お知らせ • 17h
Nurix Therapeutics Provides Updated Clinical Data for Bexobrutideg in Phase 1A/1B Study in CLL and SLL
Nurix Therapeutics, Inc. issued a press release announcing the presentation at the European Hematology Association Congress of updated clinical data from the Phase 1a/1b study of the Company's novel Bruton's tyrosine kinase (BTK) degrader bexobrutideg (NX-5948) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The updated data from the Phase 1a/1b study of bexobrutideg (NX-5948-301) in patients with CLL and SLL include safety findings across all CLL/SLL patients, updated safety findings for patients treated at the recommended Phase 2 dose (RP2D) of 600 mg once daily, updated Phase 1a results with extended follow-up, and new data from two Phase 1b cohorts evaluating bexobrutideg in earlier lines of treatment, including a cohort of BTK inhibitor (BTKi)-treated and BCL-2 inhibitor (BCL2i)-na ve patients and a cohort of BTKi-na ve patients, including treatment-na ve patients. As of the January 1, 2026 data cutoff, the Phase 1a/1b safety population included 142 patients with CLL/SLL, including 86 patients treated at the 600 mg dose. Bexobrutideg was well tolerated across the Phase 1a/1b population, consistent with prior disclosures. The treatment-emergent adverse event (TEAE) profile was comparable between the overall patient population and patients receiving the 600 mg dose, with the most common TEAEs in patients including purpura/contusion, neutropenia, petechiae, diarrhea and fatigue. There were no dose-limiting toxicities. Three Grade 5 adverse events were reported, all of which were deemed not related to treatment. The Phase 1a population had received a median of four prior lines of therapy (range = 2-12), including prior BTK inhibitors (97.9%), prior BCL2 inhibitors (83.3%) and prior non-covalent BTK inhibitors (27.1%). At baseline, many patients had mutations associated with BTK inhibitor resistance, including mutations in BTK (38.3%) and PLCG2 (14.9%). Poor prognostic features were common, including TP53 mutations (44.7%). Five patients (10.4%) in the Phase 1a population had central nervous system (CNS) involvement at baseline. The updated Phase 1a data included 48 patients with relapsed or refractory CLL/SLL treated at starting dose levels ranging from 50 mg to 600 mg once daily, with a median follow-up of 22.4 months. Among the 47 response-evaluable patients, the objective response rate (ORR) was 83.0%, including two patients (4.3%) with a complete response, one patient (2.1%) with nodal partial response, and 36 patients (76.6%) with partial response. Six patients (12.8%) showed stable disease and two patients (4.3%) experienced progressive disease. Median progression-free survival was 22.1 months (95% Confidence Interval: 14.0 months to Not Reached). Clinical responses were observed across difficult-to-treat subgroups, including patients with BTK inhibitor resistance mutations, high-risk molecular features and CNS involvement. The Phase 1b earlier-line cohorts include Cohort 5, which enrolled BTKi-treated and BCL2i-na ve patients, and Cohort 15, which enrolled BTKi-na ve patients, including treatment-na ve patients. Cohort 5 enrolled 19 patients, 18 of whom remained on treatment as of the data cutoff. Among the 14 patients evaluable for response, the ORR was 92.9% with a median follow-up of 5.2 months. Cohort 15 enrolled 20 patients, including 10 treatment-na ve patients, 19 of whom remained on treatment as of the data cutoff. Among the 19 patients evaluable for response, the ORR was 84.2% with a median follow-up of 4.9 months. Across all Phase 1a b CLL patients (n 142), bexobrutideg was well tolerated, consistent with prior disclosures, with safety findings generally comparable between patients treated at the 600 mg RP2D and the broader study population. As of the January 1, 2026, data cutoff, no dose-limiting toxicities were observed. No treatment-related Grade 5 adverse events were reported. Treatment discontinuations due to adverse events occurred in only 5.6% of patients. The most common treatment-emergent adverse events included purpura contusion, neutropenia, petechiae, diarrhea, and fatigue. The Phase 1a dose escalation study enrolled 48 patients with relapsed refractory CLL SLL treated with bexobrutideg at doses ranging from 50 mg to 600 mg once daily. Patients were heavily pretreated, having received a median of four prior lines of therapy (range 2 12), including prior BTK inhibitors (97.9%), prior BCL2 inhibitors (83.3%), and prior non-covalent BTK inhibitors (27.1%). Baseline high-risk features included BTK inhibitor resistance mutations (38.3%), TP53 mutations (44.7%), PLCG2 mutations (14.9%), and central nervous system (CNS) involvement (10.4%). As of the January 1, 2026, data cutoff, median follow-up was 22.4 months. Median progression-free survival (PFS) was 22.1 months (95% CI 14.0 NR). Objective response rate (ORR) was 83.0% (95% CI 69.2 92.4). Responses included two complete responses, one nodal partial response, and 36 partial responses. Responses were observed across patients with BTK inhibitor resistance mutations, high-risk molecular features, and CNS involvement. In Cohort 5 (n 19), patients had received prior BTK inhibitor therapy but no prior BCL2 inhibitor. ORR was 92.9% (95% CI 66.1 99.8) among evaluable patients (n 14). 18 of 19 patients remained on treatment at data cutoff. Median follow-up was 5.2 months. Five patients have not yet reached their first scan but remain on treatment. In Cohort 15 (n 20), which included BTKi-na ve and treatment-na ve patients, ORR was 84.2% (95% CI 60.4 96.6) among evaluable patients (n 19). 19 of 20 patients remained on treatment at data cutoff. Median follow-up was 4.9 months. Three patients with stable disease remain on treatment. Bexobrutideg (NX-5948) is an investigational, orally bioavailable, brain-penetrant, highly selective small-molecule degrader of Bruton's tyrosine kinase (BTK) being developed by Nurix and Roche as a potential best-in-class therapy across oncology, immunology and neurology. Bexobrutideg is currently being evaluated in the DAYBreak CLL-201 clinical trial (NCT07221500), a pivotal single-arm Phase 2 study in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), and in the NX-5948-301 Phase 1a 1b clinical trial (NCT05131022) in patients with relapsed or refractory B-cell malignancies. A new tablet formulation of bexobrutideg is also being evaluated in a first-in-human single-ascending-dose and multiple-ascending-dose study in healthy volunteers (NCT06717269) to support future development in immunology and neurology indications. Additional information about ongoing clinical trials can be found at clinicaltrials.gov.