A Single-arm, Phase 2, Open-label, Multicenter Study to Evaluate NX-5948 in Adults With Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Previously Exposed to a Bruton's Tyrosine Kinase Inhibitor (BTKi) and a B-cell Lymphoma-2 Inhibitor (BCL-2i)
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.
Arms & interventions
- DrugNX-5948
Oral dose administered once daily. NX-5948 will be given in continuous 28-day cycles.
Outcome measures
Primary
Objective response rate without partial response with lymphocytosis (PR-L) as determined by an Independent Review Committee (IRC)
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.
Time frame: Up to approximately 5 years
Secondary
Objective response rate with PR-L as determined by IRC
Time frame: Up to approximately 5 years
Objective response rate with and without PR-L as determined by investigator
Time frame: Up to approximately 5 years
Duration of response as determined by IRC and by investigator
Time frame: Up to approximately 5 years
Progression-free survival as determined by IRC and by investigator
Time frame: Up to approximately 5 years
Complete response rate as determined by IRC and by investigator
Time frame: Up to approximately 5 years
Time to response as determined by IRC and by investigator
Time frame: Up to approximately 5 years
Overall survival
Time frame: Up to approximately 5 years
Number of participants with treatment-emergent adverse events (TEAEs), Grade 3 or higher TEAEs, serious adverse events, and TEAEs leading to study drug discontinuation
Time frame: Up to approximately 3 years
Number of participants with clinically significant changes from baseline in laboratory parameters
Time frame: Up to approximately 3 years
Number of participants with clinically significant changes from baseline in vital signs
Time frame: Up to approximately 3 years
Pharmacokinetic profile of NX-5948
Time frame: Up to approximately 1 year
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)
Time frame: Baseline and up to approximately 5 years
Change from baseline in EuroQol-5 Dimensions, 5-level Questionnaire (EQ-5D-5L)
Time frame: Baseline and up to approximately 5 years
Eligibility criteria
Study locations (18)
City of Hope
Duarte, California, 91010
Colorado Blood Institute
Denver, Colorado, 80218
University of Miami
Coral Gables, Florida, 33146
Florida Cancer Specialists
Sarasota, Florida, 34232
Fort Wayne Oncology and Hematology
Fort Wayne, Indiana, 46804
Hematology Oncology of Indiana
Indianapolis, Indiana, 46260
University of Iowa
Iowa City, Iowa, 52242
Maryland Oncology Hematology
Silver Spring, Maryland, 20904
Duke University
Durham, North Carolina, 27705
Novant Health Cancer Institute
Winston-Salem, North Carolina, 27103
University of Cincinnati
Cincinnati, Ohio, 45221
Oncology Hematology Care
Fairfield, Ohio, 45014
SCRI Oncology Partners
Nashville, Tennessee, 37203
Texas Oncology - Center South
Austin, Texas, 78705
University of Utah
Salt Lake City, Utah, 84112
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
Oncology & Hematology Associates of Southwest VA
Norfolk, Virginia, 23502
Virginia Oncology Associates
Norfolk, Virginia, 23502