Nurix Therapeutics presents updated data from ongoing trial of bexobrutideg

Nurix Therapeutics (NRIX) announced clinical data from the Company’s ongoing NX-5948-301 study, a Phase 1a/b clinical trial of bexobrutideg in patients with relapsed or refractory B-cell malignancies. The data include findings from the fully enrolled Phase 1a dose escalation study in patients with relapsed/refractory chronic lymphocytic leukemia and the ongoing Phase 1a/1b cohorts of patients with Waldenstrom macroglobulinemia. Talha Munir, consultant hematologist at Leeds Teaching Hospitals NHS Trust, deputy chair of the United Kingdom National Cancer Research Institute CLL Study Group, and Dima El-Sharkawi, Consultant Haematologist, Royal Marsden NHS Foundation Trust, Sutton, U.K., will present these data at the 30th European Hematology Association Congress, taking place June 12-15, 2025, in Milan, Italy. “These data demonstrate an impressive safety and efficacy profile for bexobrutideg with improvement in responses in patients over time, including the notable achievement of a complete response in a patient with CLL and a history of two lines of prior therapy who has been on bexobrutideg treatment for over two years,” said Dr. Munir. “Patients with relapsed or refractory CLL and WM who have failed treatments with commonly prescribed BTK inhibitors and other agents due to intolerance or acquired resistance have few therapeutic options. Nurix’s bexobrutideg has the potential to address this unmet need and provide a life-changing treatment for patients with CLL and WM.” Data presented at EHA2025 include efficacy and safety findings for patients with CLL/SLL in the fully enrolled Phase 1a dose escalation study. This cohort of CLL patients was a heavily pretreated population that had received a median of four prior lines of therapy including prior covalent BTK inhibitors, prior BCL2 inhibitors, and prior non-covalent BTK inhibitors. At baseline, many patients had mutations associated with BTK inhibitor resistance, including mutations in BTK and PLC2G. Poor prognostic features were common, including TP53 mutations, and five patients had central nervous system involvement. Patients were treated with bexobrutideg at doses ranging from 50 mg to 600 mg once daily by oral administration in the Phase 1a dose escalation study. As of the March 12 data cut, the median follow up was 9.0 months with most patients still on treatment. Bexobrutideg was well tolerated across all doses evaluated with the most common treatment emergent adverse events of purpura/contusion, neutropenia and thrombocytopenia, primarily low grade. No new onset atrial fibrillation was observed. Among the efficacy evaluable patients with CLL, bexobrutideg treatment resulted in a robust objective response rate of 80.9% across all doses tested with a median time to first response of 1.9 months. Many patients experienced deepening of their response with longer time, with multiple conversions from stable disease to partial responses and one patient, who has been on treatment for over two years, experienced a complete response. The median duration of response has not been reached, with 18 patients on treatment for more than a year. Responses were observed across all populations regardless of prior treatment, baseline mutations, or CNS involvement. The data presented at EHA included patients with WM treated with bexobrutideg at doses ranging from 50 mg to 600 mg once daily by oral administration from both the Phase 1a dose escalation and Phase 1b cohort expansion. Among the 22 WM patients, the median age was 72.5 years and the median number of prior lines of therapy was 3. All 22 patients previously had been treated with a covalent BTK inhibitor, 21 had received prior chemotherapy/chemo-immunotherapy, four had received prior non-covalent BTK inhibitor, and one patient had received prior treatment with a BCL2 inhibitor. Baseline mutation status in MYD88 and CXCR4 was captured from patient records. 15 patients had mutations in MYD88, and five patients had mutations in CXCR4. Bexobrutideg was well tolerated in patients with WM with a profile that was consistent with the overall study population and previous disclosures. Adverse events were predominantly low grade; with the most common being petechiae, diarrhea, purpura/contusion, neutropenia, and thrombocytopenia. There were no dose limiting toxicities observed and no grade 5 AEs. Two treatment emergent AEs led to drug discontinuation. No new onset atrial fibrillation was observed. As of the March 12, 2025 data cut, 19 patients were evaluable for responses. Objective response was observed in 16 patients, including two patients with very good partial response, 11 patients with partial response, and three patients with minor response. Three patients had a best response of stable disease. Responses were observed in patients regardless of their baseline mutations in MYD88 and CXCR4. Steady reductions in IgM levels were observed starting from the first assessment at four weeks, which continued to deepen, and three patients achieved IgM reductions of greater than 90%.