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

Katherine M. Bever; Dwayne L. Thomas; Jiajia Zhang; Ernie A. Diaz Rivera; Gary L. Rosner; Qingfeng Zhu; Julie M. Nauroth; Brian Christmas; Elizabeth D. Thompson; Robert A. Anders; Carol Judkins; Meizheng Liu; Elizabeth M. Jaffee; Nita Ahuja; Lei Zheng; Nilofer S. Azad

doi:10.1186/s13148-021-01014-8

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

Katherine M. Bever, Dwayne L. Thomas, Jiajia Zhang, Ernie A. Diaz Rivera, Gary L. Rosner, Qingfeng Zhu, Julie M. Nauroth, Brian Christmas, Elizabeth D. Thompson, Robert A. Anders, Carol Judkins, Meizheng Liu, Elizabeth M. Jaffee, Nita Ahuja, Lei Zheng, Nilofer S. Azad

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	25
Journal	Clinical Epigenetics
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/s13148-021-01014-8
State	Published - Dec 2021

Keywords

Colorectal cancer
Epigenetic therapy
GVAX
Immunotherapy

ASJC Scopus subject areas

Molecular Biology
Genetics
Developmental Biology
Genetics(clinical)

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10.1186/s13148-021-01014-8

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Bever, K. M., Thomas, D. L., Zhang, J., Diaz Rivera, E. A., Rosner, G. L., Zhu, Q., Nauroth, J. M., Christmas, B., Thompson, E. D., Anders, R. A., Judkins, C., Liu, M., Jaffee, E. M., Ahuja, N., Zheng, L., & Azad, N. S. (2021). A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint. Clinical Epigenetics, 13(1), Article 25. https://doi.org/10.1186/s13148-021-01014-8

Bever, KM, Thomas, DL, Zhang, J, Diaz Rivera, EA, Rosner, GL , Zhu, Q , Nauroth, JM, Christmas, B, Thompson, ED, Anders, RA, Judkins, C, Liu, M, Jaffee, EM, Ahuja, N, Zheng, L & Azad, NS 2021, 'A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint', Clinical Epigenetics, vol. 13, no. 1, 25. https://doi.org/10.1186/s13148-021-01014-8

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abstract = "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.",

keywords = "Colorectal cancer, Epigenetic therapy, GVAX, Immunotherapy",

author = "Bever, {Katherine M.} and Thomas, {Dwayne L.} and Jiajia Zhang and {Diaz Rivera}, {Ernie A.} and Rosner, {Gary L.} and Qingfeng Zhu and Nauroth, {Julie M.} and Brian Christmas and Thompson, {Elizabeth D.} and Anders, {Robert A.} and Carol Judkins and Meizheng Liu and Jaffee, {Elizabeth M.} and Nita Ahuja and Lei Zheng and Azad, {Nilofer S.}",

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doi = "10.1186/s13148-021-01014-8",

language = "English (US)",

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AU - Diaz Rivera, Ernie A.

AU - Rosner, Gary L.

AU - Zhu, Qingfeng

AU - Nauroth, Julie M.

AU - Christmas, Brian

AU - Thompson, Elizabeth D.

AU - Anders, Robert A.

AU - Judkins, Carol

AU - Liu, Meizheng

AU - Jaffee, Elizabeth M.

AU - Ahuja, Nita

AU - Zheng, Lei

AU - Azad, Nilofer S.

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

Abstract

Keywords

ASJC Scopus subject areas

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