Relapsed/Refractory Multiple Myeloma
Conditions
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.
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.
Interventions
DRUGSonrotoclax
Administered orally daily
DRUGDexamethasone
Once weekly either orally or intravenously
DRUGCarfilzomib
Administered intravenously weekly
DRUGDaratumumab
Administered subcutaneously weekly
DRUGPomalidomide
Administered orally daily
Sponsors
BeOne Medicines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be assigned sequentially in Part 1. In Part 2 participants will be assigned in parallel
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Area under the plasma concentration-time curve time 0 to the last measurable concentration (AUClast) After a Single Dose of Sonrotoclax | Cycle 1 (each cycle is up to 28 days) | — |
| Part 1: Maximum observed plasma concentration (Cmax) After a Single Dose of Sonrotoclax | Cycle 1 (each cycle is up to 28 days) | — |
| Part 1: Time to reach Cmax (tmax) After a Single Dose of Sonrotoclax | Cycle 1 (each cycle is up to 28 days) | — |
| Part 1: At Steady-state: AUC last, ss | Cycle 2 (each cycle is up to 28 days) | — |
| Part 1: At Steady-state: Cmax, ss | Cycle 2 (each cycle is up to 28 days) | — |
| Part 1: At Steady-state: trough plasma concentration (Ctrough) ss | Cycle 2 (each cycle is up to 28 days) | — |
| Part 1: At Steady-state: time to reach Cmax (tmax,ss) | Cycle 2 (each cycle is up to 28 days) | — |
| Part 2: Time to response (TTR) as Assessed by Investigator | Approximately 4 years | TTR is defined as the time from start of treatment (for nonrandomized cohorts) or date of randomization (for randomized cohorts to first documentation of response of Partial Response (PR) or better |
| Part 2: Duration of response (DOR) as Assessed by Investigator | Approximately 4 years | DOR is defined as the time from the date of the first documented response (PR or better) after treatment initiation until the date of first documented disease progression or death due to any cause, whichever occurs first. DOR will be analyzed only for patients who have achieved an overall response of at least PR. The distribution of DOR will be summarized by the Kaplan-Meier method. |
| Part 2: Progression-free survival (PFS) as Assessed by Investigator | Approximately 4 years | PFS is defined as time from start of treatment （for nonrandomized cohorts） or date of randomization （for randomized cohorts） to the first documentation of disease progression or death, whichever occurs first |
| Part 2: Overall survival (OS) as Assessed by Investigator | Approximately 4 years | OS defined as the time from start of treatment (for nonrandomized cohorts) or date of randomization (for randomized cohorts to the date of death due to any cause |
Countries
Australia, Brazil, Canada, China, France, Germany, Greece, Italy, Singapore, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTBeOne Medicines
Outcome results
None listed