Updated results from an early-phase chronic lymphocytic leukemia trial of heavily pretreated patients showed that once-daily dosing of the Bruton’s tyrosine kinase (BTK) inhibitor bexobrutideg was well tolerated.
The data were presented in an oral abstract session at the Thirteenth Annual Meeting of the Society of Hematologic Oncology, held September 3–6 in Houston, Texas.
In this trial, 48 patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) received six daily dose levels: 50 mg (n=3), 100 mg (n=5), 200 mg (n=9), 300 mg (n=8), 450 mg (n=7), and 600 mg (n=16). The median patient age was 68.5 years with a median of four prior lines of therapy; nearly all had prior BTKi exposure and 83% had received a BCL2 inhibitor.
Common treatment-emergent adverse events were mostly low grade, including purpura/contusion (42%), fatigue (31%), neutropenia (29% with 23% grade ≥3), rash (29%), and diarrhea (29%); there were no dose-limiting toxicities and only one discontinuation due to a TEAE.
Among 47 response-evaluable patients, the overall response rate was 80.9% (all partial responses), with a median time to first response of 1.9 months and a median duration of response not yet reached; durable responses beyond 12–18 months occurred regardless of prior therapies, high-risk mutations (TP53, BTK, PLCG2, BCL2), or central nervous system involvement.
“Bexobrutideg was well tolerated in patients, including those with longer treatment durations and higher doses,” the authors noted, adding that a phase 1b dose expansion is underway with pivotal trials planned for 2025.
Reference
Omer Z, Danilov A, Forconi F. Bexobrutideg (NX-5948), a novel Bruton’s tyrosine kinase degrader, demonstrates rapid and durable clinical responses in relapsed/refractory chronic Lymphocytic leukemia: updated findings from an ongoing phase 1a study. Abstract# CLL-563. Presented at the Thirteenth Annual Meeting of the Society of Hematologic Oncology (SOHO 2025); September 3-6, 2025; Houston, Texas.
