899P - Safety and efficacy of a novel CAR-T cell therapy (BRG01) targeting the Epstein-Barr Virus envelope glycoprotein in advanced metastatic nasopharyngeal cancer patients

Background

Epstein-Barr virus (EBV) infection accounts for nearly 100% of nasopharyngeal cancers (NPC). The EBV envelope glycoprotein Gp350 detected on NPC serves as a tumor-specific antigen with minimal on-target off-tumor effects. BRG01 is a first-in-class autologous chimeric antigen receptor (CAR)-T cell therapy targeting Gp350. Here we present the safety and efficacy evaluation of BRG01 in subjects with advanced metastatic NPC in an investigational new drug (IND)-enabling Phase I trial (NCT05864924).

Methods

Eleven subjects were enrolled with advanced metastatic NPC, failing at least two lines of standard therapies, including anti-PD1 treatment. Other criteria include EBER+ and Gp350+ positivity on tumor biopsies. A single dose of BRG01 was infused after a lymphodepletion regimen (cyclophosphamide 250-350 mg/m²/day, fludarabine 25-30 mg/m²/day for three days). Safety profile, pharmacokinetics (PK), plasma EBV DNA, and tumor size were monitored after BRG01 treatment.

Results

Eleven patients received 3, 9, and 15×10⁶ CAR-T cells/kg in three dose groups, involving two, three, and six patients, respectively. All recruited subjects showed 60%-100% Gp350 expression on tumor tissues (H score range 60-180, median 90). Efficacy was evaluable in nine patients. Importantly, BRG01 was well tolerated in all infused patients without severe adverse effects related to lymphodepletion or BRG01 treatment, demonstrating its safety profile. More efficient disease control and tumor shrinkage effects were observed with dose escalation. In addition, four patients were evaluated for efficacy by PET-CT before and after administration in the 15×10⁶ dose group. Three patients showed necrosis and metabolic reduction of tumor lesions. The plasma EBV DNA levels dropped significantly in two patients from the medium dose group and four patients from the high dose group, with four patients experiencing a 2-log reduction.

Conclusions

BRG01 is well tolerated and expanded in patients with no dose-limiting toxicity. Its dose-dependent antiviral and antitumor efficacy support further clinical investigation in a phase II trial.

Clinical trial identification

NCT05864924.

Editorial acknowledgement

Legal entity responsible for the study

Biosyngen Pte Ltd.

Funding

Biosyngen Pte Ltd.

Disclosure

X. Zhang, D. Han, J.P. Thiery: Financial Interests, Personal, Full or part-time Employment: Biosyngen Pte Ltd. All other authors have declared no conflicts of interest.