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

被引：17

作者：

Bever, Katherine M. ^{[1
]}

Thomas, Dwayne L., II ^{[1
,2
]}

Zhang, Jiajia ^{[1
]}

Rivera, Ernie A. Diaz ^{[1
]}

Rosner, Gary L. ^{[3
]}

Zhu, Qingfeng ^{[1
]}

Nauroth, Julie M. ^{[1
]}

Christmas, Brian ^{[1
]}

Thompson, Elizabeth D. ^{[1
,2
]}

Anders, Robert A. ^{[2
]}

Judkins, Carol ^{[1
]}

Liu, Meizheng ^{[1
]}

Jaffee, Elizabeth M. ^{[1
]}

Ahuja, Nita ^{[1
,4
,5
,6
,7
]}

Zheng, Lei ^{[1
,4
]}

Azad, Nilofer S. ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Bloomberg Kimmel Inst Canc Immunotherapy, Dept Oncol,Sch Med, 1650 Orleans St,Off 4M10, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Div Biostat & Bioinformat, Baltimore, MD USA

[4] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA

[5] Yale Univ, Sch Med, Dept Surg, Smilow Comprehens Canc Ctr, New Haven, CT 06510 USA

[6] Yale Univ, Sch Med, Smilow Comprehens Canc Ctr, Dept Oncol, New Haven, CT USA

[7] Yale Univ, Sch Med, Dept Pathol, Smilow Comprehens Canc Ctr, New Haven, CT 06510 USA

来源：

CLINICAL EPIGENETICS | 2021年 / 13卷 / 01期

关键词：

GVAX; Immunotherapy; Epigenetic therapy; Colorectal cancer;

D O I：

10.1186/s13148-021-01014-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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.

引用

页数：9

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