Clinical Study of SYNCAR-100 in the Treatment of Relapsed/Refractory Acute B-Lymphoblastic Leukemia

The purpose of this study is to assess the safety, tolerability, and preliminary efficacy of SYNCAR-100 in patients with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). Participants who have signed the informed consent form will undergo screening against the inclusion and exclusion criteria. Eligible participants will receive study drug administration once weekly for a total of four doses, followed by a 1-year safety and efficacy follow-up observation period. After the completion of the study, long-term follow-up may be required for participants to monitor their health and survival status until 15 years post-treatment, or until the occurrence of patient death, loss to follow-up, or withdrawal of consent.

Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the clonal abnormal proliferation and accumulation of lymphoid precursor cells (B or T lineage) in the bone marrow, peripheral blood and other organs. B-cell acute lymphoblastic leukemia (B-ALL) is the more common subtype, accounting for approximately 80% of all cases. For adult patients with relapsed or refractory B-ALL, only about 5-30% can achieve complete remission (CR) following salvage therapy. In addition, among patients who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), approximately 35% experience disease relapse, with a median overall survival of no more than 6 months; the estimated 1-year, 2-year and 5-year overall survival rates are about 30%, 15% and 10%, respectively. Relapse after allo-HSCT remains a major challenge in the treatment of hematologic malignancies, and there is no effective therapeutic approach recommended by clinical practice guidelines or consensus statements. Therapies such as retransplantation, donor lymphocyte infusion (DLI) and blinatumomab yield overall suboptimal efficacy, creating an urgent unmet medical need for novel and effective therapeutic strategies. SYNCAR-100 is a next-generation nucleic acid drug candidate developed by Bisheng (Beijing) Biotechnology Co., Ltd. based on circular RNA (circRNA) technology. The safety of SYNCAR-100 will be evaluated by assessing indicators including dose-limiting toxicities (DLT), vital sign measurements, physical examinations, laboratory tests, 12-lead electrocardiography (ECG), peripheral blood B-cell and T-cell levels, and adverse events (AE). The efficacy of SYNCAR-100 in patients with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) will be evaluated by measuring endpoints including the overall response rate (ORR) within 12 weeks, the rate of complete remission with minimal residual disease (MRD)-negativity, duration of response (DOR), progression-free survival (PFS), as well as the ORR within 48 weeks, the rate of patients achieving CR with MRD negativity, DOR, PFS and overall survival (OS). After the completion of the study, long-term follow-up may be required for participants to monitor their health and survival status until 15 years post-treatment, or until the occurrence of patient death, loss to follow-up, or withdrawal of informed consent.