Phase I/II updated safety and efficacy results of oral bruton tyrosine kinase (BTK) inhibitor rilzabrutinib in relapsed/refractory immune thrombocytopenia (ITP).

Background: Immune thrombocytopenia (ITP) is characterized by immune-mediated platelet destruction and impaired production, triggering thrombocytopenia, and a predisposition to bleeding. Despite recent therapeutic advances, durable remission remains an unmet need for relapsed/refractory ITP patients. Rilzabrutinib is an oral, reversible, covalent inhibitor of BTK that targets immune-mediated ITP activities and has simultaneous rapid anti-inflammatory effects and neutralization and prevention of autoantibody signaling preclinically. The ongoing phase I/II study (NCT03395210) assesses the safety and efficacy of rilzabrutinib in patients with relapsed or refractory ITP who previously responded to >=1 prior ITP therapy and have no available treatment options. Initial results have shown rapid and durable clinical activity and a well-tolerated safety profile in patients responding to rilzabrutinib. Aim(s): Phase II evaluation of rilzabrutinib in the overall study population and patients initiating 400 mg BID rilzabrutinib. Method(s): Eligible patients with 2 baseline platelet counts <30x109/L received oral rilzabrutinib at starting doses of 200 mg QD, 400 mg QD, 300 mg BID, or 400 mg BID; intrapatient dose escalation was allowed to improve efficacy. Rilzabrutinib was given for 24 weeks; additional long-term therapy was administered at the 400 mg BID dose in responders only. Stable doses of concomitant ITP medication (corticosteroids and thrombopoietin-receptor agonists) were permitted for patients without adequate platelet response. The primary endpoints are safety and >=2 consecutive platelet counts >=50x109/L and increased >=20x109/L from baseline without requiring rescue medication. All patients provided informed consent. Result(s): The overall study population comprises 59 patients, of whom 44 had a starting dose of 400 mg BID; data cutoff was 09Nov2020. Overall, patients had a median age 50 years (range, 21-74), median duration of ITP 6.4 years (range, 0.4-52.5), and