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

Clinical Epigenetics

Ernie A. Diaz Rivera¹  Meizheng Liu¹  Carol Judkins¹  Elizabeth M. Jaffee¹  Julie M. Nauroth¹  Brian Christmas¹  Katherine M. Bever¹  Qingfeng Zhu¹  Nilofer S. Azad¹  Jiajia Zhang¹  Elizabeth D. Thompson²  Dwayne L. Thomas²  Lei Zheng³  Nita Ahuja⁴  Robert A. Anders⁵  Gary L. Rosner⁶ 

[1] Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, 21287, Baltimore, MD, USA;Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, 21287, Baltimore, MD, USA;Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, 21287, Baltimore, MD, USA;Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, 1650 Orleans Street, Office 4M10, 21287, Baltimore, MD, USA;Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Departments of Surgery, Oncology, and Pathology, Smilow Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT, USA;Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA;

关键词: GVAX;    Immunotherapy;    Epigenetic therapy;    Colorectal cancer;   

DOI  :  10.1186/s13148-021-01014-8

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY