Tacabrutideg and Sonrotoclax, With Response-Guided Obinutuzumab, for the Treatment of Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Phase 2 Study of Time-Limited BGB-16673 and Sonrotoclax With MRD-Guided Addition of Obinutuzumab for Treatment-Naïve Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
2 other identifiers
interventional
30
1 country
1
Brief Summary
This phase II trial tests how well tacabrutideg and sonrotoclax, with response-guided addition of obinutuzumab, works in treating patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Tacabrutideg is a drug that degrades a protein called Bruton's tyrosine kinase (BTK). By degrading BTK, tacabrutideg inhibits the activation of signaling pathways that help cancer cells survive, inhibiting the growth of cancer cells that express the BTK protein. Sonrotoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving tacabrutideg together with sonrotoclax may kill more cancer cells than giving either drug alone, and giving obinutuzumab after initial treatment with tacabrutideg and sonrotoclax may improve disease response in patients whose CLL or SLL didn't respond completely to initial treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jan 2027
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 15, 2026
CompletedFirst Posted
Study publicly available on registry
October 21, 2026
CompletedStudy Start
First participant enrolled
January 1, 2027
ExpectedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2031
Study Completion
Last participant's last visit for all outcomes
July 1, 2032
October 21, 2026
October 1, 2026
4.5 years
October 15, 2026
October 15, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Proportion of participants who have undetectable measurable residual disease at a sensitivity of 10^-4 (uMRD4)
After completion of cycle 14 (cycle length = 28 days)
Secondary Outcomes (4)
Incidence of treatment-emergent adverse events
Up to 30 days after last treatment
Incidence of discontinuation due to adverse events
Up to completion of 14-20 cycles (cycle length = 28 days)
Proportion of participants who achieve both a complete response (or complete clinical response) and uMRD4
Up to completion of 14-20 cycles (cycle length = 28 days)
Proportion of patients with uMRD4 after addition of obinutuzumab, if needed
After completion of cycles 15-20 (cycle length = 28 days)
Study Arms (1)
Treatment (tacabrutideg, sonrotoclax, obinutuzumab)
EXPERIMENTALPatients receive tacabrutideg PO QD on days 1-28 of cycles 1-14 and sonrotoclax PO QD on days 1-28 of cycles 3-14. Cycles repeat every 28 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients who are MRD positive after cycle 14 continue receiving tacabrutideg PO QD and sonrotoclax PO QD on days 1-28 of cycles 15-20 and also receive obinutuzumab IV on days 8, 9, 15 and 22 of cycle 15 and day 8 of cycles 16-20. Cycles repeat every 28 days for up to 6 additional cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo TTE or MUGA at screening and undergo CT and collection of blood samples throughout the trial.
Interventions
Given PO
Given PO
Given IV
Undergo CT
Undergo TTE
Undergo collection of blood samples
Undergo MUGA
Eligibility Criteria
You may qualify if:
- Age \>= 18 at time of study enrollment who are capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
- Confirmed diagnosis of CLL/SLL by 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
- Meets criteria for treatment for iwCLL criteria
- Measurable disease, as defined by at least one of the following:
- At least one lymph node \> 1.5 cm in longest diameter, as measurable by computed tomography (CT) or magnetic resonance imaging (MRI)
- Clonal lymphocytes \>= 5 x 10\^9/L present on peripheral blood cytometry
- Bone marrow involvement of at least 30% by flow cytometry with peripheral blood cytopenias
- Has not received any other CLL-directed therapy (e.g., must be TN). Patients who have received treatment for the treatment of immune thrombocytopenia or autoimmune hemolytic anemia (e.g. with rituximab or steroids) will be eligible if last treatment was \>= 6 months prior to enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Absolute neutrophil count (ANC) \>= 0.75 x 10\^9/L if bone marrow involvement; otherwise, \>= 1.00 x 10\^9/L
- Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed. Patients must be free from growth factor support as evidenced by an ANC dated \>= 14 days following the most recent administration of peg-filgrastim (or other pegylated myeloid growth factors) and \>= 4 days following the most recent administration of filgrastim or other myeloid growth factors
- Hemoglobin \>= 8.0 g/dL, unless secondary to bone marrow infiltration by the underlying malignancy
- Hemoglobin \>= 80 g/L (independent of growth factor support or transfusion, defined as no growth factor support for \>= 7 days and/or transfusion for \>= 3 days); patients may have hemoglobin \< 80 g/L with or without growth factor or transfusion as above if the reduced hemoglobin is secondary to bone marrow infiltration by the underlying malignancy
- Platelets \>= 50,000/uL
- Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
- +14 more criteria
You may not qualify if:
- Diagnosis of Richter transformation
- Central nervous system disease at time of study enrollment
- Active fungal, bacterial, and/or viral infection requiring parenteral systemic therapy
- Positive serological status reflecting active hepatitis B:
- Presence of hepatitis B virus surface antigen (HBsAg)
- Patients with presence of hepatitis B virus core antibody (HBcAb), in the absence of HBsAg, with detectable hepatitis B virus (HBV) deoxyribonucleic acid (DNA)
- Note:
- Patients with presence of HBcAb but undetectable HBV DNA and who are willing to undergo HBV DNA monitoring every 4 weeks for HBV reactivation are eligible
- Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention
- Positive serological status reflecting active hepatitis C:
- Patients with the presence of hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid (RNA)
- Note:
- Participants must have completed curative anti-viral therapy for HCV at least 4 weeks prior to study enrollment and are willing to undergo HCV RNA monitoring every 4 weeks for HCV reactivation are eligible
- HIV with a detectable viral load or a CD4 count =\< 350 cells/uL at time of screening
- Participants with HIV who do not meet the above criteria are eligible if they are on a stable antiretroviral therapy (ART) regimen (ART must not be strong CYP3A4 inducers) for at least 4 weeks prior to study entry and are compliant with ART are eligible
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- BeOne Medicinescollaborator
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jennifer J. Huang, MD, PhD
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 15, 2026
First Posted
October 21, 2026
Study Start (Estimated)
January 1, 2027
Primary Completion (Estimated)
July 1, 2031
Study Completion (Estimated)
July 1, 2032
Last Updated
October 21, 2026
Record last verified: 2026-10
Data Sharing
- IPD Sharing
- Will not share