An Open, Exploratory Clinical Study of CM336 in the Treatment of Immune Thrombocytopenia

To evaluate the efficacy and safety of CM336 in the treatment of refractory adult primary immune thrombocytopenia

Immune thrombocytopenia (ITP) is an organ-specific autoimmune disease, which is characterized by decreased platelet count and skin and mucosal bleeding. ITP is a kind of disease with increased platelet destruction and impaired platelet production caused by autoimmunity. Conventional treatment of adult ITP includes first-line glucocorticoid and immunoglobulin therapy, second line TPO and TPO receptor agonist, splenectomy and other immunosuppressive treatments (such as rituximab, vincristine, azathioprine, etc.). ITP is one of the most common hemorrhagic diseases. At present, the treatment response of ITP is not good, and a considerable number of patients need drug maintenance treatment, which seriously affects the quality of life of patients and increases the economic burden of patients. Therefore, there is still a lack of effective treatment for adult ITP, especially for recurrent and refractory ITP patients, which is one of the problems that have attracted more attention and need to be solved urgently. The main pathogenesis of ITP is the loss of platelet autoantigen immune tolerance, which leads to abnormal activation of humoral and cellular immunity. It is characterized by antibody mediated platelet destruction and insufficient platelet production by megakaryocytes. The residual long-term autoreactive plasma cells may be a source of therapeutic resistance to autoimmune cytopenia. Antiplatelet specific plasma cells have been detected in the spleen of patients with rituximab refractory ITP. Therefore, the strategy of simply eliminating B cells may not work, because LLPC will continue to produce pathogenic antibodies. However, targeting LLPC becomes a new strategy to treat autoimmune diseases. B-cell maturation antigen (BCMA) is mainly restricted in some B-cell subsets and plasma cells, but not in other normal human cells and tissues. BCMA does not maintain normal B-cell homeostasis, but is necessary for long-lived plasma cell survival. Plasma cells are the main antibody-producing cells in the body, and the production of autoantibodies is the main pathogenesis of ITP. BCMA-CD3 bispecific antibody CM336 can bind BCMA-positive B cells and plasma cells, and bind CD3-positive T cells at the same time to induce T cell activation and play the role of T-cell-dependent cellular cytotoxicity (TDCC). CM336 can eliminate BCMA-positive B cells and plasma cells through the above mechanism, directly reduce the production of pathogenic antibodies, and then achieve therapeutic effect. Due to the deep clearance of immune cells by bispecific antibodies, CM336 may achieve the effect of immune reset and cure autoimmune diseases such as ITP. The BCMA-CD3 bispecific antibody teclistamab has been reported to be used in the treatment of refractory systemic lupus erythematosus, systemic sclerosis, primary Sjogren's syndrome, idiopathic inflammatory myopathy, rheumatoid arthritis and other autoimmune diseases, with significant clinical effect and good safety. Therefore, the investigators designed this clinical trial to evaluate the safety and efficacy of CM336 in the treatment of refractory ITP.