A Phase 1b/2 Study of BGB-11417 in Monotherapy and in Various Combinations With Dexamethasone and Carfilzomib in Multiple Myeloma BGB-11417

What's the purpose of this trial?

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.

This trial is currently open and accepting patients.


What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • A confirmed diagnosis of multiple myeloma (must have an M-component in serum and/or urine)
  • Measurable disease defined as:
    • 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
  • Participant has documented relapsed or progressive MM on or after any regimen or who are refractory to the most recent line of therapy.
    • 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.
    • 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.
      • Participants in Part 1 should have failed all other available options including having had ≥ 3 prior lines of therapy including a proteasome inhibitor, IMiD agent, and an anti-CD38 monoclonal antibody.
      • Participants in Part 2 should have had and failed ≥ 1 but ≤ 7 prior lines of therapy and will have had prior treatment with both a proteasome inhibitor and an IMiD agent.
      • Note: 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. Induction therapy with consolidation and maintenance following stem cell transplant is considered a single line of therapy.
      • Prior treatment with carfilzomib is allowed but the patient must not be considered carfilzomib refractory and not have had carfilzomib within the past 6 months
  • Positivity for t(11;14) by validated fluorescence in situ hybridization (FISH) testing assay in a pre-defined laboratory
    • Fresh bone marrow aspirate sample must be collected at screening and sent to central laboratory for t(11;14) FISH testing.
  • Adequate organ function defined as:
    • Hemoglobin ≥ 8.0 g/dL, within 7 days before first dose of study treatment, independent of growth factor support and transfusions
    • Platelet count ≥ 75,000/μL, within 7 days before first dose of study treatment, independent of growth factor support and transfusions
    • Absolute neutrophil count (ANC) ≥ 1000/mm3 [ANC = (% of segmented neutrophils + % of segmented bands) x total WBC count within 7 days before first dose of study treatment
    • ALT and AST ≤ 3 x upper limit of normal (ULN) and total bilirubin ≤ 2.0 x ULN Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 45 mL/min/1.73 m2 calculated by the MDRD-6 formula.

Exclusion Criteria:

  • Participant has any of the following conditions:
    • Non secretory MM (Serum free light chains < 10 mg/dL)
    • Solitary plasmacytoma
    • Active plasma cell leukemia (ie, either 20% of peripheral white blood cells or > 2.0 x 109/L circulating plasma cells by standard differential)
    • Waldenström macroglobulinemia
    • Amyloidosis.
    • Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome
    • Uncontrolled diabetes (HbA1c > 7% or 53 mmol/mol or requiring insulin at study entry
    • Chronic respiratory disease that requires continuous oxygen
  • Significant cardiovascular disease, including but not limited to:
    • Myocardial infarction ≤ 6 months before screening
    • Ejection fraction ≤ 50%
    • Unstable angina≤ 3 months before screening
    • New York Heart Association Class III or IV congestive heart failure
    • History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
    • Heart rate-corrected QT interval > 480 milliseconds based on Fridericia's formula
    • History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
    • Uncontrolled hypertension at screening, defined as systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg by ≥ 2 consecutive measurements
  • Known infection with human immunodeficiency virus (HIV)
  • Serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection as follows:
    • 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.
    • 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.

Additional Trial Information

Phase 1/2

Enrollment: 167 patients (estimated)

View More

Published Results

Sonrotoclax (BGB-11417) in Combination with Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma with t(11;14): Safety, Efficacy, and Determination of Recommended Phase 2 Dose

December 11, 2023

As of May 26, 2023, 19 patients have been enrolled in the 80-, 160-, and 320-mg (n=3 each) and 640-mg (n=10 patients) dose-escalation cohorts. The median age was 68 years (range, 52-81 years). The median prior lines of therapy was 4 (range, 1-12) and 11 patients (58%) failed on a prior anti-CD38 antibody. The most common AEs (>20% of all patients) were insomnia (n=9; 47%), fatigue (n=6; 32%), nausea (n=5; 26%), and arthralgia (n=4; 21%); none of which were severity grade ≥3. Three patients (16%) experienced grade ≥3 treatment-emergent AEs (TEAEs). One patient (33%) in the 160-mg cohort had grade 3 increases in liver enzymes and diarrhea; one patient (10%) in the 640-mg cohort had a grade 3 decrease lymphocyte count and hypokalemia; and one patient (10%) in the 640-mg cohort had grade 3 cataracts and retinal detachment. Three patients experienced COVID-19 (grade 1-2, n=2; grade ≥3, n=1). Three patients experienced TEAEs that led to treatment discontinuation (COVID-19, cancer pain, hematuria; n=1 each). No patient, across all dose levels tested, experienced a DLTs; thus, sonrotoclax 640 mg daily was the determined to be the MAD and the RP2D in combination with dexamethasone.

Four patients (21%) died while on study; however, no deaths were determined by the investigators to be associated with study treatment. One patient died from COVID-19 while receiving study therapy; three additional patients died ≥50 days after treatment discontinuation (COVID, progressive disease, and unknown causes, n=1 each).

With a median treatment duration of 120 days (range, 30-526), ORR was 58%; 11 patients had a PR or better (n=6, PR; n=2, very good PR; n=2, CR; n=1, stringent CR [sCR]; Figure). The ORR for the 640-mg cohort was 70% (n=3, PR; n=2 VGPR; n=1, CR; n=1, sCR). Nine patients remained on treatment; the longest duration of response was 483 days (20 cycles) which, at data cutoff, was still ongoing.

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

Alabama

University of Alabama at Birmingham O'Neal Comprehensive Cancer Center at UAB

Birmingham, AL

Not Yet Accepting

California

City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Not Yet Accepting

Florida

Tampa General Hospital Cancer Institute

Tampa, FL

Open and Accepting

Georgia

Winship Cancer Institute Emory University

Atlanta, GA

Open and Accepting

Illinois

University of Illinois at Chicago

Chicago, IL

Open and Accepting

Maryland

Maryland Oncology Hematology (Columbia)

Columbia, MD

Not Yet Accepting

Massachusetts

Massachusetts General Hospital

Boston, MA

Not Yet Accepting

Michigan

Barbara Ann Karmanos Cancer Institute Wayne State University

Detroit, MI

Open and Accepting

New York

Memorial Sloan Kettering Cancer Center

New York, NY

Open and Accepting

Ohio

Utah

Huntsman Cancer Institute University of Utah

Salt Lake City, UT

Not Yet Accepting

Washington

University of Washington School of Medicine

Seattle, WA

Not Yet Accepting

Wisconsin

Medical College of Wisconsin Froedtert Hospital

Milwaukee, WI

Open and Accepting
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