A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint

Epigenetic therapies may modulate the tumor microenvironment. We evaluated the safety and optimal sequence of combination DNA methyltransferase inhibitor guadecitabine with a granulocyte macrophage-colony-stimulating-factor (GM-CSF) secreting colon cancer (CRC) vaccine (GVAX) using a primary endpoin...

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Autores principales: Bever, Katherine M., Thomas, Dwayne L., Zhang, Jiajia, Diaz Rivera, Ernie A., Rosner, Gary L., Zhu, Qingfeng, Nauroth, Julie M., Christmas, Brian, Thompson, Elizabeth D., Anders, Robert A., Judkins, Carol, Liu, Meizheng, Jaffee, Elizabeth M., Ahuja, Nita, Zheng, Lei, Azad, Nilofer S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Short Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856736/
https://www.ncbi.nlm.nih.gov/pubmed/33531075
http://dx.doi.org/10.1186/s13148-021-01014-8
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author Bever, Katherine M.
Thomas, Dwayne L.
Zhang, Jiajia
Diaz Rivera, Ernie A.
Rosner, Gary L.
Zhu, Qingfeng
Nauroth, Julie M.
Christmas, Brian
Thompson, Elizabeth D.
Anders, Robert A.
Judkins, Carol
Liu, Meizheng
Jaffee, Elizabeth M.
Ahuja, Nita
Zheng, Lei
Azad, Nilofer S.
author_facet Bever, Katherine M.
Thomas, Dwayne L.
Zhang, Jiajia
Diaz Rivera, Ernie A.
Rosner, Gary L.
Zhu, Qingfeng
Nauroth, Julie M.
Christmas, Brian
Thompson, Elizabeth D.
Anders, Robert A.
Judkins, Carol
Liu, Meizheng
Jaffee, Elizabeth M.
Ahuja, Nita
Zheng, Lei
Azad, Nilofer S.
author_sort Bever, Katherine M.
collection PubMed
description Epigenetic therapies may modulate the tumor microenvironment. We evaluated the safety and optimal sequence of combination DNA methyltransferase inhibitor guadecitabine with a granulocyte macrophage-colony-stimulating-factor (GM-CSF) secreting colon cancer (CRC) vaccine (GVAX) using a primary endpoint of change in CD45RO + T cells. 18 patients with advanced CRC enrolled, 11 underwent paired biopsies and were evaluable for the primary endpoint. No significant increase in CD45RO + cells was noted. Grade 3–4 toxicities were expected and manageable. Guadecitabine + GVAX was tolerable but demonstrated no significant immunologic activity in CRC. We report a novel trial design to efficiently evaluate investigational therapies with a primary pharmacodynamic endpoint. Trial registry Clinicaltrials.gov: NCT01966289. Registered 21 October, 2013.
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spelling pubmed-78567362021-02-04 A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint Bever, Katherine M. Thomas, Dwayne L. Zhang, Jiajia Diaz Rivera, Ernie A. Rosner, Gary L. Zhu, Qingfeng Nauroth, Julie M. Christmas, Brian Thompson, Elizabeth D. Anders, Robert A. Judkins, Carol Liu, Meizheng Jaffee, Elizabeth M. Ahuja, Nita Zheng, Lei Azad, Nilofer S. Clin Epigenetics Short Report Epigenetic therapies may modulate the tumor microenvironment. We evaluated the safety and optimal sequence of combination DNA methyltransferase inhibitor guadecitabine with a granulocyte macrophage-colony-stimulating-factor (GM-CSF) secreting colon cancer (CRC) vaccine (GVAX) using a primary endpoint of change in CD45RO + T cells. 18 patients with advanced CRC enrolled, 11 underwent paired biopsies and were evaluable for the primary endpoint. No significant increase in CD45RO + cells was noted. Grade 3–4 toxicities were expected and manageable. Guadecitabine + GVAX was tolerable but demonstrated no significant immunologic activity in CRC. We report a novel trial design to efficiently evaluate investigational therapies with a primary pharmacodynamic endpoint. Trial registry Clinicaltrials.gov: NCT01966289. Registered 21 October, 2013. BioMed Central 2021-02-02 /pmc/articles/PMC7856736/ /pubmed/33531075 http://dx.doi.org/10.1186/s13148-021-01014-8 Text en © The Author(s) 2021 Open AccessThis 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Short Report
Bever, Katherine M.
Thomas, Dwayne L.
Zhang, Jiajia
Diaz Rivera, Ernie A.
Rosner, Gary L.
Zhu, Qingfeng
Nauroth, Julie M.
Christmas, Brian
Thompson, Elizabeth D.
Anders, Robert A.
Judkins, Carol
Liu, Meizheng
Jaffee, Elizabeth M.
Ahuja, Nita
Zheng, Lei
Azad, Nilofer S.
A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint
title A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint
title_full A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint
title_fullStr A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint
title_full_unstemmed A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint
title_short A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint
title_sort feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856736/
https://www.ncbi.nlm.nih.gov/pubmed/33531075
http://dx.doi.org/10.1186/s13148-021-01014-8
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