Participant that received > 3 prior line of anti-myeloma therapy.

• Medical conditions

  • Participant who has had prior treatment with mezigdomide or carfilzomib.
  • Participant who has had any investigational agents within 28 days or 5 half-lives (whichever is shorter) of initiating study intervention (Participation in another interventional clinical trial concurrent with this study is not permitted, except for those who have completed treatment with the prior investigational agent(s) and are currently in long-term follow-up.)
  • Participant has received any of the following:

• Plasmapheresis within the last 28 days of initiating study intervention.

• Major surgery (as defined by the Investigator) within 28 days of initiating study intervention.

• Radiation therapy, other than local palliative therapy, for myeloma-associated bone lesions within 14 days of initiating study intervention.

• Use of any systemic anti-myeloma drug therapy within 14 days of initiating study intervention.

  • Participant has previously received allogeneic stem cell transplant at any time or received autologous stem cell transplant within 12 weeks of initiating study treatment.
  • Participant has plasma cell leukemia, Waldenstrom macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically significant light-chain amyloidosis.
  • Participant with known central nervous system (CNS) involvement with myeloma.
  • Participant has any significant medical condition, including active or uncontrolled infection, presence of laboratory abnormality, or psychiatric illness that places the participant at an unacceptable risk for treatment-related complications, if he/she were to participate in the study.
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 14 days for mild or asymptomatic infections or 28 days for severe/critical illness prior to initiating study intervention (Acute symptoms must have resolved and there are no sequelae that would place the participant at a higher risk of receiving study intervention, based on Investigator assessment in consultation with the Sponsor Medical Monitor)
  • Participant has any condition that confounds the ability to interpret data from the study
  • Participant has any of the following laboratory abnormalities:

• Absolute neutrophil count (ANC) < 1,000/¬µL. It is not permissible to administer GCSF to achieve minimum ANC levels within 7 days prior to screening complete blood count (CBC) (or within 14 days prior for pegfilgrastim).

• Platelet count: < 75,000/¬µL for participants in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 50,000/¬µL for participants in whom 'â• 50% of bone marrow nucleated cells are plasma cells. Platelet transfusions are not permitted within 7 days prior to screening complete blood count (CBC).

• Hemoglobin < 8 g/dL (< 4.9 mmol/L).

• Estimated glomerular filtration rate (eGFR) < 30 mL/min or requiring dialysis. eGFR will be calculated using the Modification of Diet in Renal Disease (MDRD) formula (see http://mdrd.com).

• Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)

• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5xx upper limit of normal (ULN)

• Serum total bilirubin > 1.5 x ULN; > 3.0 mg/dL is allowed for participants with documented Gilbert's syndrome.

  • Participant with gastrointestinal disease or surgery (eg, gastric bypass surgery) that may significantly alter the absorption of Mezigdomide and/or other oral study intervention.
  • Participant has prior history of malignancies, other than MM, unless the participant has been free of the disease for 'â• 5 years with the exception of the following noninvasive malignancies:

• Basal cell carcinoma of the skin

• Squamous cell carcinoma of the skin in situ (Stage 0)

• 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

  • Participant has received immunosuppressive medication within the last 14 days of initiating study intervention. The following are exceptions to this criterion:

• Intranasal, inhaled, or topical corticosteroids or local corticosteroid injections (eg, intra-articular injection).

• Systemic corticosteroids at doses that do not exceed 10 mg/day of prednisone or the equivalent (see Table 7.7.2-1).

• Steroids as premedication for hypersensitivity reactions (eg, computed tomography \[CT\] scan premedication).

  - Administration of strong CYP3A modulators; administration of proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) within 2 weeks of starting study intervention.

  - Participant has impaired cardiac function or clinically significant cardiac disease, including any of the following:

• Myocardial infarction within 1 year before inclusion, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure New York Heart Association Class III-IV) or pericardial disease.

• Uncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG) abnormalities, including prolongation of QT interval on Screening ECG as defined by a QTc interval > 470 msec using Fridericia's QT correction formula

• Left ventricular ejection fraction < 40% as assessed by transthoracic echocardiogram (TTE) or multigated acquisition scan (MUGA)

  - Participant has uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.

  - Participant who has had a live vaccine within 3 months of start of study therapy.

  • Participant is unable or unwilling to undergo protocol required thromboembolism or antiviral prophylaxis
  • Participant is positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, active hepatitis A, or active hepatitis C:

• Known positive HIV status.

• Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Participants with resolved infection (ie, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR.

• Known to be seropositive for hepatitis C virus (HCV); anti-HCV antibody positive or HCV- ribonucleic acid (RNA) quantitation positive, except in the setting of a sustained virologic response (SVR), defined as viremia at least 12 weeks after completion of antiviral therapy.

• Reproductive Status

  - Participant is a female who is pregnant or breastfeeding, or who intends to become pregnant during participation in the study.

• Contraindication to investigational medicinal products (mezigdomide, carfilzomib and dexamethasone)

• Participation in another interventional study or being in the exclusion period at the end of a previous study.

• Prior/Concomitant Therapy

  - Inability to comply with restrictions and prohibited treatments as listed in Section 7.7: Concomitant Therapy.

• Physical and Laboratory Test Findings - Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with the target population

• Allergies and Adverse Drug Reaction

  • Participant has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide (including 'â• Grade 3 rash during prior thalidomide or lenalidomide therapy), carfilzomib or dexamethasone or the excipients contained in the formulations, or participant has any contraindications per local prescribing information.

• Other Exclusion Criteria - Prisoners or participants who are involuntarily incarcerated. (Note: Under certain specific circumstances and only in countries where local regulations permit, a person who has been imprisoned may be included or permitted to continue as a participant. Strict conditions apply, and BMS approval is required.) - Participants must agree to refrain from donating blood while on study intervention, during dose interruptions, and for at least 28 days following the last dose of study intervention.

Eligibility criteria for this study have been carefully considered to ensure the safety of the study participants and that the results of the study can be used. It is imperative that participants fully meet all eligibility criteria.