Study to Evaluate the Efficacy and Safety of Sonrotoclax in Participants With Waldenström's Macroglobulinemia
- Conditions
- Waldenstrom's Macroglobulinemia RefractoryWaldenstrom's Macroglobulinemia RecurrentWaldenstrom Macroglobulinemia
- Interventions
- Drug: BGB-11417Drug: Zanubrutinib
- Registration Number
- NCT05952037
- Lead Sponsor
- BeiGene
- Brief Summary
This study will evaluate the safety and efficacy of the BCL2 inhibitor BGB-11417 (sonrotoclax) 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
This study will test whether BGB-11417 (sonrotoclax) 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 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, 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. Treatments will continue until participants experience worsening disease status, too many side effects, or withdraw consent.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 105
- 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 to the most recent therapy 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.
- Adequate organ function.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2 BGB-11417 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. Cohort 4 BGB-11417 Participants with previously untreated WM will receive sonrotoclax and zanubrutinib combination therapy with fixed duration. Cohort 3 BGB-11417 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. Cohort 1 BGB-11417 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. Cohort 4 Zanubrutinib Participants with previously untreated WM will receive sonrotoclax and zanubrutinib combination therapy with fixed duration.
- Primary Outcome Measures
Name Time Method Cohort 1: Major Response Rate (MRR) Up to approximately 4 years MRR is defined as the proportion 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.
- Secondary Outcome Measures
Name Time Method All Cohorts: MRR as assessed by the Investigator Up to approximately 5 years MRR is defined as the proportion of participants achieving PR or better.
All Cohorts: CR + VGPR as assessed by the Investigator Up to approximately 5 years CR + VGPR is defined as the percentage of participants who achieve CR or VGPR.
Cohorts 1, 2, and 3: Progression-Free Survival (PFS) Up to approximately 5 years 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.
Cohorts 2 and 3: MRR as assessed by the IRC Up to approximately 5 years MRR is defined as the proportion of participants achieving PR or better.
All Cohorts: DoMR as assessed by the Investigator Up to approximately 5 years DoMR is defined as the time from first determination of major response until first documentation of progression or death, whichever occurs first.
All cohorts: ORR as assessed by the investigator Up to approximately 5 years ORR is defined as the percentage of participants with MR or better.
Cohorts 1, 2, and 3: Duration of Response (DOR) as assessed by the IRC Up to approximately 5 years DOR is defined as the time from first determination of response until first documentation of progression or death, whichever occurs first.
Cohorts 1, 2, and 3: Duration of Major Response (DoMR) as assessed by the IRC Up to approximately 5 years DoMR is defined as the time from first determination of major response until first documentation of progression or death, whichever occurs first.
Cohorts 1, 2, and 3: Complete Response (CR) + Very Good Partial Response (VGPR) as assessed by the IRC Up to approximately 5 years CR + VGPR is defined as the percentage of participants who achieve CR or VGPR.
All Cohorts: DOR as assessed by the investigator Up to approximately 5 years DOR is defined as the time from first determination of response until first documentation of progression or death, whichever occurs first.
All Cohorts: Time to major response as assessed by the investigator Up to approximately 5 years Time to major response is defined as the time from start of study treatment to the first documentation of major response.
Time to next treatment in cohort 4 Up to approximately 5 years Defined as the time from the start of treatment to the start of first subsequent therapy for WM.
Cohorts 1, 2, and 3: Overall Response Rate (ORR) as assessed by the IRC Up to approximately 5 years ORR is defined as the percentage of participants with minor response (MR) or better.
Cohorts 1, 2, and 3: Time to major response as assessed by the IRC Up to approximately 5 years Time to major response is defined as the time from start of study treatment to the first documentation of major response.
Cohorts 1, 2, and 3: Overall Survival (OS) Up to approximately 5 years OS is defined as the time from first study drug administration to the date of death due to any cause.
Number of participants reporting adverse events Up to approximately 5 years Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory abnormalities, physical examination results, and vital signs.
Health-Related Quality of Life (HRQoL): NFLymSI-18 Up to approximately 5 years 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.
Trial Locations
- Locations (72)
Lions Gate Hospital Chemotherapy Clinic
🇨🇦North Vancouver, British Columbia, Canada
Qeii Health Science Center
🇨🇦Halifax, Nova Scotia, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
Guangdong Provincial Peoples Hospital
🇨🇳Guangzhou, Guangdong, China
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Yancheng First Peoples Hospital
🇨🇳Yancheng, Jiangsu, China
Shengjing Hospital Affiliated of China Medical University
🇨🇳Shenyang, Liaoning, China
The Affiliated Hospital of Qingdao University Branch South
🇨🇳Qingdao, Shandong, China
Affiliated Zhongshan Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
The Third Peoples Hospital of Datong
🇨🇳Datong, Shanxi, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
The First Hospital of Jiaxing
🇨🇳Jiaxing, Zhejiang, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Centre Hospitalier Universitaire Damiens Hopital Sud
🇫🇷Amiens Cedex, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Hopital de La Pitie Salpetriere
🇫🇷Paris, France
Chu Hopital Lyon Sud
🇫🇷PierreBenite, France
Hopital Robert Debre
🇫🇷Reims Cedex, France
General Hospital of Athens Alexandra
🇬🇷Athens, Greece
Irccs Azienda Ospedaliero Universitaria Bologna
🇮🇹Bologna, Italy
Chu Clermont Ferrand Therapie Cellulaire and Hematolo
🇫🇷Clermont Ferrand, France
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi
🇮🇹Pavia, Italy
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Churchill Hospital Oxford University Hospital Nhs Trust
🇬🇧Headington, United Kingdom
St Jamess University Hospital
🇬🇧Leeds, United Kingdom
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Medstar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Northwestern Medicine Cancer Center
🇺🇸Warrenville, Illinois, United States
Mission Cancer and Blood
🇺🇸Des Moines, Iowa, United States
University of Maryland Greenebaum Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Hattiesburg Hematology and Oncology Clinic
🇺🇸Hattiesburg, Mississippi, United States
Memorial Sloan Kettering Cancer Center Mskcc
🇺🇸New York, New York, United States
Atrium Health Levine Cancer Institute (Lci)
🇺🇸Charlotte, North Carolina, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Ut Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
University of Washington
🇺🇸Seattle, Washington, United States
Genesiscare North Shore
🇦🇺St Leonards, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
St Vincents Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
🇮🇹Brescia, Italy
Istituto Europeo Di Oncologia
🇮🇹Milano, Italy
Fondazione Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Azienda Sanitaria Universitaria Friuli Centrale Presidio Ospedaliero Universitario Santa Maria Del
🇮🇹Udine, Italy
Hospital Universitario Vall Dhebron
🇪🇸Barcelona, Spain
Institut Catala Doncologia
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Hospital Universitari Mutua Terrassa
🇪🇸Terassa, Spain
University Hospitals Dorset
🇬🇧Bournemouth, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Nhs Highland
🇬🇧Inverness, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
The Christie Nhs Foundation Trust Manchester
🇬🇧Manchester, United Kingdom
Plymouth Hospitals Nhs Trust
🇬🇧Plymouth, United Kingdom
Royal Marsden Nhs Foundation Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
University of Miami
🇺🇸Miami, Florida, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Flinders Medical Centre
🇦🇺Bedford PK, South Australia, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Institute of Hematology and Hospital of Blood Disease
🇨🇳Tianjin, Tianjin, China