Iberdomide Maintenance Therapy in Patients With Multiple Myeloma

Inclusion Criteria:

• Age ≥ 18 years old at consent, ≥19 years old in Nebraska (age of consent)

• Willing and able to provide informed consent to and abide by the protocol

• Documented diagnosis of active measurable Multiple Myeloma (MM):

• M-protein (serum and/or urine protein electrophoresis (SPEP or UPEP)): SPEP ≥ 0.5 g/dL or UPEP ≥ 200 mg/24 hours and/or

• 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

• Prior MM therapy

• Initiation of induction therapy within 12 months of enrollment

• No prior progression after initial therapy (participants whose inductiontherapy changed because of suboptimal response or intolerance remain eligible,provided they do not meet criteria for progression as per the 2016International Myeloma Working Group (IMWG) Response Criteria and no more thantwo regimens allowed, excluding dexamethasone alone

• No prior allogeneic hematopoietic stem cell transplant or solid organtransplant

• Autologous Stem Cell Transplant (ASCT) with high dose melphalan (140-200 mg/m2) andin a documented continued partial response or better, per IMWG criteria at 80-110day post-ASCT

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

• All participants 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

• All male and female participants must follow all requirements defined in thePregnancy Prevention Plan in the protocol

• Female participants of childbearing potential (FCBP), achieved menarche at somepoint; has not undergone a hysterectomy or bilateral oophorectomy and not naturallypostmenopausal for at least 24 consecutive months, i.e, has had menses at any timein the preceding 24 consecutive months; (amenorrhea following cancer therapy doesnot rule out childbearing potential) must:

• Have two negative serum or urine pregnancy tests as verified by investigatorsprior to starting study treatment

• Must agree to ongoing pregnancy testing during the course of the study, andafter end of study treatment, even if practicing true abstinence fromheterosexual contact

• Commit to either true abstinence from heterosexual contact (reviewed on amonthly basis and source documented) or agree to use, and to comply with use oftwo forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior tostarting investigational product, during the study treatment (including doseinterruptions), and for at least 28 days after the last dose of iberdomide

• Male participants must:

• Male participants must practice complete abstinence, acceptable when thisaligns with the preferred and usual lifestyle of participant [periodicabstinence (e.g. calendar, ovulation, symptothermal or post-ovulation methods)and withdrawal are not acceptable methods] or agree to use a condom duringsexual contact with a pregnant female or a FCBP while taking iberdomide, duringdose interruptions and for at least 90 days following the last dose ofiberdomide, even if he has undergone a successful vasectomy

• Must agree to refrain from donating sperm while on study treatment, during doseinterruptions and for at least 90 days following last dose of study treatment

Exclusion Criteria:

• Participation in another clinical study with an investigational product within 28days prior to enrollment

• Female who is pregnant, nursing or breastfeeding, or who intends to become pregnantduring study participation

• Any significant medical condition or psychiatric illness that would preventparticipation in the study as determined by the treating physician

• Multiple Myeloma (MM) disease progression, as defined by 2016 International MyelomaWorking Group (IMWG) Response Criteria following Autologous Stem Cell Transplant (ASCT) prior to enrollment

• Non-secretory MM

• Plasma cell leukemia or light chain amyloidosis

• Any of the following laboratory abnormalities within 14 days of enrollment:

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

• Platelet count < 75,000/μL

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

• Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST)or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ≥ 2.0 x upper limit of normal (ULN)

• Serum total bilirubin and alkaline phosphatase > 1.5 x ULN

• Serious renal impairment ([CrCl] < 50 mL/min) or requiring dialysis

• Peripheral neuropathy ≥ Grade 2

• Gastrointestinal disease that may significantly alter absorption of iberdomide orinability to take medications by mouth

• Prior history of malignancies, other than MM, unless free of the disease for ≥ 5years prior to enrollment, excluding:

• 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 histological findings of prostate cancer such, e.g., T1a or T1busing Tumor/Node/Metastasis (TNM) classification of malignant tumors orprostate cancer that is curative

• History of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, orpomalidomide

• Received any of the following within 14 days prior to enrollment:

• Plasmapheresis

• Major surgery (as defined by investigators

• Radiation therapy other than local therapy for MM associated bone lesions

• Use of any systemic myeloma drug therapy

• Any one of the following:

• Clinically significant abnormal electrocardiogram (ECG) finding within 14 daysof enrollment

• Congestive heart failure (New York Heart Association Class III or IV)

• Myocardial infarction within 12 months prior to enrollment

• Unstable or poorly controlled angina pectoris, including the Prinzmetal variantof angina pectoris

• Current or prior use of immunosuppressive medication within 14 days prior toenrollment, excluding:

• Intranasal, inhaled, topical or local steroid injections (e.g., intra-articularinjection)

• Systemic corticosteroids at physiologic doses not exceeding 10 mg/day ofprednisone or equivalent

• Steroids as premedication for hypersensitivity reactions (e.g., computedtomography scan premedication)

• Taken a strong inhibitor or inducer of CYP3A4/5 including grapefruit, St. John'sWort or related products within two weeks prior to dosing and during the study

• Positive test for human immunodeficiency virus (HIV), chronic or active hepatitis B,or active hepatitis A or C

• Prior therapy with iberdomide

• Unable or unwilling to undergo protocol required thromboembolism prophylaxis