Nurix Therapeutics, Inc. announced the presentation of updated clinical data for NX-5948, an orally bioavailable degrader of Bruton?s tyrosine kinase (BTK), being evaluated in an ongoing Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies, including CLL and non-Hodgkin lymphoma (NHL). Dr. Kim Linton, M.B.Ch.B, MRCP, Ph.D., FRCP, senior lecturer at the University of Manchester, a consultant at The Christie NHS Foundation Trust and an investigator on the clinical trial, presented the data in an oral session at the European Hematology Association Congress, which is being held from June 13?16, 2024, in Madrid, Spain. The data presented at EHA include safety findings for all patients in the Phase 1a dose escalation study regardless of diagnosis (n=79) and include efficacy findings for those patients with relapsed or refractory CLL (n=31).

Patients were treated with NX-5948 at doses ranging from 50 mg to 600 mg once daily by oral administration. NX-5948 was well tolerated across all doses evaluated with most common treatment emergent adverse events of purpura/contusion, thrombocytopenia and neutropenia. Among the efficacy evaluable patients with CLL (n=26), NX-5948 treatment resulted in a robust objective response rate (ORR) of 69.2% across all doses tested with responses observed as early as the first scan (8 weeks) and with many patients experiencing deepening of their response with longer time on treatment.

All responses remained ongoing as of the April 17 data cutoff. This cohort of CLL patients was a heavily pretreated population that had received a median of four prior lines of therapy (range = 2?14) including prior covalent BTK inhibitors (96.8%), prior BCL2 inhibitors (90.3%), and prior non-covalent BTK inhibitors (25.8%). At baseline, a large number of patients had mutations associated with BTK inhibitor resistance including mutations in BTK (43.3%) and PLC2G (20.0%).

Poor prognostic features were common including TP53 mutations (46.7%), and two patients (6.5%) had central nervous system (CNS) involvement. Responses were observed across all populations regardless of prior treatment, baseline mutations, or CNS involvement. Dr. Linton also presented an updated case report that detailed the response of one patient who entered the study with CLL with CNS involvement after having undergone three prior therapies, including treatment with a BTK inhibitor.

After daily treatment with 100 mg, and later 300 mg, of NX-5948, the patient exhibited a deepening response approaching complete response criteria by 36 weeks, with elimination of malignant cells in the cerebrospinal fluid (CSF) by 24 weeks. Another case report presented by the company involved a patient who had received eleven prior lines of therapy, including all available BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib). After daily treatment with 200 mg of NX-5948, the patient achieved a response by week 8 which deepened over time and was ongoing with over 6 months of follow up.

NX-5948 is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK. NX-5948 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies including chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL /SLL), diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), primary central nervous system lymphoma (PCNSL) and Waldenström's macroglobulinemia (WM).