Clinical trial NCT05952037: A Study to Investigate Efficacy and Safety of BCL2 Inhibitor Sonrotoclax as Monotherapy and in Combination With Zanubrutinib in Adults With Waldenström Macroglobulinemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Waldenstrom Macroglobulinemia
Waldenstrom's Macroglobulinemia Recurrent
Waldenstrom's Macroglobulinemia Refractory
Keywords: Waldenström's macroglobulinemia
Waldenstrom's Macroglobulinemia Recurrent
Waldenstrom's Macroglobulinemia Refractory
Lymphoma
BGB-11417
BCL-2i
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2023-07-19
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cohort 1: Major Response Rate (MRR)
timeFrame: Up to approximately 4 years
Secondary outcomes:
measure: Cohorts 2 and 3: MRR as assessed by the IRC
timeFrame: Up to approximately 5 years
measure: All Cohorts: MRR as assessed by the Investigator
timeFrame: Up to approximately 5 years
measure: Cohorts 1, 2, and 3: Duration of Major Response (DoMR) as assessed by the IRC
timeFrame: Up to approximately 5 years
measure: All Cohorts: DoMR as assessed by the Investigator
timeFrame: Up to approximately 5 years
measure: Cohorts 1, 2, and 3: Complete Response (CR) + Very Good Partial Response (VGPR) as assessed by the IRC
timeFrame: Up to approximately 5 years
measure: All Cohorts: CR + VGPR as assessed by the Investigator
timeFrame: Up to approximately 5 years
measure: Cohorts 1, 2, and 3: Overall Response Rate (ORR) as assessed by the IRC
timeFrame: Up to approximately 5 years
measure: All cohorts: ORR as assessed by the investigator
timeFrame: Up to approximately 5 years
measure: Cohorts 1, 2, and 3: Duration of Response (DOR) as assessed by the IRC
timeFrame: Up to approximately 5 years
measure: All Cohorts: DOR as assessed by the investigator
timeFrame: Up to approximately 5 years
measure: Cohorts 1, 2, and 3: Progression-Free Survival (PFS)
timeFrame: Up to approximately 5 years
measure: Cohorts 1, 2, and 3: Time to major response as assessed by the IRC
timeFrame: Up to approximately 5 years
measure: All Cohorts: Time to major response as assessed by the investigator
timeFrame: Up to approximately 5 years
measure: Cohorts 1, 2, and 3: Overall Survival (OS)
timeFrame: Up to approximately 5 years
measure: Cohort 4: Time to next treatment
timeFrame: Up to approximately 5 years
measure: Number of participants reporting adverse events
timeFrame: Up to approximately 5 years
measure: All Cohorts: Change from Baseline in Health-Related Quality of Life (HRQoL): NFLymSI-18 Disease-related Symptoms-Physical and Treatment-Related Side Effects Subscales
timeFrame: Baseline and approximately months 7, 13, 19, and 25
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Washington
country: United States
facility: Medstar Georgetown University Hospital
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center
state: Illinois
city: Waukee
country: United States
facility: Mission Cancer and Blood
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Hattiesburg
country: United States
facility: Hattiesburg Hematology and Oncology Clinic
state: Mississippi
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Mskcc
state: New York
city: Charlotte
country: United States
facility: Atrium Health Levine Cancer Institute (Lci)
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Dallas
country: United States
facility: Ut Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Genesiscare North Shore
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Bedford PK
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: North Vancouver
country: Canada
facility: Lions Gate Hospital Chemotherapy Clinic
state: British Columbia
city: Halifax
country: Canada
facility: Qeii Health Science Center
state: Nova Scotia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Yancheng
country: China
facility: Yancheng First Peoples Hospital
state: Jiangsu
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical Universityshenbei Branch
state: Liaoning
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University Branch South
state: Shandong
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Datong
country: China
facility: The Third Peoples Hospital of Datong
state: Shanxi
city: Tianjin
country: China
facility: Institute of Hematology and Hospital of Blood Disease
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Jiaxing
country: China
facility: The First Hospital of Jiaxing
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Amiens Cedex
country: France
facility: Centre Hospitalier Universitaire Damiens Hopital Sud
city: Clermontferrand
country: France
facility: Chu Clermont Ferrand Therapie Cellulaire and Hematolo
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Paris
country: France
facility: Hopital de La Pitie Salpetriere
city: PierreBenite
country: France
facility: Chu Hopital Lyon Sud
city: Reims
country: France
facility: Hopital Robert Debre
city: Athens
country: Greece
facility: General Hospital of Athens Alexandra
city: Bologna
country: Italy
facility: Irccs Azienda Ospedaliero Universitaria Bologna
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Pavia
country: Italy
facility: Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Friuli Centrale Presidio Ospedaliero Universitario Santa Maria Del
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Dhebron
city: Barcelona
country: Spain
facility: Institut Catala Doncologia
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Terrassa
country: Spain
facility: Hospital Universitari Mutua Terrassa
city: Bournemouth
country: United Kingdom
facility: University Hospitals Dorset
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Headington
country: United Kingdom
facility: Churchill Hospital Oxford University Hospital Nhs Trust
city: Inverness
country: United Kingdom
facility: Nhs Highland
city: Leeds
country: United Kingdom
facility: St Jamess University Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: Manchester
country: United Kingdom
facility: The Christie Nhs Foundation Trust Manchester
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals Nhs Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Nhs Foundation Royal Marsden Hospital
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: