A Study of Belantamab Mafodotin in Combination With Nirogacestat and Pomalidomide in People With Multiple Myeloma That Has Not Responded to Treatment or Has Come Back After Treatment

Running, not enrolling · Phase 1

Conditions studied: Multiple Myeloma

In brief

The purpose of this study is to find out whether combination treatment with the study drugs belantamab mafodotin, nirogacestat, and pomalidomide is a safe treatment for people who have relapsed or refractory multiple myeloma. The researchers will test different doses of belantamab mafodotin to find the safest dose to give with nirogacestat and pomalidomide. The researchers also want to find out whether belantamab mafodotin plus nirogacestat and pomalidomide is an effective treatment for this type of bone marrow cancer, and the researchers will do tests that show whether the study treatment slows or stops the growth of cancer.

Key facts

Study ID

NCT05556798

Run by

Memorial Sloan Kettering Cancer Center

People needed

9

Starts

2022-10-04

Expected to finish

2027-10-01

Last updated by the study team

2026-07-21

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients with relapsed or refractory multiple myeloma treated with 3 or more prior lines of therapy. Relapsed/refractory multiple myeloma is defined by the International Myeloma Working Group (IMWG) updated criteria.
• Patients need to have measurable disease defined by one or more of the following:
• Serum myeloma (M)-protein greater than or equal to 0.5 g/dL (5 g/L).
• Urine M-protein ≥ 200 mg/24 h.
• Involved free light chain level ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65). Measurable plasmacytoma(s) verified by imaging or biopsy (≥1 lesion that has a single diameter of ≥2cm)
• e. A bone marrow biopsy demonstrating ≥30% infiltration of clonal plasma cells verified by CD138 immunohistochemistry.
• Have undergone autologous stem cell transplant or are considered transplant ineligible.
• Patients who have received prior CAR T cells are eligible. Patients who have received prior BCMA-directed therapy, other than belantamab mafodotin, are eligible. Patients who have received autologous stem cell transplantation >60 days prior are eligible Patients who have received prior allogeneic stem cell transplantation >100 days prior are eligible.
• Female or male patients age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2. PS-3 is permitted if PS is due solely to bone pain.
• Participants must enroll in and comply with the REMS program for pomalidomide.
• Fulfil the criteria for Adequate Organ System Function Based on Safety Assessments
• °Hematologic
• Absolute neutrophil count (ANC)a ≥1.0 × 10\^9/L
• Hemoglobin a ≥8.0 g/dL
• Platelets a ≥50 × 10\^9/L
• °Hepatic
• Total bilirubin ≤1.5 × ULN; (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%)
• ALT ≤ 2.5 × ULN °Renal
• eGFRb ≥30 mL/min\^b
• Spot urine (albumin/creatinine ratio from spot urine) ≤ 500 mg/g (56 mg/mmol) OR Urine dipstick Negative/trace (if ³1+ only eligible if confirmed <500 mg/g (56 mg/mmol) by albumin/creatinine ratio (spot urine from first void)
• °Cardiac
• Left Ventricular Ejection Fraction (LVEF) by ECHO ≥40% Note: Laboratory results obtained during Screening should be used to determine eligibility criteria. In situations where laboratory results are outside the permitted range, the Investigator may re-test the participant and the subsequent within range screening result may be used to confirm eligibility.
• Without Growth factor support for the past 14 days, excluding erythropoietin. Transfusions are allowed
• As calculated by the CKD-EPI formula.

You may not qualify if…

• Prior treatment with belantamab mafodotin
• Systemic anti-myeloma therapy (including systemic steroids) within ≤14 days, or plasmapheresis within 7 days prior to the first dose of study drug.
• Use of an investigational drug within 14 days or five half-lives (whichever is longer) preceding the first dose of study drug.
• Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs.
• Radiation therapy within 2 weeks prior to study entry (bone lesions requiring radiation may be treated with limited [i.e., ≤ 25% of bone marrow in field] radiation therapy during this period).
• Patients with a history of stem cell transplant autologous within 60 days or allogeneic within 100 days prior to study enrollment.
• Patients with AL amyloidosis will be excluded.
• Participant must not have had major surgery ≤4 weeks prior to initiating study treatment.
• Evidence of active mucosal or internal bleeding.
• Presence of active renal condition (infection or requirement for dialysis). Participants with isolated proteinuria resulting from multiple myeloma are eligible, provided they fulfill criteria given
• Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease per investigator's assessment).
• Participants with invasive malignancies other than multiple myeloma are excluded, unless the second malignancy has been considered medically stable for at least 2years. The participant must not be receiving active therapy, other than hormonal therapy for this disease with the exceptions of successfully treated non-metastatic basal cell, squamous cell skin carcinoma, or in-situ carcinoma.
• Evidence of cardiovascular risk including any of the following:
• Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities including 2nd degree (Mobitz Type II) or3rd degree atrioventricular (AV) block.
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening
• Class III or IV heart failure as defined by the New York Heart Association functional classification system.
• Uncontrolled hypertension
• Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
• Pregnant or lactating female.
• Active infection requiring treatment.
• Participant has known human immunodeficiency virus (HIV) infection, unless the participant can meet all of the following criteria:
• Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load<400 copies/mL, and
• CD4+ T-cell (CD4+) counts ≥350 cells/μL, and
• No history of acquired immunodeficiency s-defining opportunistic infections within the last 12 months.
• Note: Consideration must be given to ART and prophylactic antimicrobials that may have a drug-drug interaction and/or overlapping toxicities with belantamab mafodotin or other combination products as relevant.

Where it is running

• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States
• Memorial Sloan Kettering Cancer Center @ Suffolk-Commack (Limited protocol activities) — Commack, New York, United States
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States
• Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale, New York, United States

Full record on ClinicalTrials.gov

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