Nurix Therapeutics Reports Positive NX-5948 Trial Results in Relapsed Refractory CLL at EHA2024

Nurix Therapeutics, Inc., a clinical-stage biopharmaceutical company, has recently shared promising clinical data for its drug candidate, NX-5948. This oral treatment, designed to degrade Bruton’s tyrosine kinase (BTK), is currently under evaluation in an ongoing Phase 1a/b trial targeting adults with relapsed or refractory B-cell malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). The data was presented by Dr. Kim Linton, a senior lecturer at the University of Manchester and a consultant at The Christie NHS Foundation Trust, during an oral session at the European Hematology Association Congress held in Madrid, Spain.

The clinical trial results reveal that NX-5948 demonstrated an objective response rate (ORR) of 69.2% in heavily pretreated CLL patients, including those with mutations that confer resistance to BTK inhibitors. Patients showed rapid and deepening clinical responses over longer treatment periods. Nurix intends to advance NX-5948 to pivotal trials by 2025.

Dr. Linton expressed optimism about the potential of NX-5948 as a breakthrough therapy for relapsed CLL patients, particularly given the emerging resistance patterns to existing targeted therapies. She highlighted the significance of offering a once-daily oral drug to patients who are refractory to other treatments.

The safety profile of NX-5948 was assessed in all 79 patients in the Phase 1a dose-escalation study, covering various diagnoses. Efficacy results were reported for the 31 patients with relapsed or refractory CLL. The patients received doses from 50 mg to 600 mg daily. NX-5948 was well tolerated, with common side effects including purpura/contusion, thrombocytopenia, and neutropenia. Among the 26 efficacy-evaluable CLL patients, responses were observed as early as the first scan at eight weeks, and many patients experienced further deepening of their response over time, with all responses ongoing as of April 17.

The CLL cohort was heavily pretreated, having received a median of four prior lines of therapy, including covalent and non-covalent BTK inhibitors and BCL2 inhibitors. Many patients had baseline mutations associated with BTK inhibitor resistance, including BTK and PLC2G mutations, and poor prognostic features like TP53 mutations. Responses were observed across all patient subgroups, regardless of prior treatments, baseline mutations, or central nervous system (CNS) involvement.

A notable case involved a patient with CLL and CNS involvement who had undergone three prior therapies, including a BTK inhibitor. After daily treatment with NX-5948, the patient exhibited a deepening response approaching complete response criteria by 36 weeks, with malignant cells eliminated from the cerebrospinal fluid by 24 weeks. Another case highlighted a patient treated with eleven prior lines of therapy, including multiple BTK inhibitors, who achieved a response by week 8 with NX-5948, which deepened over time and continued with over six months of follow-up.

Paula G. O’Connor, M.D., Chief Medical Officer of Nurix, emphasized the encouraging responses across the entire CLL cohort at all dose levels. The company plans to expand the Phase 1b trial across various CLL subpopulations to prepare for pivotal clinical evaluation in 2025. While the presentation did not cover all subtypes of NHL, consistent responses have been observed, including complete responses in patients with advanced diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), primary CNS lymphoma (PCNSL), and Waldenström's macroglobulinemia (WM).

Arthur T. Sands, M.D., Ph.D., President, and CEO of Nurix, highlighted NX-5948's potential as a best-in-class medicine for CLL and NHL, citing its favorable safety profile and demonstrated CNS activity. The company aims to move rapidly towards initiating pivotal trials in 2025.

NX-5948 is an investigational, orally bioavailable, brain-penetrant small molecule degrader of BTK. It is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B-cell malignancies, including CLL/SLL, DLBCL, FL, MCL, MZL, PCNSL, and WM.

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