Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody-Positive Primary Membranous Nephropathy
In the open-label phase 1b/2a M-PLACE study, the anti-CD38 monoclonal antibody felzartamab was generally well tolerated and produced rapid reductions in anti-PLA2R autoantibody titers in high-risk primary membranous nephropathy.
Background
Primary membranous nephropathy is most often caused by autoantibodies to the phospholipase A2 receptor (PLA2R). Felzartamab is a fully human anti-CD38 monoclonal antibody that depletes CD38-positive plasma cells and plasmablasts, the main pathogenic antibody-producing cells in this disease.
Study design
M-PLACE was an open-label phase 1b/2a study enrolling 31 patients with anti-PLA2R-positive primary membranous nephropathy, including newly diagnosed or relapsed disease (cohort 1, n=18) and disease refractory to immunosuppressive therapy (cohort 2, n=13). All patients received 9 infusions of felzartamab 16 mg/kg over a 24-week treatment period, followed by a 28-week follow-up. The primary endpoint was the incidence and severity of treatment-emergent adverse events.
Key findings
Treatment-emergent adverse events occurred in 27 of 31 patients (87.1%), including infusion-related reactions (29.0%) and hypogammaglobulinemia (25.8%); five patients (16.1%) had serious events that all resolved. An immunologic response, defined as at least a 50% reduction in anti-PLA2R titer, was achieved by 20 of 26 evaluable patients (76.9%), with reductions seen as early as week 1. Partial proteinuria remission occurred in 9 of 26 patients (34.6%), and serum albumin increased from baseline in 20 of 26 patients (76.9%).
Clinical implications
In this high-risk anti-PLA2R-positive population, felzartamab was tolerated and produced rapid immunologic responses with partial improvements in proteinuria and serum albumin in some patients. The findings support continued evaluation of CD38-targeted therapy as a disease-specific option in membranous nephropathy, including patients refractory to prior immunosuppression.
Category
Research
Source
Kidney International Reports
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