CM313, a Novel Anti-CD38 Antibody, As a Potential Treatment for Primary Immune Thrombocytopenia: A Phase II Trial

Background: Primary immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Antiplatelet-specific plasma cells (PCs) have been identified in ITP patients, making PCs depletion a potential treatment for ITP. CM313, a novel anti-CD38 monoclonal antibody currently under investigation in a phase I trial for multiple myeloma, has demonstrated targeted depletion of CD38-positive cells, including PCs. This phase II trial (NCT05694767) was designed to assess the safety and efficacy of CM313 in ITP patients. Methods: The open-label phase II trial consisted of a 4-week screening period, an 8-week treatment period, and a 16-week follow-up period. The main inclusion criteria were patients (age ≥18 years) with ITP and a platelet count <30×10 9/L, who did not response to or relapsed after glucocorticoid therapy and at least one second-line therapy (including rituximab and/or thrombopoietin receptor agonists [TPO-RAs]). Eligible patients received CM313 intravenously at a dose of 16 mg/kg weekly for a total of 8 weeks. The participants were requested to maintain the stable doses of glucocorticoids or TPO-RAs for 4 weeks prior to receiving the first dose without dose escalation during the study. Prophylactic medication, including glucocorticoids, antihistamines, and acetaminophen, was administered to all patients before and after the infusion. The primary endpoints were the percentage of patients with a platelet count ≥50×10 9/L within 8 weeks after the first dose (platelet count must be consecutive on at least 2 occasions with an interval of at least 1 day) and the incidence/severity of adverse events during the study period. Results： As of June 30, 2023, a total of 21 patients had been enrolled in the study and 7 subjects had completed 8 doses of the treatment with at least 8 weeks of follow-up. The 7 subjects consisted of 2 males and 5 females, with a median age of 40 years (range 18-56), a median weight of 62 kg (range 52-93), a median duration of ITP of 30 months (range 12-200) and a median baseline platelet count of 8×10 9/L (range 2-24). Of the 7 patients, 100.0% (7/7) achieved a platelet count ≥50×10 9/L within 8 weeks after the first dose, with a median time to response of 1 week (range 1-3). Furthermore, 4 out of 7 patients (57.1%) maintained a platelet count of ≥50×10 9/L until week 16, while 2 patients experienced a relapse at week 6 and 1 patient had a relapse at week 13. Platelet count (expressed as the median with the interquartile range) of the 7 patients from baseline to week 23 are shown in Figure 1. Of all 21 patients, 6 (6/21, 28.6%) had an infusion-related reaction (IRR) at the first dose but none at subsequent doses. The severity of IRR was grade 1 or 2 (according to CTCAE version 5.0). Conclusion: CM313, a novel anti-CD38 monoclonal antibody, has demonstrated tolerable safety and preliminary efficacy in refractory/relapsed ITP patients. Figure 1: Platelet count in 7 patients.