KEY TAKEAWAYS
- The phase 3 AQUILA study is investigating DARA SC as a potential treatment for high-risk SMM.
- The study’s main objective is to assess the PFS of patients with high-risk SMM receiving DARA SC compared to those undergoing active monitoring without study medication.
- The primary endpoint is the evaluation of PFS as measured by an independent review group. Secondary endpoints include time to biochemical or diagnostic progression.
- To be eligible for the trial, patients must have a confirmed diagnosis of SMM for up to 5 years and exhibit high-risk factors, such as clonal bone marrow plasma cells of 10% or higher, along with other specified criteria.
- Based on the promising single-agent activity observed in a phase 2 SMM study with intravenous DARA, the current phase 3 trial aims to determine whether DARA SC can slow the progression of high-risk SMM to multiple myeloma compared to active monitoring.
As standard care, the current rules for SMM say that patients (pts) should be actively monitored to see if they get symptoms of MM before starting treatment. Patients with SMM at a high risk of getting worse may benefit from treatment that starts sooner. DARA, a monoclonal antibody targeting CD38, is allowed for relapsed/refractory multiple myeloma (RRMM) as a stand-alone treatment and in combination with standard care. In a phase 1b RRMM study, an SC co-formulation of DARA with recombinant human hyaluronidase (rHuPH20; DARA SC) showed low injection reaction rates and similar response rates to those seen with IV DARA in RRMM. Given that IV DARA showed promising single-agent activity in a phase 2 SMM study (12-month PFS rate of 95%), researchers thought that, compared to active tracking, DARA SC might slow the progression of high-risk SMM to MM.
AQUILA is an ongoing, phase 3, randomized, open-label, multicenter study of DARA SC (1,800 mg DARA + rHuPH20 [2,000 U/mL] given by manual injection (15 mL) over about 5 minutes at alternating abdominal locations QW for Cycles 1 and 2, Q2W for Cycles 3-6, and Q4W after that for up to 39 cycles or 36 months; 28-d cycles) versus active monitoring (no study medication). This is the first phase 3 report presented by the researchers. Eligible pts (≥18 y) who have had a confirmed diagnosis of SMM for ≤5 y and 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. As measured by an independent review group, PFS is the primary goal. Time to biochemical or diagnostic (SLiM-CRAB) progression, overall response rate, complete response rate, duration and time to response, time to first-line treatment for MM, progression-free survival on first-line treatment for MM (PFS2), the incidence of MM with destructive prognostic features, and overall survival (OS) are some of the secondary endpoints. The disease will be looked at based on the response factors of the International Myeloma Working Group. About 360 pts will be split (1:1) between the two arms.
Source: https://meetings.asco.org/abstracts-presentations/165532
Clinical Trial: http://clinicaltrials.gov/show/NCT03301220
S.Vincent Rajkumar, Peter Michael Voorhees, Hartmut Goldschmidt, Ross I. Baker, Rajesh Bandekar, Steven Kuppens, Tobias Neff, Ming Qi, Meletios A. Dimopoulos/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/J Clin Oncol 36, 2018 (suppl; abstr TPS8062) DOI10.1200/JCO.2018.36.15_suppl.TPS8062
