Safety and efficacy of anti-CEA CAR-T cells to prolong relapse-free survival of colorectal cancer liver metastases patients after radical resection.

3541 Background: Approximately 75% of colorectal cancer liver metastasis patients relapse within two years after surgery due to circulating tumor cells and microscopic residual disease. Specific chimeric antigen receptor (CAR) T-cell therapy, effective for hematological tumors, may also treat recurrent colorectal cancer liver metastases. Carcinoembryonic antigen (CEA) is a glycoprotein which is highly expressed in colorectal tumor. Therefore, this study aimed to evaluate the safety and efficacy of this therapy in postoperative colorectal cancer liver metastasis patients. Methods: We conducted a single-arm, dose-escalating phase I clinical trial (NCT05240950). Key eligibility criteria were achieving no evidence of disease status after treatment and had CEA positivity of 30% or greater. Three dose levels of 1, 3, and 6 (10^6/kg) Anti-CEA CAR-T cells were administered in a dose-escalating manner. The primary endpoint is safety which measures are incidence and severity of adverse events within 28 days and relapse-free survival at 24 months. Results: From December 2021 to December 2024, 48 subjects were screened, and 12 received CAR-T cell infusion (2 in the 1 and 3×10^6/kg group, and 8 in the 6×10^6/kg group). Three subjects who had relapsed before the infusion still asked for the infusion, so we proceeded to infuse after fully informing about the benefits and risks of the infusion. 8 subjects experienced adverse events during treatment, including lymphopenia (5 subjects), arthralgia (1 subject), fever (1 subject), and rash (1 subject). No severe adverse events occurred. The median follow-up time for the 9 pre-infusion relapse-free subjects was 23 months, of which 5 relapsed after infusion. In the 6×10^6/kg dose group, 4 subjects remained relapse-free survival of 5, 7, 10 and 15 months after infusion, and their follow-up is ongoing. By infusing CAR-T cell, 57.14% of the subjects in the 6×10^6/kg dose group were free of recurrence within two years after radical resection. Conclusions: This is the first clinical trial of Anti-CEA CAR-T therapy for prolonging relapse-free survival of postoperative colorectal cancer liver metastases patients, showing no serious adverse events and significant reduced risk of recurrence with high doses. Clinical trial information: NCT05240950 . Clinical information of 9 pre-infusion relapse-free subjects. Subhects number TNM Stage Infusion dose (×10^6/Kg) 1 Current NED status Post-infusion relapse-free survival time (months) 2 Post-infusion survival time (months) 2 Overall survival time (months) 3 S01002 T3N0M1a 1 No 3 27 33 S01037 T2N1bM1a 3 No 12 12 26 S01008 T3N0M1a 6 Yes 10 10 25 S01010 T3N1M1a 6 No 10 10 26 S01015 T3N0M1a 6 Yes 15 15 21 S01023 T3N0M1a 6 No 12 14 23 S01042 T3N2aM1a 6 No 3 10 16 S01033 T3N1bM1a 6 Yes 7 7 18 S01043 T3N1bM1a 6 Yes 5 5 14