A Phase 1/2 interventional study of Sonrotoclax and Zanubrutinib in Chronic Lymphocytic Leukemia, CLL and Mantle Cell Lymphoma, sponsored by BeOne Medicines. Recruiting at 20 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by BeOne Medicines · Phase 1/2, Interventional, and Treatment
The purpose of this study is to establish the safety of novel dosing and ramp-up schedules for sonrotoclax in participants with hematological malignancies.
This study will test the safety of novel sonrotoclax dosing with gradual increases of sonrotoclax dose over specified periods until the intended target daily dose is reached. The focus will be on tumor lysis syndrome (TLS) and related toxicity signals.
Sonrotoclax is a drug that works by blocking a protein called B-cell lymphoma-2 (BCL-2). When sonrotoclax blocks BCL-2 it slows down or stops the growth of tumor cells and helps them die. This can lead to improvements in patients with certain malignant diseases including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The start of treatment with BCL-2 inhibitor requires a gradual ramp-up over the first weeks to avoid potential consequences of initial tumor cell breakage and the release of cell content in the bloodstream. Several ramp-up schedules have already been explored, and this study aims to optimize the dosing ramp-up schedule that may be beneficial to patients and caregivers. Zanubrutinib is a commercialized product that works by blocking a protein called Bruton's tyrosine kinase (BTK) and controlling the activity and survival of malignant B cells. Zanubrutinib has received approval in over 65 countries/regions worldwide for the treatment of adult participants with B-cell malignancies, including CLL and MCL.
This study will take place at multiple centers worldwide. The overall time to participate in this study is approximately 17 months for treatment-naïve (TN) CLL participants or approximately 32 months for relapsed/refractory (R/R) MCL participants.
Participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for ≥ 7 days after the last dose of sonrotoclax or 1 month after the last dose of zanubrutinib, whichever is later.
Only for participants with Chronic Lymphocytic Leukemia (CLL):
At least 1 measurable lesion based on computed tomography (CT)/magnetic resonance imaging (MRI) and no history of prolymphocytic leukemia or Richter's transformation.
Only for participants with Mantle cell lymphoma (MCL):
Exclusion Criteria:
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Participants will receive zanubrutinib alone, followed by a combination with sonrotoclax initiated with a ramp-up according to each schedule defined in the protocol. The total treatment duration is of 15 cycles of 28 days (including the phase of sonrotoclax dose ramp-up)
Drug: Sonrotoclax · Drug: Zanubrutinib
Participants will receive zanubrutinib alone, followed by a combination with sonrotoclax initiated with a ramp-up according to each schedule defined in the protocol, for a total of 27 cycles of 28 days (including the phase of sonrotoclax ramp-up), then will continue on zanubrutinib alone until progression of their disease or other treatment discontinuation criteria.
Drug: Sonrotoclax · Drug: Zanubrutinib
Administered orally
Also known as: BGB-11417
Administered orally
Also known as: BGB-3111
Number of Participants who Experience Tumor Lysis Syndrome (TLS)
TLS will be defined by Howard criteria during the schedule-limiting toxicity (SLT) evaluation window
Time frame: Up to approximately 4 months
Number of Participants with Adverse Events (AEs)
Safety will be assessed by monitoring and recording of all treatment emergent adverse events (AEs) graded by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 and tolerability as determined by protocol-defined Cs during the SLT evaluation window
Time frame: Up to approximately 4 months
Number of Participants with Dose Modifications During the SLT Evaluation Window
Time frame: Up to approximately 4 months
Plan to share: Yes — BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.
Supporting information: Study protocol, Sap, Csr
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Leukemia, Lymphocytic, Chronic, B-Cell→
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