Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody-Positive Primary Membranous Nephropathy

Overview

Journal Kidney Int Rep

Publisher Elsevier

Specialty Nephrology

Date 2024 Sep 18

PMID 39291206

Authors

Brad H Rovin

Pierre M Ronco

Jack F M Wetzels

Sharon G Adler

Isabelle Ayoub

Philippe Zaoui

Seung Hyeok Han

Jaideep S Dudani

Houston N Gilbert

Uptal D Patel

Paul T Manser

Julia Jauch-Lembach

Nicola Faulhaber

Rainer Boxhammer

Stefan Hartle

Ben Sprangers

Affiliations

Soon will be listed here.

Abstract

Introduction: Primary membranous nephropathy (PMN) is most often caused by autoantibodies to phospholipase A2 receptor (PLA2R). M-PLACE (NCT04145440) is an open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk anti-PLA2R+ PMN.

Methods: Patients with newly diagnosed or relapsed PMN (cohort 1 [C1]; = 18) or PMN refractory to immunosuppressive therapy (IST) (cohort 2 [C2]; = 13) received 9 infusions of felzartamab 16 mg/kg in the 24-week treatment period, followed by a 28-week follow-up. The primary end point was the incidence and severity of treatment-emergent adverse events (TEAEs).

Results: A total of 31 patients were enrolled and received felzartamab. Twenty-seven patients (87.1%) had TEAEs, including infusion-related reactions (IRRs) (29.0%), hypogammaglobulinemia (25.8%), peripheral edema (19.4%), and nausea (16.1%). Five patients (16.1%) had serious TEAEs that all resolved. Immunologic response (anti-PLA2R titer reduction ≥50%) was achieved by 20 of 26 efficacy-evaluable patients (76.9%) (C1, 13/15 [86.7%]; C2, 7/11 [63.6%]). Anti-PLA2R titer reductions were rapid (week 1 response, 44.0%; response 7 months after last felzartamab dose [end of study, EOS], 53.8%). Partial proteinuria remission (urine protein-to-creatinine ratio [UPCR] reduction ≥50%, UPCR <3.0 g/g, and stable estimated glomerular filtration rate [eGFR]) was achieved by 9 of 26 patients (34.6%) (C1, 7/15 [46.7%]; C2, 2/11 [18.2%]) before or at EOS (median follow-up, 366 days). Serum albumin increased from baseline to EOS in 20 of 26 patients (76.9%) (C1, 12/15 [80.0%]; C2, 8/11 [72.7%]).

Conclusion: In this population with high-risk anti-PLA2R+ PMN, felzartamab was tolerated and resulted in rapid partial and complete immunologic responses and partial improvements in proteinuria and serum albumin in some patients.

Citing Articles

Combination Therapy With Rituximab and Low-Dose Cyclophosphamide and Prednisone in Membranous Nephropathy.

Vink C, Wetzels J, Logt A Kidney Int Rep. 2024; 9(12):3439-3445.

PMID: 39698354 PMC: 11652067. DOI: 10.1016/j.ekir.2024.08.033.

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