Treatment of Relapsed/Refractory Multiple Myeloma With t 11;14 Translocation Using BGB-11417 With Dexamethasone; Also Using BGB-11417 in Combination With Dexamethasone and Carfilzomib.

• Status: Recruiting
• Trial end date: 2025-09-01
• Target enrollment: 0
• Participant gender: All

Summary

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)

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: BeiGene
• Treatments: BB 1101; Dexamethasone; Dexamethasone acetate

Criteria

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. R/R MM is defined as in relapse after ≥ 1 prior therapy, previously exposed to both a proteosome inhibitor and an IMiD, and in need for systemic treatment or disease that is unresponsive to therapy. Prior treatment with carfilzomib is allowed but the patient must have obtained at least a PR and not have had carfilzomib within the past 6 months.

a. induction therapy with consolidation and maintenance, following stem cell transplant is considered a single line of therapy.

b. 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.

c. Participant must have received prior treatment with ≥ 1 but ≤ 5 prior lines of therapy for MM. A line of therapy consists of greater ≥ 1 complete cycle of a single agent, a regimen consisting of combination of several drugs, or a planned sequential therapy of various regimens.

5. Positivity for t(11;14) by local fluorescence in situ hybridization (FISH) testing fresh bone marrow aspirate sample must be collected at screening and sent to central laboratory for t(11;14) FISH testing.

6. Confirmation by the central laboratory is required prior to progression to cohort expansion (Part 2)

7. Adequate organ function defined as:

1. Hemoglobin ≥ 9.0 g/dL

2. Platelet count > 100,000/μL

3. Absolute neutrophil count (ANC) > 1000

4. Alanine aminotransferase (ALT) and aspartate aminotransferase < 3 x upper limit of normal (ULN) and total bilirubin < 2.0 x ULN

5. Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 mL/min/1.73 m2 calculated by the MDRD-6 formula

Exclusion Criteria:

1. Participant has any of the following conditions:

a. Non secretory MM (Serum free light chains < 10 mg/dL) b. Solitary plasmacytoma c. Active plasma cell leukemia (ie, either 20% of peripheral white blood cells or > 2.0 x 109/L circulating plasma cells by standard differential) d. Waldenström macroglobulinemia e. Amyloidosisf. f. Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome g. Uncontrolled diabetes (HbA1c > 7% or 53 mmol/mol or requiring insulin at study entry h. Chronic respiratory disease that requires continuous oxygen

2. Significant cardiovascular disease, including but not limited to:

1. Myocardial infarction ≤ 6 months before screening

2. Unstable angina≤ 3 months before screening

3. New York Heart Association Class III or IV congestive heart failure (see Appendix 5)

4. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes)

5. Heart rate-corrected QT interval > 480 milliseconds based on Fridericia's formula

6. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place

7. Uncontrolled hypertension at screening, defined as systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg by ≥ 2 consecutive measurements

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:

a. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if HBV DNA is undetectable (< 20 IU/mL), and if they are willing to undergo monthly monitoring for HBV reactivation.

b. Presence of HCV antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable (< 15 IU/mL).

5. Use of the following substances prior to the first dose of study drug:

a. ≤ 45 days prior to the first dose of study drug i. Any biologic and/or immunologic-based therapy (including, but not limited to, monoclonal antibody therapy and/or cancer vaccine therapy but not including IMiD agents)

b. ≤ 14 days prior to the first dose of study drug Systemic chemotherapy or therapeutic radiation therapy (palliative radiation therapy for bone lesions is acceptable

c. ≤ 7 days prior to the first dose of study drug i. Corticosteroid given with antineoplastic intent ii. BTK inhibitor, tyrosine kinase inhibitor, or other targeted small molecule (with 5 half-lives ≤ 7 days) given with antineoplastic intent

Note: Other protocol defined Inclusion/Exclusion criteria may apply.