ICML 2023 | Phase Ib/IIa study of AZD4573 and acalabrutinib in patients with R/R DLBCL

So the Phase I/II study of acalabrutinib and AZD4573, a selective CDK9 inhibitor in DLBDL enrolled 31 patients. This combination showed preliminary efficacy and good tolerability in patients with diffuse large B-cell lymphoma. This was a heavily pretreated group of patients with median four lines of therapy before patients received this experimental therapy, and some patients received chimeric antigen receptor T-cells as well. The treatment was quite well tolerated with main toxicities being neutropenia, nausea, diarrhea, as well as some transient elevations in AST and ALT. But overall toxicities were well managed, and the regimen was also associated with impressive efficacy in this heavily pretreated group of patients with overall response rate of almost 50% and complete response rate of 20%. And in some patients, responses were durable, particularly in patients who achieved complete response, the duration of response approached ten months and few patients actually remained in remission as long as 12 months later while continuing treatment on study. Of course, CDK9 inhibition is a very desirable target in diffuse large B-cell lymphoma. It’s associated with downregulation of the antiapoptotic family member MCL-1, as well as downregulation of MYC transcriptional program, which we know is highly oncogenic in lymphomas. So continued investigation of CDK9 inhibitors is a very promising area in lymphoma.