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

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Full Title:
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)
Myeloma stage or condition:
Relapsed/Refractory Multiple Myeloma
Study phase:
Phase 1/Phase 2
Summary/Purpose:
Study consists of two parts, a part 1 dose escalation and a part 2 cohort expansion in combination with dexamethasone and carfilzomib intravenously across two cohorts with a monotherapy component as well.
Detailed Description:
Not available
Treatments:
Drug : Sonrotoclax

Administered orally daily

Drug : Dexamethasone

Once weekly either orally or intravenously

Drug : Carfilzomib

Administered intravenously weekly

Drug : Daratumumab

Administered subcutaneously weekly

Drug : Pomalidomide

Administered orally daily

Study Arms:
Experimental : Part 1 Dose Escalation
Dose-escalation and de-escalation to determine maximum tolerated dose (MTD)
Experimental : Part 2 Cohort Expansion
There will be 5 expansion cohorts to further evaluate the safety and efficacy of BGB-11417
Study Type:
Interventional
Study Design:
Allocation: Randomized
Intervention Model: Parallel
Intervention Model Description: Participants will be assigned sequentially in Part 1. In Part 2 participants will be assigned in parallel
Primary Purpose: Treatment
Masking: None
Recruitment status:
Recruiting
Eligibility criteria:
usion 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 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 should have relapsed or progressive disease and have had ≥ 1 prior line of therapy 3. Prior treatment with carfilzomib is allowed but the patient must not be considered carfilzomib refractory by the investigator. 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 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.
Locations / Centres:

Cross Cancer Institute, Edmonton, Alberta – Recruiting

British Columbia Cancer Agency the Vancouver Centre, Vancouver, British Columbia – Recruiting

Princess Margaret Cancer Centre, Toronto, Ontario – Recruiting

Jewish General Hospital, Montreal, Quebec – Recruiting

Contacts:
Name: BeiGene
Phone: 1.877.828.5568
Email: [email protected]
Publications:
???
First posted:
Not available
Actual start date:
2021-09-16
Last updated:
2025-02-18
Estimated enrollment:
167
Estimated completion date:
2026-11-01
Estimated primary completion date:
2026-11-01
Condition:
Relapsed/Refractory Multiple Myeloma
Gender:
All
Ages:
18 Years-
Accepts healthy volunteers:
Not available
Listed location countries:
Not available
NCT number:
NCT04973605
Other study ID numbers:
BGB-11417-105
Has Data monitoring committee:
Yes
U.S. FDA-regulated product:
Yes
IPD Sharing Statement :
???
Responsible party:
Sponsor
Study sponsor:
lead_sponsor
BeiGene
Industry
Collaborators:
???
Investigators:
Not available
Protocol Registration and Results System:
???
Verification date:
2025-02-01