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, Venetoclax, Obinutuzumab, Rituximab
Brief summary
The study will evaluate NX-5948 (bexobrutideg) in combination with venetoclax with or without an anti-CD20 antibody (rituximab or obinutuzumab) in second-line or higher (2L+) relapsed/refractory (R/R) or first-line (1L) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Detailed description
Bexobrutideg is an investigational drug designed to target a protein called Bruton tyrosine kinase (BTK), which helps cancer cells grow in certain blood cancers like CLL and SLL. Bexobrutideg is a protein degrader, which means it finds and destroys the BTK in the cell. Venetoclax, rituximab, and obinutuzumab are approved medications that are used to treat CLL/SLL. The study will look at: * How safe bexobrutideg is for patients with CLL or SLL when taken with these other treatments * The effects of bexobrutideg in the body when taken with these other treatments * How well bexobrutideg treats CLL or SLL when taken with these other treatments
Interventions
DRUGNX-5948
Administered orally once daily as a capsule
DRUGvenetoclax
Administered orally once daily as a tablet per prescribing information
DRUGrituximab
Administered as an intravenous (IV) infusion per prescribing information
DRUGobinutuzumab
Administered as an IV infusion per prescribing information
Sponsors
Nurix Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
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 * Measurable disease by computed tomography (CT) per iwCLL * For R/R CLL/SLL, prior therapy must include treatment with a Bruton tyrosine kinase inhibitor (BTKi) * For 1L CLL/SLL, confirmed previously untreated CLL/SLL with a clinical indication for systemic treatment that meets iwCLL criteria * Must sign an informed consent form indicating understanding of the study purpose and procedures and willingness to participate 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 * Radiotherapy within 2 weeks of the first dose of study drug except for focal palliative radiation * Use of systemic corticosteroids (\>20 mg/day prednisone or equivalent) within the 7 days prior to initiation of study treatment excepting those used as prophylaxis for radiodiagnostic contrast * Previously treated with a BTK degrader * Previously treated with a BCL-2 inhibitor (BCL-2i) unless eligible for retreatment * Known central nervous system (CNS) lymphoma or leukemia * 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 |
|---|---|
| Number of participants with treatment-emergent adverse events | Up to approximately 7 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in European Quality of Life 5-Dimensions, 5-Level Questionnaire (EQ-5D-5L) | Baseline and up to approximately 27 months | Percentage of participants with a clinically meaningful change from baseline using the EQ-5D-5L questionnaire to assess health outcomes |
| Overall survival | Up to approximately 7 years | Time from the start date of study treatment to the date of death from any cause |
| Pharmacokinetic profile of NX-5948 | Up to approximately 1 year | NX-5948 concentrations in blood samples |
| Complete response rate as determined by investigator | Up to approximately 7 years | The percentage of participants with CR or CRi as determined according to 2018 iwCLL guidelines; includes CR + CRi for participants with CLL. |
| Time to response as determined by investigator | Up to approximately 7 years | Time from the start date of study treatment to the date of the first assessment of a response |
| Objective response rate as determined by investigator | Up to approximately 7 years | The percentage of participants with response as determined according to 2018 iwCLL guidelines; response includes complete response (CR)/CR with incomplete marrow recovery (CRi), partial response (PR), PR with lymphocytosis (PR-L), and nodular PR |
| Duration of response as determined by investigator | Up to approximately 7 years | Time from the date of the first response to the date of documented progressive disease or death due to any cause, whichever is earlier |
| Progression-free survival as determined by investigator | Up to approximately 7 years | Time from the date of the first dose of study drug to the date of documented progressive disease or death due to any cause, whichever is earlier |
| Change from baseline in Global Health Status/Quality of Life on the European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30) | Baseline and up to approximately 27 months | Percentage of participants with a clinically meaningful change from baseline using the EORTC QLQ-C30 questionnaire to assess the overall quality of life |
| Pharmacokinetic profile of venetoclax | Up to approximately 1 year | Venetoclax concentrations in blood samples |
Countries
United States
Contacts
CONTACTAdditional Site Contact Information
STUDY_DIRECTORStudy Director
Nurix Therapeutics, Inc.
Outcome results
None listed