531 Phase I study to assess the safety, immunogenicity, and preliminary antitumor activity of the EBV mRNA vaccine (WGc-043 injection) in patients with R/R lymphoma
Year: 2026
Type: conference-abstract
Abstract: Background Epstein-Barr virus (EBV) is closely linked to the pathogenesis of various lymphomas, including EBV-associated B-cell and T/NK cell lymphomas. Notably, over 90% of NK/T cell lymphomas (NKTCL) are EBV-positive, which serves as a key driver of tumorigenesis, invasion, and progression. WGc-043, a therapeutic mRNA vaccine, shows promise against EBV-positive cancers and may provide therapeutic benefit to EBV-positive lymphoma patients by targeting EBV-driven oncogenesis. This phase I study evaluates the safety, immunogenicity, and preliminary antitumor activity of WGc-043 in patients with lymphoma (ChiCTR2500108428).Methods This multi-center, open-label, phase I study enrolled 20 patients with EBV-positive relapsed or refractory (R/R) lymphoma in China. The primary inclusion criteria were patients diagnosed with R/R lymphoma refractory to standard treatment, with EBER positivity in tumor tissue confirmed by ISH or FISH assay, and an ECOG performance status of 0-2. WGc-043 was administered intramuscularly at doses ranging from 100 µg to 500 µg, including 5 doses of base immunization followed by optional personalized treatment. The primary endpoints were safety, DLT and its incidence, as well as MTD or RP2D; the secondary endpoints included ORR, DCR, DoR, PFS, pharmacokinetic, and immunogenicity.Results The enrolled subjects consisted of patients diagnosed with NKTCL, Hodgkin’s lymphoma, diffuse large B-cell lymphoma, and peripheral T-cell lymphoma. No serious adverse reactions (SARs) or dose-limiting toxicities (DLTs) were reported in any subjects receiving WGc-043 at doses ranging from 100 µg to 500 µg. A total of 95.0% (19/20) of subjects experienced treatment-related adverse events (TRAEs), all of which were grade 1 or 2, indicating good overall tolerability. The most common TRAEs were fever (17/20), injection site pain (11/20), anemia (10/20), neutropenia (8/20), leukopenia (6/20), and injection site induration (6/20). A total of 12 patients with R/R NKTCL had at least one efficacy assessment result, with ORR of 41.7% (5/12) and DCR of 58.3% (7/12). Notably, one patient in each of the 300 µg and 500 µg dose groups achieved PR after 5 doses and CR after 7 doses, demonstrating promising therapeutic potential of the vaccine.Conclusions WGc-043 is well tolerated with a safety profile that reflects its potential for favorable patient outcomes. The observed efficacy in the R/R NKTCL cohort suggests a promising clinical benefit. Further research is needed to confirm these findings and to explore the full potential of the vaccine in larger studies.
Institutions: Sichuan University, West China Hospital of Sichuan University, State Key Laboratory of Biotherapy, Shanghai Jiao Tong University, Ruijin Hospital, Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Zhengzhou University, Henan Cancer Hospital, First Affiliated Hospital of Zhengzhou University, Sun Yat-sen University, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225318823