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Mogamulizumab in Combination with Nivolumab in a Phase I/II Study of Patients with Locally Advanced or Metastatic Solid Tumors

PURPOSE: The aim of the study was to determine safety, antitumor activity, and pharmacodynamic profile of mogamulizumab, an anti-CCR4 monoclonal antibody targeting effector regulatory T cells (Treg) in combination with the checkpoint inhibitor nivolumab in patients with locally advanced or metastati...

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Autores principales: Hong, David S., Rixe, Olivier, Chiu, Vi K., Forde, Patrick M., Dragovich, Tomislav, Lou, Yanyan, Nayak-Kapoor, Asha, Leidner, Rom, Atkins, James N., Collaku, Agron, Fox, Floyd E., Marshall, Margaret A., Olszanski, Anthony J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9401557/
https://www.ncbi.nlm.nih.gov/pubmed/34753777
http://dx.doi.org/10.1158/1078-0432.CCR-21-2781
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author Hong, David S.
Rixe, Olivier
Chiu, Vi K.
Forde, Patrick M.
Dragovich, Tomislav
Lou, Yanyan
Nayak-Kapoor, Asha
Leidner, Rom
Atkins, James N.
Collaku, Agron
Fox, Floyd E.
Marshall, Margaret A.
Olszanski, Anthony J.
author_facet Hong, David S.
Rixe, Olivier
Chiu, Vi K.
Forde, Patrick M.
Dragovich, Tomislav
Lou, Yanyan
Nayak-Kapoor, Asha
Leidner, Rom
Atkins, James N.
Collaku, Agron
Fox, Floyd E.
Marshall, Margaret A.
Olszanski, Anthony J.
author_sort Hong, David S.
collection PubMed
description PURPOSE: The aim of the study was to determine safety, antitumor activity, and pharmacodynamic profile of mogamulizumab, an anti-CCR4 monoclonal antibody targeting effector regulatory T cells (Treg) in combination with the checkpoint inhibitor nivolumab in patients with locally advanced or metastatic solid tumors. PATIENTS AND METHODS: This was a multicenter, dose-finding (phase I), and dose expansion (phase II) study (NCT02705105) in patients with locally advanced or metastatic solid tumors. There were no dose-limiting toxicities in phase I with mogamulizumab 1 mg/kg every week for cycle 1 followed by 1 mg/kg every 2 weeks plus nivolumab 240 mg every 2 weeks intravenously, and cohort expansion occurred at this dose level. RESULTS: All 114 patients treated with mogamulizumab 1 mg/kg plus nivolumab 240 mg in phases I (n = 4) and II (n = 110) were assessed for safety and efficacy. Mogamulizumab plus nivolumab showed acceptable safety and tolerability. Objective response rate was 10.5% [95% confidence interval (CI), 5.6–17.7; 3 complete and 9 partial responses]. Disease control rate was 36.8%. Median duration of response was 14.4 months. Median progression-free survival was 2.6 (95% CI, 2.3–3.1) months, and median overall survival was 9.5 (95% CI, 5.9–13.5) months. CONCLUSIONS: Combination of mogamulizumab with nivolumab for treatment of patients with locally advanced or metastatic solid tumors did not result in enhanced efficacy. Tolerability of mogamulizumab 1 mg/kg plus nivolumab 240 mg was acceptable.
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spelling pubmed-94015572023-01-05 Mogamulizumab in Combination with Nivolumab in a Phase I/II Study of Patients with Locally Advanced or Metastatic Solid Tumors Hong, David S. Rixe, Olivier Chiu, Vi K. Forde, Patrick M. Dragovich, Tomislav Lou, Yanyan Nayak-Kapoor, Asha Leidner, Rom Atkins, James N. Collaku, Agron Fox, Floyd E. Marshall, Margaret A. Olszanski, Anthony J. Clin Cancer Res Clinical Trials: Immunotherapy PURPOSE: The aim of the study was to determine safety, antitumor activity, and pharmacodynamic profile of mogamulizumab, an anti-CCR4 monoclonal antibody targeting effector regulatory T cells (Treg) in combination with the checkpoint inhibitor nivolumab in patients with locally advanced or metastatic solid tumors. PATIENTS AND METHODS: This was a multicenter, dose-finding (phase I), and dose expansion (phase II) study (NCT02705105) in patients with locally advanced or metastatic solid tumors. There were no dose-limiting toxicities in phase I with mogamulizumab 1 mg/kg every week for cycle 1 followed by 1 mg/kg every 2 weeks plus nivolumab 240 mg every 2 weeks intravenously, and cohort expansion occurred at this dose level. RESULTS: All 114 patients treated with mogamulizumab 1 mg/kg plus nivolumab 240 mg in phases I (n = 4) and II (n = 110) were assessed for safety and efficacy. Mogamulizumab plus nivolumab showed acceptable safety and tolerability. Objective response rate was 10.5% [95% confidence interval (CI), 5.6–17.7; 3 complete and 9 partial responses]. Disease control rate was 36.8%. Median duration of response was 14.4 months. Median progression-free survival was 2.6 (95% CI, 2.3–3.1) months, and median overall survival was 9.5 (95% CI, 5.9–13.5) months. CONCLUSIONS: Combination of mogamulizumab with nivolumab for treatment of patients with locally advanced or metastatic solid tumors did not result in enhanced efficacy. Tolerability of mogamulizumab 1 mg/kg plus nivolumab 240 mg was acceptable. American Association for Cancer Research 2022-02-01 2021-11-09 /pmc/articles/PMC9401557/ /pubmed/34753777 http://dx.doi.org/10.1158/1078-0432.CCR-21-2781 Text en ©2021 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
spellingShingle Clinical Trials: Immunotherapy
Hong, David S.
Rixe, Olivier
Chiu, Vi K.
Forde, Patrick M.
Dragovich, Tomislav
Lou, Yanyan
Nayak-Kapoor, Asha
Leidner, Rom
Atkins, James N.
Collaku, Agron
Fox, Floyd E.
Marshall, Margaret A.
Olszanski, Anthony J.
Mogamulizumab in Combination with Nivolumab in a Phase I/II Study of Patients with Locally Advanced or Metastatic Solid Tumors
title Mogamulizumab in Combination with Nivolumab in a Phase I/II Study of Patients with Locally Advanced or Metastatic Solid Tumors
title_full Mogamulizumab in Combination with Nivolumab in a Phase I/II Study of Patients with Locally Advanced or Metastatic Solid Tumors
title_fullStr Mogamulizumab in Combination with Nivolumab in a Phase I/II Study of Patients with Locally Advanced or Metastatic Solid Tumors
title_full_unstemmed Mogamulizumab in Combination with Nivolumab in a Phase I/II Study of Patients with Locally Advanced or Metastatic Solid Tumors
title_short Mogamulizumab in Combination with Nivolumab in a Phase I/II Study of Patients with Locally Advanced or Metastatic Solid Tumors
title_sort mogamulizumab in combination with nivolumab in a phase i/ii study of patients with locally advanced or metastatic solid tumors
topic Clinical Trials: Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9401557/
https://www.ncbi.nlm.nih.gov/pubmed/34753777
http://dx.doi.org/10.1158/1078-0432.CCR-21-2781
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