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

Last updated: July 3, 2025
Sponsor: BeiGene
Overall Status: Active - Recruiting

Phase

2

Condition

Waldenstrom Macroglobulinemia

Leukemia

Lymphoproliferative Disorders

Treatment

Zanubrutinib

Sonrotoclax

BGB-11417

Clinical Study ID

NCT05952037
BGB-11417-203
2023-503235-18-00
U1111-1291-4524
2023-503235-18
CTR20232718
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

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 participantshad intolerance to the most recent therapy. Refractory disease is defined as notattaining at least a major response, or progressing while on or within 6 months ofcompleting therapy. Relapsed disease is defined as attaining at least a majorresponse to therapy and meeting the criteria for disease progression beyond 6 monthsafter completing therapy.

  • For Cohort 4, patients must not have received prior therapy for WM (except forplasmapheresis).

  • Adequate organ function.

Exclusion

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 parenteralantimicrobial therapy that was completed ≤ 14 days before the first dose of thestudy drug.

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

Study Design

Total Participants: 105
Treatment Group(s): 3
Primary Treatment: Zanubrutinib
Phase: 2
Study Start date:
September 28, 2023
Estimated Completion Date:
August 31, 2028

Study 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.

Connect with a study center

  • Concord Repatriation General Hospital

    Concord, New South Wales 2139
    Australia

    Active - Recruiting

  • Genesiscare North Shore

    St Leonards, New South Wales 2065
    Australia

    Active - Recruiting

  • Princess Alexandra Hospital

    Brisbane, Queensland 4102
    Australia

    Site Not Available

  • Princess Alexandra Hospital

    Woolloongabba, Queensland 4102
    Australia

    Active - Recruiting

  • Flinders Medical Centre

    Bedford PK, South Australia 5042
    Australia

    Active - Recruiting

  • Monash Health

    Clayton, Victoria 3168
    Australia

    Active - Recruiting

  • St Vincents Hospital Melbourne

    Fitzroy, Victoria 3065
    Australia

    Active - Recruiting

  • Linear Clinical Research

    Nedlands, Western Australia 6009
    Australia

    Active - Recruiting

  • Royal Perth Hospital

    Perth, Western Australia 6000
    Australia

    Active - Recruiting

  • Cross Cancer Institute

    Edmonton, Alberta T6G 1Z2
    Canada

    Active - Recruiting

  • Lions Gate Hospital Chemotherapy Clinic

    North Vancouver, British Columbia V7L 2L7
    Canada

    Active - Recruiting

  • Qeii Health Science Center

    Halifax, Nova Scotia B3H 2Y9
    Canada

    Active - Recruiting

  • Princess Margaret Cancer Centre

    Toronto, Ontario M5G 2M9
    Canada

    Active - Recruiting

  • The First Affiliated Hospital of Xiamen University

    Xiamen, Fujian 361003
    China

    Active - Recruiting

  • Guangdong Provincial Peoples Hospital

    Guangzhou, Guangdong 510080
    China

    Active - Recruiting

  • Henan Cancer Hospital

    Zhengzhou, Henan 450000
    China

    Active - Recruiting

  • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology

    Wuhan, Hubei 430030
    China

    Active - Recruiting

  • Yancheng First Peoples Hospital

    Yancheng, Jiangsu 224006
    China

    Active - Recruiting

  • Shengjing Hospital Affiliated of China Medical University

    Shenyang, Liaoning 110022
    China

    Active - Recruiting

  • Shengjing Hospital of China Medical University

    Shenyang, Liaoning 110004
    China

    Active - Recruiting

  • Shengjing Hospital of China Medical Universityshenbei Branch

    Shenyang, Liaoning 110134
    China

    Active - Recruiting

  • The Affiliated Hospital of Qingdao University Branch South

    Qingdao, Shandong 266000
    China

    Active - Recruiting

  • Affiliated Zhongshan Hospital of Fudan University

    Shanghai, Shanghai 200032
    China

    Active - Recruiting

  • The Third Peoples Hospital of Datong

    Datong, Shanxi 037008
    China

    Active - Recruiting

  • Institute of Hematology and Hospital of Blood Disease

    Tianjin, Tianjin 300020
    China

    Active - Recruiting

  • The First Affiliated Hospital, Zhejiang University School of Medicine

    Hangzhou, Zhejiang 310003
    China

    Active - Recruiting

  • The First Hospital of Jiaxing

    Jiaxing, Zhejiang 314001
    China

    Active - Recruiting

  • The First Affiliated Hospital of Wenzhou Medical University

    Wenzhou, Zhejiang 325000
    China

    Active - Recruiting

  • Centre Hospitalier Universitaire Damiens Hopital Sud

    Amiens Cedex, 80054
    France

    Active - Recruiting

  • Chu Clermont Ferrand Therapie Cellulaire and Hematolo

    Clermont Ferrand, 63003
    France

    Site Not Available

  • Chu Clermont Ferrand Therapie Cellulaire and Hematolo

    Clermontferrand, 63100
    France

    Active - Recruiting

  • Institut Paoli Calmettes

    Marseille, 13009
    France

    Active - Recruiting

  • Hopital de La Pitie Salpetriere

    Paris, 75013
    France

    Active - Recruiting

  • Chu Hopital Lyon Sud

    PierreBenite, 69495
    France

    Active - Recruiting

  • Hopital Robert Debre

    Reims, 51100
    France

    Active - Recruiting

  • Hopital Robert Debre

    Reims Cedex, 51056
    France

    Site Not Available

  • General Hospital of Athens Alexandra

    Athens, 115 28
    Greece

    Active - Recruiting

  • Irccs Azienda Ospedaliero Universitaria Bologna

    Bologna, 40138
    Italy

    Active - Recruiting

  • Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

    Brescia, 25123
    Italy

    Active - Recruiting

  • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

    Milano, 20162
    Italy

    Active - Recruiting

  • Istituto Europeo Di Oncologia

    Milano, 20141
    Italy

    Active - Recruiting

  • Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi

    Pavia, 27100
    Italy

    Active - Recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli

    Roma, 00168
    Italy

    Active - Recruiting

  • Azienda Sanitaria Universitaria Friuli Centrale Presidio Ospedaliero Universitario Santa Maria Del

    Udine, 33100
    Italy

    Active - Recruiting

  • Hospital Clinic de Barcelona

    Barcelona, 8036
    Spain

    Active - Recruiting

  • Hospital Universitario Vall Dhebron

    Barcelona, 08035
    Spain

    Active - Recruiting

  • Institut Catala Doncologia

    Barcelona, 08908
    Spain

    Active - Recruiting

  • Hospital Universitario Fundacion Jimenez Diaz

    Madrid, 28040
    Spain

    Active - Recruiting

  • Hospital Universitario de Salamanca

    Salamanca, 37007
    Spain

    Active - Recruiting

  • Hospital Universitario Virgen Del Rocio

    Sevilla, 41013
    Spain

    Active - Recruiting

  • Hospital Universitari Mutua Terrassa

    Terassa, 8221
    Spain

    Site Not Available

  • Hospital Universitari Mutua Terrassa

    Terrassa, 8221
    Spain

    Active - Recruiting

  • University Hospitals Dorset

    Bournemouth, BH7 7DW
    United Kingdom

    Active - Recruiting

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN
    United Kingdom

    Active - Recruiting

  • Churchill Hospital Oxford University Hospital Nhs Trust

    Headington, OX3 7LE
    United Kingdom

    Active - Recruiting

  • Nhs Highland

    Inverness, IV2 3BW
    United Kingdom

    Active - Recruiting

  • St Jamess University Hospital

    Leeds, LS9 7TF
    United Kingdom

    Active - Recruiting

  • University College Hospital

    London, NW1 2PG
    United Kingdom

    Active - Recruiting

  • The Christie Nhs Foundation Trust Manchester

    Manchester, M20 4BX
    United Kingdom

    Active - Recruiting

  • Plymouth Hospitals Nhs Trust

    Plymouth, PL6 8DH
    United Kingdom

    Active - Recruiting

  • Royal Marsden Nhs Foundation Royal Marsden Hospital

    Sutton, SM2 5PT
    United Kingdom

    Active - Recruiting

  • City of Hope National Medical Center

    Duarte, California 91010-3012
    United States

    Active - Recruiting

  • Colorado Blood Cancer Institute

    Denver, Colorado 80218
    United States

    Active - Recruiting

  • Medstar Georgetown University Hospital

    Washington, District of Columbia 20007-2113
    United States

    Active - Recruiting

  • University of Miami

    Miami, Florida 33136-2107
    United States

    Active - Recruiting

  • Northwestern Medicine Cancer Center

    Warrenville, Illinois 60555-3269
    United States

    Active - Recruiting

  • Mission Cancer and Blood

    Des Moines, Iowa 50309
    United States

    Site Not Available

  • Mission Cancer and Blood

    Waukee, Iowa 50263
    United States

    Active - Recruiting

  • University of Maryland Greenebaum Comprehensive Cancer Center

    Baltimore, Maryland 21201-1544
    United States

    Active - Recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts 02215-5418
    United States

    Active - Recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts 02215
    United States

    Active - Recruiting

  • Mayo Clinic Rochester

    Rochester, Minnesota 55905-0001
    United States

    Active - Recruiting

  • Hattiesburg Hematology and Oncology Clinic

    Hattiesburg, Mississippi 39401-7233
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Cancer Center Mskcc

    New York, New York 10065-6800
    United States

    Active - Recruiting

  • Atrium Health Levine Cancer Institute (Lci)

    Charlotte, North Carolina 28204-2990
    United States

    Active - Recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio 43210-1280
    United States

    Active - Recruiting

  • Ut Southwestern Medical Center

    Dallas, Texas 75390-7208
    United States

    Active - Recruiting

  • Huntsman Cancer Institute

    Salt Lake City, Utah 84112-5550
    United States

    Active - Recruiting

  • Virginia Commonwealth University Massey Cancer Center

    Richmond, Virginia 23298
    United States

    Active - Recruiting

  • University of Washington

    Seattle, Washington 98195
    United States

    Active - Recruiting

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