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RecruitingInterventionalPhase 1/Phase 2

A Phase 1b/2 Dose-Escalation and Cohort-Expansion Study to Determine the Safety and Efficacy of BGB-11417as Monotherapy, in Combination With Dexamethasone, Dexamethasone/Carfilzomib, Dexamethasone/Daratumumab, and Dexamethasone/Pomalidomide in Patients With Relapsed/Refractory Multiple Myeloma and t(11;14)

NCT ID: NCT04973605Sponsor: BeOne MedicinesLast updated: 2026-05-11

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.

Arms & interventions

  • DrugSonrotoclax

    Administered orally daily

  • DrugDexamethasone

    Once weekly either orally or intravenously

  • DrugCarfilzomib

    Administered intravenously weekly

  • DrugDaratumumab

    Administered subcutaneously weekly

  • DrugPomalidomide

    Administered orally daily

Outcome measures

Primary

  • Part 1: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs)

    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.

    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

    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

    Time frame: Approximately 4 years

  • Part 2: Very Good Partial Response (VGPR) or Better Response Rate as Assessed by Investigator

    Defined as the percentage of participants with a documented VGPR or better (including sCR, CR, and VGPR)

    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

    defined as the percentage of participants with a documented CR or sCR

    Time frame: Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years])

Secondary

  • Part 1: Area under the plasma concentration-time curve time 0 to the last measurable concentration (AUClast) After a Single Dose of Sonrotoclax

    Time frame: Cycle 1 (each cycle is up to 28 days)

  • Part 1: Maximum observed plasma concentration (Cmax) After a Single Dose of Sonrotoclax

    Time frame: Cycle 1 (each cycle is up to 28 days)

  • Part 1: Time to reach Cmax (tmax) After a Single Dose of Sonrotoclax

    Time frame: Cycle 1 (each cycle is up to 28 days)

  • Part 1: At Steady-state: AUC last, ss

    Time frame: Cycle 2 (each cycle is up to 28 days)

  • Part 1: At Steady-state: Cmax, ss

    Time frame: Cycle 2 (each cycle is up to 28 days)

  • Part 1: At Steady-state: trough plasma concentration (Ctrough) ss

    Time frame: Cycle 2 (each cycle is up to 28 days)

  • Part 1: At Steady-state: time to reach Cmax (tmax,ss)

    Time frame: Cycle 2 (each cycle is up to 28 days)

  • Part 2: Time to response (TTR) as Assessed by Investigator

    Time frame: Approximately 4 years

  • Part 2: Duration of response (DOR) as Assessed by Investigator

    Time frame: Approximately 4 years

  • Part 2: Progression-free survival (PFS) as Assessed by Investigator

    Time frame: Approximately 4 years

  • Part 2: Overall survival (OS) as Assessed by Investigator

    Time frame: Approximately 4 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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.

Study locations (16)

University of Alabama At Birmingham Hospital

Birmingham, Alabama, 35294-0004

Recruiting

City of Hope National Medical Center

Duarte, California, 91010-3012

Recruiting

City of Hope Irvine Lennar

Irvine, California, 92618-2377

Recruiting

University of Miami

Miami, Florida, 33136-2107

Recruiting

Emory University Winship Cancer Center

Atlanta, Georgia, 30322-1013

Recruiting

University of Chicago Medical Center

Chicago, Illinois, 60637-1443

Recruiting

Massachusetts General Hospital

Boston, Massachusetts, 02114

Completed

Washington University School of Medicine

St Louis, Missouri, 63110-1010

Recruiting

Hackensack University Medical Center

Hackensack, New Jersey, 07601-1915

Recruiting

Weill Cornell Medical College Newyork Presbyterian Hospital

New York, New York, 10065-4870

Recruiting

Memorial Sloan Kettering Cancer Center Mskcc

New York, New York, 10065-6800

Recruiting

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

Columbus, Ohio, 43210-1240

Recruiting

Huntsman Cancer Institute

Salt Lake City, Utah, 84112-5550

Recruiting

University of Washington

Seattle, Washington, 98195

Recruiting

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792-0001

Recruiting

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226-1222

Recruiting
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 | Cancerify