| Literature DB >> 33531075 |
Katherine M Bever1, Dwayne L Thomas1,2, Jiajia Zhang1, Ernie A Diaz Rivera1, Gary L Rosner3, Qingfeng Zhu1, Julie M Nauroth1, Brian Christmas1, Elizabeth D Thompson1,2, Robert A Anders2, Carol Judkins1, Meizheng Liu1, Elizabeth M Jaffee1, Nita Ahuja1,4,5, Lei Zheng1,4, Nilofer S Azad6.
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.Entities:
Keywords: Colorectal cancer; Epigenetic therapy; GVAX; Immunotherapy
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Year: 2021 PMID： 33531075 PMCID： PMC7856736 DOI： 10.1186/s13148-021-01014-8
Source DB: PubMed Journal: Clin Epigenetics ISSN： 1868-7075 Impact factor: 7.259