A Study to Investigate Sonrotoclax Combined With Zanubrutinib Versus Zanubrutinib Alone in Participants With Previously Untreated Chronic Lymphocytic Leukemia

A Multicenter, Open-Label, Phase 2 Study to Investigate the Efficacy and Safety of Sonrotoclax Combined With Zanubrutinib Compared With Zanubrutinib Monotherapy in Adult Patients With Previously Untreated Chronic Lymphocytic Leukemia

The purpose of this study is to support the registration plan of sonrotoclax plus zanubrutinib treatment in participants with previously untreated chronic lymphocytic leukemia (CLL). This study is designed to assess the contribution of sonrotoclax to the efficacy outcome of the combination of zanubrutinib and sonrotoclax.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Sonrotoclax; Drug: Zanubrutinib

Detailed Description

This study will test how effective and safe Sonrotoclax plus Zanubrutinib treatment compared with Zanubrutinib alone in participants with previously untreated chronic lymphocytic leukemia (CLL).

The main goals of the study are to determine how many participants may no longer have evidence of cancer or have some improvement in the signs and symptoms of cancer after treatment and to determine what adverse events, or side effects, patients might experience.

Sonrotoclax is an experimental drug that works by blocking a protein called B-cell lymphoma-2 (Bcl-2). This protein helps certain types of blood tumor cells to survive and grow. 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 CLL disease.

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.

The study will enroll approximately 87 participants who will be randomly assigned by a computer program to receive one of the following treatments: sonrotoclax + zanubrutinib or zanubrutinib.

The study will take place at multiple centers worldwide. The overall time to participate in this study is approximately 5 years.

Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

• Study Type: Interventional
• Enrollment (Estimated): 94
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Florianópolis, Brazil, 88034-000
    • Centro de Pesquisas Oncologicas Cepon
  • Porto AlegreRS, Brazil, 900350-903
    • Hospital de Clínicas de Porto Alegre
  • São Paulo, Brazil, 05652-900
    • Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
  • São Paulo, Brazil, 01401-004
    • Instituto Dor de Pesquisa E Ensino Sao Paulo
• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • The First Peoples Hospital of Changzhou
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200025
      • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University School of Medicine
• Italy
  • Brescia, Italy, 25123
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
  • Florence, Italy, 50134
    • Aou Careggi, Servizio Sanitario Toscana
  • Modena, Italy, 41124
    • Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco
  • Palermo, Italy, 90146
    • Aoor Villa Sofia Cervello
• Poland
  • Katowice, Poland, 40-519
    • Pratia Onkologia Katowice
  • Krakow, Poland, 30-727
    • PRATIA MCM Kraków
  • Lublin, Poland, 20-090
    • Uniwersytecki Szpital Kliniczny Nr 4 W Lublinie
  • Wroclaw, Poland, 50-367
    • Uniwersytecki Szpital Kliniczny Hematology
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Gijón, Spain, 33394
    • Hospital de Cabuenes
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Díaz
• United States
  • Florida
    • Weston, Florida, United States, 33331-3609
      • Cleveland Clinic Florida
  • Georgia
    • Marietta, Georgia, United States, 30060-1152
      • Northwest Georgia Oncology Centers Marietta
  • Illinois
    • Niles, Illinois, United States, 60714-5905
      • Illinois Cancer Specialists (Niles) Usor
  • Maryland
    • Baltimore, Maryland, United States, 21201-1544
      • University of Maryland Greenebaum Comprehensive Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68130-2042
      • Nebraska Cancer Specialists
    • Omaha, Nebraska, United States, 68130-2042
      • Nebraska Cancer Specialists (Satellite Site)
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oncology Associates of Oregon Willamette Valley Cancer Center
  • Texas
    • Dallas, Texas, United States, 75231-7001
      • Texas Oncology Dfw
    • Tyler, Texas, United States, 75702-7522
      • Texas Oncology Tyler
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Utah Cancer Specialists Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Previously untreated adult patient ≥ 18 years with a confirmed diagnosis of CLL.
2. CLL requiring treatment as per pre-defined criteria.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0,1, or 2.
4. Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI).
5. Adequate marrow function.
6. Adequate liver function as indicated by aspartate aminotransferase (AST) alanine aminotransferase (ALT) and serum total bilirubin.
7. Adequate renal function.
8. Life expectancy > 6 months.
9. Signed informed consent and able to comply with the study protocol in the investigator's judgment.
10. Women of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 90 days after the last dose of study drug.

Exclusion Criteria:

1. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
2. Known central nervous system involvement
3. Received previous systemic treatment for CLL
4. Clinically significant cardiovascular disease
5. Severe or debilitating pulmonary disease
6. History of prior malignancy
7. Active fungal, bacterial, and/or viral infection requiring systemic therapy
8. Positive human immunodeficiency virus (HIV) serology (HIVAb) status or serologic status reflecting active hepatitis B or C infection
9. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring treatment
10. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
11. History of stroke or intracranial hemorrhage ≤ 6 months before the first dose of study treatment
12. Unable to swallow capsules or tablets or diseases significantly affecting GI function
13. Hypersensitivity to zanubrutinib, sonrotoclax, or any of its excipients
14. Use of investigational agents within the last 4 weeks before screening
15. Pregnant and lactating females

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: Combination Therapy: Sonrotoclax + Zanubrutinib; Participants will receive sonrotoclax in combination with zanubrutinib daily for a fixed duration of 15 cycles.	Drug: Sonrotoclax; Administered orally; Other Names: BGB-11417; Drug: Zanubrutinib; Administered orally; Other Names: BGB-3111; BRUKINSA
Active Comparator: Arm B: Monotherapy: Zanubrutinib; Participants will receive zanubrutinib monotherapy daily until disease progression or unacceptable toxicity, whichever occurs first.	Drug: Zanubrutinib; Administered orally; Other Names: BGB-3111; BRUKINSA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR)/ Complete Response with Incomplete Bone Marrow Recovery (CRi) Rate	Best CR/CRi rate per the Independent Review Committee (IRC) response assessment using the 2018 International Workshop on Chronic Lymphocytic Leukemia guidelines with modification for treatment-related lymphocytosis for participants with CLL	Month 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Undetectable Minimal Residual Disease at < 10^-4Sensitivity (uMRD4) Rate	uMRD4 rate measured in both peripheral blood and bone marrow aspirate	Month 16
Time to Response (TTR) per IRC and Investigator Response Assessment	TTR is defined as the time from treatment initiation to the first documentation of response	Up to 66 Months
Progression-free Survival (PFS) per Investigator Response Assessment	PFS is defined as the time from the start of treatment to the first documentation of disease progression or death, whichever occurs first	Up to 66 Months
Overall Survival (OS)	OS is defined as the time from treatment initiation to death due to any cause	Up to 66 Months
CR/CRi Rate per Investigator Response Assessment	CR/CRi Rate (CRR) is defined as the percentage of participants with best overall response of CR or CRi	Month 16
Overall Response Rate (ORR) per IRC and Investigator Response Assessment	ORR is defined as the percentage of participants achieving overall response (CR+CRi+partial response [PR]+nodular PR) per the IRC and the investigator response assessment.	Up to 66 Months
Duration of Response (DOR) per Investigator Response Assessment	DOR is defined as the time from first qualifying response (PR, nodular PR, CR,or CRi) until CLL progression or death.	Up to 66 Months
Landmark Progression-free Survival Rate at 24 Months per Investigator Assessment	The 24-month landmark PFS rate is defined as the percentage of participants who remain alive and progression-free at 24 months since the start of treatment	24 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	From first dose of study drug to 30 days after last dose; up to 66 months for Arm A and Arm B

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: October 9, 2024
• First Submitted That Met QC Criteria: October 9, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: CLL
• 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; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; zanubrutinib
• Other Study ID Numbers: BGB-11417-204; 2024-513970-23-00 (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