Phase 1b Study to Assess Safety and Efficacy of Elotuzumab, CC-92480, and Dexamethasone in Relapsed/Refractory Myeloma After CD38- and BCMA-Targeted Therapies
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.
• Patients 18 years of age or older with evidence of relapsed or refractory disease as defined by International Myeloma Working Group (IMWG) criteria and measurable disease as defined by any of the following:
‣ Serum M-protein \>= 1.0 g/dl
⁃ Urine monoclonal protein \>= 200 mg/24h
⁃ Involved free light chain (FLC) level \>= 10mg/dl (\>= 100mg/l) and an abnormal serum free light chain ratio (\< 0.26, or \> 1.65)
• Patients must have had at least 2 prior lines of therapy including lenalidomide, proteasome inhibitor (PI), anti-CD38 directed antibody, and BCMA-targeted therapy
‣ Prior elotuzumab is permitted but patients with progressive disease (PD) as best reponse on elotuzumab are excluded; at least 6 months must have lapsed from prior elotuzumab exposure
• Patients must have hemoglobin \>= 7g/dL
• Absolute neutrophil count (ANC) \>= 1000/uL
• Platelets \>= 70,000/uL
‣ If plasma cell percentage on bone marrow biopsy aspirate or core is \> 30%, platelet requirement will be adjusted to 50,000/ul
• Total bilirubin =\< 1.5 x the upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase \< 2.5 x the ULN
• Calculated creatinine clearance of \>= 45ml/min using Modification of Diet in Renal Disease (MDRD) formula
• Left ventricular ejection fraction \>= 30%; baseline echocardiography (ECHO) is not required if ECHO was done within the preceding one year and patients do not have new signs/symptoms suggestive of heart failure
• No uncontrolled arrhythmias
• No New York Heart Association class III-IV heart failure
• 12-lead electrocardiogram (ECG) with QT interval calculated by Fridericia formula (QTcF) interval of =\< 470 msec
• Patient must be able to swallow capsule or tablet
• Patients must provide informed consent
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of \< 2
• Women of child bearing potential (WOCBP) must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device \[IUD\], hormonal \[birth control pills, injections, hormonal patches, vaginal rings or implants\] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin 4 weeks prior to dosing and continue to 6 months after study treatment ending. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy
• Investigators shall counsel WOCBP and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy
• A negative pregnancy test will be required for all WOCBP within 24 hours before starting treatment drugs
• Breast feeding is not permitted while taking study drug, during dose interruptions, and for 28 days after the last dose of study drug.
• Females should refrain from ova donation during this time and continue for 28 days after study treatment ending.
• Male patients must agree to use an adequate method of contraception (latex or synthetic condom) while taking the study drug, during dose interruptions, and up to 28 days following the last dose of study drug
• Criteria also applies to azoospermic males and those who have had vasectomy
• Males should refrain from sperm donation during this time and continue for 6 months after study treatment ending