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

NCT ID: NCT05952037

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

105 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-28

Study Completion Date

2028-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Waldenstrom Macroglobulinemia Waldenstrom's Macroglobulinemia Recurrent Waldenstrom's Macroglobulinemia Refractory

Keywords

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Waldenström's macroglobulinemia Waldenstrom's Macroglobulinemia Recurrent Waldenstrom's Macroglobulinemia Refractory Lymphoma BGB-11417 BCL-2i

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Sonrotoclax

Intervention Type DRUG

Administered orally as a tablet.

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.

Group Type EXPERIMENTAL

Sonrotoclax

Intervention Type DRUG

Administered orally as a tablet.

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.

Group Type EXPERIMENTAL

Sonrotoclax

Intervention Type DRUG

Administered orally as a tablet.

Cohort 4

Participants with previously untreated WM will receive sonrotoclax and zanubrutinib combination therapy for a fixed duration.

Group Type EXPERIMENTAL

Sonrotoclax

Intervention Type DRUG

Administered orally as a tablet.

Zanubrutinib

Intervention Type DRUG

Administered orally as a capsule.

Interventions

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Sonrotoclax

Administered orally as a tablet.

Intervention Type DRUG

Zanubrutinib

Administered orally as a capsule.

Intervention Type DRUG

Other Intervention Names

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BGB-11417 BRUKINSA BGB-3111

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BeOne Medicines

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

BeOne Medicines

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status RECRUITING

Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status RECRUITING

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status COMPLETED

University of Miami

Miami, Florida, United States

Site Status RECRUITING

Northwestern Medicine Cancer Center

Warrenville, Illinois, United States

Site Status COMPLETED

Mission Cancer and Blood

Waukee, Iowa, United States

Site Status COMPLETED

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status COMPLETED

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Hattiesburg Hematology and Oncology Clinic

Hattiesburg, Mississippi, United States

Site Status COMPLETED

Memorial Sloan Kettering Cancer Center Mskcc

New York, New York, United States

Site Status RECRUITING

Atrium Health Levine Cancer Institute (Lci)

Charlotte, North Carolina, United States

Site Status RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status RECRUITING

Ut Southwestern Medical Center

Dallas, Texas, United States

Site Status COMPLETED

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status RECRUITING

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Site Status COMPLETED

University of Washington

Seattle, Washington, United States

Site Status RECRUITING

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Site Status RECRUITING

Genesiscare North Shore

St Leonards, New South Wales, Australia

Site Status RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status RECRUITING

Flinders Medical Centre

Bedford PK, South Australia, Australia

Site Status RECRUITING

Monash Health

Clayton, Victoria, Australia

Site Status RECRUITING

St Vincents Hospital Melbourne

Fitzroy, Victoria, Australia

Site Status RECRUITING

Linear Clinical Research

Nedlands, Western Australia, Australia

Site Status RECRUITING

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status RECRUITING

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status COMPLETED

Lions Gate Hospital Chemotherapy Clinic

North Vancouver, British Columbia, Canada

Site Status COMPLETED

Qeii Health Science Center

Halifax, Nova Scotia, Canada

Site Status COMPLETED

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status COMPLETED

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Site Status COMPLETED

Guangdong Provincial Peoples Hospital

Guangzhou, Guangdong, China

Site Status RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status RECRUITING

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

Wuhan, Hubei, China

Site Status RECRUITING

Yancheng First Peoples Hospital

Yancheng, Jiangsu, China

Site Status RECRUITING

Shengjing Hospital of China Medical Universityshenbei Branch

Shenyang, Liaoning, China

Site Status COMPLETED

The Affiliated Hospital of Qingdao University Branch South

Qingdao, Shandong, China

Site Status RECRUITING

Affiliated Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

The Third Peoples Hospital of Datong

Datong, Shanxi, China

Site Status RECRUITING

Institute of Hematology and Hospital of Blood Disease

Tianjin, Tianjin Municipality, China

Site Status RECRUITING

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status RECRUITING

The First Hospital of Jiaxing

Jiaxing, Zhejiang, China

Site Status RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Site Status RECRUITING

Centre Hospitalier Universitaire Damiens Hopital Sud

Amiens, , France

Site Status RECRUITING

Chu Clermont Ferrand Therapie Cellulaire and Hematolo

Clermontferrand, , France

Site Status RECRUITING

Institut Paoli Calmettes

Marseille, , France

Site Status RECRUITING

Hopital de La Pitie Salpetriere

Paris, , France

Site Status RECRUITING

Chu Hopital Lyon Sud

PierreBenite, , France

Site Status COMPLETED

Hopital Robert Debre

Reims, , France

Site Status COMPLETED

General Hospital of Athens Alexandra

Athens, , Greece

Site Status RECRUITING

Irccs Azienda Ospedaliero Universitaria Bologna

Bologna, , Italy

Site Status RECRUITING

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Brescia, , Italy

Site Status COMPLETED

Istituto Europeo Di Oncologia

Milan, , Italy

Site Status COMPLETED

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status RECRUITING

Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi

Pavia, , Italy

Site Status RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli

Roma, , Italy

Site Status RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale Presidio Ospedaliero Universitario Santa Maria Del

Udine, , Italy

Site Status COMPLETED

Hospital Universitario Vall Dhebron

Barcelona, , Spain

Site Status COMPLETED

Institut Catala Doncologia

Barcelona, , Spain

Site Status COMPLETED

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status RECRUITING

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Site Status RECRUITING

Hospital Universitari Mutua Terrassa

Terrassa, , Spain

Site Status RECRUITING

University Hospitals Dorset

Bournemouth, , United Kingdom

Site Status RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status RECRUITING

Churchill Hospital Oxford University Hospital Nhs Trust

Headington, , United Kingdom

Site Status RECRUITING

Nhs Highland

Inverness, , United Kingdom

Site Status COMPLETED

St Jamess University Hospital

Leeds, , United Kingdom

Site Status RECRUITING

University College Hospital

London, , United Kingdom

Site Status RECRUITING

The Christie Nhs Foundation Trust Manchester

Manchester, , United Kingdom

Site Status RECRUITING

Plymouth Hospitals Nhs Trust

Plymouth, , United Kingdom

Site Status RECRUITING

Royal Marsden Nhs Foundation Royal Marsden Hospital

Sutton, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Canada China France Greece Italy Spain United Kingdom

Central Contacts

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Study Director

Role: CONTACT

Phone: 1-877-828-5568

Email: [email protected]

Other Identifiers

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U1111-1291-4524

Identifier Type: REGISTRY

Identifier Source: secondary_id

CTR20232718

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-503235-18-00

Identifier Type: CTIS

Identifier Source: secondary_id

BGB-11417-203

Identifier Type: -

Identifier Source: org_study_id