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Evaluating NX-5948 for advanced B-cell cancers

A Phase 1, Dose Escalation, and Cohort Expansion Study Evaluating NX-5948, a Bruton's Tyrosine Kinase (BTK) Degrader, in Adults With Relapsed/Refractory B-cell Malignancies

Phase 1 Interventional Nurix Therapeutics, Inc. · NCT05131022

This study is testing a new drug called NX-5948 to see if it can safely help adults with tough-to-treat B-cell cancers feel better.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment572 (estimated)
Ages18 Years and up
SexAll
SponsorNurix Therapeutics, Inc. Industry-sponsored
Drugs / interventionsChimeric antigen receptor, chemotherapy, radiation, prednisone
Locations62 sites (Duarte, California and 61 other locations)
Trial IDNCT05131022 on ClinicalTrials.gov

What this trial studies

This Phase 1 multicenter study aims to assess the safety and anti-cancer activity of NX-5948 in adults with relapsed or refractory B-cell malignancies. The trial consists of a dose escalation phase to determine the optimal dosage and a safety expansion phase involving multiple cohorts of patients with various B-cell malignancies. Participants must have previously undergone at least one or two lines of therapy, depending on their specific condition. The study will also explore the drug's effectiveness in treating specific types of lymphomas and leukemias.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed or refractory B-cell malignancies who have received prior therapies.

Not a fit: Patients with early-stage B-cell malignancies or those who have not received prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced B-cell malignancies who have limited treatment alternatives.

How similar studies have performed: Other studies involving BTK inhibitors and degraders have shown promise, suggesting potential for success with this novel approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

* Age ≥18 years
* Patients in Phase 1a (Dose Escalation) must have histologically confirmed R/R CLL, SLL, DLBCL (subgroups include Richter-transformed DLBCL, germinal center B-cell type, activated B-cell type, high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements, high-grade B-cell lymphomas NOS), FL, MCL, MZL (subtypes include EMZL, MALT, NMZL, SMZL), WM, or PCNSL.
* Patients in Phase 1a must meet the following:

  o For non-PCNSL indications, received at least 2 prior lines of therapy and have no other available therapies known to provide clinical benefit. For PCNSL, received at least 1 prior line of therapy
* Patients in Phase 1b (Safety and Cohort Expansion) must have 1 of the following histologically documented B-cell malignancies, must meet criteria for systemic treatment, and must have received prior therapies and/or molecular features based on details described for each cohort: CLL or SLL, DLBCL, MCL, FL, MZL, WM, or PCNSL/SCNSL.
* Measurable disease per response criteria specific to the malignancy.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (0-2 for patients with PCNSL and secondary CNS involvement).
* Adequate organ and bone marrow function

Key Exclusion Criteria:

* Known or suspected active prolymphocytic leukemia or Richter's transformation to Hodgkin's lymphoma prior to study enrollment
* Prior treatment for the indication under study for anti-cancer intent that includes:

  1. Radiotherapy within 2 weeks of planned start of study drug (excluding limited palliative radiation).
  2. Prior systemic chemotherapy within 2 weeks of planned start of study drug.
  3. Prior monoclonal antibody therapy within 4 weeks of planned start of study drug, except for patients enrolling in Cohort 16 (CLL with secondary wAIHA) where a 16-week washout period is required.
  4. Prior small molecule therapy within 2 weeks or 5 half-lives (whichever is shorter) of planned start of study drug.
  5. Autologous or allogeneic stem cell transplant within 100 days prior to planned start of study drug.
  6. Chimeric antigen receptor (CAR) T-cell therapy within 100 days prior to start of study drug (within 60 days prior to start of study drug for Phase 1b).
  7. Use of systemic corticosteroids outside of dosing limits described below and within 7 days prior to initiation of study treatment excepting those used as prophylaxis for radio diagnostic contrast. Patients with PCNSL/SCNSL: no greater than 40 mg/day prednisone, or equivalent. Patients with PCNSL/SCNSL using greater than 20 mg/day prednisone, or equivalent, must be clinically stable at that dose for 7 days. All other diagnoses: no greater than 20 mg/day prednisone or equivalent.
  8. Use of systemic immunosuppressive drugs other than systemic corticosteroids for any medical condition within 60 days prior to first dose of study drug
  9. Previously treated with a BTK degrader
* Active, uncontrolled autoimmune hemolytic anemia (except for patients enrolling in Cohort 16) or active, uncontrolled autoimmune thrombocytopenia.
* Patient has any of the following within 6 months of planned start of study drug:

  1. Myocardial infarction, unstable angina, unstable symptomatic ischemic heart disease, or placement of a coronary arterial stent
  2. Uncontrolled atrial fibrillation or other clinically significant arrhythmias, conduction abnormalities, or New York Heart Association (NYHA) class III or IV heart failure
  3. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), stroke, or intracranial hemorrhage
  4. Any other significant cardiac condition (e.g., pericardial effusion, restrictive cardiomyopathy, severe untreated valvular stenosis, severe congenital heart disease, or persistent uncontrolled hypertension defined as systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg despite optimal medical management)
* Bleeding diathesis, or other known risk for acute blood loss.
* History of Grade ≥ 2 hemorrhage within 28 days of planned start of study drug.
* Active known concurrent malignancy or malignancy other than the one under study within the past 3 years. (Exceptions include, but are not limited to, patients with more recent history of basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast may enroll if they have undergone curative therapy and have no evidence of disease).

Where this trial is running

Duarte, California and 61 other locations

+12 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Chronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaDiffuse Large B Cell LymphomaFollicular LymphomaMantle Cell LymphomaMarginal Zone LymphomaWaldenstrom MacroglobulinemiaPrimary Central Nervous System Lymphoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.