Background: DARA, a human IgGκ monoclonal antibody targeting CD38, is approved in the United States and Europe for use as a monotherapy and in combination with bortezomib/dexamethasone or lenalidomide/dexamethasone in pts with RRMM. In a phase 1b study, DARA + pom-dex demonstrated efficacy and tolerability in pts with RRMM, leading to the approval of this regimen for pts with RRMM in the United States. This phase 3 study will evaluate the efficacy and safety of DARA + pom-dex versus pom-dex alone in RRMM. Methods: This is an ongoing multicenter, open-label, phase 3 study of DARA + pom-dex versus pom-dex alone. RRMM pts who have received prior antimyeloma therapy, including a proteasome inhibitor and a lenalidomide-containing regimen, have responded to prior therapy, and have progressed on or after their last regimen, are eligible. Pts who have received only 1 prior line of therapy must have progressed ≤60 days of completing the lenalidomide-containing regimen. All pts will receive pom 4 mg orally on Days 1-21 of a 28-day cycle + dex 40 mg QW (20 mg for pts ≥75 year of age). Following a protocol amendment, pts in the DARA group will receive subcutaneous DARA (1,800 mg co-formulated with recombinant human hyaluronidase [rHuPH20]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter. All pts will receive preinfusion medications (including diphenhydramine, paracetamol, dexamethasone, and an optional leukotriene inhibitor), and postinfusion medications (diphenhydramine, lung disease control medications, and a short-acting β2 adrenergic receptor agonist) will be recommended for pts with a higher risk of respiratory complications. Progression-free survival is the primary endpoint. Secondary endpoints include safety, overall survival, overall response rate, duration of response, and minimal-residual-disease-negative rate. Approximately 302 pts will be enrolled across 11 countries. Clinical trial information: NCT03180736