B-cell Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Conditions
Keywords
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Degrader, B-cell malignancy, BTKi, Bexobrutideg, Pirtobrutinib
Brief summary
The study will evaluate the efficacy and safety of NX-5948 (bexobrutideg) versus pirtobrutinib in participants with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who are relapsed or refractory to prior covalent Bruton tyrosine kinase inhibitor (cBTKi) treatment.
Interventions
DRUGNX-5948
Administered orally once daily
DRUGPirtobrutinib
Administered orally once daily per prescribing information
Sponsors
Nurix Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 * Adequate organ and bone marrow function * Confirmed diagnosis of CLL/SLL that meets iwCLL 2018 criteria for diagnosis and systemic treatment * Received at least 1 prior line of therapy for CLL/SLL that included a cBTKi and must have documented disease progression during treatment with, or after discontinuation of, the cBTKi * Participants with SLL must have measurable disease by computed tomography (CT) per iwCLL Key
Exclusion criteria
* Known or suspected prolymphocytic leukemia or Richter's transformation at any time preceding enrollment * Investigational agent or anticancer therapy within 5 half-lives or 14 days (whichever is shorter) prior to planned start of study treatment * Ongoing systemic corticosteroids ≥10 mg/day prednisone or equivalent * Previously treated with a BTK degrader or a noncovalent BTKi * Myocardial infarction, unstable angina, unstable symptomatic ischemic heart disease, placement of a coronary arterial stent, or any other significant cardiac condition within 6 months of planned start of study treatment * Thromboembolic events, stroke, or intracranial hemorrhage within 6 months of planned start of study treatment Note: Other Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) as assessed by Independent Review Committee (IRC) | Up to approximately 3.5 years | Time from randomization to disease progression per 2018 International Workshop on CLL (iwCLL) or death due to any cause, whichever is earlier |
| Objective response rate (ORR) without partial response with lymphocytosis (PR-L) as assessed by IRC | Up to approximately 2.5 years | Percentage of participants with best overall response of complete response (CR)/CR with incomplete marrow recovery (CRi), partial response (PR), or nodular PR, as assessed per 2018 iwCLL guidelines |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Up to approximately 7 years | Time from randomization to death from any cause |
| PFS as assessed by the investigator | Up to approximately 3.5 years | Time from randomization to disease progression or death due to any cause, whichever is earlier |
| Objective response rate (ORR) with and without partial response with lymphocytosis (PR-L) as assessed by IRC and investigator | Up to approximately 3.5 years | Percentage of participants with best overall response of complete response (CR)/CR with incomplete marrow recovery (CRi), partial response (PR) or nodular PR, or PR-L (for ORR with PR-L), as assessed per 2018 International Workshop on CLL (iwCLL) guidelines |
| Duration of response with and without PR-L as assessed by IRC and investigator | Up to approximately 3.5 years | Time from the date of the first response to documented disease progression or death due to any cause, whichever is earlier |
| Time to next anti-CLL/SLL treatment as assessed by IRC and by investigator | Up to approximately 3.5 years | Time from randomization to the date of next anti-CLL/SLL treatment |
| Change from baseline in global health status/quality of life on the European Organization for Research and Treatment of Cancer Quality of Life Cancer Questionnaire C30 with CLL module (EORTC QLQ-C30-CLL17) | Baseline and up to approximately 3.5 years | Percentage of participants with a clinically meaningful change from baseline using the EORTC QLQ-C30-CLL17 questionnaire to assess global health and overall quality of life |
| Change from baseline in EuroQol-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) | Baseline and up to approximately 3.5 years | Percentage of participants with a clinically meaningful change from baseline using the EQ-5D-5L questionnaire to assess health outcomes |
| Number of participants with treatment-emergent adverse events | Up to approximately 3.5 years | — |
| Pharmacokinetic profile of NX-5948 | Up to Cycle 13 Day 1 (each cycle is 28 days) | NX-5948 concentrations in blood samples |
| Number of participants with clinically significant changes from baseline in laboratory parameters | Up to approximately 3.5 years | Laboratory parameters may include hematology, clinical chemistry, and urinalysis |
| Number of participants with clinically significant changes from baseline in vital signs | Up to approximately 3.5 years | Vital signs include blood pressure, heart and respiratory rates, pulse oximetry, and temperature |
Countries
United States
Contacts
CONTACTAdditional Site Contact Information
STUDY_DIRECTORStudy Director
Nurix Therapeutics, Inc.
Outcome results
None listed