An exploratory study to assess the safety, immunogenicity, and preliminary anti-tumor activity of the EBV mRNA vaccine (WGc-043 injection) combined with PD-1 antibody in patients with relapsed or refractory ENKTL.

7077 Background: Extranodal NK/T cell lymphoma (ENKTL) is a rare and aggressive lymphoma associated with Epstein-Barr virus (EBV) infection and requires novel therapeutic strategies. WGc-043, a therapeutic mRNA vaccine, showed promise against ENKTL patients alone by targeting EBV-driven oncogenesis in our previous study. This study evaluates the safety, immunogenicity, and preliminary anti-tumor activity of WGc-043 combined with PD-1 antibody in patients with relapsed or refractory ENKTL (r/r ENKTL). Methods: This single-center, open-label, exploratory study enrolled 5 patients with EBER1/2 positive r/r ENKTL. The primary inclusion criteria were patients with an ECOG of 0-2 who have failed an asparaginase-based regimen. WGc-043 was administered intramuscularly, including 5 doses of base immunization followed by optional personalized treatment. The base immunization was given at week 1, 2, 3, 4 and 7. Tislelizumab (PD-1 antibody) was administered every three weeks until disease progression, for a maximum of two years. The primary endpoint is safety. Secondary endpoints include immunogenicity, ORR and DCR. The exploratory analysis focuses on immune biomarkers predictive of therapeutic response. Results: WGc-043 combined with PD-1 antibody (Tislelizumab) demonstrated a favorable safety and efficacy in patients with r/r ENKTL. It was well tolerated with only grade 1 adverse events. The most common adverse events were injection site reactions (100%, 4/4) , hemoglobin decreased (50%, 2/4), TSH elevated (50%, 2/4), fever (25%, 1/4), weakness (25%, 1/4) and lymphopenia (25%, 1/4). Importantly, this combo showed good, durable responses, with 2 patients achieving CR in 4 evaluable patients, and both remained CR status on the Jan 11, 2026. This result indicates that the combination of WGc-043 and PD-1 antibody is promising as part of the therapeutic strategy for this challenging lymphoma. Conclusions: WGc-043 combined with PD-1 antibody is well tolerated with a safety profile and yields encouraging CR rate and durable responses. Further investigations are warranted to validate these findings and to explore the full potential of this regimen in larger studies. Clinical trial information: 2200065962. Efficacy and safety. Response category Number of subjects CR 2 PR 0 SD 0 PD 2 Total 4 ORR 50% DCR 50% Adverse events Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Any adverse event 4/4 (100%) 0 0 0 0 Injection site reaction 4/4 (100%) 0 0 0 0 Hemoglobin decreased 2/4 (50%) 0 0 0 0 TSH elevated 2/4 (50%) 0 0 0 0 Fever 1/4 (25%) 0 0 0 0 Weakness 1/4 (25%) 0 0 0 0 Lymphopenia 1/4 (25%) 0 0 0 0