Abstract
TPS8114 Background: MM is rarely curable and pts typically relapse or become refractory to current treatments. Elo is a humanized monoclonal IgG1 antibody targeting the cell surface glycoprotein CS1, which is highly expressed on >95% of MM cells with little to no expression on normal tissues. The mechanism of action of Elo is primarily natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) against myeloma cells. Elo + Bort significantly enhanced antimyeloma activity in a mouse xenograft model vs either agent alone. The addition of Bort enhanced the ADCC activity of Elo in preclinical studies. In a phase I study of Elo + Bort in pts with RR MM, objective response rate (ORR) was 48%, median progression-free survival (PFS) was 9.5 months, and activity was observed in 2/3 patients (67%) refractory to Bort (Jakubowiak et al. J Clin Oncol, in press). This study will assess if the addition of Elo to Bort/Dex improves PFS and, if so, whether magnitude of the improvement is linked to FcγRIIIa polymorphism. Methods: Pts (N=150) with RR MM after 1 or 2 prior therapies will be randomized in a 1:1 ratio to receive Bort 1.3 mg/m2 IV or SQ (Cycles 1-8: days 1, 4, 8, and 11; Cycles ≥9: days 1, 8, and 15) and Dex with or without Elo. Elo dose and schedule is 10 mg/kg IV (Cycles 1-2: days 1, 8, and 15 [21-day cycles]; Cycles 3-8: days 1 and 11 [21-day cycles]; Cycles ≥9: days 1 and 15 [28-day cycles]). In the arm without Elo, Dex 20 mg PO is scheduled for Cycles 1-8: days 1, 2, 4, 5, 8, 9, 11, and 12; and Cycles ≥9: days 1, 2, 8, 9, 15, 16. In the arm with Elo, Dex 20 mg PO is scheduled for Cycles 1-2: days 2, 4, 5, 9, and 11; Cycles 3-8: days 2, 4, 5, 8, 9, 12; Cycles ≥9: days 2, 8, 9, and 16) on weeks without Elo, and on weeks with Elo, Dex 8 mg PO and 8 mg IV is scheduled on the same day as Elo. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. Patients refractory or intolerant to Bort will be excluded. Efficacy will be assessed on day 1 of each cycle by IMWG criteria. The primary endpoint is PFS. Secondary endpoints include ORR and PFS/ORR in pts with ≥1 FcγRIIIa V allele. As of February 1, 2012, 1 pt was enrolled. NCT01478048.
Published Version
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