BRISBANE, Calif., Aug. 4, 2026
Nurix Therapeutics, Inc. announced the enrollment of the first patient in the registrational Phase 3 DAYBreak CLL-306 trial evaluating bexobrutideg (NX-5948) for patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent Bruton’s tyrosine kinase (BTK) inhibitor. Conducted in collaboration with Roche, the global study marks the first Phase 3 trial for bexobrutideg and is designed to compare the investigational BTK degrader directly against pirtobrutinib, the current standard of care for patients whose disease has progressed after prior covalent BTK inhibitor therapy. The trial aims to support future global regulatory submissions if successful.
Global Registrational Study Targets Superiority Over Current Standard of Care
The randomized DAYBreak CLL-306 study is expected to enroll approximately 620 patients worldwide with relapsed/refractory CLL/SLL. Participants will be randomized in a 1:1 ratio to receive either bexobrutideg 600 mg once daily or pirtobrutinib. The study’s dual primary endpoints are objective response rate (ORR) and progression-free survival (PFS), both assessed by an independent review committee. The trial is specifically designed to determine whether targeted BTK protein degradation can provide superior clinical outcomes compared with non-covalent BTK inhibition in this treatment setting.
Bexobrutideg Expands Broad Clinical Development Program
Bexobrutideg is an investigational, orally available, brain-penetrant, highly selective BTK-targeted protein degrader being jointly developed by Nurix and Roche for applications across oncology, immunology, and neurology. Beyond the Phase 3 DAYBreak CLL-306 trial, the molecule is currently being evaluated in multiple ongoing studies, including the DAYBreak CLL-201 pivotal Phase 2 trial, the NX-5948-301 Phase 1a/1b study in relapsed or refractory B-cell malignancies, and the NX-5948-203 Phase 1/2 combination trial assessing bexobrutideg with venetoclax, with or without an anti-CD20 antibody. A separate first-in-human study evaluating a tablet formulation in healthy volunteers is also underway to support future immunology and neurology development.
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Phase 3 Milestone Strengthens Nurix’s Targeted Protein Degradation Strategy
The initiation of DAYBreak CLL-306 represents a significant advancement for Nurix’s targeted protein degradation platform, which aims to eliminate disease-causing proteins rather than simply inhibit their activity. By directly comparing BTK degradation with the leading non-covalent BTK inhibitor in a registrational setting, the company seeks to establish a differentiated therapeutic approach for patients with relapsed or refractory CLL/SLL who continue to face substantial unmet medical needs after prior BTK inhibitor treatment. Positive results could position bexobrutideg as a potential best-in-class therapy while supporting broader expansion across oncology, autoimmune diseases, and neurological disorders.
Source: Nurix Therapeutics press release
