A Study to Investigate Efficacy and Safety of BCL2 Inhibitor Sonrotoclax as Monotherapy and in Combination With Zanubrutinib in Adults With Waldenström Macroglobulinemia

An Open-Label, Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of the BCL2 Inhibitor Sonrotoclax (BGB-11417) as Monotherapy and in Combination With Zanubrutinib (BGB-3111) in Patients With Waldenström Macroglobulinemia

This study will evaluate the safety and efficacy of the BCL2 inhibitor sonrotoclax (BGB-11417) in participants with relapsed/refractory Waldenström's Macroglobulinemia (R/R WM) and in combination with zanubrutinib in adult participants with previously untreated WM.

Study Overview

• Status: Active, not recruiting
• Conditions: Waldenstrom Macroglobulinemia; Waldenstrom's Macroglobulinemia Recurrent; Waldenstrom's Macroglobulinemia Refractory
• Intervention / Treatment: Drug: Sonrotoclax; Drug: Zanubrutinib

Detailed Description

This study will test whether sonrotoclax (BGB-11417) can be used to improve outcomes in participants with Waldenström's Macroglobulinemia (WM) both when used alone in those who have not responded well to conventional treatments and when used in combination with zanubrutinib in those who have not yet received treatment. The main goals of the study are to determine how many participants 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, participants might experience.

BCL2 is a key protein involved in cell death, and abnormal levels of BCL2 are associated with many cancers. Blocking the action of BCL2 proteins is a promising approach with potential therapeutic benefits in participants with different types of cancers, including WM. This study will enroll approximately 105 participants. All participants will receive sonrotoclax orally as a tablet.

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

Note: 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 (Actual): 114
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, NSW 2139
      • Concord Repatriation General Hospital
    • St Leonards, New South Wales, Australia, NSW 2065
      • GenesisCare North Shore
  • Queensland
    • Woolloongabba, Queensland, Australia, QLD 4102
      • Princess Alexandra Hospital
  • South Australia
    • Bedford PK, South Australia, Australia, SA 5042
      • Flinders Medical Centre
  • Victoria
    • Clayton, Victoria, Australia, VIC 3168
      • Monash Health
    • Fitzroy, Victoria, Australia, VIC 3065
      • St Vincents Hospital Melbourne
  • Western Australia
    • Nedlands, Western Australia, Australia, WA 6009
      • Linear Clinical Research
    • Perth, Western Australia, Australia, WA 6000
      • Royal Perth Hospital
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • North Vancouver, British Columbia, Canada, V7L 2L7
      • Lions Gate Hospital Chemotherapy Clinic
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Qeii Health Science Center
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
• China
  • Fujian
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial Peoples Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
  • Jiangsu
    • Yancheng, Jiangsu, China, 224006
      • Yancheng First Peoples Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110134
      • Shengjing Hospital of China Medical Universityshenbei Branch
  • Shandong
    • Qingdao, Shandong, China, 266000
      • The Affiliated Hospital of Qingdao University Branch South
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Affiliated Zhongshan Hospital of Fudan University
  • Shanxi
    • Datong, Shanxi, China, 037008
      • The Third Peoples Hospital of Datong
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Institute of Hematology and Hospital of Blood Disease
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University School of Medicine
    • Jiaxing, Zhejiang, China, 314001
      • The First hospital of Jiaxing
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University
• France
  • Amiens, France, 80054
    • Centre Hospitalier Universitaire Damiens Hopital Sud
  • Clermontferrand, France, 63100
    • Chu Clermont Ferrand Therapie Cellulaire and Hematolo
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Paris, France, 75013
    • Hôpital de la Pitié Salpêtrière
  • PierreBenite, France, 69495
    • Chu Hopital Lyon Sud
  • Reims, France, 51100
    • Hopital Robert Debre
• Greece
  • Athens, Greece, 115 28
    • General Hospital of Athens Alexandra
• Italy
  • Bologna, Italy, 40138
    • Irccs Azienda Ospedaliero Universitaria Bologna
  • Brescia, Italy, 25123
    • Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia
  • Milan, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Pavia, Italy, 27100
    • Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Udine, Italy, 33100
    • Azienda Sanitaria Universitaria Friuli Centrale Presidio Ospedaliero Universitario Santa Maria Del
• Spain
  • Barcelona, Spain, 8036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall Dhebron
  • Barcelona, Spain, 08908
    • Institut Catala Doncologia
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Terrassa, Spain, 8221
    • Hospital Universitari Mutua Terrassa
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • University Hospitals Dorset
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Headington, United Kingdom, OX3 7LE
    • Churchill Hospital Oxford University Hospital Nhs Trust
  • Inverness, United Kingdom, IV2 3BW
    • Nhs Highland
  • Leeds, United Kingdom, LS9 7TF
    • St Jamess University Hospital
  • London, United Kingdom, NW1 2PG
    • University College Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie Nhs Foundation Trust Manchester
  • Plymouth, United Kingdom, PL6 8DH
    • Plymouth Hospitals Nhs Trust
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Nhs Foundation Royal Marsden Hospital
• United States
  • California
    • Duarte, California, United States, 91010-3012
      • City of Hope National Medical Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007-2113
      • MedStar Georgetown University Hospital
  • Florida
    • Miami, Florida, United States, 33136-2107
      • University of Miami
  • Illinois
    • Warrenville, Illinois, United States, 60555-3269
      • Northwestern Medicine Cancer Center
  • Iowa
    • Waukee, Iowa, United States, 50263
      • Mission Cancer and Blood
  • Maryland
    • Baltimore, Maryland, United States, 21201-1544
      • University of Maryland Greenebaum Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5418
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Mayo Clinic Rochester
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401-7233
      • Hattiesburg Hematology and Oncology Clinic
  • New York
    • New York, New York, United States, 10065-6800
      • Memorial Sloan Kettering Cancer Center Mskcc
  • North Carolina
    • Charlotte, North Carolina, United States, 28204-2990
      • Atrium Health Levine Cancer Institute (Lci)
  • Ohio
    • Columbus, Ohio, United States, 43210-1280
      • Ohio State University Comprehensive Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390-7208
      • UT southwestern Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112-5550
      • Huntsman Cancer Institute
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Clinical and definitive histologic diagnosis of WM.
• Meeting ≥ 1 criterion for treatment according to consensus panel criteria from the 2nd International Workshop on Waldenström's Macroglobulinemia (IWWM).
• For Cohorts 1-3, refractory or relapsed disease at study entry unless participants had intolerance to the most recent therapy. Refractory disease is defined as not attaining at least a major response, or progressing while on or within 6 months of completing therapy. Relapsed disease is defined as attaining at least a major response to therapy and meeting the criteria for disease progression beyond 6 months after completing therapy.
• For Cohort 4, patients must not have received prior therapy for WM (except for plasmapheresis).
• Adequate organ function.

Exclusion Criteria:

• Central nervous system (CNS) involvement by WM.
• Transformation to aggressive lymphoma, such as diffuse large B-cell lymphoma.
• History of other malignancies ≤ 2 years before study entry.
• Uncontrolled active systemic infection or recent infection requiring parenteral antimicrobial therapy that was completed ≤ 14 days before the first dose of the study drug.

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants with R/R disease to both Bruton tyrosine kinase (BTK) inhibitor and anti-CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor will receive sonrotoclax at a standard dose, given orally once daily.	Drug: Sonrotoclax; Administered orally as a tablet.; Other Names: BGB-11417
Experimental: Cohort 2; Participants with R/R disease to anti-CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor and were intolerant to BTK inhibitor will receive sonrotoclax at a standard dose, given orally once daily.	Drug: Sonrotoclax; Administered orally as a tablet.; Other Names: BGB-11417
Experimental: Cohort 3; Participants with R/R disease to a BTK inhibitor treatment and are unsuitable for chemoimmunotherapy will receive sonrotoclax at a standard dose, given orally once daily.	Drug: Sonrotoclax; Administered orally as a tablet.; Other Names: BGB-11417
Experimental: Cohort 4; Participants with previously untreated WM will receive sonrotoclax and zanubrutinib combination therapy for a fixed duration.	Drug: Sonrotoclax; Administered orally as a tablet.; Other Names: BGB-11417; Drug: Zanubrutinib; Administered orally as a capsule.; Other Names: BGB-3111; BRUKINSA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1: Major Response Rate (MRR)	MRR is defined as the percentage of participants achieving partial response (PR) or better, as assessed by the Independent Review Committee (IRC) per the 11th International Workshop on Waldenström Macroglobulinemia (IWWM-11) WM response criteria.	Up to approximately 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants reporting adverse events	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory abnormalities, physical examination results, and vital signs.	Up to approximately 5 years
Cohorts 1, 2, and 3: Duration of Major Response (DoMR) as assessed by the IRC	DoMR is defined as the time from first determination of major response until first documentation of progression or death, whichever occurs first.	Up to approximately 5 years
All Cohorts: DoMR as assessed by the Investigator	DoMR is defined as the time from first determination of major response until first documentation of progression or death, whichever occurs first.	Up to approximately 5 years
Cohorts 1, 2, and 3: Complete Response (CR) + Very Good Partial Response (VGPR) as assessed by the IRC	CR + VGPR is defined as the percentage of participants who achieve CR or VGPR.	Up to approximately 5 years
All Cohorts: CR + VGPR as assessed by the Investigator	CR + VGPR is defined as the percentage of participants who achieve CR or VGPR.	Up to approximately 5 years
Cohorts 1, 2, and 3: Overall Response Rate (ORR) as assessed by the IRC	ORR is defined as the percentage of participants with minor response (MR) or better.	Up to approximately 5 years
All cohorts: ORR as assessed by the investigator	ORR is defined as the percentage of participants with MR or better.	Up to approximately 5 years
Cohorts 1, 2, and 3: Duration of Response (DOR) as assessed by the IRC	DOR is defined as the time from first determination of response until first documentation of progression or death, whichever occurs first.	Up to approximately 5 years
All Cohorts: DOR as assessed by the investigator	DOR is defined as the time from first determination of response until first documentation of progression or death, whichever occurs first.	Up to approximately 5 years
Cohorts 1, 2, and 3: Progression-Free Survival (PFS)	PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the IRC and by the investigator.	Up to approximately 5 years
Cohorts 1, 2, and 3: Time to major response as assessed by the IRC	Time to major response is defined as the time from start of study treatment to the first documentation of major response.	Up to approximately 5 years
All Cohorts: Time to major response as assessed by the investigator	Time to major response is defined as the time from start of study treatment to the first documentation of major response.	Up to approximately 5 years
Cohorts 1, 2, and 3: Overall Survival (OS)	OS is defined as the time from first study drug administration to the date of death due to any cause.	Up to approximately 5 years
Cohorts 2 and 3: MRR as assessed by the IRC	MRR is defined as the percentage of participants achieving PR or better.	Up to approximately 5 years
All Cohorts: MRR as assessed by the Investigator	MRR is defined as the percentage of participants achieving PR or better.	Up to approximately 5 years
Cohort 4: Time to next treatment	Defined as the time from the start of treatment to the start of first subsequent therapy for WM.	Up to approximately 5 years
All Cohorts: Change from Baseline in Health-Related Quality of Life (HRQoL): NFLymSI-18 Disease-related Symptoms-Physical and Treatment-Related Side Effects Subscales	HRQoL based on participant-reported outcomes using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index - 18 Item (NFLymSI-18) Version 4. The questionnaire contains 18 items, each of which utilizes a Likert scale with 5 possible responses ranging from 0 'Not at all' to 4 'Very much' and is divided into a total score.	Baseline and approximately months 7, 13, 19, and 25

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2023
• Primary Completion (Estimated): September 22, 2026
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: July 11, 2023
• First Submitted That Met QC Criteria: July 18, 2023
• First Posted (Actual): July 19, 2023

Study Record Updates

• Last Update Posted (Estimated): January 2, 2026
• Last Update Submitted That Met QC Criteria: December 30, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Lymphoma; Waldenström's macroglobulinemia; BGB-11417; Waldenstrom's Macroglobulinemia Recurrent; Waldenstrom's Macroglobulinemia Refractory; BCL-2i
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Lymphoma; Waldenstrom Macroglobulinemia; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; zanubrutinib
• Other Study ID Numbers: BGB-11417-203; U1111-1291-4524 (Registry Identifier: World Health Organization); CTR20232718 (Registry Identifier: ChinaDrugTrials); 2023-503235-18-00 (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