Sonrotoclax plus zanubrutinib versus venetoclax plus acalabrutinib for adults with untreated CLL

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

This tests whether a fixed-duration combination of sonrotoclax plus zanubrutinib works as well as or better than venetoclax plus acalabrutinib for adults with previously untreated CLL who need treatment.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 500 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: BeOne Medicines (Industry-sponsored)
• Drugs / interventions: zanubrutinib, acalabrutinib
• Locations: 29 sites (Blacktown, New South Wales and 28 other locations)
• Trial ID: NCT07277231 on ClinicalTrials.gov

What this trial studies

This phase 3, randomized comparison enrolls adults with previously untreated CLL requiring therapy to receive one of two fixed-duration targeted regimens: sonrotoclax (BGB-11417) plus zanubrutinib (BGB-3111) or venetoclax plus acalabrutinib. Participants must have measurable disease, ECOG 0–2, and adequate bone marrow and organ function, with key exclusions for prior systemic CLL therapy, CNS involvement, Richter's transformation, or history of PML. The trial will compare efficacy and safety outcomes with regular imaging and laboratory monitoring during and after the fixed treatment period. Standard supportive care and monitoring for expected toxicities (for example, tumor lysis and cardiovascular events) are included in the protocol.

Who should consider this trial

Good fit: Adults with confirmed, treatment‑naïve CLL who require therapy, have measurable disease, ECOG performance status 0–2, and adequate bone marrow and organ function are the ideal candidates.

Not a fit: Patients with prior systemic CLL therapy, known CNS involvement, Richter's transformation, history of PML, uncontrolled hypertension, or significant cardiovascular disease are unlikely to qualify and may not benefit from participation.

Why it matters

Potential benefit: If successful, this regimen could offer an effective fixed-duration targeted option that achieves deep remissions with a manageable safety profile.

How similar studies have performed: Combinations that include venetoclax and BTK inhibitors have shown strong activity in prior studies, while sonrotoclax-containing regimens are newer and have mainly been explored in earlier‑phase trials.

Eligibility criteria

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.

Where this trial is running

Blacktown, New South Wales and 28 other locations

• Blacktown Cancer and Haematology Centre — Blacktown, New South Wales, Australia (Recruiting)
• Concord Repatriation General Hospital — Concord, New South Wales, Australia (Recruiting)
• Genesiscare North Shore — St Leonards, New South Wales, Australia (Recruiting)
• Princess Alexandra Hospital — Woolloongabba, Queensland, Australia (Recruiting)
• Monash Health — Clayton, Victoria, Australia (Recruiting)
• Austin Health — Heidelberg, Victoria, Australia (Recruiting)
• Cabrini Hospital Malvern — Malvern East, Victoria, Australia (Recruiting)
• The Alfred Hospital — Melbourne, Victoria, Australia (Recruiting)
• Instituto Dor de Pesquisa E Ensino Distrito Federal — Brasília, Brazil (Recruiting)
• Centro Gaucho Integrado de Oncologia Hospital Mae de Deus — Porto Alegre, Brazil (Recruiting)
• Instituto Dor de Pesquisa E Ensino Sao Paulo — São Paulo, Brazil (Recruiting)
• Ciusss Nim Hscm — Montreal, Quebec, Canada (Recruiting)
• Jewish General Hospital — Montreal, Quebec, Canada (Recruiting)
• Ciusss de Lestrie Chus — Sherbrooke, Quebec, Canada (Recruiting)
• Chu de Quebec Universite Laval, Hopital de Lenfant Jesus, Centre Integre de Cancerologie (Cic) — Québec, Canada (Recruiting)
• Zhujiang Hospital of Southern Medical University — Guangzhou, Guangdong, China (Recruiting)
• Jiangsu Province Hospital — Nanjing, Jiangsu, China (Recruiting)
• The Second Affiliated Hospital of Xian Jiaotong University — Xi'an, Shaanxi, China (Recruiting)
• North Shore Hospital — Auckland, New Zealand (Recruiting)
• Auckland City Hospital — Auckland, New Zealand (Recruiting)
• Health New Zealand Canterbury — Christchurch, New Zealand (Recruiting)
• Wellington Regional Hospital (Ccdhb) — Wellington, New Zealand (Recruiting)
• Seoul National University Bundang Hospital — Seongnam-si, Gyeonggi-do, South Korea (Recruiting)
• The Catholic University of Korea, Seoul St Marys Hospital — SeochoGu, Seoul Teugbyeolsi, South Korea (Recruiting)
• Severance Hospital Yonsei University Health System — SeodaemunGu, Seoul Teugbyeolsi, South Korea (Recruiting)
• Seoul National University Hospital — Seoul, Seoul Teugbyeolsi, South Korea (Recruiting)
• Asan Medical Center — SongpaGu, Seoul Teugbyeolsi, South Korea (Recruiting)
• University Hospitals Dorset Royal Bournemouth Hospital — Bournemouth, United Kingdom (Recruiting)
• Kings College Hospital — London, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Study Director

Conditions Chronic Lymphocytic Leukemia; B-cell Lymphoma-2 Inhibitor; Bruton Tyrosine Kinase Inhibitor