Dose Escalation Study of GCC19CART CoupledCAR ® Technology for Patients with Relapsed or Refractory 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: November 2021

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. Data presented here are from a single participating institution.
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 of 1x10 6, 2x10 6, or 3x10 6 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: 5 subjects have been enrolled to dose level 1 (1x10 6 cells/kg) and 5 subjects have been enrolled to dose level 2 (2x10 6 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 10/10 subjects (Grade 1 9/10 (90%) or Grade 2 1/10 (10%)) and diarrhea in 10/10 subjects (Grade 1 3/10 (30%) Grade 2 1/10 (10%) Grade 3 6/10 (60%)). Neurotoxicity was observed in 1/10 (10%) subjects at Grade 4 and resolved with corticosteroids. The combined overall response rate (ORR) for both dose levels was 50% (5/10). For dose level 1, the overall response rate (ORR) per RECIST 1.1 was 40% (2/5). Two subjects demonstrated a partial response (PR) while an additional subject had partial metabolic response (PMR) on PET/CT with stable disease (SD) 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.

Disclosures
Pu: Innovative Cellular Therapeutics: Current Employment. Zhu: Innovative Cellular Therapeutics: Current Employment. Huang: https://www.accme.org/accreditation-rules/standards-for-integrity-independence-accredited-ce/eligibility: Current Employment. Tang: Innovative Cellular Therapeutics: Current Employment. Jia: Innovative Cellular Therapeutics: Current Employment. Chen: Innovative Cellular Therapeutics: Current Employment. Kennedy: Innovative Cellular Therapeutics: Current Employment. Wu: Innovative Cellular Therapeutics: Current Employment. Xiao: Innovative Cellular Therapeutics: Current Employment.