This phase Ib trial tests the safety, side effects, and best dose of CC-92480 in combination with elotuzumab and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that does not respond to treatment or has not responded to previous treatment (refractory). Multiple myeloma (MM) remains the second most common hematologic malignancy in the United States. A number of therapies have been approved for patients with MM, including CD38- and B-cell maturating antigen (BCMA)-targeted therapies (antibody and plasma cell treatments that help the body’s immune system to kill cancer cells); however, patients will often relapse and become refractory to these therapies. Because of this, it is important to identify effective treatment options for patients progressing on anti-CD38 therapy and BCMA-directed therapies. Elotuzumab is a humanized IgG1 monoclonal antibody, which is a type of protein that can bind to other target cells to prevent them from working the way they should or cause them to act differently. Elotuzumab works by targeting a protein called SLAMF7, which is present on myeloma cells, and makes it easier for the immune system to target the cancer. CC-92480 works by binding to a protein called CRBN that triggers the breakdown of proteins: Ikaros and Aiolos, leading to cell death in multiple myeloma cells. Dexamethasone is a synthetic adrenocortical steroid, or steroid normally naturally made by the adrenal gland in the brain which has been produced in a laboratory, that helps to regulate the amount of different chemicals and water that are being processed by the kidneys. It is also used in patients with myeloma to help treat their disease. The combination of CC-92480 with elotuzumab and dexamethasone may be a safe and effective treatment when given to patients with relapsed or recurrent MM.
Additional locations may be listed on ClinicalTrials.gov for NCT05981209.
Locations matching your search criteria
United States
Ohio
Columbus
Ohio State University Comprehensive Cancer CenterStatus: Active
Contact: Abdullah Mohammad Khan
Phone: 614-293-3196
PRIMARY OBJECTIVE:
I. To evaluate the safety and tolerability of elotuzumab, mezigdomide (CC-92480), and dexamethasone (E480d) in patients with relapsed/refractory multiple myeloma (RRMM) who have received >= 2 prior regimens including CD38- and BCMA-targeted therapies.
SECONDARY OBJECTIVES:
I. To evaluate additional measures of efficacy (time to response [TTR], the duration of response [DOR], very good partial response [VGPR] or better and complete response [CR] rates, progression free survival [PFS] at 1 year, and overall survival [OS] at 1 year of E480d.
II. Check minimal residual disease (MRD) negativity rates by next generation sequencing in patients who are suspected of attaining a complete response (CR).
III. Correlative studies will include changes in lymphocyte subsets with therapy, immunophenotype of MM cells, and expression of CRBN, Ikaros, and Aiolos.
IV. Quality of life (QOL) will be assessed.
OUTLINE: This is a dose-escalation study of CC-92480, followed by a dose-expansion study.
Patients receive elotuzumab intravenously (IV) on days 1, 8, 15, and 22 of cycles 1 and 2 and then on day 1 of each subsequent cycle. Patients also receive CC-92480 orally (PO) on days 1-21 of each cycle and dexamethasone IV or PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo an echocardiography (ECHO) during screening and undergo magnetic resonance imaging (MRI), computed tomography (CT), or x-ray imaging during screening and on study as clinically indicated. Patients also undergo blood sample collection as well as bone marrow biopsy and aspiration during screening and on study.
After completion of study treatment, patients are followed up at 30 and 60 days and then every 12 weeks for up to 2 years.
Lead OrganizationOhio State University Comprehensive Cancer Center
Principal InvestigatorAbdullah Mohammad Khan
