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.
CITATION STYLE
Bever, K. M., Thomas, D. L., Zhang, J., Diaz Rivera, E. A., Rosner, G. L., Zhu, Q., … Azad, N. S. (2021). A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint. Clinical Epigenetics, 13(1). https://doi.org/10.1186/s13148-021-01014-8
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