C-CAR066, a novel fully human anti-CD20 CAR-T therapy for relapsed or refractory large B-cell lymphoma after failure of anti-CD19 CAR-T therapy: A phase I clinical study.

ABSTRACT

Managing large B-cell lymphoma (LBCL) that is refractory to or relapsed after chimeric antigen receptor (CAR)-T therapy remains a significant challenge. Here we aimed to investigate the safety and efficacy of C-CAR066, an autologous fully human anti-CD20 specific CAR-T, for relapsed/refractory LBCL after failure of anti-CD19 CAR-T therapy. This first-in-human, single-arm, phase 1 study was conducted at two sites in China. Eligible patients had to be histologically confirmed with CD20-positive LBCL and must have received prior anti-CD19 CAR-T therapy. Patients received a single intravenous infusion of C-CAR066 at a target dose of 2.0 × 106 or 3.0 × 106 CAR-T cells/kg. The primary endpoint was the incidence of adverse events (AEs). As of October 10, 2023, 14 patients had received C-CAR066. The most common AEs of Grade 3 or higher were hematological toxicities. Cytokine release syndrome occurred in 12 (85.7%) patients, with only one was Grade 4 event. No patient experienced immune effector cell-associated neurotoxicity syndrome events. The overall response rate was 92.9% with a complete response rate of 57.1%. With a median follow-up of 27.7 months (range, 3.3-40.9), the median progression-free survival and overall survival were 9.4 months (95% CI, 2.0 to NA) and 34.8 months (95% CI, 7.5 to NA), respectively. C-CAR066 demonstrated a manageable safety profile and promising efficacy in patients in whom prior anti-CD19 CAR-T therapies had failed, providing a promising treatment option for those patients. This trial was registered with ClinicalTrials.gov, NCT04316624 and NCT04036019.