Elranatamab and Isatuximab for the Treatment of Relapsed and Refractory Multiple Myeloma
This phase II trial tests how well elranatamab and isatuximab work for treating multiple myeloma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Elranatamab and isatuximab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving elranatamab and isatuximab may kill more cancer cells in patients with relapsed or refractory multiple myeloma.
Inclusion Criteria
- This study will enroll patients with relapsed and refractory multiple myeloma who have had at least 2 prior lines of therapy including patients who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). Prior therapy with anti-CD38 and anti-B cell maturation antigen (BCMA) target will be permitted except an anti-BCMA T cell engager. Patients cannot be refractory to an anti-CD38 antibody
- Measurable disease of multiple myeloma as defined by at least one of the following: * Serum monoclonal protein ≥ 0.5 g/dL. Patients with IgD disease and lower amounts of monoclonal protein may be permitted to enroll with principal investigator (PI) approval * ≥ 200 mg of monoclonal protein in the urine on 24-hour electrophoresis * Serum free light chain ≥ 100 mg/L (10 mg/dL) and abnormal serum free kappa to serum free lambda light chain (FLC) ratio (< 0.26 or > 1.65)
- Age ≥ 18 years. * The effects of elranatamab and isatuximab on the developing human fetus are unknown. For this reason and because anti-BCMA bispecific antibodies are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 months after the last dose of elranatamab and 5 months after the last dose of isatuximab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
- Absolute neutrophil count (ANC) ≥ 1000/μL. Granulocyte colony-stimulating factor (G-CSF) is not permitted within 7 days of screening
- Platelet count ≥ 50,000/µL. Platelet transfusion is not permitted within 7 days of screening
- Hemoglobin ≥ 8 g/dL. Red blood cell transfusions are permitted to meet eligibility criteria
- Calculated creatinine clearance of ≥ 30 mL/min by Cockcroft-Gault equation
- Serum bilirubin values < 2 mg/dL
- Serum aspartate transaminase (ALT) and/or aspartate transaminase (AST) values < 2.5 × the upper limit of normal (ULN) of the institutional laboratory reference range. Patients with elevated bilirubin due to Gilbert’s syndrome may be permitted with PI approval (i.e., total bilirubin < 3 mg/dL and normal direct bilirubin)
- Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria
- Patients with active plasma cell leukemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, or amyloidosis are excluded from this trial
- Stem cell transplant within 12 weeks prior to enrollment, or active graft versus host disease (GVHD)
- Ongoing grade ≥ 2 peripheral sensory or motor neuropathy
- History of any grade peripheral sensory or motor neuropathy with prior BCMA directed therapy. History of Guillain Barré Syndrome (GBS) or GBS variants, or history of any grade ≥ 3 peripheral motor polyneuropathy
- Previous treatment with an anti-BCMA bispecific T cell engager. * Prior treatment with anti-BCMA chimeric antigen receptor t cell (CAR-T) and/or antibody-drug conjugates (ADC) therapy is permitted; however, the participant cannot be refractory to this therapy if it was administered as the last line prior to study enrollment
- Participants who are receiving any investigational agents currently
- Participants who have had myeloma therapy or investigational drug within 2 weeks prior to start of treatment or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
- Known or suspected hypersensitivity to the study drug or any components of the device (e.g. adhesive which contains acrylic)
- Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as any of the following within 6 months prior to enrollment: * Acute myocardial infarction, acute coronary syndromes (e.g., unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, pericardial effusion) * Clinically significant cardiac arrhythmias (e.g., uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia) * Thromboembolic or cerebrovascular events (e.g., transient ischemic attack, cerebrovascular accident, deep vein thrombosis [unless associated with a central venous access complication] or pulmonary embolism)
- Participants with known active hepatitis B virus (HBV), hepatitis C virus (HCV), HIV, or any active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 14 days prior to enrollment. Per institutional protocol, HBV deoxyribonucleic acid (DNA) testing by polymerase chain reaction (PCR) is mandatory for subjects at risk for HBV reactivation
- Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ and or other cancers treated with curative intent
- Other surgical (including major surgery within past 14 days prior to enrollment) medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study
- Live attenuated vaccine within 30 days of the first dose of study intervention
Additional locations may be listed on ClinicalTrials.gov for NCT06832865.
Locations matching your search criteria
United States
Massachusetts
Boston
PRIMARY OBJECTIVE:
I. To evaluate the objective response rate (ORR) of elranatamab in combination with isatuximab in patients with relapsed or refractory multiple myeloma (RRMM) using the International Myeloma Working Group (IMWG) Uniform Response criteria.
SECONDARY OBJECTIVES:
I. To evaluate the safety profile of elranatamab in combination with isatuximab in patients with RRMM using Common Terminology Criteria for Adverse Events (CTCAE) version 5.
II. To evaluate the progression free survival (PFS) of elranatamab in combination with isatuximab in patients with RRMM.
III. To evaluate the overall survival (OS) of elranatamab in combination with isatuximab in patients with RRMM.
IV. To evaluate minimal residual disease (MRD) negative status in participants who have achieved very good partial response (VGPR) or complete response (CR) by IMWG response criteria and evaluate sustained MRD negative status for ≥ 6 and ≥ 12 months.
EXPLORATORY OBJECTIVE:
I. To evaluate biomarkers on bone marrow and peripheral blood samples in responders versus non-responders.
OUTLINE:
Patients receive elranatamab subcutaneously (SC) on days 1, 4, 8, 15 and 22 of cycle 1. For cycles 2-6, patients receive elranatamab SC and isatuximab SC on days 1 and 15 of each cycle. Starting with cycle 7, patients receive elranatamab SC and isatuximab SC on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography and chest x-ray during screening and bone marrow aspiration and biopsy, positron emission tomography (PET)/computed tomography (CT), CT, or magnetic resonance imaging (MRI), and blood and urine sample collection throughout the study.
After completion of study treatment, patients are followed up at day 14 and every 12 weeks for 5 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorNoopur S. Raje
- Primary ID24-727
- Secondary IDsNCI-2025-05952
- ClinicalTrials.gov IDNCT06832865