Background: Combination treatment (Tx) with immunomodulatory agents and proteasome inhibitors can provide deep and durable responses in patients (pts) with RRMM (Richardson, Blood, 2013). PVD showed promising activity and was well tolerated in a Ph 1 dose-escalation study (Richardson, ASCO, 2014). MM-007 is a global, multicenter, randomized, open-label Ph 3 trial designed to compare efficacy and safety of PVD vs VD in pts with RRMM (target enrollment: 782 pts; NCT01734928). Methods: Pts must have received 1-3 prior lines of anti-MM Tx, including ≥ 2 consecutive cycles (C) of a lenalidomide-containing regimen. Exclusion criteria include refractory to prior BORT 1.3 mg/m² twice weekly, ANC < 1000/μL, platelet count < 75,000/µL ( < 30,000/μL for pts with ≥ 50% bone marrow plasma cells), CrCl < 30 mL/min requiring dialysis, hemoglobin < 8 g/dL, and peripheral neuropathy ≥ grade 2. Pts will be randomized 1:1 to continuous Tx with PVD or VD q3w until progression or unacceptable toxicity. PVD (arm A): POM 4 mg on D1-14; BORT SC 1.3 mg/m² on D1, 4, 8, 11 for C1-8, D1, 8 for C9+; and D 20 mg (10 mg for pts > 75 y) on D1, 2, 4, 5, 8, 9, 11, 12 for C1-8, D1, 2, 8, 9 for C9+. VD (arm B): BORT and D same as arm A. Thromboprophylaxis with low-dose aspirin or equivalent is required for pts treated with PVD (VD if prior history of deep vein thrombosis or pulmonary embolism). The primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival (OS), safety, overall response rate by modified IMWG criteria, and duration of response. Exploratory endpoints include evaluation of PFS2, clinical benefit rate, PK, and HRQOL. Minimal residual disease, genomic, molecular/mechanistic, and immune biomarkers will be evaluated. Upon Tx discontinuation, follow-up will continue for subsequent anti-MM Tx, OS, and second primary malignancies. As of Jan 2015, 62 sites have opened in the US and 53 pts have been enrolled. Top enrolling US sites include Dana-Farber Cancer Inst, MA; UT SW Medical Ctr, TX; Gabrail Cancer Ctr, OH; and NW Georgia Oncology Ctr, GA. Sites are planned for Italy, Spain, France, and the rest of the world. Clinical trial information: NCT01734928