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An Integrated Analysis of Dostarlimab Immunogenicity

Monoclonal antibodies that block the interaction between programmed cell death 1 (PD-1) and its ligand (PD-L1) have revolutionized cancer immunotherapy. However, immunogenic responses to these new therapies—such as the development of antidrug antibodies (ADAs) and neutralizing antibodies (NAbs)—may...

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Autores principales: Lu, Sharon, Bowsher, Ronald R., Clancy, Amanda, Rosen, Amy, Zhang, Mingxuan, Yang, Ying, Koeck, Kathleen, Gao, Minggeng, Potocka, Elizabeth, Guo, Wei, Jen, Kai Yu, Im, Ellie, Milton, Ashley
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321970/
https://www.ncbi.nlm.nih.gov/pubmed/34324079
http://dx.doi.org/10.1208/s12248-021-00624-7
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author Lu, Sharon
Bowsher, Ronald R.
Clancy, Amanda
Rosen, Amy
Zhang, Mingxuan
Yang, Ying
Koeck, Kathleen
Gao, Minggeng
Potocka, Elizabeth
Guo, Wei
Jen, Kai Yu
Im, Ellie
Milton, Ashley
author_facet Lu, Sharon
Bowsher, Ronald R.
Clancy, Amanda
Rosen, Amy
Zhang, Mingxuan
Yang, Ying
Koeck, Kathleen
Gao, Minggeng
Potocka, Elizabeth
Guo, Wei
Jen, Kai Yu
Im, Ellie
Milton, Ashley
author_sort Lu, Sharon
collection PubMed
description Monoclonal antibodies that block the interaction between programmed cell death 1 (PD-1) and its ligand (PD-L1) have revolutionized cancer immunotherapy. However, immunogenic responses to these new therapies—such as the development of antidrug antibodies (ADAs) and neutralizing antibodies (NAbs)—may represent a significant challenge to both efficacy and safety in some patients. Dostarlimab (TSR-042) is an approved, humanized, anti-PD-1 monoclonal antibody that has shown efficacy in multiple solid tumor types. Here, we report the results of an immunogenicity analysis of dostarlimab monotherapy in patients enrolled in the GARNET trial, a multicenter, open-label, single-arm phase 1 study. Overall, 477 of 478 patients (99.8%) were included in the analysis of dostarlimab antibody prevalence, and 349 out of 478 enrolled patients (73.0%) were evaluable for treatment-emergent antibodies to dostarlimab. The incidence of treatment-emergent ADAs was 2.5% at the recommended therapeutic dose (500 mg Q3W for the first 4 doses, 1000 mg Q6W until discontinuation), which is comparable to other anti-PD-(L)1 drugs. NAbs were detected in only 1.3% of patients. In the small percentage of patients who developed ADAs, there was no evidence of altered efficacy or safety of dostarlimab at the recommended dosing regimen. These findings demonstrated that treatment with dostarlimab was associated with a low risk of eliciting clinically meaningful ADAs over the course of this study, and dostarlimab is already approved by health authorities. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1208/s12248-021-00624-7.
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spelling pubmed-83219702021-08-19 An Integrated Analysis of Dostarlimab Immunogenicity Lu, Sharon Bowsher, Ronald R. Clancy, Amanda Rosen, Amy Zhang, Mingxuan Yang, Ying Koeck, Kathleen Gao, Minggeng Potocka, Elizabeth Guo, Wei Jen, Kai Yu Im, Ellie Milton, Ashley AAPS J Research Article Monoclonal antibodies that block the interaction between programmed cell death 1 (PD-1) and its ligand (PD-L1) have revolutionized cancer immunotherapy. However, immunogenic responses to these new therapies—such as the development of antidrug antibodies (ADAs) and neutralizing antibodies (NAbs)—may represent a significant challenge to both efficacy and safety in some patients. Dostarlimab (TSR-042) is an approved, humanized, anti-PD-1 monoclonal antibody that has shown efficacy in multiple solid tumor types. Here, we report the results of an immunogenicity analysis of dostarlimab monotherapy in patients enrolled in the GARNET trial, a multicenter, open-label, single-arm phase 1 study. Overall, 477 of 478 patients (99.8%) were included in the analysis of dostarlimab antibody prevalence, and 349 out of 478 enrolled patients (73.0%) were evaluable for treatment-emergent antibodies to dostarlimab. The incidence of treatment-emergent ADAs was 2.5% at the recommended therapeutic dose (500 mg Q3W for the first 4 doses, 1000 mg Q6W until discontinuation), which is comparable to other anti-PD-(L)1 drugs. NAbs were detected in only 1.3% of patients. In the small percentage of patients who developed ADAs, there was no evidence of altered efficacy or safety of dostarlimab at the recommended dosing regimen. These findings demonstrated that treatment with dostarlimab was associated with a low risk of eliciting clinically meaningful ADAs over the course of this study, and dostarlimab is already approved by health authorities. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1208/s12248-021-00624-7. Springer International Publishing 2021-07-29 /pmc/articles/PMC8321970/ /pubmed/34324079 http://dx.doi.org/10.1208/s12248-021-00624-7 Text en © The Author(s) 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Lu, Sharon
Bowsher, Ronald R.
Clancy, Amanda
Rosen, Amy
Zhang, Mingxuan
Yang, Ying
Koeck, Kathleen
Gao, Minggeng
Potocka, Elizabeth
Guo, Wei
Jen, Kai Yu
Im, Ellie
Milton, Ashley
An Integrated Analysis of Dostarlimab Immunogenicity
title An Integrated Analysis of Dostarlimab Immunogenicity
title_full An Integrated Analysis of Dostarlimab Immunogenicity
title_fullStr An Integrated Analysis of Dostarlimab Immunogenicity
title_full_unstemmed An Integrated Analysis of Dostarlimab Immunogenicity
title_short An Integrated Analysis of Dostarlimab Immunogenicity
title_sort integrated analysis of dostarlimab immunogenicity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321970/
https://www.ncbi.nlm.nih.gov/pubmed/34324079
http://dx.doi.org/10.1208/s12248-021-00624-7
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