Dendritic cell–based vaccines (KSD-101) against EBV-associated lymphoproliferative diseases: Results from an ongoing phase I clinical study.

e14515 Background: The Epstein–Barr Virus (EBV) infects over 95% of the global population. The WHO has definitively identified EBV as the first human tumor-associated virus, thereby underscoring the necessity for novel therapeutic options. KSD-101, a First-in-class autologous dendritic cell (DC) vaccine which is loaded with the EBV-related antigen, is specifically tailored to target EBV-associated lymphoproliferative diseases (EBV-LPDs). Methods: Patients (pts) with EBV-LPDs and have not respond to or relapsed after standard treatment will be enrolled. Pts will receive monotherapy with KSD-101 via subcutaneous injection once every 2 weeks for 3-5 doses, without requiring pre-treatment lymphodepletion. The study used a 3+3 dose-escalation design, aiming primarily to assess tolerability, safety, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD), with secondary objective to explore clinical efficacy and immune responses. Results: Between January 16, 2023, and May 21, 2024, 11 pts were ultimately enrolled and treated with KSD-101. In the escalation phase, 3 pts received 5.0 × 10 6 cells/dose and 2 pts received 7.5 × 10 6 cells/dose. Based on the safety, preliminary efficacy, and feasibility assessment, we decided to cancel the third dose group and apply 5.0 × 10 6 cells/dose to the expansion phase. In all pts, neither DLT nor MTD were explored. Vaccinations were well tolerated. Pts experienced KSD-101-related adverse events were injection site reactions (grade 1, 90.9%), fever (grade ≤ 2, 72.7%), lymphadenopathy (grade 1, 54.5%) and lymphocythemia (grade 1, 9.1%). The data cutoff was August 14, 2024 and the median follow-up was 54.1 weeks (range, 5.9-71.1 weeks). Two hemophagocytic lymphohistiocytosis pts discontinued from the study due to rapid early-stage disease progression and subsequently received alternative therapeutic interventions. The best ORR was 88.9% (8/9), with all pts achieving complete remission (CR). The DCR was 100% (9/9), with one pt demonstrating stable disease following vaccination. After vaccinations, we found that the peak proportion of EBV-specific T cells in CD3 + CD8 + cells (average, 4.21%) was significantly increased ( p < 0.05) compared to baseline (average, 0.61%) and the peak number of immune cells also increased, such as activated T cells ( p < 0.05, average increased to 2.61-fold), NK cells ( p < 0.01, average increased to 1.77-fold) and CD8 + T cells ( p < 0.05, average increased to 2.02-fold). We also found that the valley number of T-regs significantly reduced ( p < 0.01, average reduced to 58.14%). Conclusions: AS of now, KSD-101 has demonstrated good safety and efficacy and could activate immune system. Our study highlights its potential as a promising therapeutic agent for the treatment of EBV-LPDs. Larger prospective studies and a longer follow-up period is needed to be conducted. Clinical trial information: NCT05635591 .