Carfilzomib, Iberdomide (CC-220) and Dexamethasone (KID) in Transplant Eligible Multiple Myeloma

Inclusion Criteria:

1. Documented newly diagnosed multiple myeloma a. At least 25% of patients accrued should be high risk as defined by IMWG or mSMARTcriteria.

2. Patient should be deemed transplant eligible.

3. Patients may not have had more than 1 cycle of prior induction therapy. If a patienthas had 1 cycle of prior multiple myeloma therapy, the patient must have haddocumented measurable disease prior to initiation of cycle 1.

4. Subjects must satisfy the following criteria to be enrolled in the study:

5. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).

6. Subject must understand and voluntarily sign an ICF prior to any study-relatedassessments/procedures being conducted.

7. Subject is willing and able to adhere to the study visit schedule and otherprotocol requirements.

8. Subjects must have a documented diagnosis of MM and have measurable disease definedas:

9. M-protein (serum and/or urine protein electrophoresis (sPEP or uPEP)): sPEP≥0.5g/dL or uPEP ≥ 200 mg/24 hours and/or

10. Light chain MM without measurable disease in the serum or urine: serumimmunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serumimmunoglobulin kappa lambda free light chain ratio

11. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.

12. A female of childbearing potential (FCBP) is a female who: 1) has achieved menarcheat some point, 2) has not undergone a hysterectomy or bilateral salpingectomy, or 3)has not been naturally postmenopausal (amenorrhea following cancer therapy does notrule out childbearing potential) for at least 24 consecutive months (ie, has hadmenses at any time in the preceding 24 consecutive months) and must: a. Have two negative pregnancy tests as verified by the Investigator prior tostarting study treatment. She must agree to ongoing pregnancy testing during thecourse of the study, and after end of study treatment. This applies even if thesubject practices true abstinence from heterosexual contact.

13. Either commit to true abstinence from heterosexual contact (which must be reviewedon a monthly basis and source documented) or agree to use, and be able to complywith two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to startinginvestigational product, during the study treatment (including dose interruptions),and for at least 28 days after the last dose of iberdomide.

14. Male subjects must: a. Male subjects must practice complete abstinence (True abstinence is acceptablewhen this is in line with the preferred and usual lifestyle of the subject. Periodicabstinence [e.g. calendar, ovulation, symptothermal or post-ovulation methods] andwithdrawal are not acceptable methods of contraception.) or agree to use a condomduring sexual contact with a pregnant female or a FCBP while taking iberdomide,during dose interruptions and for at least 28 days following the last dose ofiberdomide even he has undergone a successful vasectomy.

15. Males must agree to refrain from donating sperm while on study treatment, duringdose interruptions and for at least 28 days following last dose of study treatment.

16. All subjects must agree to refrain from donating blood while on study treatment,during dose interruptions and for at least 28 days following the last dose of studytreatment.

17. All male and female subjects must follow all requirements defined in the PregnancyPrevention Program.

Note: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

Exclusion Criteria:

1. Subject has any significant medical condition, laboratory abnormality, orpsychiatric illness that would prevent the subject from participating in the study

2. Subject has any condition including the presence of laboratory abnormalities, whichplaces the subject at unacceptable risk if he/she were to participate in the study

3. Subject has any condition that confounds the ability to interpret data from thestudy

4. Subject has nonsecretory multiple myeloma

5. Subjects with Plasma Cell leukemia or amyloidosis (with the exception of isolatedmarrow involvement).

6. Any of the following laboratory abnormalities:

7. Absolute neutrophil count (ANC) < 1,000/μL

8. Platelet count < 50,000/μL. It is not permissible to transfuse subjects toachieve minimum platelet counts.

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

10. Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST)or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ≥ 2.5 x upper limit of normal (ULN)

11. Serum total bilirubin, direct bilirubin, or alkaline phosphatase ≥ 1.5 x ULN

12. Subjects with serious renal impairment ([CrCl] < 30 mL/min) or requiringdialysis would be excluded

13. Subjects with peripheral neuropathy ≥ Grade 2

14. Subjects with gastrointestinal disease that may significantly alter the absorptionof iberdomide

15. Subjects with a prior history of malignancies, other than MM, unless the subject hasbeen free of the disease for ≥ 3 years with the exception of the followingnoninvasive malignancies:

16. Basal cell carcinoma of the skin

17. Squamous cell carcinoma of the skin

18. Carcinoma in situ of the cervix

19. Carcinoma in situ of the breast

20. Incidental histological findings of prostate cancer such as T1a or T1b usingthe Tumor/Node/Metastasis (TNM) classification of malignant tumors or prostatecancer that is curative

21. Subject has a history of anaphylaxis or hypersensitivity to thalidomide,lenalidomide, or pomalidomide

22. Contraindications to the other treatment regimens, as per local prescribinginformation

23. Subject has received any of the following within the last 14 days of initiating IP:

24. Plasmapheresis

25. Major surgery (as defined by the Investigator)

26. Radiation therapy other than local therapy for MM associated bone lesions

27. Use of any systemic myeloma drug therapy

28. Subject has been treated with an investigational agent (ie, an agent notcommercially available) within 28 days or 5 half-lives (whichever is longer) ofinitiating IP

29. Subject has any one of the following:

30. Active congestive heart failure (New York Heart Association Class III to IV),symptomatic ischemia, uncontrolled arrhythmias, screening ECG with corrected QTinterval (QTc) of > 470 msec, pericardial disease, or myocardial infarctionwithin 4 months prior to randomization.

31. Unstable or poorly controlled angina pectoris, including the Prinzmetal variantof angina pectoris

32. Subject experienced a cardiac event within 6 months prior to the first dose ofIP

33. Subject has current or prior use of immunosuppressive medication within 14 daysprior to the first dose of IP. The following are exceptions to this criterion:

34. Intranasal, inhaled, topical or local steroid injections (eg, intra-articularinjection)

35. Glucocorticoid therapy within 14 days prior to randomization that exceeds acumulative dose of 160 mg of dexamethasone or equivalent dose of othercorticosteroids.

36. Steroids as premedication for hypersensitivity reactions (eg, computedtomography [CT] scan premedication)

37. Subject has taken a strong inhibitor or inducer of CYP3A4/5 including grapefruit,St. John's Wort or related products within two weeks prior to dosing and during thecourse of study

38. Subject known to test positive for human immunodeficiency virus (HIV), uncontrolledor active viral hepatitis.

39. Subject is unable or unwilling to undergo protocol required thromboembolismprophylaxis

40. Subject is a female who is pregnant, nursing or breastfeeding, or who intends tobecome pregnant during the participation in the study, or who will not agree tocomply with contraceptive requirements or pregnancy monitoring requirements

41. Left ventricular ejection fraction (LVEF) < 40% as determined by echocardiogram (ECHO)

42. Prior use of iberdomide

43. Subject is pregnant

44. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior toenrollment. Uncontrolled hypertension is defined as: a subject whose blood pressureexceeds ≥ 160 mmHg systolic or ≥ 100 mmHg diastolic when taken in accordance withthe European Society of Hypertension/European Society of Cardiology 2018 guidelines