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Kidney Week

Abstract: PO1647

Felzartamab in Patients with Anti-Phospholipase A2 Receptor Autoantibody Positive (Anti-PLA2R+) Membranous Nephropathy (MN): Interim Results from the M-PLACE Study

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Adler, Sharon G., The Lundquist Institute, Torrance, California, United States
  • Hoxha, Elion, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Sprangers, Ben, University Hospitals Leuven, Leuven, Belgium
  • Stahl, Rolf A., University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Wetzels, Jack F., Radboud Universiteit, Nijmegen, Gelderland, Netherlands
  • Schwamb, Bettina, MorphoSys AG, Martinsried, Bayern, Germany
  • Boxhammer, Rainer, MorphoSys AG, Martinsried, Bayern, Germany
  • Nguyen, Quynh, MorphoSys AG, Martinsried, Bayern, Germany
  • Haertle, Stefan, MorphoSys AG, Martinsried, Bayern, Germany
  • Ronco, Pierre M., Sorbonne Universite, Paris, France
Background

Primary MN is a rare autoimmune kidney disease. In ∼70% of cases, autoantibodies to PLA2R on podocytes form immune complexes that damage the glomerular filtration barrier and typically lead to nephrotic syndrome. Current MN therapies fail to directly target CD20−/CD38+ plasma cells that are the main source of autoantibodies. Depleting plasma cells by targeting CD38 may be an effective strategy for MN, particularly in patients (pts) with high anti-PLA2R Ab titers. Here we report proof-of-mechanism data for felzartamab (MOR202), a fully human anti-CD38 monoclonal antibody (Ab).

Methods

M-PLACE (NCT04145440) is an open-label, multi-national Phase Ib/IIa study of adults with anti-PLA2R+ MN requiring immunosuppressive therapy (IST). Cohort 1 includes de novo and IST-relapsed pts (n=20) and Cohort 2 IST-refractory pts (n=10). Participants receive nine felzartamab infusions (16 mg/kg) over six 28-day cycles (weekly in Cycle 1; monthly thereafter), followed by a 28-week observational follow-up. Concomitant IST use is prohibited. The primary endpoint is the incidence and severity of treatment-emergent adverse events. The key secondary endpoint is the immunologic response rate, as determined by anti-PLA2R Ab reductions. Exploratory endpoints include evaluations of proteinuria and kidney function.

Results

As of April 2021, 12/30 planned pts were enrolled (Cohort 1, n=8; Cohort 2, n=4). Median age was 62.5 years (range 43 to 77 years), 83% were male, and median baseline anti-PLA2R Ab titer was 178 U/mL (18 to 1027 U/mL). Seven pts had received ≥4 weeks of felzartamab therapy. At Week 4, 5/7 pts had a >50% reduction from baseline in anti-PLA2R Ab (Cohort 1, n=3; Cohort 2, n=2); the other 2/7 pts had reductions from baseline of −16.8% and −5.0% (both Cohort 1). Mean % decline in anti-PLA2R Ab from baseline to Week 4 was −53.0% (−92.0% to −5.0%). B-cell counts were not markedly changed from baseline. Felzartamab was well tolerated.

Conclusion

The M-PLACE proof-of-concept study has so far shown that felzartamab rapidly and substantially reduces anti-PLA2R Ab titers in pts with anti-PLA2R+ MN. Longer follow-up is required to assess felzartamab safety and efficacy in this population.

Funding

  • Commercial Support