RECRUITING

A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies

Conditions

Chronic Lymphocytic Leukemia (CLL)Small Lymphocytic Lymphoma (SLL)Diffuse Large B Cell Lymphoma (DLBCL)Follicular Lymphoma (FL)Mantle Cell Lymphoma (MCL)Marginal Zone Lymphoma (MZL)Waldenstrom Macroglobulinemia (WM)Primary Central Nervous System Lymphoma (PCNSL)BTK Degrader BTK Inhibitor B-Cell Malignancy Lymphoma C481 C481S Bruton's Tyrosine Kinase NX-5948 Targeted Protein Degradation Chimeric Targeting Molecule (CTM)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a first-in-human Phase 1a/1b multicenter, open-label study designed to evaluate the safety and anti-cancer activity of NX-5948 in patients with advanced B-cell malignancies.

Official Title

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

Quick Facts

Study Start:2022-04-13

Study Completion:2027-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05131022

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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: * Patients in Phase 1b (Cohort Expansion) must have 1 of the following histologically documented R/R B-cell malignancies, must meet criteria for systemic treatment, and must have received prior therapies based on indication: 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	* Known or suspected prolymphocytic leukemia or Richter's transformation to Hodgkin's lymphoma at any time preceding 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. Note: Use of intrathecal chemotherapy is allowed per Institutional guidelines. 3. Prior monoclonal antibody therapy within 4 weeks of planned start of study drug. 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 14 days prior to initiation of study treatment excepting those used as prophylaxis for radio diagnostic contrast. Patients with CNSL: no greater than 40 mg/day prednisone, or equivalent, central nervous system lymphoma (CNSL, including both primary and secondary CNSL) patients using greater than 20 mg/day prednisone, or equivalent must be clinically stable at that dose for 14 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 or 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 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).

Inclusion Criteria

Exclusion 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:
* Patients in Phase 1b (Cohort Expansion) must have 1 of the following histologically documented R/R B-cell malignancies, must meet criteria for systemic treatment, and must have received prior therapies based on indication: 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

* Known or suspected prolymphocytic leukemia or Richter's transformation to Hodgkin's lymphoma at any time preceding 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. Note: Use of intrathecal chemotherapy is allowed per Institutional guidelines.
3. Prior monoclonal antibody therapy within 4 weeks of planned start of study drug.
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 14 days prior to initiation of study treatment excepting those used as prophylaxis for radio diagnostic contrast. Patients with CNSL: no greater than 40 mg/day prednisone, or equivalent, central nervous system lymphoma (CNSL, including both primary and secondary CNSL) patients using greater than 20 mg/day prednisone, or equivalent must be clinically stable at that dose for 14 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 or 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 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).

Contacts and Locations

Study Contact

Additional Site Contact Information

CONTACT

+1 (415) 417-3441

NX5948301@nurixtx.com

Principal Investigator

Paula O'Connor, MD

STUDY_DIRECTOR

Nurix Therapeutics, Inc.

Study Locations (Sites)

City of Hope

Duarte, California, 91010

United States

University of California, San Francisco

San Francisco, California, 94143

United States

Yale Cancer Center

New Haven, Connecticut, 06510

United States

University of Miami

Miami, Florida, 33136

United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322

United States

Northwestern University

Chicago, Illinois, 60611

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Duke University Medical Center

Durham, North Carolina, 27705

United States

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219

United States

Cleveland Clinic

Cleveland, Ohio, 44195

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: Nurix Therapeutics, Inc.

Paula O'Connor, MD, STUDY_DIRECTOR, Nurix Therapeutics, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-04-13

Study Completion Date2027-01

Study Record Updates

Study Start Date2022-04-13

Study Completion Date2027-01

Terms related to this study

Keywords Provided by Researchers

BTK Degrader
BTK Inhibitor
B-Cell Malignancy
Lymphoma
C481
C481S
Bruton's Tyrosine Kinase
NX-5948
Targeted Protein Degradation
Chimeric Targeting Molecule (CTM)

Additional Relevant MeSH Terms

Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Diffuse Large B Cell Lymphoma (DLBCL)
Follicular Lymphoma (FL)
Mantle Cell Lymphoma (MCL)
Marginal Zone Lymphoma (MZL)
Waldenstrom Macroglobulinemia (WM)
Primary Central Nervous System Lymphoma (PCNSL)