By: Emily Hayes
Attendees of SOHO 2025 got a closer look at positive early safety and efficacy data for the novel Bruton’s tyrosine kinase (BTK)-targeted drug bexobrutideg in heavily pretreated Waldenström macroglobulinemia (WM).
Orally available bexobrutideg (bexdeg for short) is designed to eliminate BTK in B cells, through degradation of the ubiquitin proteasome system, according to developer Nurix Therapeutics, which is based in San Francisco. It is being tested in an ongoing phase I a/b study for treatment of relapsed or refractory B cell malignancies, including Waldenström macroglobulinemia.
At SOHO 2025, researchers presented data as of March 12, 2025, for 22 mainly elderly WM patients treated with one of four different once-daily doses (200 mg, 300 mg, 450 mg, and 600 mg) and who had received a median of three prior treatments. This was a tough-to-treat population. All participants had previously received a BTK inhibitor and most had prior chemotherapy or chemo-immunotherapy (95.5%). Furthermore, 68.2% had MYD88 mutations, and 22.7% had CXCR4 mutations.
The overall response rate (ORR) was 84.2% in 19 patients who were evaluable, including two very good partial responses (VGPR). Good outcomes were seen across patients, regardless of their prior exposure to BTK inhibitors or mutation status, researchers noted.
Responses were rapid and durable, with two patients reaching more than one year of follow-up, regardless of prior therapy or mutation status. Furthermore, levels of IgM steadily declined during the study, dropping by 90% in three patients.
Across the doses tested, the drug was also well-tolerated, with a median follow-up of 3.7 months. Most adverse events were grade 1-2, the most common being petechiae (27.3%, all < grade 3), diarrhea (22.7%, all < grade 3), purpura/contusion (18.2%, all < grade 3), neutropenia (18.2%, with one ≥ grade 3), and thrombocytopenia (18.2%, with one ≥ grade 3). No dose limiting toxicities or deaths were reported.
Bexdeg has orphan drug status for treatment of WM with the US Food and Drug Administration and the European Medicines Agency.
Reference
Shah N, El-Sharkawi D, Lewis D. Bexobrutideg (NX-5948), a Novel Bruton’s Tyrosine Kinase (BTK) Degrader, Shows High Clinical Activity and Tolerable Safety in an Ongoing Phase 1a/b Study in Patients With Waldenström Macroglobulinemia (WM). Abstract #IBCL-675. Presented at the thirteenth annual meeting of the Society of Hematologic Oncology (SOHO 2025); September 3-6, 2025; Houston, Texas.
Visit the SOHO 2025 meeting news page for more coverage from the meeting.
