In a Chinese phase I dose-escalation and dose-expansion study reported in the Journal of Clinical Oncology, Qi et al found that guanylyl cyclase 2C (GUCY2C)-targeted chimeric antigen receptor (CAR) T-cell therapy had an “acceptable” safety profile and was active in patients with previously treated metastatic colorectal cancer with GUCY2C expression.
Study Details
In the multicenter trial, between May 2022 and April 2023, 20 patients received a total of four dose levels in the dose-escalation phase, including 3 × 108, 6 × 108, 12 × 108 (dose level 3 [DL3]), and 20 × 108 (DL4) CAR T cells. No dose-limiting toxicity was observed, and DL3 was selected for the dose-expansion phase.
Key Results
Among 20 patients receiving treatment, grade 3 cytokine-release syndrome and grade 3 neurotoxicity were observed in one patient each. Grade 3 diarrhea occurred in 11 patients (55.0%).
Among 19 evaluable patients, the objective response rate was 26.3%; all responders were in the DL3 and DL4 groups. Of 10 patients in the DL3 group, the objective response rate was 40.0%, and median progression-free survival was 7.0 months. Among patients showing medium-to-high GUCY2C expression in the DL3 group, the objective response rate was 50.0% and median progression-free survival was 9.0 months.
The investigators concluded; “GUCY2C CAR T showed acceptable safety profile and high response rate in patients with third- or later-line colorectal cancer, and the clinical efficacy was associated with CAR T dose level.”
Changsong Qi, MD, of Peking University Cancer Hospital and Institute, Beijing, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the National Natural Science Foundation of China, National Key Research and Development Program of China, and others. For full disclosures of the study authors, visit ascopubs.org.
