Abstract 1130: A phase 1 dose escalation study of GCC19CART - a novel CoupledCAR therapy for subjects with metastatic colorectal cancer

作者：Naifei Chen, Chengfei Pu, Lingling Zhao, Ning Li, Chang Wang, Yu‐Sheng Huang, Suxia Luo, Xun Li, Zhenzhou Yang, Jun Bie, Ruihong Zhu, Xi Huang, Haiyang Tang, Tingting Liang, Yizhuo Wang, Beibei Jia, Dongqi Chen, Zhao Wu, Yongping Song, Victor M. Lu, Lei Xiao, Jiuwei Cui · 发表于：Cancer Research · 年份：2023 · DOI：10.1158/1538-7445.am2023-1130 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Cancer Research and Treatments、Biosimilars and Bioanalytical Methods

Abstract Background: Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in hematologic malignancies but limited success in solid tumors. GCC19CART, the first clinical candidate from the CoupledCAR solid tumor platform, is designed to overcome the limitations of conventional CAR T-cells in solid tumor malignancies by pairing solid tumor CAR T-cells with CD19 targeting CAR T-cells to amplify proliferation and activation of the solid tumor CAR T component. GCC19CART targets guanylate cyclase-C (GCC) which is expressed in the metastatic lesions of 70%-80% of subjects with colorectal cancers. A Phase 1 investigator-initiated clinical trial is underway in China for patients with relapsed or refractory metastatic colorectal cancer who have received at least 2 prior lines of therapy. Based on a data cutoff on October 20, 2022 21 subjects have been enrolled in 2 dose escalation groups at 5 hospitals in China. Methods: Subjects are screened for GCC expression by immunohistochemistry. Eligible subjects undergo leukapheresis, a single dose of lymphodepleting chemotherapy (fludarabine 30mg/m2 and cyclophosphamide 300mg/m2) 3 days prior to infusion, and then administration of a single infusion of GCC19CART at one of two preassigned doses: 1 × 106 or 2 × 106 CAR T-cells/kg. Endpoints are safety and preliminary evidence of efficacy as determined by CT or PET/CT per RECIST 1.1 or PERCIST 1.0. All responses were confirmed by an independent third-party imaging...