644 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, Victor M. Lu, Zhao Wu, Yongping Song, Lei Xiao, Jiuwei Cui · 发表于：Regular and Young Investigator Award Abstracts · 年份：2023 · DOI：10.1136/jitc-2023-sitc2023.0644 · 研究领域：CAR-T cell therapy research、Biosimilars and Bioanalytical Methods、Cancer Immunotherapy and Biomarkers

Background GCC19CART, the first clinical candidate from the CoupledCAR® solid tumor platform, targets guanylate cyclase-C (GCC) which is expressed in colorectal cancers. CoupledCAR utilizes multiple vectors to make both solid tumor targeting CAR-T and CD19 CAR-T in a single manufacturing step. An investigator-initiated dose escalation trial in China for patients with relapsed or refractory metastatic colorectal cancer (R/R mCRC) is reported here. Methods Subjects are screened for GCC expression by immunohistochemistry. Eligible subjects undergo leukapheresis, a single dose of lymphodepleting chemotherapy (fludarabine 30mg/m 2 and cyclophosphamide 300mg/m 2 ) 3 days prior to infusion, and then administration of a single infusion of GCC19CART at one of two preassigned doses: 1x10 6 or 2x10 6 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 contract research organization (CRO). Results 13 subjects have been enrolled to dose level 1 (1x10 6 cells/kg) and 8 subjects have been enrolled to dose level 2 (2x10 6 cells/kg). The most common adverse events were cytokine release syndrome (CRS) in 21/21 subjects (Grade 1 19/21 (90.48%) or Grade 2 2/21 (9.52%)) and diarrhea in 21/21 subjects (Grade 1 6/21 (28.57%) Grade 2 5/21 (23.81%) Grade 3 9/21 (42.86%) or Grade 4 1/21 (4.76%)). All patients with grade 3 and higher side effect...