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

Research output: Contribution to journalArticlepeer-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 languageEnglish (US)
Article number25
JournalClinical Epigenetics
Volume13
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • Colorectal cancer
  • Epigenetic therapy
  • GVAX
  • Immunotherapy

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

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