642P A phase I dose escalation study of GCC19CART: A novel CoupledCAR therapy for subjects with metastatic colorectal cancer

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. Based on a data cutoff of October 20, 2022, 21 subjects have been enrolled and treated, with all subjects completing ≥1 evaluation of response and being evaluable. 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: Dose 1 (1x106) or Dose 2 (2x106) CAR T-cells/kg. Endpoints are safety and preliminary evidence of efficacy. 13 subjects have been enrolled to dose level 1 (1x106 cells/kg) and 8 subjects have been enrolled to dose level 2 (2x106 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 effects were well managed. Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 2/21 (9.52%) subjects at Grade 3 or 4 and resolved with corticosteroids. For dose level 1, the overall response rate (ORR) per RECIST 1.1 was 15.4% (2/13). The median PFS was 2.0 months and the median overall survival was also 13.3 months. For dose level 2, The ORR per RECIST 1.1 was 50% (4/8). The median PFS was 6.3 months and the median follow-up was also 21.3 months. Preliminary results demonstrate that GCC19CART has meaningful dose-dependent 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 phase 1 trial of GCC19CART in the US has opened for accrual and is expected to enroll patients in mid-2022.