Inclusion Criteria:

• Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• Females of childbearing potential (FCBP) must:
  • Have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence* from heterosexual contact;
  • Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with two reliable forms of contraception as defined in the Pregnancy Prevention Plan (PPP) without interruption, 28 days prior to starting CC-92480, during the study treatment (including during dose interruptions), and for 28 days after the last dose of CC-92480, 7 months after the last dose of BTZ (for Cohorts A, D and G), 90 days after the last dose of DARA (for Cohorts B and E), 6 months after the last dose of CFZ or ELO (for Cohorts C and F and Cohorts H and J), or 5 months after the last dose of ISA (for Cohorts I and K), whichever is later.
• Note: A female of childbearing potential (FCBP) is a female who:
  • has achieved menarche at some point; and
  • has not undergone a hysterectomy or bilateral oophorectomy; or
  • has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
• Male subjects must:
  • Practice true abstinence* (which must be reviewed on a monthly basis) or agree to use of a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study (even during dose interruptions) and for at least 3 months following study treatment discontinuation, even if he has undergone a successful vasectomy.

* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and coitus interruptus (withdrawal) are not acceptable methods of contraception.

• Males must agree to refrain from donating sperm or semen while on study treatment, and for at least 3 months following last dose of study treatment. Females must refrain from egg cell (ova) donation while on study treatment, and for 28 days after the last dose of CC-92480.
• All subjects must agree to refrain from donating blood while on study treatment and for 28 days after the last dose of study treatment.
• All male and female subjects must follow all requirements defined in the PPP. 

Exclusion Criteria:

• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject has any of the following laboratory abnormalities:
  • Absolute neutrophil count (ANC) < 1,000/µL (for Phase 1 without growth factor support for ≥ 7 days [≥ 14 days for pegfilgrastim])  prior to the screening complete blood count (CBC);
  • Platelet count: < 75,000/µL (it is not permissible to transfuse a subject to reach this level);
  • Hemoglobin < 8 g/dL (< 4.9 mmol/L);
  • Creatinine clearance (CrCl) < 45 mL/min (< 30 mL/min for Cohort G);
  • Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L);
  • Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN;
  • Serum total bilirubin > 1.5 x ULN or > 3.0 mg/dL for subjects with documented Gilbert’s syndrome;
  • Prothrombin time (PT)/international normalized ration (INR) > 1.5 x ULN or partial thromboplastin time (PTT) > 1.5 x ULN, (for subjects not receiving therapeutic anticoagulation).
• Note: Subjects receiving therapy for a thromboembolic event that occurred > 3 months prior to enrollment are eligible as long as they are on a stable regimen of anticoagulation with warfarin, low-molecular weight heparin or other approved therapeutic anticoagulation regimen.
• Subject has peripheral neuropathy ≥ Grade 2.
• Subject with gastrointestinal disease that may significantly alter the absorption of CC92480. 7. Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years with the exception of the following non-invasive malignancies:
  • Basal cell carcinoma of the skin;
  • Squamous cell carcinoma of the skin;
  • Carcinoma in situ of the cervix;
  • Carcinoma in situ of the breast;
  • Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative.
• Subject has plasma cell leukemia, Waldenstrom’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or clinically significant amyloidosis. 
• Subject with known central nervous system (CNS) involvement with myeloma.
• Subject has received immunosuppressive medication within the last 14 days of initiating study treatment. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical or local corticosteroid injections (e.g., intra-articular injection);
  • Systemic corticosteroids at doses that do not exceed 10 mg/day of prednisone or the equivalent;
  • Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication).
• Subject has impaired cardiac function or clinically significant cardiac disease, including any of the following:
  • Left ventricular ejection fraction (LVEF) < 45% as determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan at Screening;
  • Complete left bundle branch, bifascicular block or other clinically significant abnormal electrocardiogram (ECG) finding at Screening;
  • A prolongation of QT interval on Screening ECG as defined by repeated demonstration of a QTc interval > 470 milliseconds (msec) using Fridericia’s QT correction formula; a history of or current risk factors for Torsades de Pointe (e.g., heart failure, hypokalemia, or a family history of Long QT Syndrome); and concurrent administration of medications that prolong the QT/QTc interval;
  • Congestive heart failure (New York Heart Association Class III or IV);
  • Myocardial infarction within 12 months prior to starting study treatment.
  • Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris;
  • History of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, pericardial disease or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker. 
• Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment. 
• Concurrent administration of strong CYP3A modulators; concurrent administration of proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, pantoprazole) ≤ 2 weeks prior to starting CC-92480.
• Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become pregnant during the participation in the study.
• Subject is positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, or active hepatitis A or C.
• Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide, BTZ (for Cohorts A, D and G), DARA (for Cohorts B and E), CFZ (for Cohorts C and F), ELO (for Cohorts H and J), ISA (for Cohorts I and K), or dexamethasone.
• Subject has known or suspected hypersensitivity to the excipients contained in the formulation of CC-92480, BTZ (for Cohorts A, D and G), DARA (for Cohorts B and E), CFZ (for Cohorts C and F), ELO (for Cohorts H and J), ISA (for Cohorts I and K), or dexamethasone.
• Contraindications to the standard treatment regimens, per local prescribing information. 
• Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis.

Eligibility last updated 3/18/22. Questions regarding updates should be directed to the study team contact.