Metastatic Colorectal Cancer CAR-T Clinical Trial Enrolls First Patient

The first patient has been enrolled in the phase 1 clinical trial (CARAPIA-1; NCT05319314) of Innovative Cellular Therapeutics' GCC19CART, an investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of relapsed/refractory metastatic colorectal cancer (r/r mCRC).¹

Thirty-five patients were previously treated with GCC19CART in an IRB-approved trial in China. Data from the trial were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL, from June 3-7, 2022.² Of the 21 patients who were included in the data analysis, which had a cutoff date of May 3, 2022, patients in the lower dose level group (n=13; 1×10⁶ cells/kg) had an overall response rate (ORR) of 15.4% (2 of 13). The ORR for the higher dose level group (2×10⁶ cells/kg) was 50% (4 of 8). The other 4 participants in the higher dose level achieved a best ORR of stable disease, making the disease control rate 100% out to 3 months. Common adverse events included grade 1 cytokine release syndrome (CRS) in 90.4% of patients and grade 1 to 3 diarrhea in 20 of 21 patients. A single patient experienced grade 3 CRS. One patient experienced grade 3 neurotoxicity and another experienced grade 4 neurotoxicity, but both cases resolved with corticosteroids.

"This is an important and exciting milestone for Innovative Cellular Therapeutics," Larry Lei Xiao, chief executive officer, Innovative Cellular Therapeutics, said in a statement regarding the news.¹ "There is a significant unmet medical need for r/r mCRC patients. We believe that GCC19CART has the potential to provide significant clinical benefit to these patients."

GCC19CART was designed using Innovative Cellular Therapeutics' CoupledCAR technology platform, which was described in previous coverage by CGTLive when the therapy received fast-track designation from the FDA in April 2022.

The open-label, multicenter dose-escalation CARAPIA-1 trial aims to enroll 30 patients 18 years of age and older who have been diagnosed with mCRC Guanylate Cyclase- (GCC) positive metastatic disease. Participants are required to have limited liver disease, defined as less than 5 lesions with the largest lesion being less than 3 cm, and no surgical options with curative intent. Patients additionally must have been previously treated with fluoropyrimidine-based, oxaliplatin-based, and irinotecan-based chemotherapy in the metastatic setting, or palliative therapy within 1 year of adjuvant therapy. Patients with unresectable or metastatic microsatellite instability-high or mismatch repair deficient tumors and patients with an active infection requiring systemic therapy will be excluded from the study.

Patients will receive a single intravenous infusion of GCC19CART at an assigned dose level. The trial includes plans for 2 dose level escalations and 1 dose de-escalation if necessary. Primary end points include the incidence of dose-limiting toxicities, the maximum tolerated dose, and the recommended phase 2 dose. Secondary end points include best overall response, duration of response, progression free survival, overall survival, copy number of Guanylate Cyclase C determined by quantitative polymerase chain reaction (qPCR), copy number of each individual CD19 determined by qPCR, and cytokine level in serum.

The study is currently recruiting at University of California San Francisco Medical Center with an estimated date of completion of October 2024.

REFERENCES

1. Innovative Cellular Therapeutics (ICT) announces first patient enrolled for the company’s phase I trial of GCC19CART for relapsed/refractory metastatic colorectal cancer. News release. Innovative Cellular Therapeutics, Inc. August 18, 2022. https://www.ictbio.com/news/innovative-cellular-therapeutics-ict-announces-first-patient-enrolled-for-the-companys-phase-i-trial-of-gcc19cart-for-relapsed-refractory-metastatic-colorectal-cancer/ 

2. Innovative Cellular Therapeutics (ICT) announces presentation at 2022 American Society of Clinical Oncology (ASCO) annual meeting. News release. Innovative Cellular Therapeutics, Inc. May 26, 2022. https://www.ictbio.com/news/innovative-cellular-therapeutics-ict-announces-presentation-at-2022-american-society-of-clinical-oncology-asco-annual-meeting/