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NCT04973605PHASE1, PHASE2Recruiting

A Phase 1b/2 Study of Sonrotoclax (BGB-11417) as Monotherapy and in Various Combinations With Dexamethasone Plus Carfilzomib, Dexamethasone Plus Daratumumab, and Dexamethasone Plus Pomalidomide in Multiple Myeloma

BeOne Medicines

Start Date

9/16/2021

Completion Date

11/1/2026

Summary

The purpose of this study is to assess the safety, tolerability, and efficacy of sonrotoclax as monotherapy and in various combinations in patients with relapsed/refractory (R/R) multiple myeloma (MM) and chromosomal translocation t(11;14). The study investigates sonrotoclax alone and in combination with dexamethasone and other agents, including carfilzomib, daratumumab, and pomalidomide.

Detailed Description

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.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 2. A confirmed diagnosis of multiple myeloma (must have an M-component in serum and/or urine) 3. Measurable disease defined as: i. M-spike ≥ 500mg/dL, or ii. Urine protein M-spike of ≥ 200 mg/day, or iii. Serum free light chains ≥ 10 mg/dL, and an abnormal κ:λ ratio 4. Participant has documented relapsed or progressive MM on or after any regimen or who are refractory to the most recent line of therapy. i. Relapsed MM is defined as previously treated MM that progresses and requires initiation of salvage therapy but does not meet the criteria for refractory MM. ii. Refractory MM is defined as disease that is nonresponsive (failure to achieve minimal response or development of progressive disease) while on primary or salvage therapy or progresses within 60 days of last therapy. 1. In Part 1 and Part 2 Cohorts 1 and 2 participants should have relapsed or progressive disease and have had ≥ 3 prior lines of therapy including a proteasome inhibitor, an IMiD, and an anti-CD38 monoclonal antibody, and no more available approved therapies. 2. Participants in Part 2 Cohorts 3, 4, and 5 should have relapsed or progressive disease and have had ≥ 1 prior line of therapy. Prior treatment with carfilzomib is allowed but the patient must not be considered carfilzomib refractory by the investigator. 3. Participants in Part 2 Cohorts 6 and 7 should have relapsed or progressive disease and have had 1 to 3 prior lines of therapy and previously treated with a proteasome inhibitor and an IMiD 5. Positivity for t(11;14) translocation must be confirmed by validated fluorescence in situ hybridization (FISH) testing assay in a pre-defined laboratory a. fresh bone marrow aspirate sample must be collected at screening and sent to central laboratory for t(11;14) FISH testing. 6. Adequate organ function defined as: 1. Hemoglobin ≥ 8.0 g/dL within 7 days before first dose of study treatment, (transfusions, in accordance with institutional guidelines, are permitted) 2. Platelet count ≥ 75,000/μL, within 7 days before first dose of study treatment, independent of growth factor support and transfusions 3. Absolute neutrophil count (ANC) ≥ 1000/mm\^3 within 7 days before first dose of study treatment 4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) and total bilirubin ≤ 2.0 x ULN N (total bilirubin must be \< 3 x ULN for patients with Gilbert's syndrome) Exclusion Criteria: 1. Participant has any of the following conditions: 1. Non secretory MM (Serum free light chains \< 10 mg/dL) 2. Solitary plasmacytoma 3. Active plasma cell leukemia (ie, either 20% of peripheral white blood cells or \> 2.0 x 109/L circulating plasma cells by standard differential) 4. Waldenström macroglobulinemia (WM) 5. Amyloidosis. 6. Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome 7. Chronic respiratory disease that requires continuous oxygen 2. Significant cardiovascular disease, including but not limited to: 1. Myocardial infarction ≤ 6 months before screening 2. Ejection fraction ≤ 50% 3. Unstable angina≤ 3 months before screening 4. New York Heart Association Class III or IV congestive heart failure 5. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes) 6. Heart rate-corrected QT interval \> 480 milliseconds based on Fridericia's formula 7. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place 8. Uncontrolled hypertension at screening, defined as systolic blood pressure \> 170 mmHg and diastolic blood pressure \> 105 mmHg by ≥ 2 consecutive measurements. Prior therapy with sonrotoclax or other agents inhibiting BCL2 activity (eg, venetoclax) 3. Known infection with human immunodeficiency virus (HIV) 4. Serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection as follows: 1. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Participants with presence of HBcAb, but absence of HBsAg, are eligible if HBV DNA is undetectable (limitation of sensitivity \< 20 IU/mL) ,), and if they are willing to undergo monthly monitoring for HBV reactivation. 2. Presence of HCV antibody. Participants with presence of HCV antibody are eligible if HCV RNA is undetectable (limitation of sensitivity \< 15 IU/mL). Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Interventions

DRUG

Sonrotoclax

DRUG

Dexamethasone

DRUG

Carfilzomib

DRUG

Daratumumab

DRUG

Pomalidomide

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Conditions

Relapsed/Refractory Multiple Myeloma

Locations

University of Alabama At Birmingham Hospital

Birmingham, Alabama 35294-0004

United States

City of Hope National Medical Center

Duarte, California 91010-3012

United States

City of Hope Irvine Lennar

Irvine, California 92618-2377

United States

University of Miami

Miami, Florida 33136-2107

United States

Emory University Winship Cancer Center

Atlanta, Georgia 30322-1013

United States

University of Chicago Medical Center

Chicago, Illinois 60637-1443

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Washington University School of Medicine

St Louis, Missouri 63110-1010

United States

Hackensack University Medical Center

Hackensack, New Jersey 07601-1915

United States

Weill Cornell Medical College Newyork Presbyterian Hospital

New York, New York 10065-4870

United States

Memorial Sloan Kettering Cancer Center Mskcc

New York, New York 10065-6800

United States

The James Cancer Hospital and Solove Research Institute At Ohio State University

Columbus, Ohio 43210-1240

United States

Huntsman Cancer Institute

Salt Lake City, Utah 84112-5550

United States

University of Washington

Seattle, Washington 98195

United States

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin 53792-0001

United States

Medical College of Wisconsin

Milwaukee, Wisconsin 53226-3522

United States

Canberra Hospital

Garran, Australian Capital Territory ACT 2605

Australia

Nepean Hospital

Kingswood, New South Wales NSW 2747

Australia

Monash Health

Clayton, Victoria VIC 3168

Australia

St Vincents Hospital Melbourne

Fitzroy, Victoria VIC 3065

Australia

The Alfred Hospital

Melbourne, Victoria VIC 3004

Australia

Royal Perth Hospital

Perth, Western Australia WA 6000

Australia

Hospital Sirio Libanes Brasilia

Brasília, 70200-730

Brazil

Instituto Dor de Pesquisa E Ensino Distrito Federal

Brasília, 70390140

Brazil

Centro Gaucho Integrado de Oncologia Hospital Mae de Deus

Porto Alegre, 90110-270

Brazil

Hospital Sao Rafael (Rede Dor)

Salvador, 41253-190

Brazil

Hospital Sirio Libanes

São Paulo, 01308-050

Brazil

Instituto Dor de Pesquisa E Ensino Sao Paulo

São Paulo, 01401-004

Brazil

Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein

São Paulo, 05652-900

Brazil

Cross Cancer Institute

Edmonton, Alberta T6G 1Z2

Canada

British Columbia Cancer Agency the Vancouver Centre

Vancouver, British Columbia V5Z 4E6

Canada

Princess Margaret Cancer Centre

Toronto, Ontario M5G 2M9

Canada

Peking University Third Hospital

Beijing, Beijing Municipality 100000

China

Beijing Chao Yang Hospital

Beijing, Beijing Municipality 100020

China

Peking University Peoples Hospital

Beijing, Beijing Municipality 100044

China

Chongqing Cancer Hospital

Chongqing, Chongqing Municipality 400030

China

Fujian Medical University Union Hospital

Fuzhou, Fujian 350001

China

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian 361003

China

Sun Yat Sen University Cancer Center

Guangzhou, Guangdong 510060

China

The Second Hospital of Hebei Medical University

Shijiazhuang, Hebei 050000

China

Henan Cancer Hospital

Zhengzhou, Henan 450000

China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan 450052

China

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

Wuhan, Hubei 430022

China

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

Wuhan, Hubei 430030

China

Hunan Cancer Hospital

Changsha, Hunan 410013

China

Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School

Nanjing, Jiangsu 210008

China

Jiangsu Province Hospital

Nanjing, Jiangsu 210029

China

The First Affiliated Hospital of Nanchang University Branch Xianghu

Nanchang, Jiangxi 332000

China

The First Hospital of China Medical University

Shenyang, Liaoning 110001

China

Qingdao Municipal Hospital

Qingdao, Shandong 266000

China

Affiliated Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality 200032

China

Shanghai Fourth Peoples Hospital Affiliated to Tongji University

Shanghai, Shanghai Municipality 200434

China

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality 300052

China

Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciencestuanbo Branch

Tianjin, Tianjin Municipality 301617

China

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang 310003

China

Hopital Claude Huriez Chu Lille

Lille, 59000

France

Centre Hospitalier Universitaire Nantes Hotel Dieu

Nantes, 44000

France

Chu de Poitiers Site de La Mileterie

Poitiers, 86000

France

Universitaetsklinikum Aachen

Aachen, 52074

Germany

Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden

Dresden, 01307

Germany

Universitatsklinikum Hamburg Eppendorf

Hamburg, 20251

Germany

Universitatsklinikum Wurzburg

Würzburg, 97080

Germany

University Hospital of Alexandroupolis

Alexandroupoli, 68100

Greece

General Hospital of Athens Alexandra

Athens, 115 28

Greece

Azienda Ospedaliera Universitaria Delle Marche

Ancona, 60020

Italy

Azienda Ospedaliera Policlinico Di Bari

Bari, 70124

Italy

Policlinico Sorsola Malpighi, Aou Di Bologna

Bologna, 40138

Italy

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst

Meldola, 47014

Italy

Istituto Europeo Di Oncologia

Milan, 20141

Italy

Istituto Di Candiolo Irccs

Torino, 10060

Italy

National University Hospital Singapore

Singapore, 119074

Singapore

Samsung Medical Center

GangnamGu, Seoul Teugbyeolsi 06351

South Korea

The Catholic University of Korea, Seoul St Marys Hospital

SeochoGu, Seoul Teugbyeolsi 06591

South Korea

Severance Hospital Yonsei University Health System

SeodaemunGu, Seoul Teugbyeolsi 03722

South Korea

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi 03080

South Korea

Asan Medical Center

SongpaGu, Seoul Teugbyeolsi 05505

South Korea

Hospital Clinic de Barcelona

Barcelona, 08036

Spain

Hospital San Pedro de Alcantara

Cáceres, 10002

Spain

Hospital Universitario Virgen de La Victoria

Málaga, 29010

Spain

Hospital Universitario Virgen Del Rocio

Seville, 41013

Spain

Oxford University Hospitals Nhs Trust Churchill Hospital

Headington, OX3 7LE

United Kingdom

University College Hospital

London, NW1 2PG

United Kingdom

Royal Marsden Nhs Foundation Royal Marsden Hospital

Sutton, SM2 5PT

United Kingdom

Royal Cornwall Hospitalsnhs Trust

Truro, TR1 3LJ

United Kingdom