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Abstract: SA-PO679

Safety and Efficacy of Felzartamab (MOR202) in Anti-Phospholipase A2 Receptor (PLA2R) Autoantibody-Positive Membranous Nephropathy: The M-PLACE Study

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Ronco, Pierre M., Sorbonne Université and INSERM UMRS 1155, Paris, France
  • Wetzels, Jack F., Radboud University Medical Center, Nijmegen, Netherlands
  • Adler, Sharon G., Lundquist Research Institute at Harbor UCLA, Torrance, California, United States
  • Ayoub, Isabelle, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Zaoui, Philippe, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, Auvergne-Rhône-Alpes , France
  • Han, Seung Hyeok, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  • Jauch-Lembach, Julia, MorphoSys AG, Planegg, Germany
  • Faulhaber, Nicola, MorphoSys AG, Planegg, Germany
  • Cui, Jie, MorphoSys US Inc., Boston, Massachusetts, United States
  • Haertle, Stefan, MorphoSys AG, Planegg, Germany
  • Sprangers, Ben, University Hospitals Leuven, Leuven, Belgium
Background

Primary membranous nephropathy (MN) is an autoimmune kidney disease. Depleting CD20−/CD38+ plasma cells, potentially a main source of autoantibodies, may be an effective treatment (Tx) strategy for MN, particularly in patients (pts) with high PLA2R Ab titers. This interim analysis reports proof-of-mechanism data for felzartamab, a fully human IgG1 anti-CD38 mAb.

Methods

M-PLACE (NCT04145440) is a Phase Ib/IIa, open-label, multicenter, multinational study of adults with anti-PLA2R Abs-associated MN requiring immunosuppressive therapy (IST). Cohort 1: newly diagnosed and IST-relapsed pts; Cohort 2: IST-refractory pts. Pts received 9 felzartamab infusions (16 mg/kg) over six 28-day cycles, followed by a 28-week follow-up. Primary endpoints are incidence and severity of Tx-emergent adverse events (TEAEs); key secondary endpoint is the immunologic response rate based on anti-PLA2R Ab reductions; exploratory endpoints include the effect of Tx on 24h UPCR reduction.

Results

By April 10, 2022, 31 pts were enrolled from 21 sites in N. America, Asia-Pacific, and Europe (Cohort 1, n=18; Cohort 2, n=13); 23 pts have completed the Tx phase (Cohort 2, n=9). Mean (SD) age was 57.5 (11.8) years and 77.4% were male. At baseline, mean circulating anti-PLA2R Ab titer was 247.1 (259.3) U/mL; mean UPCR was 6.4 (2.2) g/g; mean eGFR was 60.2 (20.0) mL/min/1.73m2. Overall, 27 pts (87%) had at least one TEAE; TEAEs were mostly mild/moderate in severity and the majority resolved. The most commonly reported TEAE was infusion-related reaction (29% of pts; one Grade 3). Five pts (16%) experienced serious TEAEs. A ≥50% reduction in anti-PLA2R Ab titer from baseline was shown in 26/31 pts (84%). Change in anti-PLA2R Ab titer was generally followed by a timely change in UPCR. At ~12 months, 4/12 pts with EOS data showed >50% reduction in UPCR, including one refractory pt.

Conclusion

Longer follow-up of the M-PLACE study shows safety data consistent with the safety profile previously described and as expected in this underlying population. The early and pronounced anti-PLA2R Ab responses observed with felzartamab are encouraging, including in hard-to-treat patients; long-term UPCR responses will be further evaluated.

Funding

  • Commercial Support