Clinical trial NCT06970743: A Study of BGB-16673 Compared to Investigator's Choice in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Covalent Bruton Tyrosine Kinase (BTK) Inhibitors
Official title: A Phase 3, Open-Label, Randomized Study of BGB-16673 Compared to Investigator's Choice in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Covalent BTK Inhibitors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Keywords: CLL
SLL
BTK-targeted protein degrader
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2025-05-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the efficacy and safety of BGB-16673 compared with investigator's choice (bendamustine plus rituximab or high-dose methylprednisolone plus rituximab) in participants with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously exposed to covalent Bruton tyrosine kinase inhibitor(s) (cBTKi).

Detailed description: Chronic lymphocytic leukemia and small lymphocytic lymphoma are types of blood cancer that affects people around the world. People with CLL and SLL suffer from enlarged lymph nodes, spleen, or liver, or have symptoms like night sweats, weight loss and fever. They have shorter life expectancy compared to healthy people. There is an urgent need for new treatment to prolong life and control disease-related symptoms.

In this study, participants with R/R CLL or SLL who were previously exposed to a covalent BTKi will receive BGB-16673 or the investigator's choice of bendamustine plus rituximab or high-dose methylprednisolone plus rituximab. The main purpose of this study is to compare the length of time that participants live without their CLL or SLL worsening between those participants who receive BGB-16673 versus the investigator's choice of treatment. Approximately 150 participants will be included in this study in Mainland China and Taiwan. Participants will be randomly allocated to receive either BGB-16673 or the investigator's choice of treatment.

Eligibility criteria: Inclusion Criteria:

1. Confirmed diagnosis of CLL/SLL, requiring treatment, based on 2018 international workshop on chronic lymphocytic leukemia (iwCLL) criteria.
2. Previously received treatment for CLL/SLL with a covalent BTKi.
3. Measurable disease by computer tomography/magnetic resonance imaging for patients with SLL.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
5. Adequate bone marrow function
6. Adequate kidney and liver function
7. Adequate blood clotting function

Exclusion Criteria:

1. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
2. 2. Prior autologous stem cell transplant (unless ≥ 3 months after transplant) or chimeric antigen receptor-T cell (unless ≥ 6 months after cell infusion)
3. History of severe allergic reactions or hypersensitivity to the active ingredient and excipients of study treatment (BGB-16673, bendamustine, or rituximab)
4. Current or history of central nervous system involvement
5. History of ischemic stroke or intracranial hemorrhage within 6 months before first dose of study drug
6. History of confirmed progressive multifocal leukoencephalopathy.
7. Active fungal, bacterial, and/or viral infection requiring parenteral systemic therapy
8. Clinically significant cardiovascular disease

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Progression-Free Survival (PFS) by IRC
timeFrame: Approximately 23 Months
Secondary outcomes:
measure: PFS as Assessed by the Investigator
timeFrame: Approximately 12 Months
measure: Overall Survival (OS)
timeFrame: Approximately 21 Months
measure: Overall Response Rate (ORR) by IRC and Investigator Assessment
timeFrame: Approximately 23 Months
measure: Rate of Partial Response with Lymphocytosis (PR-L) or Higher Determined by Investigator Assessment
timeFrame: Approximately 23 Months
measure: Duration of Response (DOR) by IRC and Investigator Assessment
timeFrame: Approximately 9 Months
measure: Time to Response (TTR) by IRC and Investigator Assessment
timeFrame: Approximately 6 Months
measure: Time to Next Anti-CLL/SLL Treatment (TTNT)
timeFrame: Approximately 14 Months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Approximately 14 Months
measure: Change from baseline in European Organization of Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Chronic Lymphocytic Leukemia Module 17 Items (QLQ-CLL17) Symptom Burden and Physical Condition Scales
timeFrame: Baseline and up to approximately 23 Months
measure: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Questionnaire -Core 30 (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) and Physical Functioning Scales
timeFrame: Baseline and up to approximately 23 Months
Other outcomes:
Locations:
Study officials:
affiliation: BeiGene
name: Study Director Study Director
role: STUDY_DIRECTOR
References: