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

Eligibility 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:
• 4. Participant has documented relapsed or progressive MM on or after any regimen or who are refractory to the most recent line of 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
• 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)
• 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).