Nurix Therapeutics, Inc.  announced that the first patient has been enrolled in the global Phase 3 DAYBreak CLL-306 study (NCT07516093) evaluating bexobrutideg, a potential best-in-class targeted protein degrader of Bruton’s tyrosine kinase (BTK), in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have previously received a covalent BTK inhibitor. The global study is being conducted under the collaboration between Nurix and Roche and marks the first Phase 3 trial for bexobrutideg. The registrational study is designed to demonstrate the superiority of bexobrutideg versus the non-covalent BTK inhibitor pirtobrutinib, the current standard of care in this treatment setting for patients whose disease has progressed following prior covalent BTK inhibitor therapy.

"This is an important milestone for the global bexobrutideg development program with the potential to redefine the treatment landscape for patients with CLL through a head-to-head comparison of BTK degradation versus non-covalent inhibition," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "We believe targeted protein degradation offers a fundamentally differentiated approach to addressing disease targets as compared to traditional small molecule inhibition, and this trial is designed to test whether that differentiation translates into superior outcomes for patients. Together with Roche, we are committed to advancing an ambitious global development program intended to fully realize the potential of BTK degradation across oncology, immunology and neurology."

The randomized Phase 3 trial is expected to enroll approximately 620 patients with relapsed/refractory CLL/SLL who have previously progressed on a covalent BTK inhibitor. Patients will be randomized 1:1 to receive either bexobrutideg 600 mg orally once per day or pirtobrutinib. The dual primary endpoints are objective response rate (ORR) and progression free survival (PFS), as assessed by an independent review committee. The study is designed to evaluate the potential superiority of bexobrutideg relative to pirtobrutinib and support global regulatory submissions.

"Bexobrutideg has demonstrated robust clinical activity in the setting of relapsed/refractory CLL with a favorable safety and tolerability profile," said Paula O'Connor, M.D., chief medical officer of Nurix. "The initiation of DAYBreak CLL-306 reflects our commitment to bringing innovative treatment options to patients with CLL who continue to face significant unmet medical needs."