A Study of NX-5948 in Adults With CLL/SLL Previously Treated With a Bruton's Tyrosine Kinase Inhibitor and a B-cell Lymphoma-2 Inhibitor (DAYBreak CLL-201)

A Single-arm, Phase 2, Open-label, Multicenter Study to Evaluate NX-5948 in Adults With Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Previously Exposed to a Bruton's Tyrosine Kinase Inhibitor (BTKi) and a B-cell Lymphoma-2 Inhibitor (BCL-2i)

This is a study for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received treatment with a BTK inhibitor (covalent and non-covalent) and a BCL-2 inhibitor. The main purpose of this study is to test if NX-5948 (bexobrutideg) works to treat patients with CLL/SLL. Participation could last up to 5 years, and possibly longer, if the disease does not progress.

Study Overview

• Status: Recruiting
• Conditions: Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)
• Intervention / Treatment: Drug: NX-5948

Detailed Description

The main purpose of this study is to test if NX-5948 works to treat patients with R/R CLL/SLL. NX-5948 is a BTK degrader and works by destroying the BTK protein to stop all its actions. This is different from a BTK inhibitor which works by blocking only the kinase action of BTK. This study aims to answer these questions:

• How well does NX-5948 work to treat patients who have previously received a BTK inhibitor and a BCL-2 inhibitor?
• How safe is NX-5948 and can patients take NX-5948 as long as they need to?
• What is the amount of NX-5948 in the bloodstream over time when given to patients with CLL/SLL?

All patients in the study will receive NX-5948 orally until their cancer gets worse or if there are other reasons to stop taking NX-5948. Patients will have their cancer and other health check-ups regularly while they are taking NX-5948. If a patient's cancer has not gotten worse and they stop taking NX-5948, they will continue to have cancer check-ups until their cancer gets worse.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Additional Site Contact Information; Phone Number: 415-417-3418; Email: clinicaltrials@nurixtx.com

Study Locations

• France
  • Nantes, France, 44000
    • Recruiting
    • CHU de Nantes
• Italy
  • Ravenna, Italy, 48121
    • Recruiting
    • AUSL della Romagna UO Ematologia
• Poland
  • Katowice, Poland, 40-519
    • Recruiting
    • Pratia Hematologia Sp. z o.o.
  • Krakow, Poland, 30-225
    • Recruiting
    • Pratia S.A.
  • Skorzewo, Poland, 60-185
    • Recruiting
    • AIDPORT Sp. z o.o.
  • Warsaw, Poland, 02-172
    • Recruiting
    • Pratia Warszawa / Pratia MTZ
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Recruiting
    • The Royal Marsden NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
  • Oxford
    • Headington, Oxford, United Kingdom, OX3 9D
      • Recruiting
      • Oxford University Hospitals NHS Foundation Trust
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Colorado Blood Institute
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
  • Maryland
    • Silver Spring, Maryland, United States, 20904
      • Recruiting
      • Maryland Oncology Hematology
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Novant Health Cancer Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45221
      • Recruiting
      • University of Cincinnati
    • Fairfield, Ohio, United States, 45014
      • Recruiting
      • Oncology Hematology Care
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Austin, Texas, United States, 78705
      • Recruiting
      • Texas Oncology - Center South
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists, PC
    • Norfolk, Virginia, United States, 23502
      • Recruiting
      • Virginia Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: ≥ 18 years
• Confirmed relapsed/refractory CLL/SLL that meets iwCLL criteria for diagnosis and systemic treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Must have received a covalent BTK inhibitor (BTKi), a non-covalent BTKi, and a BCL-2 inhibitor either in separate lines of treatment or in combination
• Measurable disease by radiographic assessment
• Adequate organ and bone marrow function
• Must sign an informed consent form indicating that he or she understands the purpose of the procedures required for the study and is willing to participate

Exclusion Criteria:

• Known or suspected prolymphocytic leukemia or Richter's transformation before entering study

• Investigational agent or anticancer therapy within 5 half-lives or 14 days (whichever is shorter) before planned start of study drug

  • Antibody therapy must stop at least 4 weeks before the first dose of study drug
  • No other systemic anticancer therapy is allowed at the same time as this study; exception: continuation of hormonal therapy for breast and prostate cancer is allowed, if they are not on the list of prohibited concomitant medications in this study
• Radiotherapy within 2 weeks of the first dose of study drug except for focal palliative radiation
• Use of systemic corticosteroids >20 mg/day prednisone or equivalent within the 7 days before start of study drug except for those used as premedication for radio diagnostic contrast
• Use of systemic immunosuppressive drugs other than systemic corticosteroids within 60 days before the first dose of study drug
• Previously treated with a BTK degrader
• Previous chimeric antigen receptor (CAR) T-cell therapy or autologous hematopoietic cell transplant <1 year prior to enrollment
• Thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), stroke, or intracranial hemorrhage within 6 months of planned start of study drug

Note: Other Inclusion/Exclusion criteria may apply as defined in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NX-5948	Drug: NX-5948; Oral dose administered once daily. NX-5948 will be given in continuous 28-day cycles.; Other Names: Bexobrutideg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate without partial response with lymphocytosis (PR-L) as determined by an Independent Review Committee (IRC)	The percentage of participants with response as determined according to 2018 International Workshop on CLL (iwCLL) guidelines. Response will include complete response (CR)/CR with incomplete marrow recovery (CRi), partial response (PR), and nodular PR.	Up to approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response as determined by IRC and by investigator	Time from the date of the first response to the date of documented progressive disease or death due to any cause, whichever is earlier	Up to approximately 5 years
Progression-free survival as determined by IRC and by investigator	Time from the date of the first dose of study drug to the date of documented progressive disease or death due to any cause, whichever is earlier	Up to approximately 5 years
Complete response rate as determined by IRC and by investigator	The percentage of participants with CR or CRi as determined according to 2018 iwCLL guidelines	Up to approximately 5 years
Time to response as determined by IRC and by investigator	Time from the start date of study treatment to the date of the first assessment of a response	Up to approximately 5 years
Overall survival	Time from the start date of study treatment to the date of death from any cause	Up to approximately 5 years
Number of participants with treatment-emergent adverse events (TEAEs), Grade 3 or higher TEAEs, serious adverse events, and TEAEs leading to study drug discontinuation		Up to approximately 3 years
Number of participants with clinically significant changes from baseline in laboratory parameters	Laboratory parameters may include hematology, clinical chemistry, and urinalysis	Up to approximately 3 years
Number of participants with clinically significant changes from baseline in vital signs	Vital signs include blood pressure, heart and respiratory rates, pulse oximetry, and temperature	Up to approximately 3 years
Pharmacokinetic profile of NX-5948	NX-5948 concentrations in blood samples	Up to approximately 1 year
Objective response rate with PR-L as determined by IRC	The percentage of participants with response as determined according to 2018 iwCLL guidelines. Response will include CR/CRi, PR, and nodular PR.	Up to approximately 5 years
Objective response rate with and without PR-L as determined by investigator	The percentage of participants with response as determined according to 2018 iwCLL guidelines. Response will include CR/CRi, PR, and nodular PR.	Up to approximately 5 years
Change from baseline in Global Health Status/Quality of Life on the European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30)	Percentage of participants with a clinically meaningful change from baseline using the EORTC QLQ-C30 questionnaire to assess the overall quality of life	Baseline and up to approximately 5 years
Change from baseline in EuroQol-5 Dimensions, 5-level Questionnaire (EQ-5D-5L)	Percentage of participants with a clinically meaningful change from baseline using the EQ-5D-5L questionnaire to assess health outcomes	Baseline and up to approximately 5 years

Collaborators and Investigators

• Sponsor: Nurix Therapeutics, Inc.
• Investigators: Study Director: Nurix Study Director, Nurix Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): October 1, 2030

Study Registration Dates

• First Submitted: October 24, 2025
• First Submitted That Met QC Criteria: October 24, 2025
• First Posted (Actual): October 28, 2025

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Lymphoma; Chronic Lymphocytic Leukemia (CLL); BTK Inhibitor; Small Lymphocytic Lymphoma (SLL); Bruton's Tyrosine Kinase; BTK Degrader; NX-5948; Targeted Protein Degradation; Chimeric Targeting Molecule (CTM); B-cell Malignancy; BCL-2 Inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell
• Other Study ID Numbers: NX-5948-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No