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NCT Number: NCT07277231

A Study to Investigate Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Acalabrutinib in Adults With Previously Untreated Chronic Lymphocytic Leukemia

The purpose of this study is to investigate the efficacy and safety of fixed-duration sonrotoclax (also known as BGB-11417) plus zanubrutinib (also known as BGB-3111) (SZ) compared with fixed-duration of venetoclax plus acalabrutinib (AV) in participants with previously untreated chronic lymphocytic leukemia (CLL).

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Blacktown Cancer and Haematology Centre, Blacktown, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Treatment-naïve (TN) adults with confirmed diagnosis of CLL which requires treatment
  • Eastern Cooperative Oncology Group (ECOG) score 0, 1, or 2
  • Measurable disease by Computer Tomography/Magnetic Resonance Imaging
  • Adequate bone marrow and organ function

Exclusion criteria

  • Previous systemic treatment for CLL
  • Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
  • Known central nervous system involvement
  • History of confirmed progressive multifocal leukoencephalopathy (PML)
  • Uncontrolled hypertension or clinically significant cardiovascular disease

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

Treatment and study plan

Sonrotoclax

Drug

Administered orally.

Other names: BGB-11417

Zanubrutinib

Drug

Administered orally.

Other names: BGB-3111, Brukinsa

Acalabrutinib

Drug

Administered orally.

Other names: Calquence

Venetoclax

Drug

Administered orally.

Other names: Venclexta, Venclyxto

Primary outcomes

  1. Progression-Free Survival (PFS) as Determined by Independent Review Committee (IRC)

    Time frame: Up to approximately 70 months

    PFS is defined as the time from the date of randomization to the date of disease progression as determined by IRC or death due to any cause, whichever occurs first.

  2. Rate of Undetectable Minimal Residual Disease at < 10^-4 sensitivity (uMRD4)

    Time frame: Up to approximately 16 months

    Rate of uMRD4 is defined as the percentage of participants that achieved uMRD4 measured in both peripheral blood (PB) and bone marrow aspirate (BMA) at the post-treatment follow-up visit (PTFU1) based on next generation sequencing (NGS).

Secondary outcomes

  1. PFS in High-Risk Participants

    Time frame: Up to approximately 70 months

    PFS is defined as the time from the date of randomization to the date of disease progression as determined by IRC or death due to any cause, whichever occurs first.

  2. Overall Survival (OS)

    Time frame: Up to approximately 70 months

    OS is defined as the time from the date of randomization to the date of death due to any cause.

  3. Overall Response Rate (ORR) as Determined by IRC

    Time frame: Up to approximately 70 months

    ORR is defined as the percentage of participants with a complete response (CR), complete response with incomplete hematopoietic recovery (CRi), nodal partial response (nPR), or partial response (PR), before disease progression, death, or the start of new anti-CLL treatment (whichever is earlier), as assessed by IRC.

  4. Rate of Undetectable Minimal Residual Disease at < 10^-5 sensitivity (uMRD5)

    Time frame: Up to approximately 16 months

    Rate of uMRD5 is defined as the percentage of participants who achieved uMRD5 measured in both PB and BMA at the PTFU1 Visit based on NGS, before disease progression, death, or the start of new anti-CLL treatment (whichever is earlier).

  5. Number of Participants with Adverse Events

    Time frame: Up to approximately 70 months

    Number of participants with treatment-emergent adverse events (TEAEs), adverse events of clinical interest, and serious adverse events (SAEs), including laboratory values, vital signs, and physical examination findings.

  6. PFS Determined by Investigator Assessment

    Time frame: Up to approximately 70 months

    PFS is defined as the time from the date of randomization to the date of disease progression as determined by investigator or death due to any cause, whichever occurs first.

  7. Complete Response Rate (CRR) by IRC and Investigator Assessment

    Time frame: Up to approximately 70 months

    CRR is defined as the percentage of participants with a CR or CRi before disease progression, death, or the start of new anti-CLL treatment (whichever is earlier).

  8. ORR Determined by Investigator Assessment

    Time frame: Up to approximately 70 months

    ORR is defined as the percentage of participants with a complete response or partial response, before disease progression, death, or the start of new anti-CLL treatment (whichever is earlier), as assessed by investigator.

  9. Duration of Response (DOR)

    Time frame: Up to approximately 70 months

    Duration of response (determined by both IRC and investigator assessment) is defined as the time from the first qualifying response (CR, CRi, nPR, or PR) until CLL progression or death. DOR analysis will only include responders.

  10. Time to Next Treatment (TTNT)

    Time frame: Up to approximately 70 months

    TTNT is defined as the time from randomization to the start of the next treatment for CLL.

  11. Change from Baseline in Score on European Organization for Research and Treatment of Cancer (EORTC) Item Library (IL)-409 Questionnaire

    Time frame: At baseline and up to approximately 70 months

    Patient-reported symptoms of global health status (GHS), role functioning, and physical functioning, symptom burden and physical condition/fatigue will be measured using the European Organization for Research and Treatment of Cancer quality of life questionnaire EORTC IL-409 (an itemized version of [EORTC] quality of life questionnaire core 30 [QLQ-C30] and its CLL module CLL17). The EORTC-IL-409 consists of 17 questions answered on a 4-point scale where 1 = Not at all (best) to 4 = Very Much (worst) and 2 global health questions answered on a 7-point scale where 1 = Very poor (worst) to 7 = Excellent (best). Higher scores in GHS and functional scales and lower scores in symptom scales indicate better quality of life.

Study contacts

Contact information is provided by the study sponsor or research team.

Study Director

CONTACT

[email protected]

8778285568

Sponsors and collaborators

Lead sponsor

BeOne Medicines

Industry

Registry information

Official study title

A Phase 3, Open-Label, Randomized Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Acalabrutinib in Patients With Previously Untreated Chronic Lymphocytic Leukemia

Important dates

Study start
2026
Primary completion
2031
Study completion
2031
First posted
Dec 11, 2025
Registry last updated
Jul 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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