping Liu, Zhen Wang, Huamao Yuan, Daijing Xiao, Jun Ma, Hong Wang, Wei Li, Zonghai Shen, Lin Nat Med Article Despite success in hematologic malignancies, the treatment landscape of chimeric antigen receptor (CAR) T cell therapy for solid tumors remains limited. Claudin18.2 (CLDN18.2)-redirected CAR T cells showed promising efficacy against gastric cancer (GC) in a preclinical study. Here we report the interim analysis results of an ongoing, open-label, single-arm, phase 1 clinical trial of CLDN18.2-targeted CAR T cells (CT041) in patients with previously treated, CLDN18.2-positive digestive system cancers (NCT03874897). The primary objective was safety after CT041 infusion; secondary objectives included CT041 efficacy, pharmacokinetics and immunogenicity. We treated 37 patients with one of three CT041 doses: 2.5 × 10(8), 3.75 × 10(8) or 5.0 × 10(8) cells. All patients experienced a grade 3 or higher hematologic toxicity. Grade 1 or 2 cytokine release syndrome (CRS) occurred in 94.6% of patients. No grade 3 or higher CRS or neurotoxicities, treatment-related deaths or dose-limiting toxicities were reported. The overall response rate (ORR) and disease control rate (DCR) reached 48.6% and 73.0%, respectively. The 6-month duration of response rate was 44.8%. In patients with GC, the ORR and DCR reached 57.1% and 75.0%, respectively, and the 6-month overall survival rate was 81.2%. These initial results suggest that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive digestive system cancers, particularly in those with GC. Nature Publishing Group US 2022-05-09 2022 /pmc/articles/PMC9205778/ /pubmed/35534566 http://dx.doi.org/10.1038/s41591-022-01800-8 Text en © The Author(s) 2022 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 Qi, Changsong Gong, Jifang Li, Jian Liu, Dan Qin, Yanru Ge, Sai Zhang, Miao Peng, Zhi Zhou, Jun Cao, Yanshuo Zhang, Xiaotian Lu, Zhihao Lu, Ming Yuan, Jiajia Wang, Zhenghang Wang, Yakun Peng, Xiaohui Gao, Huiping Liu, Zhen Wang, Huamao Yuan, Daijing Xiao, Jun Ma, Hong Wang, Wei Li, Zonghai Shen, Lin Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results |
title | Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results |
title_full | Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results |
title_fullStr | Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results |
title_full_unstemmed | Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results |
title_short | Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results |
title_sort | claudin18.2-specific car t cells in gastrointestinal cancers: phase 1 trial interim results |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205778/ https://www.ncbi.nlm.nih.gov/pubmed/35534566 http://dx.doi.org/10.1038/s41591-022-01800-8 |
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