|The following article features coverage from the European Society of Medical Oncology (ESMO) Congress 2021. Click here to read more of Hematology Advisor’s conference coverage.|
Orelabrutinib and MIL62 combination therapy was generally well tolerated without unexpected toxicities and showed encouraging clinical activity in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL), according to study results presented at the European Society of Medical Oncology (ESMO) Congress 2021.
The phase 1/2a dose escalation and dose expansion study investigated orelabrutinib (ICP-022), a novel and highly selective irreversible Bruton’s tyrosine kinase (BTK) inhibitor, in combination with MIL62, a glycoengineered anti-CD20 antibody, for treating patients with relapsed/refractory B-cell NHL. Dose escalation was done with a standard 3+3 dose scheme in different combinations of orelabrutinib 100 mg or 150 mg oral daily with MIL62 injection 800 mg or 1000 mg, respectively.
A total of 25 patients (18 with diffuse large B-cell lymphoma [DLBCL] and 7 with other B-cell NHL) have been treated with orelabrutinib and MIL62 combination therapy at 5 centers in China as of June 30, 2021. Participants’ median age was 67 years (range, 38-77), and 60% of patients were female. They had a median of 2 previous therapies and 96% were previously treated with CD20 antibody therapy.
Of the cohort, 52% of patients had any grade of treatment-related adverse events (TRAEs), and 12% had grade ≥3 TRAEs. Also, 12% of participants had a TRAE that resulted in treatment discontinuation or dose reduction. The most common TRAEs were neutropenia (16%), leukopenia (12%), thrombocytopenia (28%), infusion-related reaction (16%), and rash(12%).
In the 20 patients who were evaluable for antitumor activity with at least 1 post-treatment assessment, the overall response rate (ORR) was 65.0% (95% CI, 40.8, 84.6), and the complete response (CR) rate was 35.0% for all dose groups.
For patients with DLBCL, the ORR was 61.5% (95% CI, 31.6, 86.1), including 4 CRs and 4 partial responses (PRs) in 13 assessed patients. The ORR was 71.4% for those with other B-NHL, including 3 CRs and 2 PRs of 7 patients. The ORR was 62.5%, including 2 CRs and 3 PRs, in 8 patients with rituximab-refractory DLBCL.
The median duration of treatment was 2.4 months (range, 0.03-10.4 months) for the 20 assessed patients, and 15 (75.0%) patients remain on therapy.
“The combination therapy demonstrated encouraging antitumor activity,” stated the investigators, who noted that the phase 2a expansion is ongoing.
Disclosure: The study was sponsored by Beijing Mabworks Biotech Co Ltd and Beijing Innocare Pharma Tech Co, Ltd. Some of the study authors reported affiliations with Beijing Mabworks Biotech Co Ltd and Beijing Innocare Pharma Tech.
Shi Y, Qin Y, Zhang W, et al. Preliminary phase I/II study results of orelabrutinib combined with MIL62 in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Presented at: European Society of Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract 840P.