A phase III, randomized, open-label study of isatuximab (SAR650984) plus pomalidomide (Pom) and dexamethasone (Dex) versus Pom and Dex in relapsed/refractory multiple myeloma.

Abstract

TPS8057 Background: Treatment for refractory or relapsed and refractory multiple myeloma (MM) remains an unmet need. Isatuximab (ISA), an anti-CD38 monoclonal antibody with multiple mechanisms of tumor killing, has shown efficacy and an acceptable tolerability profile in Phase 1/2 studies in patients with refractory or relapsed and refractory MM (RRMM) (Richter et al. ASCO 2016; Vij et al. ASCO 2016). Methods: This Phase III, prospective, multicenter, randomized, open-label study (NCT02990338; ICARIA-MM) is being conducted to evaluate the clinical benefit of ISA in combination with Pom and low-dose Dex (Pom/Dex) versus Pom/Dex for the treatment of adult patients with RRMM and demonstrated disease progression within 60 days of the last therapy, and who have received at least 2 prior lines of therapy, including lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) alone or in combination. Patients will be randomly assigned in a 1:1 ratio to either ISA (10 mg/kg IV on Days 1, 8, 15, and 22 in the 1st cycle; Days 1 and 15 in subsequent cycles) plus Pom (4 mg on Days 1–21) and Dex (40 mg for patients < 75 years of age and 20 mg for patients ≥75 years of age, on Days 1, 8, 15, and 22) or Pom and Dex. Treatment cycles will be 28 days each. Patients will continue therapy until disease progression, occurrence of unacceptable adverse events (AEs), or their decision to discontinue the study, whichever comes first. The primary endpoint is progression-free survival (PFS), i.e. time from randomization to progressive disease or death from any cause. Response will be determined by IMWG criteria (2016). Key secondary endpoints include overall response rate and overall survival (OS). Safety evaluations include treatment-emergent AEs/serious AEs (including infusion-associated reactions), laboratory parameters, vital signs and assessment of physical examination. Statistical analyses will be conducted according to a pre-specified plan; approximately 300 patients (150 in each arm) are expected to be enrolled in this study. The first patient was recruited in January 2017. Study funding: Sanofi. Clinical trial information: NCT02990338.