Trial Filter

BETA

An intelligent search tool for clinical trials

Sign In
Back|NCT05131022Recruiting
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

Phase
Phase 1
Sponsor
Nurix Therapeutics, Inc.
Enrollment
572
Timeline
Apr 2022 → Jan 2028
About This Study

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.

Eligibility Criteria

Inclusion Criteria

  • 1Age ≥18 years
  • 2Patients 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.
  • 3Patients in Phase 1a must meet the following:
  • 4o For non-PCNSL indications, received at least 2 prior lines of therapy and have no other available therapies known to provide clinical benefit. For PCNSL, received at least 1 prior line of therapy
  • 5Patients in Phase 1b (Safety and Cohort Expansion) must have 1 of the following histologically documented B-cell malignancies, must meet criteria for systemic treatment, and must have received prior therapies and/or molecular features based on details described for each cohort: CLL or SLL, DLBCL, MCL, FL, MZL, WM, or PCNSL/SCNSL.
  • 6Measurable disease per response criteria specific to the malignancy.
  • 7Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (0-2 for patients with PCNSL and secondary CNS involvement).
  • 8Adequate organ and bone marrow function

Exclusion Criteria

  • 1Known or suspected active prolymphocytic leukemia or Richter's transformation to Hodgkin's lymphoma prior to study enrollment
  • 2Prior treatment for the indication under study for anti-cancer intent that includes:
  • 3Radiotherapy within 2 weeks of planned start of study drug (excluding limited palliative radiation).
  • 4Prior systemic chemotherapy within 2 weeks of planned start of study drug.
  • 5Prior monoclonal antibody therapy within 4 weeks of planned start of study drug, except for patients enrolling in Cohort 16 (CLL with secondary wAIHA) where a 16-week washout period is required.
  • 6Prior small molecule therapy within 2 weeks or 5 half-lives (whichever is shorter) of planned start of study drug.
  • 7Autologous or allogeneic stem cell transplant within 100 days prior to planned start of study drug.
  • 8Chimeric 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).
  • 9Use of systemic corticosteroids outside of dosing limits described below and within 7 days prior to initiation of study treatment excepting those used as prophylaxis for radio diagnostic contrast. Patients with PCNSL/SCNSL: no greater than 40 mg/day prednisone, or equivalent. Patients with PCNSL/SCNSL using greater than 20 mg/day prednisone, or equivalent, must be clinically stable at that dose for 7 days. All other diagnoses: no greater than 20 mg/day prednisone or equivalent.
  • 10Use of systemic immunosuppressive drugs other than systemic corticosteroids for any medical condition within 60 days prior to first dose of study drug
  • 11Previously treated with a BTK degrader
  • 12Active, uncontrolled autoimmune hemolytic anemia (except for patients enrolling in Cohort 16) or active, uncontrolled autoimmune thrombocytopenia.
  • 13Patient has any of the following within 6 months of planned start of study drug:
  • 14Myocardial infarction, unstable angina, unstable symptomatic ischemic heart disease, or placement of a coronary arterial stent
  • 15Uncontrolled atrial fibrillation or other clinically significant arrhythmias, conduction abnormalities, or New York Heart Association (NYHA) class III or IV heart failure
  • 16Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), stroke, or intracranial hemorrhage
  • 17Any 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)
  • 18Bleeding diathesis, or other known risk for acute blood loss.
  • 19History of Grade ≥ 2 hemorrhage within 28 days of planned start of study drug.
  • 20Active known concurrent malignancy or malignancy other than the one under study within the past 3 years. (Exceptions include, but are not limited to, 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).

Locations

61 sites participating in this study

Winship Cancer Institute of Emory University

Atlanta, Georgia 30322

Recruiting

City of Hope

Duarte, California 91010

Recruiting

University of California, San Francisco

San Francisco, California 94143

Recruiting
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →