• Dose-limiting Toxicities (DLT) [ Time Frame: UP to approximately 2 years from enrollment ]
  Number of participants with DLTs in the first cycle of the treatment
• Adverse Events (AEs) [ Time Frame: From first subject first visit until 28 days after the last subject discontinues study treatment. ]
  Type, frequency, seriousness and severity of adverse events (AEs), and relationship of AEs to study treatment
• Overall response rate (ORR) [ Time Frame: UP to approximately 3 years from enrollment ]
  Defined as the proportion of subjects who achieve partial response (PR)or better according to the International Myeloma Working Group (IMWG) Uniform Response Criteria .

• Time-to-response (TTR) [ Time Frame: UP to approximately 3 years from enrollment ]
  Time from first dose to the first documentation of response (PR or greater)
• Duration of response (DOR) [ Time Frame: Up to approximately 3 years from enrollment ]
  Time from the first documentation of response (PR or greater) to the first documentation of progressive disease (PD) or death
• Complete Response (CR) rate [ Time Frame: Up to approximately 3 years from enrollment ]
  Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria
• Very good partial response (VGPR) rate [ Time Frame: Up to approximately 3 years from enrollment ]
  Percentage of subjects who achieved VGPR or better according to IMWG Uniform Response Criteria

• Drug: CC-92480
  CC-92480
• Drug: Bortezomib
  Bortezomib
• Drug: Dexamethasone
  Dexamethasone
• Drug: Daratumumab
  Daratumumab
• Drug: Carfilzomib
  Carfilzomib
• Drug: Elotuzumab
  Elotuzumab
• Drug: Isatuximab
  Isatuximab

• Experimental: Cohort A: CC-92480 with bortezomib and dexamethasone
  • Oral CC-92480 at specified cohort A dose administered over a 21-day cycle
  • Subcutaneous bortezomib 1.3 mg/m2 administered over a 21-day cycle
  • Oral dexamethasone 20 mg/day (≤ 75 years old) or 10 mg/day (> 75 years old) on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle in the first 8 cycles and on days 1, 2, 8 and 9 after Cycle 8
  Interventions:

  • Drug: CC-92480
  • Drug: Bortezomib
  • Drug: Dexamethasone
• Experimental: Cohort B: CC-92480 with daratumumab and dexamethasone
  • Oral CC-92480 at specified cohort B dose administered over a 28-day cycle
  • Intravenous (IV) DARA administered at a dose of 16 mg/kg.
  • Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight administered over a 28-day cycle
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Daratumumab
• Experimental: Cohort C: CC-92480 with carfilzomib and dexamethasone
  • Oral CC-92480 at specified cohort C dose administered over a 28-day cycle
  • Intravenous (IV) carfilzomib 20 mg/m2 then 56 mg/m2 administered over a 28-day cycle
  • Oral/IV dexamethasone 40 mg/day (20 mg/day for subjects > 75 years old) administered over a 28-day cycle
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Carfilzomib
• Experimental: Cohort H: CC-92480 with elotuzumab and dexamathasone
  • Oral CC-92480 at specified cohort H dose administered over a 28-day cycle
  • Intravenous ELO 10 mg/kg then 20 mg/kg administered over a 28-day cycle
  • Oral (28 mg)/IV (8 mg) dexamethasone for total 36 mg/day (oral [8 mg]/IV [8 mg] dexamethasone for total 16 mg/day for subjects > 75 years old) on ELO dosing days, and oral dexamethasone 40 mg/day (20 mg/day for subjects > 75 years old) on non-ELO dosing days, administered over a 28-day cycle
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Elotuzumab
• Experimental: Cohort I: CC-92480 with isatuximab and dexamathasone
  • Oral CC-92480 at specified cohort I dose administered over a 28-day cycle
  • Intravenous ISA 10 mg/kg administered over a 28-day cycle
  • Oral/IV dexamethasone 40 mg weekly (20 mg weekly for subjects > 75 years old)
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Isatuximab
• Experimental: Cohort D: CC-92480 with bortezomib and dexamethasone
  • Oral CC-92480 at RP2D administered over a 21-day cycle
  • Subcutaneous bortezomib 1.3 mg/m2 administered over a 21-day cycle
  • Oral dexamethasone 20 mg/day (≤ 75 years old) or 10 mg/day (> 75 years old) on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle in the first 8 cycles and on days 1, 2, 8 and 9 after Cycle 8
  Interventions:

  • Drug: CC-92480
  • Drug: Bortezomib
  • Drug: Dexamethasone
• Experimental: Cohort E: CC-92480 with daratumumab and dexamethasone
  • Oral CC-92480 at RP2D administered over a 28-day cycle
  • Subcutaneous (SC) DARA administered at a dose of 1800 mg over 3 to 5 minutes. If SC DARA is not available, IV DARA may be administered as per cohort B.
  • Oral/IV dexamethasone 40 mg weekly or 20 mg weekly for subjects older than 75 years or underweight administered over a 28-day cycle
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Daratumumab
• Experimental: Cohort F: CC-92480 with carfilzomib and dexamethasone
  • Oral CC-92480 at RP2D administered over a 28-day cycle
  • Intravenous (IV) carfilzomib 20 mg/m2 then 56 mg/m2 administered over a 28-day cycle
  • Oral/IV dexamethasone 40 mg/day (20 mg/day for subjects > 75 years old) administered over a 28-day cycle
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Carfilzomib
• Experimental: Cohort J: CC-92480 with elotuzumab and dexamathasone
  • Oral CC-92480 at RP2D administered over a 28-day cycle
  • Intravenous ELO 10 mg/kg then 20 mg/kg administered over a 28-day cycle
  • Oral (28 mg)/IV (8 mg) dexamethasone for total 36 mg/day (oral [8 mg]/IV [8 mg] dexamethasone for total 16 mg/day for subjects > 75 years old) on ELO dosing days, and oral dexamethasone 40 mg/day (20 mg/day for subjects > 75 years old) on non-ELO dosing days, administered over a 28-day cycle
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Elotuzumab
• Experimental: Cohort K: CC-92480 with isatuximab and dexamathasone
  • Oral CC-92480 at RP2D administered over a 28-day cycle
  • Intravenous ISA 10 mg/kg administered over a 28-day cycle
  • Oral/IV dexamethasone 40 mg weekly (20 mg weekly for subjects > 75 years old)
  Interventions:

  • Drug: CC-92480
  • Drug: Dexamethasone
  • Drug: Isatuximab
• Experimental: Cohort G: CC-92480 with bortezomib and dexamethasone
  • Oral CC-92480 at RP2D administered over a 21-day cycle
  • Subcutaneous bortezomib 1.3 mg/m2 administered over a 21-day cycle up to Cycle 6
  • Oral dexamethasone 20 mg/day (≤ 75 years old) or 10 mg/day (> 75 years old) on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle up to Cycle 6
  Interventions:

  • Drug: CC-92480
  • Drug: Bortezomib
  • Drug: Dexamethasone

Inclusion Criteria:

Key Inclusion criteria

• Subject is ≥ to 18 years of age the time of signing the informed consent form (ICF).
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.

For subjects in Cohorts A, B, C, D, E, F, H, I, J, and K the following inclusions will also apply:

• Subject has documented diagnosis of MM and measurable disease, defined as: M-protein quantities ≥ 0.5 g/dL by serum protein electrophoresis (sPEP) or ≥ 200 mg/24-hour urine collection by urine protein electrophoresis (uPEP) and/or Serum free light chain (FLC) levels > 100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambda (κ/λ) ratio in subjects without measurable disease in the serum or urine
• Subject has received 2 to 4 (for Cohorts A, B, C, H, and I) or 1 to 3 (Cohorts D, E, and F) or ≥ 2 (Cohorts J and K) prior anti-myeloma regimens.
• Subject has received prior treatment with a lenalidomide-containing regimen for at least 2 consecutive cycles.
• Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen.
• Subject must have documented disease progression during or after their last anti-myeloma regimen.

For Cohorts J and K:

• Subject has also received prior treatment with a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) given alone or in combination for at least 2 consecutive cycles AND
• Subject has failed therapy with lenalidomide and a proteasome inhibitor, given alone or in combination, defined as progression on or within 60 days of treatment, or disease progression within 6 months after achieving at least a partial response.

Subject is refractory (progressed on or within 60 days of treatment) to their last treatment.

• Cohort F: Prior therapy with a proteasome inhibitor (PI), excluding carfilzomib, is allowed as long as the subject had at least a PR to prior PI therapy, was not removed from PI therapy due to toxicity, and will have at least a 6-month PI treatment-free interval from last dose received until first study treatment (Subjects may receive maintenance therapy with drugs that are not in PI class during this 6-month treatment free interval).
• For subjects in Cohort G, the following inclusions will also apply:

Considered by the investigator to be eligible for high-dose chemotherapy and autologous stem cell transplantation (ASCT) according to the institution's criteria based on age, medical history, cardiac and pulmonary status, overall health and condition, co-morbid condition(s), physical examination, and laboratory.

Subject must have documented diagnosis with previously untreated symptomatic MM AND have measurable disease, as assessed by central laboratory.

Exclusion Criteria:

Key Exclusion criteria

• Subject has any of the following laboratory abnormalities:

  1. Absolute neutrophil count (ANC) < 1,000/µL (for Phase 1 without growth factor support for ≥ 7 days [≥ 14 days for pegfilgrastim])
  2. Platelet count: < 75,000/µL (it is not permissible to transfuse a subject to reach this level)
  3. Hemoglobin < 8 g/dL (< 4.9 mmol/L)
  4. Creatinine clearance (CrCl) < 45 mL/min (< 30 mL/min for Cohort G)
  5. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
  6. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN
  7. Serum total bilirubin > 1.5 x ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome
  8. 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).
• Subject has peripheral neuropathy ≥ Grade 2
• Subject with gastrointestinal disease that may significantly alter the absorption of CC-92480.
• 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 (eg, 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 (eg, computed tomography [CT] scan premedication).

• Subject has impaired cardiac function or clinically significant cardiac disease, including any of the following:

  1. 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

  2. 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 (eg, 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).
  3. Myocardial infarction within 12 months prior to starting study treatment. Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris
  4. 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
  5. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.
  6. Concurrent administration of strong CYP3A modulators; concurrent administration of proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, pantoprazole) ≤ 2 weeks prior to starting CC-92480 (refer to Section 8.2).
• 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.

For subjects in Cohorts A, B, C, D, E, F, H, I, J, and K, the following exclusions will also apply:

• Subject received any of the following within the last 14 days of initiating study treatment:

  1. Plasmapheresis
  2. Major surgery (as defined by the Investigator)
  3. Radiation therapy other than local therapy for myeloma associated bone lesions
  4. Use of any systemic anti-myeloma drug therapy
  5. Cohorts A and D: Subjects who had progression during treatment or within 60 days of the last dose of BTZ or discontinued BTZ due to toxicity.
  6. Cohorts B and I: Subjects who had progression during treatment or within 60 days of the last dose of DARA/ISA or discontinued DARA/ISA due to toxicity.
  7. Cohort C: Subjects who had progression during treatment or within 60 days of the last dose of CFZ or discontinued CFZ due to toxicity.
  8. Cohorts D, E, F, J, and K: Previous treatment with pomalidomide (POM).
  9. Cohorts E and K: Previous treatment with DARA or ISA.
  10. Cohort F: Previous treatment with CFZ.
  11. Subject used any investigational agents within 28 days or 5 half-lives (whichever is longer) of initiating study treatment.
  12. Subject has received previous allogeneic stem cell transplantation or received autologous stem cell transplantation within 12 weeks prior to starting study treatment.
  13. Cohorts B, E, I, and K: Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal. Note that forced expiratory testing (FEV1) is required for subjects suspected of having COPD and subjects must be excluded if FEV1 is < 50% of predicted normal.
  14. Cohorts B, E, I, and K: Subject has known moderate or severe persistent asthma, or currently has uncontrolled asthma of any classification.
  15. Cohorts C and F: Subject has mild hepatic impairment defined as elevated bilirubin 1.0 but < 1.5 x ULN or normal bilirubin with any elevation of AST.
  16. Cohort H: Subjects who had progression during treatment or within 60 days of the last dose of ELO or discontinued ELO due to toxicity

  17. Cohort J: Previous treatment with ELO

      For subjects in Cohort G, the following exclusion criteria will also apply:

• Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid [ie, less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of initiating study treatment]).