Dose Escalation Study of GCC19CART CoupledCAR ^® Technology for Patients with Relapsed or Refractory Colorectal Cancer

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.