@article{1988b7e0a43349928801756a0f4cb14e,
title = "A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint",
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.}",
note = "Funding Information: This study was supported by the Zhang Family Gift Fund directly to L.Z. and indirectly through the Susie{\textquoteright}s Cause Colon Cancer Foundation to L.Z, as well as the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Core Grant (P30 CA006973). Funding Information: We gratefully acknowledge the patients who participated in the study and their families. Kelly Gemmill assisted in the manuscript preparation. We also thank the Johns Hopkins University School of Medicine Tumor Microenvironment Core for PD-L1 immunostaining. Funding Information: Through a licensing agreement with Aduro Biotech, Dr. Jaffee and the Johns Hopkins University have the potential to receive royalties on the sale of GVAX. N. Ahuja has received grant funding from Cepheid and Astex and has served as consultant to Ethicon. She has licensed methylation biomarkers to Cepheid. No potential conflict of interest were disclosed by the other authors. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1186/s13148-021-01014-8",
language = "English (US)",
volume = "13",
journal = "Clinical Epigenetics",
issn = "1868-7075",
publisher = "Springer Verlag",
number = "1",
}