GCC19CART Demonstrates Preliminary Antitumor Activity in Refractory mCRC

The administration of GCC19CART, a novel CAR T-cell therapy, led to clinical antitumor activity in patients with refractory metastatic colorectal cancer (mCRC), according to preliminary findings from an ongoing trial phase 1 (NCT05319314) presented at the 2025 Gastrointestinal Cancers Symposium.

Results revealed that at dose level 1 (1 x 10⁶ cells/kg), evaluable patients (n = 4) experienced an overall response rate (ORR) of 25.0%, including 1 patient achieving a confirmed partial response (PR) and 2 others showing partial metabolic responses with stable disease (SD). At dose level 2 (2 x 10⁶ cells/kg; n = 5), the ORR was 80.0%, with 1 patient achieving a pathological complete response and 3 others reaching PR; the fifth patient had a complete metabolic response on PET/CT. The ORR in the overall population between both dose levels (n = 9) was 56%. The disease control rate was 75% for dose level 1, 80% for dose level 2, and 78% for both dose levels.

The median progression-free survival (PFS) was 5.0 months in dose level 1 and 7.8 months in dose level 2 at median follow-ups of 16.6 months and 7.4 months, respectively.

“Preliminary results indicate that GCC19CART exhibits significant clinical antitumor activity in patients with refractory mCRC. The trial is ongoing, and updated data will be presented," lead study author Bridget Keenan, MD, PhD, of UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, California, and colleagues wrote in a poster presentation.

Cytokine release syndrome (CRS) was observed in 100% of patients; CRS occurred at grade 1 (66.7%) and grade 2 (33.3%). Immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 2 patients at grade 2 (11.1%) and grade 3 (11.1%). Diarrhea was reported in 8 of 9 patients at grade 1 (33.3%), grade 2 (33.3%), and grade 3 (22.2%).

One patient treated at dose level 2 experienced a dose-limiting toxicity. This patient had grade 3 diarrhea, grade 4 enterocolitis, and grade 5 sepsis; the cause of death was fungal sepsis 48 days following the infusion of GCC19CART.

“Adverse [effects (AEs)] were related to the GCC19CART mechanism and were consistent with what has been observed with other CAR T-cell products. Strategies to further optimize the management of treatment-related diarrhea and colitis are currently being implemented,” Keenen noted.

Design of the Study

Study investigators noted that, “GCC19CART [is] the first clinical candidate from the CoupledCAR solid tumor platform, [which] pairs solid tumor CAR T cells with CD19-targeting CAR T cells to enhance proliferation, activation, and persistence against solid tumors.” GCC19CART is designed to target GCC, a known mucosal marker.

Investigators initially screened patients for GCC expression prior to enrollment, but this practice was discontinued after 95% of screened patients (n = 95/98) with mCRC were GCC positive by immunohistochemistry.

Eligible patients with mCRC that was refractory to standard chemotherapy underwent leukapheresis followed by a lymphodepleting chemotherapy regimen consisting of fludarabine at 30 mg/m² and cyclophosphamide at 300 mg/m² administered on day –3. On day 0, patients received a single infusion of GCC19CART at their assigned dose level.

The primary end point of the trial was safety; secondary end points included ORR, duration of response, PFS, overall survival, and pharmacokinetics. Responses were assessed locally using RECIST 1.1 criteria.

The median age of the 9 patients treated across the 2 dose levels was 48 years (range, 39-57). The majority of patients were male (56%), and patients received a median of 3 prior lines of therapy (range, 2-5). The origin of the disease was primarily from the left colon (44%) and rectum (44%), with a smaller proportion originating from the rectosigmoid (11%). Patients had a median of 2 disease sites (range, 1-4).

Results also revealed reductions in tumor size in 3 of 4 patients treated at dose level 1 and 4 of 5 patients treated at dose level 2. However, 1 patient treated at dose level 1 who had a best response of SD and experienced a reduction in tumor size experienced disease progression due to the appearance of a new lesion at month 2.

Reference

Keenan BP, Lieu CH, Fakih M, et al. A phase 1 dose-escalation study of GCC19CART: A novel CAR T-cell therapy for metastatic colorectal cancer in the United States. J Clin Oncol. 2025;43(suppl 4):175. doi:10.1200/JCO.2025.43.4_suppl.175