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
Dexamethasone: Once weekly either orally or intravenously
Carfilzomib: Administered intravenously weekly
Daratumumab: Administered subcutaneously weekly
Pomalidomide: Administered orally daily
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Part 1: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs) — Up to 28 days DLTs will be based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and will include most grade 3 or higher events, as defined in the protocol.
Part 1 And 2: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation and Adverse Events of Special Interest (AESIs). — Up to 30 days after last dose of study drug
Part 2: Overall response rate (ORR) as Assessed by Investigator — Approximately 4 years Defined as the percentage of participants who achieved a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per International Myeloma Working Group (IMWG) criteria
Part 2: Very Good Partial Response (VGPR) or Better Response Rate as Assessed by Investigator — Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years] Defined as the percentage of participants with a documented VGPR or better (including sCR, CR, and VGPR)
Part 2: Complete Response (CR) or Stringent Complete Response (sCR) as Assessed by Investigator — Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years]) defined as the percentage of participants with a documented CR or sCR
Trial sites (78)
Facility
City
Region
Status
University of Alabama At Birmingham Hospital
Birmingham
Alabama
Recruiting
City of Hope National Medical Center
Duarte
California
Recruiting
City of Hope Irvine Lennar
Irvine
California
Recruiting
University of Miami
Miami
Florida
Recruiting
Emory University Winship Cancer Center
Atlanta
Georgia
Recruiting
University of Chicago Medical Center
Chicago
Illinois
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Completed
Washington University School of Medicine
St Louis
Missouri
Recruiting
Hackensack University Medical Center
Hackensack
New Jersey
Recruiting
Weill Cornell Medical College Newyork Presbyterian Hospital
New York
New York
Recruiting
Memorial Sloan Kettering Cancer Center Mskcc
New York
New York
Recruiting
The James Cancer Hospital and Solove Research Institute At Ohio State University
Columbus
Ohio
Recruiting
Huntsman Cancer Institute
Salt Lake City
Utah
Recruiting
University of Washington
Seattle
Washington
Recruiting
University of Wisconsin Carbone Cancer Center
Madison
Wisconsin
Recruiting
Medical College of Wisconsin
Milwaukee
Wisconsin
Recruiting
Canberra Hospital
Garran
Australian Capital Territory
Recruiting
Nepean Hospital
Kingswood
New South Wales
Recruiting
Monash Health
Clayton
Victoria
Recruiting
St Vincents Hospital Melbourne
Fitzroy
Victoria
Recruiting
The Alfred Hospital
Melbourne
Victoria
Recruiting
Royal Perth Hospital
Perth
Western Australia
Recruiting
Hospital Sirio Libanes Brasilia
Brasília
Brazil
Recruiting
Instituto Dor de Pesquisa E Ensino Distrito Federal
Brasília
Brazil
Recruiting
Centro Gaucho Integrado de Oncologia Hospital Mae de Deus
Porto Alegre
Brazil
Recruiting
Hospital Sao Rafael (Rede Dor)
Salvador
Brazil
Recruiting
Hospital Sirio Libanes
São Paulo
Brazil
Recruiting
Instituto Dor de Pesquisa E Ensino Sao Paulo
São Paulo
Brazil
Recruiting
Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
São Paulo
Brazil
Recruiting
Cross Cancer Institute
Edmonton
Alberta
Recruiting
British Columbia Cancer Agency the Vancouver Centre
Vancouver
British Columbia
Recruiting
Princess Margaret Cancer Centre
Toronto
Ontario
Recruiting
Peking University Third Hospital
Beijing
Beijing Municipality
Recruiting
Beijing Chao Yang Hospital
Beijing
Beijing Municipality
Recruiting
Peking University Peoples Hospital
Beijing
Beijing Municipality
Recruiting
Chongqing Cancer Hospital
Chongqing
Chongqing Municipality
Recruiting
Fujian Medical University Union Hospital
Fuzhou
Fujian
Completed
The First Affiliated Hospital of Xiamen University
Xiamen
Fujian
Completed
Sun Yat Sen University Cancer Center
Guangzhou
Guangdong
Recruiting
The Second Hospital of Hebei Medical University
Shijiazhuang
Hebei
Completed
+ 38 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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