CM313, an anti-CD38 monoclonal antibody, showed rapid, durable platelet responses and was well tolerated in a phase II trial for patients with persistent/chronic immune thrombocytopenia (ITP), supporting its potential as a novel autoimmune therapy by targeting autoantibody-secreting plasma cells.
Immune thrombocytopenia (ITP) is an autoimmune disease characterised by autoantibody-mediated platelet destruction and a relapsing disorder that often requires multiple lines of treatment. CM313 is a novel anti-CD38 monoclonal antibody that targets and depletes CD38-expressing cells, including plasma cells.1 Preliminary phase I-II trial (NCT05694767) results showed that anti-CD38 targeted therapy rapidly increased platelet counts by blocking antibody-dependent cytotoxicity, with sustained long-term efficacy through plasma depletion, and primarily low-grade toxicity.2 The ability to eliminate autoantibody-secreting cells suggests feasibility for autoimmune disease treatment with CM313. At EHA 2025, the safety and efficacy results of a phase II trial (NCT06199089) evaluating CM313 in adult patients with persistent or chronic ITP were presented.3
Study design
This phase II, multi-centre, randomised, double-blind, placebo-controlled trial evaluated CM313 in adult patients with persistent or chronic ITP who had failed or relapsed after glucocorticoid therapy and had previously responded to standard first-line treatment. Patients received weekly intravenous (IV) CM313 (16 mg/kg) or placebo for eight weeks. The primary endpoint was overall response rate (ORR) at week eight, defined as at least two consecutive platelet counts >30×109/L without bleeding.
Results
In total, 45 patients were enrolled and randomised (2:1) to receive either CM313 (N= 30) or placebo (N= 15). By week eight, the ORR was higher with CM313 (83%) compared to placebo (20%). The median time to achieve a platelet count >50×109/L was one week with CM313, while this level was not reached in the placebo group during the same period. Median cumulative duration of platelet count >50×109/L was eighteen weeks with CM313 vs three weeks with placebo. In addition, the number of patients with bleeding decreased from 37% to 13% at week 24 in the CM313 group, while the percentage of patients with bleeding increased from 27% to 33% in the placebo group. Treatment-emergent adverse events (TEAEs) occurred in 83% of CM313-treated patients and 80% of placebo-treated patients. The most common TEAEs were infusion-related reactions (30% vs 13%), petechiae (27% vs 67%) and upper respiratory tract infections (13% vs 13%).
Conclusion
Anti-CD38 targeted therapy with CM313 rapidly boosted platelet levels by inhibiting antibody-dependent cell-mediated cytotoxicity on platelets and showed durable responses by clearing plasma cells. CM313 was well tolerated with a favourable safety profile.
References
1. Piedra-Quintero ZL, Wilson Z, Nava P, et al. CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity. Front Immunol. 2020;11:597959.
2. Chen Y, Xu Y, Li H, et al. A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia. N Engl J Med. 2024;390(23):2178-90.
3. Xu Y, Chen Y, Dai J, et al. Safety and efficacy of CM313 in adult patients with immune thrombocytopenia: a randomised placebo-controlled trial. Presented at EHA 2025: Abstract LB4004.
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