Recruiting
Phase 1
Phase 2

Sonrotoclax

Sponsor:

BeOne Medicines

Code:

NCT04973605

Conditions

Relapsed/Refractory Multiple Myeloma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Sonrotoclax

Dexamethasone

Carfilzomib

Daratumumab

Pomalidomide

Study Details

Brief 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.

Conditions

Relapsed/Refractory Multiple Myeloma

Study ID

NCT04973605

Start date

Sep 16, 2021

Status verified date

Aug, 2026

Completion date

Nov, 2026

Anticipated

Primary completion date

Nov, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

246 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1 Dose Escalation

Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) of sonrotoclax plus dexamethasone, sonrotoclax plus dexamethasone plus carfilzomib, sonrotoclax plus dexamethasone plus daratumumab, and sonrotoclax plus dexamethasone plus pomalidomide.

experimental: Part 2 Cohort Expansion

There will be up to 7 expansion cohorts to further evaluate the safety and efficacy of sonrotoclax monotherapy, sonrotoclax plus dexamethasone in combination with dexamethasone plus carfilzomib, and in combination with dexamethasone plus daratumumab

Interventions

Sonrotoclax

Administered orally daily

Dexamethasone

Once weekly either orally or intravenously

Carfilzomib

Administered intravenously weekly

Daratumumab

Administered subcutaneously weekly

Pomalidomide

Administered orally daily

Primary outcome measure

  • Part 1: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs) [ Time Frame: Up to 28 days ]
  • 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). [ Time Frame: Up to 30 days after last dose of study drug ]
  • Part 2: Overall response rate (ORR) as Assessed by Investigator [ Time Frame: Approximately 4 years ]
  • Part 2: Very Good Partial Response (VGPR) or Better Response Rate as Assessed by Investigator [ Time Frame: Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years] ]
  • Part 2: Complete Response (CR) or Stringent Complete Response (sCR) as Assessed by Investigator [ Time Frame: Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years]) ]

Central Contacts and Locations

Central contacts

Locations

University of Alabama At Birmingham Hospital

Recruiting

Birmingham, Alabama, United States, 35294-0004

City of Hope National Medical Center

Recruiting

Duarte, California, United States, 91010-3012

City of Hope Irvine Lennar

Recruiting

Irvine, California, United States, 92618-2377

University of Miami

Recruiting

Miami, Florida, United States, 33136-2107

Emory University Winship Cancer Center

Recruiting

Atlanta, Georgia, United States, 30322-1013

University of Chicago Medical Center

Recruiting

Chicago, Illinois, United States, 60637-1443

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110-1010

Hackensack University Medical Center

Recruiting

Hackensack, New Jersey, United States, 07601-1915

Weill Cornell Medical College Newyork Presbyterian Hospital

Recruiting

New York, New York, United States, 10065-4870

Memorial Sloan Kettering Cancer Center Mskcc

Recruiting

New York, New York, United States, 10065-6800

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

Recruiting

Columbus, Ohio, United States, 43210-1240

Huntsman Cancer Institute

Recruiting

Salt Lake City, Utah, United States, 84112-5550

University of Washington

Recruiting

Seattle, Washington, United States, 98195

University of Wisconsin Carbone Cancer Center

Recruiting

Madison, Wisconsin, United States, 53792-0001

Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226-3522

Cross Cancer Institute

Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

British Columbia Cancer Agency the Vancouver Centre

Recruiting

Vancouver, British Columbia, Canada, V5Z 4E6

Princess Margaret Cancer Centre

Recruiting

Toronto, Ontario, Canada, M5G 2M9

More Information

Sponsor

BeOne Medicines

Last update posted

Aug 24, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by BeOne Medicines on 2026-08-24.