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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Sonrotoclax; Drug: Zanubrutinib; Drug: Acalabrutinib; Drug: Venetoclax

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 8778285568; Email: clinicaltrials@beonemed.com

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, NSW 2148
      • Recruiting
      • Blacktown Cancer and Haematology Centre
    • Concord, New South Wales, Australia, NSW 2139
      • Recruiting
      • Concord Repatriation General Hospital
    • St Leonards, New South Wales, Australia, NSW 2065
      • Recruiting
      • GenesisCare North Shore
  • Queensland
    • Woolloongabba, Queensland, Australia, QLD 4102
      • Recruiting
      • Princess Alexandra Hospital
  • Victoria
    • Clayton, Victoria, Australia, VIC 3168
      • Recruiting
      • Monash Health
    • Heidelberg, Victoria, Australia, VIC 3084
      • Recruiting
      • Austin Health
    • Malvern, Victoria, Australia, VIC 3144
      • Recruiting
      • Cabrini Hospital Malvern
    • Melbourne, Victoria, Australia, VIC 3004
      • Recruiting
      • The Alfred Hospital
• Brazil
  • Brasília, Brazil, 70390140
    • Recruiting
    • Instituto Dor de Pesquisa E Ensino Distrito Federal
  • Porto Alegre, Brazil, 90110-270
    • Recruiting
    • Centro Gaucho Integrado de Oncologia Hospital Mae de Deus
  • São Paulo, Brazil, 01401-004
    • Recruiting
    • Instituto Dor de Pesquisa E Ensino Sao Paulo
• Canada
  • Québec, Canada, G1J 1Z4
    • Recruiting
    • Chu de Quebec Universite Laval, Hopital de Lenfant Jesus, Centre Integre de Cancerologie (Cic)
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Recruiting
      • Juravinski Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, QC H3t 1E2
      • Recruiting
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H4J 1C5
      • Recruiting
      • Ciusss Nim Hscm
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Recruiting
      • Ciusss de Lestrie Chus
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Zhujiang Hospital of Southern Medical University
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Recruiting
      • The First Affiliated Hospital of Guangxi Medical University
  • Guizhou
    • Guiyang, Guizhou, China, 550002
      • Recruiting
      • Guizhou Provincial Peoples Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Recruiting
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • Henan Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • The Second Xiangya Hospital of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Jiangsu Province Hospital
    • Nantong, Jiangsu, China, 201203
      • Recruiting
      • Affiliated Hospital of Nantong University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The Second Affiliated Hospital of Nanchang University
  • Shaanxi
    • Xi'an, Shaanxi, China, 710004
      • Recruiting
      • The Second Affiliated Hospital of Xian Jiaotong University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200025
      • Recruiting
      • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
  • Sichuan
    • Chengdu, Sichuan, China, 610071
      • Recruiting
      • Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Recruiting
      • Institute of Hematology and Hospital of Blood Disease
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • Recruiting
      • First Affiliated Hospital of Kunming Medical University
• Czechia
  • Ostrava, Czechia, 708 00
    • Recruiting
    • Fakultni nemocnice Ostrava
• France
  • Bordeaux, France, 33000
    • Recruiting
    • Centre de Lutte Contre Le Cancer Institut Bergonie
  • ClermontFerrand, France, 63100
    • Recruiting
    • Chu Clermont Ferrand Therapie Cellulaire and Hematolo
  • Le Mans, France, 72037
    • Recruiting
    • Centre Hospitalier Le Mans
  • Lille, France, 59000
    • Recruiting
    • Hopital Claude Huriez Chu Lille
  • Lyon, France, 69373
    • Recruiting
    • Centre Leon Berard
  • Montpellier, France, 34090
    • Recruiting
    • Chu Montpellier Hopital Saint Eloi
  • Toulouse, France, 31100
    • Recruiting
    • Iuc Toulouse Oncopole
• Germany
  • Deggendorf, Germany, 94469
    • Recruiting
    • Donauisar Klinikum Deggendorf Klinik Fur Onkologie Und Hamatologie
• Italy
  • Florence, Italy, 50134
    • Recruiting
    • Aou Careggi, Servizio Sanitario Toscana
  • Milan, Italy, 20132
    • Recruiting
    • Ospedale San Raffaele
  • Padova, Italy, 35128
    • Recruiting
    • Azienda Ospedaliera Di Padova
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli
• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • Auckland City Hospital
  • Auckland, New Zealand, 0622
    • Recruiting
    • North Shore Hospital
  • Christchurch, New Zealand, 8011
    • Recruiting
    • Health New Zealand Canterbury
  • Dunedin, New Zealand, 9016
    • Recruiting
    • Dunedin Hospital
  • Wellington, New Zealand, 6021
    • Recruiting
    • Wellington Regional Hospital (Ccdhb)
• Poland
  • Katowice, Poland, 40-519
    • Recruiting
    • Pratia Onkologia Katowice
  • Lublin, Poland, 20-090
    • Recruiting
    • Uniwersytecki Szpital Kliniczny nr 4 w Lublinie
  • Wroclaw, Poland, 50-367
    • Recruiting
    • Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu
• Romania
  • Bucureti, Romania, 022328
    • Recruiting
    • Institutul Clinic Fundeni
  • ClujNapoca, Romania, 400015
    • Recruiting
    • Institutul Oncologic Prof Dr Ion Chiricuta Cluj Napoca
• South Korea
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Recruiting
      • Seoul National University Bundang Hospital
  • Seoul Teugbyeolsi
    • SeochoGu, Seoul Teugbyeolsi, South Korea, 06591
      • Recruiting
      • The Catholic University of Korea, Seoul St Marys Hospital
    • SeodaemunGu, Seoul Teugbyeolsi, South Korea, 03722
      • Recruiting
      • Severance Hospital Yonsei University Health System
    • Seoul, Seoul Teugbyeolsi, South Korea, 03080
      • Recruiting
      • Seoul National University Hospital
    • SongpaGu, Seoul Teugbyeolsi, South Korea, 05505
      • Recruiting
      • Asan Medical Center
• Spain
  • Granada, Spain, 18014
    • Recruiting
    • Hospital Universitario Virgen de las Nieves
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Majadahonda, Spain, 28222
    • Recruiting
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Murcia, Spain, 30120
    • Recruiting
    • Hospital Clinico Universitario Virgen de la Arrixaca
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Recruiting
    • University Hospitals Dorset Royal Bournemouth Hospital
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • Kings College Hospital
• United States
  • Washington
    • Seattle, Washington, United States, 98109-4433
      • Recruiting
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Sonrotoclax plus Zanubrutinib; Participants will receive sonrotoclax and zanubrutinib for a fixed duration followed by observation.	Drug: Sonrotoclax; Administered orally.; Other Names: BGB-11417; Drug: Zanubrutinib; Administered orally.; Other Names: Brukinsa; BGB-3111
Active Comparator: Arm B: Venetoclax plus Acalabrutinib; Participants will receive venetoclax and acalabrutinib for a fixed duration followed by observation.	Drug: Acalabrutinib; Administered orally.; Other Names: Calquence; Drug: Venetoclax; Administered orally.; Other Names: Venclexta; Venclyxto

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) as Determined by Independent Review Committee (IRC)	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.	Up to approximately 70 months
Rate of Undetectable Minimal Residual Disease at < 10^-4 sensitivity (uMRD4)	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).	Up to approximately 16 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS in High-Risk Participants	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.	Up to approximately 70 months
Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause.	Up to approximately 70 months
Overall Response Rate (ORR) as Determined by IRC	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.	Up to approximately 70 months
Rate of Undetectable Minimal Residual Disease at < 10^-5 sensitivity (uMRD5)	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).	Up to approximately 16 months
Number of Participants with Adverse Events	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.	Up to approximately 70 months
PFS Determined by Investigator Assessment	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.	Up to approximately 70 months
Complete Response Rate (CRR) by IRC and Investigator Assessment	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).	Up to approximately 70 months
ORR Determined by Investigator Assessment	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.	Up to approximately 70 months
Duration of Response (DOR)	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.	Up to approximately 70 months
Time to Next Treatment (TTNT)	TTNT is defined as the time from randomization to the start of the next treatment for CLL.	Up to approximately 70 months
Change from Baseline in Score on European Organization for Research and Treatment of Cancer (EORTC) Item Library (IL)-409 Questionnaire	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.	At baseline and up to approximately 70 months

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicines

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2026
• Primary Completion (Estimated): February 1, 2031
• Study Completion (Estimated): November 1, 2031

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 2, 2025
• First Posted (Actual): December 11, 2025

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Bruton Tyrosine Kinase Inhibitor; B-cell Lymphoma-2 Inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Lymphocytic, Chronic, B-Cell; zanubrutinib; venetoclax; acalabrutinib
• Other Study ID Numbers: BGB-11417-304; 2025-524366-21-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No