Abstract 2747: Novel coupledCAR࣪technology for treating colorectal cancer
Authors: Chen Naifei , Pu Chengfei , Zhao Lingling , Wang Chang , Zhu Ruihong , Liang Tingting , Huang Xi , Tang Haiyang , Wang Yizhuo , Jia Beibei , Chen Dongqi , Kennedy Eugene , Wu Zhao , Xiao Lei , Cui Jiuwei 
Published: June 2022

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, targets guanylate cyclase-C (GCC) which is expressed in colorectal cancers. A Phase 1 investigator-initiated dose escalation trial is underway in China for patients with relapsed or refractory metastatic colorectal cancer. Based on a data cutoff on September 10, 2021, 15 patients enrolled and 12 patients completed ≥1 evaluation of response and were evaluable.
Methods: Subjects with relapsed or refractory metastatic colorectal cancer are screened for GCC expression, with 70% to 80% of subjects expected to demonstrate GCC per historical data. 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 three doses from 1x106, or 2x106 cells/kg. Endpoints are safety and preliminary evidence of efficacy as determined by CT or PET/CT per RECIST1.1 or PERCIST 1.0.
Results: 7 subjects have been enrolled to dose level 1 (1x106 cells/kg) and 5 subjects have been enrolled to dose level 2 (2x106 cells/kg) and have a 1 month post-infusion imaging study available for review. The most common adverse events were cytokine release syndrome (CRS) in 11/12 subjects (Grade 1 10/12 (83.33%) or Grade 2 1/12 (8.33%)) and diarrhea in 12/12 subjects (Grade 1 2/12 (16.67%) Grade 2 2/12 (16.67%) Grade 3 8/12 (66.67%)). Neurotoxicity was observed in 1/12 (8.33%) subjects at Grade 4 and resolved with corticosteroids. The combined overall response rate (ORR) for both dose levels was 41.67% (5/12). For dose level 1, the overall response rate (ORR) per RECIST 1.1 was 28.57% (2/7). Two subjects demonstrated a partial response (PR) while 2 additional subjects had partial metabolic response (PMR) on PET/CT with stable disease (SD) or progressive disease (PD) per RECIST 1.1. For dose level 2, The ORR per RECIST 1.1 was 60% (3/5). 3 subjects demonstrated a PR (2 at month 1, 1 at month 3 after being SD at month 1) and an additional subject had PMR on PET/CT with SD per RECIST 1.1.
Conclusions: GCC19CART demonstrated meaningful clinical activity and an acceptable safety profile in relapsed or refractory metastatic colorectal cancer. This trial is ongoing and updated data will be presented. A United States based Phase 1 trial of GCC19CART is anticipated for early 2022.
Citation Format: Naifei Chen, Chengfei Pu, Lingling Zhao, Chang Wang, Ruihong Zhu, Tingting Liang, Xi Huang, Haiyang Tang, Yizhuo Wang, Beibei Jia, Dongqi Chen, Eugene Kennedy, Zhao Wu, Lei Xiao, Jiuwei Cui. Novel coupledCAR࣪technology for treating colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2747.