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, Baltimore, MD, 21287, USA.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Clin Epigenetics. 2021 Feb 2;13(1):25. doi: 10.1186/s13148-021-01014-8.
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.
表观遗传学疗法可能调节肿瘤微环境。我们评估了 DNA 甲基转移酶抑制剂 guadecitabine 与粒细胞巨噬细胞集落刺激因子（GM-CSF）分泌的结肠癌（CRC）疫苗（GVAX）联合应用的安全性和最佳顺序，主要终点为 CD45RO+T 细胞的变化。共招募了 18 名晚期 CRC 患者，其中 11 名患者进行了配对活检，并对主要终点进行了评估。未观察到 CD45RO+细胞的显著增加。预计会出现 3-4 级毒性，但可管理。Guadecitabine+GVAX 是可耐受的，但在 CRC 中未显示出显著的免疫活性。我们报告了一种新的试验设计，可有效地评估具有主要药效动力学终点的研究性治疗方法。试验注册Clinicaltrials.gov：NCT01966289。于 2013 年 10 月 21 日注册。
