Phase 1 study of claudin18.2-specific CAR T cells for previously treated gastrointestinal cancers

Despite success in hematologic malignancies, the treatment landscape of chimeric antigen receptor (CAR) T cell therapy for solid tumors remains limited. Claudine18.2 (CLDN18.2) is the gastric-specific isoform of the tight junction protein CLDN18. It is highly expressed in cancers of the digestive system. A multicenter phase 1 trial in China evaluates CLDN18.2-targeted CAR T cells (CT041) in patients with previously treated, CLDN18.2-positive digestive system cancers. Interim analysis of the study found that cytokine release syndrome and neurotoxicities were grade 1 or 2. The ORR and DCR were 48.6% and 73.0%, respectively. In 44.8% of the patients the duration of response was at least six months. The authors conclude that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive digestive system cancers.