Metastatic Colorectal Cancer Therapy CAR-T GCC19CART Improves Upon Third-Line SOC Therapies

GCC19CART (Innovative Cellular Therapeutics), an investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy being evaluated in an investigator-initiated clinical trial (ChiCTR2000040645) in China for the treatment of relapsed/refractory metastatic colorectal cancer (r/r mCRC), has demonstrated efficacy improvements over standard of care (SOC) third-line therapies, according to data presented at the American Association for Cancer Research (AACR) Annual Meeting 2023, held April 14-19, 2023, in Orlando, Florida.

Among the 21 patients included in the efficacy analysis, superior results were observed in patients (n=8) who received the higher dose level (2x10⁶ CAR-T cells/kg; DL2) than in patients (n=13) who received the lower dose level (1x10⁶ CAR-T cells/kg; DL1). The objective response rate (ORR) was 50% (n=4) for DL2, 15% (n=2) for DL1, and 29% (n=6) for all patients. Meanwhile, the median overall survival (OS) for DL2 was not reached with a median followup of 20.02 months, while the median OS for DL1 was 13.32 months; the overall median OS was also not reached. Progression-free survival (PFS) for patients treated at DL2 was reported as 6.3 months with the caveat that PFS data was based on imaging for 7 of the patients and clinical criteria for 1 of the patients, the latter of whom’s imaging study is pending.

Victor Lu, PhD, the chief technology officer of Innovative Cellular Therapeutics, who presented the data, drew comparisons between these data and results seen in clinical trials for SOC third-line therapies. Specifically, he pointed out that in the phase 3 CORRECT trial (NCT01103323) for regorafenib the median OS was 6.4 months and in the phase 3 RECOURSE trial (NCT01607957) for Lonsurf the median OS was 7.1 months. Lu also noted that these SOC therapies showed PFSs of 1.9 to 2 months and ORRs of 1% to 1.6%.

In terms of safety, Lu stated that most of the treated patients (95%) experienced cases of cytokine release syndrome (CRS); however, only a small fraction had grade 3 cases of CRS. He also pointed out that a small number of patients (10%) had cases of immune effector cell-associated neurotoxicity syndrome (ICANS). Among these patients, 1 patient experienced a grade 3 case of ICANS; however, this patient recovered quickly. In response to an audience question, Lu added that B-cell aplasia, and later recovery, was also observed among the treated patients. He also discussed cases of diarrhea, which were experienced by most patients (95%) in the trial. He noted that this adverse event (AE) is specific to GCC19CART because it targets the antigen guanylyl cyclase C (GCC), which is expressed in 80% of tumor metastases in patients with CRC.

“The new AE specific to this product is diarrhea because the target is GCC, which plays a role in intestinal homeostasis... So, that's expected, theoretically,” Lu stated. “Most patients treated with this product experienced diarrhea, but it can be controlled and because of the diarrhea management most of the patients actually recovered very quickly.”

The ages of the patients treated in the trial ranged from 27 years to 60 years (median, 44). Nine of the patients (43%) were men while 12 patients (57%) were women. The patients had received between 1 and 4 prior lines of therapy (median, 3). Eleven patients (52%) had disease that originated in the colon and 10 patients (48%) had disease that originated in the rectum.

Lu concluded his presentation by mentioning that in addition to the clinical trial in China, a phase 1 clinical trial (NCT05319314; CARAPIA-1) has been launched in the United States. This trial follows a dose escalation design and is taking place at the University of California, San Francisco; Dana Farber Cancer Institute; Baylor Scott & White Research Institute; and University of Colorado. Lu reported that 7 patients enrolled in this trial have completed apheresis and 2 patients have received an infusion of GCC19CART.

REFERENCE
1. Lu, V. A phase 1 dose escalation study of GCC19CART - a novel CoupledCAR therapy for subjects with metastatic colorectal cancer. Presented at: AACR Annual Meeting. April 14-19, 2023; Orlando, FL. Abstract 1130.