840P Preliminary phase I/II study results of orelabrutinib combined with MIL62 in patients with relapsed or refractory B-cell non-Hodgkin lymphoma

MIL62 is a glycoengineered anti-CD20 antibody with nearly completely afucosylated N-glycans in Fc region that demonstrated superior activity comparison rituximab and obinutuzumab vitro vivo, respectively. Orelabrutinib (ICP-022) novel highly selective irreversible Bruton’s tyrosine kinase (BTK) inhibitor does not affect IL2-associated (ITK) or antibody-dependent cellular cytotoxicity, making it an attractive candidate for combined therapy antibodies. This was phase I/IIa dose escalation expansion study (NCT 04304040), which investigated orelabrutinib combination the treatment of patients relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL). The conducted standard 3 + scheme different combinations 100 mg 150 oral daily injection 800 1000 mg, A total 14 r/r CD20-positive NHL(10 diffuse large [DLBCL], 2 mantle cell lymphoma, 1 follicular marginal zone lymphoma) were enrolled across 5 centers China. Median age 62.5 (range, 38‒77) years 50% male. Overall, 78.6% had received ≥2 lines systemic therapies. No dose-limiting toxicity (DLT) unexpected adverse events observed. emergent (TEAE) any grade thrombocytopenia (5/14, 35.7%), infusion-related reaction (3/14, 21.4%) hyperuricemia 21.4%). Only observed ≥3 TEAE, one leukopenia/neutropenia deeming related. Ten evaluable efficacy as data cut-off on Apr. 21, 2021. Objective response rate (ORR) 70%, complete (CR) 4 partial (PR). ORR 71.4% DLBCL, including CR, PR. All except remain longest duration 8.5 months at date. generally well tolerated without toxicities encouraging clinical NHL.