Recruiting
Phase 1/Phase 2
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
Condition(s) studied
Relapsed/Refractory Multiple Myeloma
Investigational drug(s) / intervention(s)
SonrotoclaxDexamethasoneCarfilzomibDaratumumabPomalidomide
Sonrotoclax: Administered orally daily
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
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.