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NCT07221500PHASE2Recruiting

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)

Nurix Therapeutics, Inc.

Start Date

10/15/2025

Completion Date

10/1/2030

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

NX-5948

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Conditions

Chronic Lymphocytic Leukemia (CLL)Small Lymphocytic Lymphoma (SLL)

Locations

City of Hope

Duarte, California 91010

United States

Colorado Blood Institute

Denver, Colorado 80218

United States

University of Miami

Coral Gables, Florida 33146

United States

Florida Cancer Specialists

Sarasota, Florida 34232

United States

Fort Wayne Oncology and Hematology

Fort Wayne, Indiana 46804

United States

Hematology Oncology of Indiana

Indianapolis, Indiana 46260

United States

University of Iowa

Iowa City, Iowa 52242

United States

Maryland Oncology Hematology

Silver Spring, Maryland 20904

United States

Karmanos Cancer Center

Detroit, Michigan 48201

United States

Duke University

Durham, North Carolina 27705

United States

Novant Health Cancer Institute

Winston-Salem, North Carolina 27103

United States

University of Cincinnati

Cincinnati, Ohio 45221

United States

Oncology Hematology Care

Fairfield, Ohio 45014

United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania 15232

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

Texas Oncology - Center South

Austin, Texas 78705

United States

University of Utah

Salt Lake City, Utah 84112

United States

Virginia Cancer Specialists, PC

Fairfax, Virginia 22031

United States

Oncology & Hematology Associates of Southwest VA

Norfolk, Virginia 23502

United States

Virginia Oncology Associates

Norfolk, Virginia 23502

United States

CHU de Nantes

Nantes, 44000

France

Azienda Ospedaliero-Universitaria di Alessandria SS. Antonio e Biagio e Cesare Arrigo

Alessandria, 15121

Italy

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola

Bologna, 40138

Italy

Ospedale San Raffaele S.r.l.

Milan, 20132

Italy

AUSL della Romagna UO Ematologia

Ravenna, 48121

Italy

Pratia Hematologia Sp. z o.o.

Katowice, 40-519

Poland

Pratia S.A.

Krakow, 30-225

Poland

Aidport Sp. z o.o.

Skorzewo, 60-185

Poland

Pratia Warszawa / Pratia MTZ

Warsaw, 02-172

Poland

Oxford University Hospitals NHS Foundation Trust

Headington, Oxford OX3 9D

United Kingdom

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ

United Kingdom

The Christie NHS Foundation Trust

Manchester, M20 4BX

United Kingdom