Johnson & Johnson has submitted regulatory applications to both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) seeking approval for daratumumab and hyaluronidase-fihj (Darzalex Faspro) as a subcutaneous monotherapy for adults with high-risk smoldering multiple myeloma. This submission is based on data from the ongoing phase 3 AQUILA study (NCT03301220), with initial findings slated for presentation at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH).
Addressing Unmet Needs in Smoldering Multiple Myeloma
Smoldering multiple myeloma, a precursor to active multiple myeloma, is characterized by the presence of abnormal cells in the bone marrow, often without noticeable symptoms. The current standard of care involves monitoring patients until the disease progresses biochemically or causes end-organ damage, at which point therapy is initiated. Yusri Elsayed, MD, MHSc, PhD, global therapeutic area head of Oncology and Innovative Medicine at Johnson & Johnson, emphasized the unmet need for early interventions that are both effective and well-tolerated in patients with high-risk smoldering multiple myeloma.
Daratumumab, a CD38-targeting antibody, is formulated as a subcutaneous injection with recombinant human hyaluronidase PH20 (rHuPH20) to enhance drug delivery. If approved, daratumumab could become the first approved treatment for patients with high-risk smoldering multiple myeloma, potentially shifting the treatment paradigm.
The AQUILA Trial: Design and Endpoints
The multi-center, randomized phase 3 AQUILA trial is evaluating subcutaneous daratumumab against active surveillance in 390 patients with high-risk smoldering multiple myeloma. Patients in the experimental arm receive subcutaneous daratumumab at 1800 mg plus rHuPH20 at 2000 U/mL weekly for cycles 1 and 2, then every 2 weeks for cycles 3 to 6, and every 4 weeks thereafter. The comparator arm involves active surveillance with disease evaluations at similar intervals.
The trial's primary endpoint is progression-free survival (PFS) as defined by the International Myeloma Working Group (IMWG) criteria. Secondary endpoints include time to biochemical or diagnostic progression, overall response rate, complete response rate, duration of response, time to response, time to frontline treatment for multiple myeloma, PFS on first-line treatment, overall survival, safety, pharmacokinetics, and quality of life.
Eligibility and Exclusion Criteria
Eligible patients are 18 years or older, diagnosed with high-risk smoldering multiple myeloma per IMWG guidelines, have clonal bone marrow plasma cells of 10% or higher, and an ECOG performance status of 0 or 1. Exclusion criteria include primary systemic amyloid light-chain amyloidosis, prior exposure to daratumumab or anti-CD38 antibodies, and prior therapies for smoldering or active multiple myeloma.
