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