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RecruitingInterventionalPhase 2

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)

NCT ID: NCT07221500Sponsor: Nurix Therapeutics, Inc.Last updated: 2026-06-16

Summary

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.

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.

Arms & interventions

  • DrugNX-5948

    Oral dose administered once daily. NX-5948 will be given in continuous 28-day cycles.

Outcome measures

Primary

  • 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.

    Time frame: Up to approximately 5 years

Secondary

  • Objective response rate with PR-L as determined by IRC

    Time frame: Up to approximately 5 years

  • Objective response rate with and without PR-L as determined by investigator

    Time frame: Up to approximately 5 years

  • Duration of response as determined by IRC and by investigator

    Time frame: Up to approximately 5 years

  • Progression-free survival as determined by IRC and by investigator

    Time frame: Up to approximately 5 years

  • Complete response rate as determined by IRC and by investigator

    Time frame: Up to approximately 5 years

  • Time to response as determined by IRC and by investigator

    Time frame: Up to approximately 5 years

  • Overall survival

    Time frame: 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

    Time frame: Up to approximately 3 years

  • Number of participants with clinically significant changes from baseline in laboratory parameters

    Time frame: Up to approximately 3 years

  • Number of participants with clinically significant changes from baseline in vital signs

    Time frame: Up to approximately 3 years

  • Pharmacokinetic profile of NX-5948

    Time frame: Up to approximately 1 year

  • 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)

    Time frame: Baseline and up to approximately 5 years

  • Change from baseline in EuroQol-5 Dimensions, 5-level Questionnaire (EQ-5D-5L)

    Time frame: Baseline and up to approximately 5 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 therapy or in combination; a line of therapy is considered 2 or more consecutive cycles of a systemic anti-CLL/SLL regimen * Participants with SLL must have 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 * Palliative limited-field radiotherapy within 7 days of the first dose of study or broad field radiotherapy within 28 days of first dose of study drug * 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 allogeneic or autologous hematopoietic cell transplant within the past 90 days 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 locations (18)

City of Hope

Duarte, California, 91010

Recruiting

Colorado Blood Institute

Denver, Colorado, 80218

Recruiting

University of Miami

Coral Gables, Florida, 33146

Recruiting

Florida Cancer Specialists

Sarasota, Florida, 34232

Recruiting

Fort Wayne Oncology and Hematology

Fort Wayne, Indiana, 46804

Recruiting

Hematology Oncology of Indiana

Indianapolis, Indiana, 46260

Recruiting

University of Iowa

Iowa City, Iowa, 52242

Recruiting

Maryland Oncology Hematology

Silver Spring, Maryland, 20904

Recruiting

Duke University

Durham, North Carolina, 27705

Recruiting

Novant Health Cancer Institute

Winston-Salem, North Carolina, 27103

Recruiting

University of Cincinnati

Cincinnati, Ohio, 45221

Recruiting

Oncology Hematology Care

Fairfield, Ohio, 45014

Recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203

Recruiting

Texas Oncology - Center South

Austin, Texas, 78705

Recruiting

University of Utah

Salt Lake City, Utah, 84112

Recruiting

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031

Recruiting

Oncology & Hematology Associates of Southwest VA

Norfolk, Virginia, 23502

Recruiting

Virginia Oncology Associates

Norfolk, Virginia, 23502

Recruiting