ELOQUENT-1: A phase III, randomized, open-label trial of lenalidomide/dexamethasone with or without elotuzumab in subjects with previously untreated multiple myeloma (CA204-006).

TPS8113 Background: Elotuzumab (Elo) is a humanized monoclonal IgG1 antibody targeting the cell surface glycoprotein CS1, which is highly expressed on >95% of MM cells. In a MM xenograft mouse model, the combination of Elo + lenalidomide (Len) significantly reduced tumor volume in a synergistic manner compared with either agent alone. In a phase 2 study (N=73) of Elo (10 or 20 mg/kg) in combination with Len and low-dose-dexamethasone (Dex) in pts with RR MM, the 10 mg/kg dose group (n=36) demonstrated objective response rates (ORR) of 92% in all pts, and 100% in pts who had received only 1 prior therapy (n=16). The higher response rate in pts with fewer prior lines of therapy provides a rationale for investigating this combination earlier in the disease course. This randomized, open-label, phase 3 trial will determine if the addition of Elo to Len/Dex improves progression-free survival (PFS) in pts with newly diagnosed, untreated MM. Methods: Pts (N=750) with newly diagnosed symptomatic MM ineligible for stem cell transplant will be randomized in a 1:1 ratio to receive 28-day cycles of Len 25 mg PO (days1-21) and Dex 40 mg PO (days 1, 8, 15 and 22) with or without Elo. Elo dose and schedule is 10 mg/kg IV on days 1, 8, 15, 22 in the first 2 cycles and on days 1 and 15 of cycles 3-18 followed by 20 mg/kg on day 1 of cycle 19 onward. Dex 8 mg IV + 28 mg PO is used during the weeks with Elo. Treatment will continue until disease progression, death, or withdrawal of consent. Pts will be followed up for response every 4 weeks until progressive disease and for survival every 16 weeks. The primary endpoint is PFS (90% power for a hazard ratio [experimental to control arm] of 0.74) and the secondary endpoints are ORR and overall survival. Exploratory endpoints are safety, time to response, duration of response, time to subsequent therapy, health-related quality of life, and pharmacokinetics and immunogenicity of Elo. Potential biomarkers will also be assessed. As of January 1, 2012, 13 pts were enrolled and 9 pts were treated. NCT01335399.