Pomalidomide in Combination With Low-dose Dexamethasone or Pomalidomide in Combination With Low-dose Dexamethasone and Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Following Lenalidomide-based Therapy in the First or Second Line Setting

Inclusion Criteria

• Subjects must satisfy the following criteria to be enrolled in the study:
• Adults (age ≥ 18 years at the time of signing the ICD) with documented diagnosis of MM and measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours).
• Subjects enrolling in Cohort A (POM+LD-dex) must have received 2 prior treatment lines of anti-myeloma therapy. Subjects enrolling in Cohort B and Cohort C (POM+DARA+LD-dex) must have received 1 or 2 prior treatment lines of anti-myeloma therapy.
• All subjects must have received prior treatment with LEN or a LEN-containing regimen for at least 2 consecutive cycles as the most recent treatment regimen.
• All subjects must have documented disease progression during or after their last antimyeloma therapy.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Subjects must understand and voluntarily sign an ICD prior to any study related assessments/procedures being conducted.
• Subjects must be able to adhere to the study visit schedule and other protocol requirements.
• All subjects must provide an adequate bone marrow sample at screening that definitively evaluates the presence or absence of myelodysplastic changes.
• Females with child-bearing potential (FCBP†) must agree to use 2 reliable forms of contraception* simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including during dose interruptions), and for at least 28 days after study treatment discontinuation and must agree to regular pregnancy testing during this timeframe. For subjects enrolled in Cohort B and Cohort C, pregnancy prevention and testing will continue until 3 months after last dose of daratumumab.
• Females must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation. Female subjects enrolled in Cohort B and Cohort C must agree to abstain from breastfeeding and donating eggs during study participation and until 3 months after last dose of daratumumab.
• Males must agree to use a latex condom during any sexual contact with FCBP while participating in the study and for 28 days following discontinuation from this study, even if he has undergone a successful vasectomy. Male subjects enrolled in Cohort B and Cohort C must agree to use a latex condom during any sexual contact with FCBP while participating in the study and until 3 months after last dose of daratumumab.
• Males must also agree to refrain from donating semen or sperm during the treatment phase and for 28 days after discontinuation from this study treatment. Male subjects enrolled in Cohort B and Cohort C must also agree to refrain from donating semen or sperm during the treatment phase and until 3 months after last dose of daratumumab.
• All subjects must agree to refrain from donating blood while on study therapy and for 28 days after discontinuation from this study treatment.
• All subjects must agree not to share medication.

Exclusion Criteria

The presence of any of the following will exclude a subject from study enrollment:

• Any of the following laboratory abnormalities:
• Absolute neutrophil count 11.5 mg/dL (> 2.8 mmol/L)
• Hemoglobin 3.0 x the upper limit of normal (ULN)
• Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or > 3.0 x ULN for subjects with hereditary benign hyperbilirubinemia
• Prior history of malignancies, other than MM, unless the subject has been free of the disease for more than 5 years. Allowed exceptions include the following:

•Basal or squamous cell carcinoma of the skin

•Carcinoma in situ of the cervix or breast

• Incidental histological finding of prostate cancer (TNM [tumor, nodes, metastasis] stage of T1a or T1b)
• Previous therapy with pomalidomide or daratumumab
• Hypersensitivity to thalidomide, LEN, or dex (this includes ≥ Grade 3 rash during prio