Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
Conditions
Keywords
BTK Degrader, BTK Inhibitor, BCL-2 Inhibitor, B-cell Malignancy, Lymphoma, Bruton's Tyrosine Kinase, NX-5948, Targeted Protein Degradation, Chimeric Targeting Molecule (CTM), Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
Brief summary
This is a study for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received treatment with a BTK inhibitor (covalent and non-covalent) and a BCL-2 inhibitor. The main purpose of this study is to test if NX-5948 (bexobrutideg) works to treat patients with CLL/SLL. Participation could last up to 5 years, and possibly longer, if the disease does not progress.
Detailed description
The main purpose of this study is to test if NX-5948 works to treat patients with R/R CLL/SLL. NX-5948 is a BTK degrader and works by destroying the BTK protein to stop all its actions. This is different from a BTK inhibitor which works by blocking only the kinase action of BTK. This study aims to answer these questions: * How well does NX-5948 work to treat patients who have previously received a BTK inhibitor and a BCL-2 inhibitor? * How safe is NX-5948 and can patients take NX-5948 as long as they need to? * What is the amount of NX-5948 in the bloodstream over time when given to patients with CLL/SLL? All patients in the study will receive NX-5948 orally until their cancer gets worse or if there are other reasons to stop taking NX-5948. Patients will have their cancer and other health check-ups regularly while they are taking NX-5948. If a patient's cancer has not gotten worse and they stop taking NX-5948, they will continue to have cancer check-ups until their cancer gets worse.
Interventions
DRUGNX-5948
Oral dose administered once daily. NX-5948 will be given in continuous 28-day cycles.
Sponsors
Nurix Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single Group
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age: ≥ 18 years * Confirmed relapsed/refractory CLL/SLL that meets iwCLL criteria for diagnosis and systemic treatment * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Must have received a covalent BTK inhibitor (BTKi), a non-covalent BTKi, and a BCL-2 inhibitor either in separate lines of therapy or in combination; a line of therapy is considered 2 or more consecutive cycles of a systemic anti-CLL/SLL regimen * Participants with SLL must have measurable disease by radiographic assessment * Adequate organ and bone marrow function * Must sign an informed consent form indicating that he or she understands the purpose of the procedures required for the study and is willing to participate
Exclusion criteria
* Known or suspected prolymphocytic leukemia or Richter's transformation before entering study * Investigational agent or anticancer therapy within 5 half-lives or 14 days (whichever is shorter) before planned start of study drug * Antibody therapy must stop at least 4 weeks before the first dose of study drug * No other systemic anticancer therapy is allowed at the same time as this study; exception: continuation of hormonal therapy for breast and prostate cancer is allowed, if they are not on the list of prohibited concomitant medications in this study * Palliative limited-field radiotherapy within 7 days of the first dose of study or broad field radiotherapy within 28 days of first dose of study drug * Use of systemic corticosteroids \>20 mg/day prednisone or equivalent within the 7 days before start of study drug except for those used as premedication for radio diagnostic contrast * Use of systemic immunosuppressive drugs other than systemic corticosteroids within 60 days before the first dose of study drug * Previously treated with a BTK degrader * Previous chimeric antigen receptor (CAR) T-cell therapy or allogeneic or autologous hematopoietic cell transplant within the past 90 days prior to enrollment * Thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), stroke, or intracranial hemorrhage within 6 months of planned start of study drug Note: Other Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate without partial response with lymphocytosis (PR-L) as determined by an Independent Review Committee (IRC) | Up to approximately 5 years | The percentage of participants with response as determined according to 2018 International Workshop on CLL (iwCLL) guidelines. Response will include complete response (CR)/CR with incomplete marrow recovery (CRi), partial response (PR), and nodular PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate with PR-L as determined by IRC | Up to approximately 5 years | The percentage of participants with response as determined according to 2018 iwCLL guidelines. Response will include CR/CRi, PR, and nodular PR. |
| Objective response rate with and without PR-L as determined by investigator | Up to approximately 5 years | The percentage of participants with response as determined according to 2018 iwCLL guidelines. Response will include CR/CRi, PR, and nodular PR. |
| Duration of response as determined by IRC and by investigator | Up to approximately 5 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 IRC and by investigator | Up to approximately 5 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 |
| Complete response rate as determined by IRC and by investigator | Up to approximately 5 years | The percentage of participants with CR or CRi as determined according to 2018 iwCLL guidelines |
| Time to response as determined by IRC and by investigator | Up to approximately 5 years | Time from the start date of study treatment to the date of the first assessment of a response |
| Overall survival | Up to approximately 5 years | Time from the start date of study treatment to the date of death from any cause |
| Number of participants with treatment-emergent adverse events (TEAEs), Grade 3 or higher TEAEs, serious adverse events, and TEAEs leading to study drug discontinuation | Up to approximately 3 years | — |
| Number of participants with clinically significant changes from baseline in laboratory parameters | Up to approximately 3 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 years | Vital signs include blood pressure, heart and respiratory rates, pulse oximetry, and temperature |
| Pharmacokinetic profile of NX-5948 | Up to approximately 1 year | NX-5948 concentrations in blood samples |
| 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 5 years | Percentage of participants with a clinically meaningful change from baseline using the EORTC QLQ-C30 questionnaire to assess the overall quality of life |
| Change from baseline in EuroQol-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) | Baseline and up to approximately 5 years | Percentage of participants with a clinically meaningful change from baseline using the EQ-5D-5L questionnaire to assess health outcomes |
Countries
France, Italy, Poland, United Kingdom, United States
Contacts
CONTACTAdditional Site Contact Information
STUDY_DIRECTORNurix Study Director
Nurix Therapeutics, Inc.
Outcome results
None listed