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 S

Inclusion Criteria:

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

1. 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).
2. 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.
3. 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.
4. All subjects must have documented disease progression during or after their last antimyeloma therapy.
5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
6. Subjects must understand and voluntarily sign an ICD prior to any study related assessments/procedures being conducted.
7. Subjects must be able to adhere to the study visit schedule and other protocol requirements.
8. All subjects must provide an adequate bone marrow sample at screening that definitively evaluates the presence or absence of myelodysplastic changes.
9. 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.
10. 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.
11. 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.
12. 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.
13. All subjects must agree to refrain from donating blood while on study therapy and for 28 days after discontinuation from this study treatment.
14. All subjects must agree not to share medication.

Exclusion Criteria:

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

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1. Any of the following laboratory abnormalities:

• Absolute neutrophil count \< 1,000/μL

• Platelet count \< 75,000/μL for subjects in whom \< 50% of bone marrow nucleated cells are plasma cells; or a platelet count \< 30,000/μL for subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells.

• Severe renal impairment (Creatinine Clearance \[CrCl\] \< 30 mL/min) requiring dialysis.
* Corrected serum calcium \> 11.5 mg/dL (\> 2.8 mmol/L)
* Hemoglobin \< 8 g/dL (\< 4.9 mmol/L; prior red blood cell transfusion or recombinant human erythropoietin use is permitted)
* Serum SGOT/AST or SGPT/ALT \> 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
2. 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)
3. Previous therapy with pomalidomide or daratumumab
4. Hypersensitivity to thalidomide, LEN, or dex (this includes ≥ Grade 3 rash during prior thalidomide or LEN therapy)
5. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study treatment and who have not discontinued immunosuppressive treatment for at least 4 weeks prior to initiation of study treatment and are currently dependent on such treatment.
6. Subjects with any one of the following:

• Congestive heart failure (NY Heart Association Class III or IV)
* Myocardial infarction within 12 months prior to starting study treatment
* Unstable or poorly controlled angina pectoris, including Prinzmetal's variant angina pectoris
7. Subjects who received any of the following within 14 days of initiation of study treatment:

• Major surgery (kyphoplasty is not considered major surgery)

• Use of any anti-myeloma drug therapy
8. Use of any investigational agents including for the treatment of multiple myeloma within 28 days or 5 half-lives (whichever is longer) of treatment, unless approved by the sponsor.
9. Incidence of gastrointestinal disease that may significantly alter the oral absorption of Pomalidomide.
10. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
11. Any serious medical condition, laboratory abnormality, or psychiatric illness, that would preclude participation in the study, or interfere with interpretation of the study results
12. Pregnant or breastfeeding females
13. Known human immunodeficiency virus (HIV) positivity; active infectious hepatitis A, B, or C; or chronic hepatitis B or C

All subjects will be tested for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (antiHBs), and hepatitis B core antibody (antiHBc). Subjects with the following serological testing are considered not eligible:
* HBsAg positive
* HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral DNA

Note:
* Subjects who are HBsAg negative, anti-HBs positive, and/or anti-HBc positive, viral DNA negative are eligible. For these subjects, DNA monitoring and prophylactic medication for HBV reactivation are recommended per local practice.
* Subjects who are seropositive because of hepatitis B virus vaccination are eligible (anti-HBs positive, anti-HBc negative, and HBsAg negative).

All subjects will be tested for hepatitis C antibody. Subjects are not eligible if known seropositive for hepatitis C virus.

Note:

• Subjects who are hepatitis C antibody positive but show no detectable viral RNA for 6 months prior to initiation of study treatment are eligible.
14. For subjects enrolling in Cohort B and Cohort C - Subject has known allergies, hypersensitivity to mannitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to the Daratumumab IB), or known sensitivity to mammalian-derived products.