Randomized, open-label, phase 3 study of subcutaneous daratumumab (DARA SC) versus active monitoring in patients (Pts) with high-risk smoldering multiple myeloma (SMM): AQUILA.

TPS8062 Background: Current guidelines for SMM recommend active monitoring for progression to symptomatic MM before initiating treatment as standard of care. Earlier treatment may benefit pts with SMM at high risk of progression. DARA, a CD38-targeted monoclonal antibody, is approved as monotherapy and in combination with standard of care for relapsed/refractory MM (RRMM). In a phase 1b RRMM study, a SC co-formulation of DARA with recombinant human hyaluronidase (rHuPH20; DARA SC) showed low infusion reaction rates and similar response rates to those seen with intravenous (IV) DARA in RRMM. Given the encouraging single-agent activity of IV DARA observed in a phase 2 SMM study (12-month PFS rate: 95%), we hypothesized that DARA SC may delay progression of high-risk SMM to MM compared with active monitoring. Methods: AQUILA is an ongoing, phase 3, randomized, open-label, multicenter study of DARA SC (1,800 mg DARA + rHuPH20 [2,000 U/mL] administered by manual injection (15 mL) over approximately 5 minutes at alternating abdominal locations QW for Cycles 1 and 2, Q2W for Cycles 3-6, and Q4W thereafter for up to 39 cycles or 36 months; 28-d cycles) versus active monitoring (no study medication). Eligible pts (≥18 y) have had a confirmed diagnosis of SMM for ≤5 y, have factors indicating a high risk of progression (clonal bone marrow plasma cells [BMPCs] ≥10% + ≥1 of the following: serum M protein ≥30 g/L, IgA SMM, immunoparesis with reduction of 2 uninvolved Ig isotypes, serum involved:uninvolved free light chain ratio ≥8- < 100, or clonal BMPCs > 50%- < 60% with measurable disease), and have an ECOG performance status of ≤1. The primary endpoint is PFS as assessed by an independent review committee. Secondary endpoints include time to biochemical or diagnostic (SLiM-CRAB) progression, ORR, complete response rate, duration of and time to response, time to first-line treatment for MM, progression-free survival on first-line treatment for MM (PFS2), incidence of MM with adverse prognostic features, and OS. Disease will be evaluated per International Myeloma Working Group response criteria. Approximately 360 pts will be randomized (1:1) to the 2 arms. Clinical trial information: NCT03301220.