Abstract 425P
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
Based on a data cutoff of April 5, 2022, 15 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.
Results
8 subjects have been enrolled to dose 1 and 7 subjects have been enrolled to dose 2. The most common adverse events were cytokine release syndrome (CRS) in 14/15 subjects (Grade 1 and 2) and diarrhea in 14/15 subjects (Grade 1, 2, and 3). Neurotoxicity was observed in 1 patient (Grade 4) and resolved with corticosteroids. The combined overall response rate (ORR) for both dose levels was 40% (6/15). For dose level 1, the ORR per RECIST 1.1 was 25% (2/8). For dose level 2, the ORR per RECIST 1.1 was 57% (4/7).
Conclusions
GCC19CART demonstrated meaningful dose dependent clinical activity and an acceptable safety profile in R/R mCRC. At a dose of 2x106 CAR T-cells/kg, the ORR is 57% (4/7). It was well tolerated and toxicity was manageable. A United States based phase I trial of GCC19CART is anticipated to begin enrolling subjects in mid-2022.
Clinical trial identification
ChiCTR2100053828.
Editorial acknowledgement
Legal entity responsible for the study
Innovative Cellular Therapeutics Inc.
Funding
Innovative Cellular Therapeutics Inc.
Disclosure
All authors have declared no conflicts of interest.