The 62nd annual meeting of the American Society of Hematology (ASH) is convened online from December 5 to 8, 2020, and a number of important clinical research progress will be announced at that time. The research paper entitled “a Feasibility and Safety Study of a Novel CD19-Directed Synthetic T-Cell Receptor and Antigen Receptor (STAR) T-Cell Therapy for Refractory and Relapsed (R/R) B Cell Acute Lymphoblastic Leukemia (B-ALL)” independently developed by China Immunotech (Beijing) Biotechnology Co., Ltd. (hereinafter referred to as "BriSTAR Immunotech Limited") is selected as the oral report at the meeting of ASH 2020 after strict review, making a voice on the international stage.

Although Chimeric Antigen Receptor T-Cell Immunotherapy (CART-T) has achieved remarkable clinical efficacy in the treatment of hematoma, it still has huge limitations in applications, including low safety caused by cytokine storm, poor infiltration to solid tumors, weak and short killing effect in vivo, easy depletion and other defects, as well as tumor recurrence caused by antigen loss at the later stage. In order to solve these problems, Professor Lin Xin, the founder of BriSTAR Immunotech Limited, adopts a new method with T cell receptor (TCR) as the basic framework, to functionally transform CART-T based on his accumulated researches for more than 20 years, with the constant region replaced with one or more antigen receptor scFv structures, and name it as synthetic innovative T cell receptor and antigen receptor T cell (hereinafter referred to as "STAR-T"). The biggest innovation of this structure is that it incorporates the advantages of both TCR-T and CART-T, which not only overcomes HLA-type restrictions and accurately targets tumor cells for efficient killing effect, but also utilizes the signal pathway of endogenous TCR cascade amplification. It features natural double-target, high efficiency and low side effects, and also retains the infiltration of cells activated by natural receptor signal pathway to solid tumors. In particular, it is worth pointing out that double-target STAR-T better prevents treatment failure caused by single target therapy-induced antigen loss.

Based on this new structural platform, BriSTAR Immunotech Limited has developed a series of blood tumor treatment products, including single-target CD19 STAR-T, double-target CD19/20STAR-T and CD19/22 STAR-T, and also developed a series of solid tumor product pipelines. At present, these pipelines have entered the stage of clinical research.

The oral report on clinical study at ASH 2020 is about the preclinical and clinical observation data of CD19 STAR-T for the treatment of recurrent or refractory B-cell acute lymphoblastic leukemia. The evaluation of preclinical animal model in this study has found that CD19 STAR-T cells are activated faster compared with the conventional CART-T cells, with higher cytokine production and stronger targeted killing effect.
The clinical phase I trial of this study was conducted in conjunction with Ludaopei Hospital. A total of 18 subjects with CD19 positive relapsed/ refractory (R/R) acute B-lymphoblastic leukemia (B-ALL) (NCT03953599) were enrolled, with main purpose to evaluate the safety and potential efficacy of STAR-T cells. The results showed that the STAR-T cells of 18 subjects were successfully prepared and re-transfused. On day 14 after cell re-transfusion (day 14), 18 subjects’ diseases were rapidly remitted, with the complete response (CR) rate of 100% (n=18) and negative minimal residual disease (MRD). At the assessment on day 28, 18 subjects still maintained morphologic complete response (CR), and only 1 subject was MRD positive. After the re-transfusion with STAR-T cells (median) for 57 days, 8 subjects were treated with bridged allogeneic hematopoietic stem cell transplantation (allo-HSCT), and still maintained CR after 110 days (median follow-up time). In the other 10 subjects who were not treated with bridged allo-HSCT, 8 of them still maintained CR as long as 6 months during the observation time. The follow-up survival and clinical results were still continuously followed up. In terms of safety, about 55.6% (10/18) of the 18 subjects developed cytokine release syndrome (CRS), of which 44.4% subjects (8/18) presented grade 1 CRS, 11.1% (2/18) demonstrated grade 2 CRS, and no subject presented grade 3 CRS or above, showing higher safety compared with conventional CART-T cells. Two (2/18) subjects developed grade 3 neurotoxicity (ICANS), which returned to normal in about 1 week after the clinical intervention.

The non-clinical results of this study showed that STAR-T cells were superior to conventional CART-T cells in terms of signal transduction, cytokine secretion and anti-tumor efficacy. The first phase I human trial of this study proved the technical feasibility, clinical safety and effectiveness of STAR-T in the treatment of CD19 +R / R B-ALL. In particular, high CR rate was achieved on day 14 after re-transfusion, and was still maintained on day 28. In addition, the safety of STAR-T was also higher than that of the conventional CART-T therapy, showing strong clinical potential for application.