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Trial record 2 of 4 for:    nurix

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05131022
Recruitment Status : Recruiting
First Posted : November 23, 2021
Last Update Posted : February 27, 2023
Sponsor:
Information provided by (Responsible Party):
Nurix Therapeutics, Inc.

Brief Summary:
This is a first-in-human dose escalation and cohort expansion multicenter, open-label study designed to evaluate the safety and preliminary efficacy of NX-5948 in patients with advanced B-cell malignancies.

Condition or disease Intervention/treatment Phase
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) Drug: NX-5948 Phase 1

Detailed Description:

There are 2 parts to this study. The phase 1a portion (dose escalation) evaluates the safety and tolerability of NX-5948 in adult patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma (DLBCL) as determined by the Hans algorithm, Richter-transformed DLBCL, high-grade B-cell lymphoma with MYC and B-cell lymphoma 2 [BCL-2] and/or BCL-6 rearrangements, high-grade B-cell lymphomas not otherwise specified, FL (grade 1-3a; eligibility for systemic treatment as determined by the Groupe d'Etude des Lymphomes Folliculaires [GELF] criteria), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL; eligible subtypes include: extranodal MZL [EMZL], mucosa-associated lymphoid tissue [MALT], nodal MZL [NMZL], and splenic MZL [SMZL]), or Waldenströms macroglobulinemia (WM), including any of the diagnoses with central nervous system (CNS) involvement of their disease, as well as primary central nervous system lymphoma (PCNSL) patients. Patients are required to have received at least 2 prior lines of therapy and have no other therapeutic options that are known to provide clinical benefit.

The phase 1b portion (cohort expansion) investigates the efficacy of NX-5948 at the dose selected in Phase 1a in patients with histologically confirmed R/R B-cell malignancy indications who have received at least 2 prior lines of therapy in up to the following 4 cohorts:

  • Cohort A: CLL or SLL with prior exposure to both a Bruton's tyrosine kinase inhibitor (BTKi) and BCL-2 inhibitor, unless previously deemed ineligible for those therapies, including those with secondary CNS involvement of their disease
  • Cohort B: Non-GCB DLBCL with prior exposure to an anthracycline and an anti-CD20 monoclonal antibody (mAb)-based chemo-immunotherapy regimen, including transformed indolent lymphoma (eg, grade 3b/transformed FL), Richter-transformed DLBCL, high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements, high-grade B-cell lymphomas NOS, and patients with secondary CNS involvement of their disease; or MCL with prior exposure to a BTKi and an anti-CD20 mAb-based chemo-immunotherapy regimen including those with secondary CNS involvement of their disease.
  • Cohort C: FL (grade 1-3a) with prior exposure to an anti-CD20 mAb-based chemo-immunotherapy regimen and 1 additional line of therapy; or MZL (EMZL, MALT, NMZL, SMZL) with prior exposure to an anti-CD20 mAb-based chemo-immunotherapy regimen and 1 additional line of therapy; or WM with prior exposure to a BTKi and 1 additional line of therapy; or FL (grade 1-3a), MZL (EMZL, MALT, NMZL, SMZL), and WM patients meeting the above criteria with secondary CNS involvement of their disease.
  • Cohort D: PCNSL patients who have progressed or had no response to at least 2 prior lines of therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 13, 2022
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : May 2024


Arm Intervention/treatment
Experimental: Phase 1a Dose Escalation
Multiple dose levels of NX-5948 to be evaluated; determination of Maximum Tolerated Dose/Phase 1b recommended dose
Drug: NX-5948
Oral NX-5948

Experimental: Phase 1b Cohort A - CLL or SLL
CLL or SLL with prior exposure to both a Bruton's tyrosine kinase inhibitor (BTKi) and BCL-2 inhibitor, unless previously deemed ineligible for those therapies, including those with secondary CNS involvement of their disease.
Drug: NX-5948
Oral NX-5948

Experimental: Phase 1b Cohort B - Non-GCB DLBCL or MCL
Non-GCB DLBCL with prior exposure to an anthracycline and an anti-CD20 monoclonal antibody (mAb)-based chemo-immunotherapy regimen, including transformed indolent lymphoma, Richter-transformed DLBCL, high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements, high-grade B-cell lymphomas NOS, and patients with secondary CNS involvement of their disease; or MCL with prior exposure to a BTKi and an anti-CD20 mAb-based chemo-immunotherapy regimen including those with secondary CNS involvement of their disease.
Drug: NX-5948
Oral NX-5948

Experimental: Phase 1b Cohort C - FL, MZL, or WM
FL with prior exposure to an anti-CD20 mAb-based chemo-immunotherapy regimen and 1 additional line of therapy; or MZL (EMZL, MALT, NMZL, SMZL) with prior exposure to an anti-CD20 mAb-based chemo-immunotherapy regimen and 1 additional line of therapy; or WM with prior exposure to a BTKi and 1 additional line of therapy; or FL, MZL (EMZL, MALT, NMZL, SMZL), and WM patients meeting the above criteria with secondary CNS involvement of their disease.
Drug: NX-5948
Oral NX-5948

Experimental: Phase 1b Cohort D - PCNSL
PCNSL patients who have progressed or had no response to at least 2 prior lines of therapy.
Drug: NX-5948
Oral NX-5948




Primary Outcome Measures :
  1. Number of participants with protocol specified dose-limiting toxicities [ Time Frame: Up to 10 months ]
    Phase 1a

  2. To establish the maximum tolerated dose and/or recommended Phase 1b dose [ Time Frame: Up to 10 months ]
    Phase 1a

  3. To evaluate the anti-tumor activity of NX-5948 at the recommended Phase 1b dose based on overall response rate (ORR) as assessed by the Investigator [ Time Frame: Up to 3 years ]
    Phase 1b

  4. Number of participants with treatment-emergent adverse events (TEAEs); Grade 3, 4, 5 TEAEs, serious adverse events (SAEs), TEAEs leading to study drug discontinuation, deaths due to TEAEs, and all deaths [ Time Frame: Up to 3 years ]
    Phase 1a/1b


Secondary Outcome Measures :
  1. Pharmacokinetic (PK) profile of NX-5948: Maximum Serum Concentration [ Time Frame: Up to 3 years ]
    Phase 1a/1b - Sampling following the first dose, pre- and post-dose at selected cycles and at the end of treatment

  2. Pharmacodynamic (PD) profile of NX-5948: Changes from baseline of BTK levels in B-cells [ Time Frame: Up to 3 years ]
    Phase 1a/1b - Sampling at screening, following the first dose, pre and post-dose at selected cycles and at the end of treatment

  3. Complete response (CR) rate / CR with incomplete marrow recovery as assessed by the Investigator [ Time Frame: Up to 3 years ]
    Phase 1a/1b

  4. Duration of response (DOR) as assessed by the Investigator [ Time Frame: Up to 3 years ]
    Phase 1a/1b

  5. Progression-free survival (PFS) as assessed by the Investigator [ Time Frame: Up to 3 years ]
    Phase 1a/1b

  6. Time to next therapy [ Time Frame: Up to 3 years ]
    Phase 1a/1b



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be ≥18 years of age.
  • Patients in Phase 1a (Dose Escalation) must have histologically confirmed R/R CLL, SLL, non-GCB DLBCL, Richter-transformed DLBCL, high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements, high-grade B-cell lymphomas NOS, FL, MCL, MZL (EMZL, MALT, NMZL, SMZL), or WM, including those with secondary CNS involvement in any disease indication listed or PCNSL.
  • Patients in Phase 1a must meet the following:

    o Received at least 2 prior lines of therapy and have no other therapies known to provide clinical benefit.

  • 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 failed 2 prior lines of therapy: CLL or SLL, Non-GCB DLBCL, MCL, FL, MZL, WM, including those with secondary CNS involvement of their disease for all above indications, or PCNSL.
  • Patients must have radiographically measurable disease per response criteria specific to the malignancy. Target lymph nodes must be > 1.5 cm and extranodal lesions must be ≥ 1.0 cm in longest diameter.
  • 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

Exclusion Criteria:

Key Exclusion Criteria:

  • 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 4 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 4 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 30 days prior to start of study drug for Phase 1b). Must have evidence of B-cell recovery if patient received prior CAR T-cell therapy.
    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) 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 immunosuppressive drugs other than systemic corticosteroids within 30 days prior to first dose of study drug
  • Active, uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia.
  • Patient has any of the following:

    1. Myocardial infarction, unstable angina, unstable symptomatic ischemic heart disease, or placement of a coronary arterial stent within 6 months of planned start of study drug.
    2. Uncontrolled atrial fibrillation or other clinically significant arrhythmias, conduction abnormalities, or New York Heart Association (NYHA) class III or IV heart failure within 6 months of planned start of study drug.
    3. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), stroke, or intracranial hemorrhage within 6 months of planned start of study drug.
    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) within 6 months of planned start of study drug.
  • Bleeding diathesis, or other known risk for acute blood loss.
  • History of Grade ≥ 2 hemorrhage within 28 days of planned start of study drug.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05131022


Contacts
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Contact: Patient Outreach (415) 230-7860 NX5948301@nurixtx.com

Locations
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United Kingdom
St. Bartholomew's Hospital, Barts NHS Trust Recruiting
London, United Kingdom, EC1A 7BE
Sarah Cannon Research Institute UK Recruiting
London, United Kingdom, W1G 6AD
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom, M20 4BX
Oxford University Hospitals NHS Foundation Trust Recruiting
Oxford, United Kingdom, OX3 7LE
University Hospitals Plymouth NHS Trust Recruiting
Plymouth, United Kingdom, PL6 8DH
University Hospital Southampton NHS Foundation Trust Recruiting
Southampton, United Kingdom, SO16 6YD
Royal Marsden NHS Foundation Trust Recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Nurix Therapeutics, Inc.
Investigators
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Study Director: Paula O'Connor, MD Nurix Therapeutics, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Nurix Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05131022    
Other Study ID Numbers: NX-5948-301
First Posted: November 23, 2021    Key Record Dates
Last Update Posted: February 27, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Nurix Therapeutics, Inc.:
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:
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Lymphoma
Neoplasms
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia
Lymphoma, B-Cell
Leukemia, B-Cell
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders