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Abstract: INFO39

A Dose Escalation and Proof-of-Concept Study of REGN5459 or REGN5458 (BCMAxCD3 Bispecific Antibodies) for Desensitization of Hemodialysis Patients Who Are Highly Sensitized to Human Leukocyte Antigen

Session Information

  • Informational Posters
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • No subcategory defined

Authors

  • Ali, Nicole M., Department of Surgery, Transplant Institute, New York University Langone Medical Center, New York, New York, United States
  • Montgomery, Robert Avery, Department of Surgery, Transplant Institute, New York University Langone Medical Center, New York, New York, United States
  • Jordan, Stanley C., Transplant Immunology Laboratory and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Reed, Elaine F., Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States
  • Knechtle, Stuart J., Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
  • Redfield, Robert R., Transplant Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States
  • Labriola-Tompkins, Emily, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Harari, Olivier A., Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Norton, Thomas D., Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Boyapati, Anita, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Mcintyre, Debra Ag, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Perlee, Lorah T., Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Rodriguez Lorenc, Cristina Karen, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Carpenter, Stephen M., Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Kroog, Glenn Scott, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Singh, Nikhil, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
Description

Despite recent efforts to improve donor kidney allocation for highly sensitized patients, many fail to receive a transplant and waitlist mortality remains high. There is a need for effective desensitization regimens that can facilitate donor transplantation by reducing the risk of antibody-mediated rejection in highly sensitized recipients.
B-cell maturation antigen (BCMA) x cluster of differentiation 3 (CD3) bispecific antibodies have shown effective depletion of plasma cells and immunoglobulins in patients with relapsed/refractory multiple myeloma. In the context of desensitization, we hypothesize that plasma cell depletion may reduce transplant-precluding alloantibody levels with less rebound than existing desensitization strategies.
In a multicenter US-based dose escalation Phase 1 and proof-of-concept study (NCT05092347), we are investigating a single cycle (3 doses over 15 days) of BCMAxCD3 monotherapy for desensitization of patients with calculated panel-reactive antibody (cPRA) levels ≥99.9 (or >98 in patients with ≥5 years on the transplant waitlist). Two different BCMAxCD3 bispecific antibodies (REGN5459 or REGN5458) with different CD3 affinity will be evaluated.
The primary objective is to assess the safety and tolerability of REGN5459 and REGN5458 to reduce human leukocyte antigen (HLA) antibody levels in highly sensitized patients with chronic kidney disease, assessed over 6 months. Secondary objectives include determining dosing regimen(s) that result in a clinically meaningful reduction of anti-HLA alloantibody levels, the effect on cPRA levels and circulating immunoglobulin isotypes, pharmacokinetics, and immunogenicity.
In a companion study (NCT05106387), patients enrolled in NCT05092347 who receive a kidney transplant will be followed for 1 year to assess rates of adverse events, graft survival, rates and classification of rejection, and emergence of anti-HLA alloantibodies.

Funding

  • This study is funded by Regeneron Pharmaceuticals, Inc.
Abstract: INFO39

A Dose Escalation and Proof-of-Concept Study of REGN5459 or REGN5458 (BCMAxCD3 Bispecific Antibodies) for Desensitization of Hemodialysis Patients Who Are Highly Sensitized to Human Leukocyte Antigen

Session Information

  • Informational Posters
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category:

  • No subcategory defined

Authors

  • Ali, Nicole M., Department of Surgery, Transplant Institute, New York University Langone Medical Center, New York, New York, United States
  • Montgomery, Robert Avery, Department of Surgery, Transplant Institute, New York University Langone Medical Center, New York, New York, United States
  • Jordan, Stanley C., Transplant Immunology Laboratory and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Reed, Elaine F., Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States
  • Knechtle, Stuart J., Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
  • Redfield, Robert R., Transplant Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States
  • Labriola-Tompkins, Emily, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Harari, Olivier A., Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Norton, Thomas D., Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Boyapati, Anita, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Mcintyre, Debra Ag, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Perlee, Lorah T., Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Rodriguez Lorenc, Cristina Karen, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Carpenter, Stephen M., Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Kroog, Glenn Scott, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Singh, Nikhil, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
Description

Despite recent efforts to improve donor kidney allocation for highly sensitized patients, many fail to receive a transplant and waitlist mortality remains high. There is a need for effective desensitization regimens that can facilitate donor transplantation by reducing the risk of antibody-mediated rejection in highly sensitized recipients.
B-cell maturation antigen (BCMA) x cluster of differentiation 3 (CD3) bispecific antibodies have shown effective depletion of plasma cells and immunoglobulins in patients with relapsed/refractory multiple myeloma. In the context of desensitization, we hypothesize that plasma cell depletion may reduce transplant-precluding alloantibody levels with less rebound than existing desensitization strategies.
In a multicenter US-based dose escalation Phase 1 and proof-of-concept study (NCT05092347), we are investigating a single cycle (3 doses over 15 days) of BCMAxCD3 monotherapy for desensitization of patients with calculated panel-reactive antibody (cPRA) levels ≥99.9 (or >98 in patients with ≥5 years on the transplant waitlist). Two different BCMAxCD3 bispecific antibodies (REGN5459 or REGN5458) with different CD3 affinity will be evaluated.
The primary objective is to assess the safety and tolerability of REGN5459 and REGN5458 to reduce human leukocyte antigen (HLA) antibody levels in highly sensitized patients with chronic kidney disease, assessed over 6 months. Secondary objectives include determining dosing regimen(s) that result in a clinically meaningful reduction of anti-HLA alloantibody levels, the effect on cPRA levels and circulating immunoglobulin isotypes, pharmacokinetics, and immunogenicity.
In a companion study (NCT05106387), patients enrolled in NCT05092347 who receive a kidney transplant will be followed for 1 year to assess rates of adverse events, graft survival, rates and classification of rejection, and emergence of anti-HLA alloantibodies.

Abstract: INFO39

A Dose Escalation and Proof-of-Concept Study of REGN5459 or REGN5458 (BCMAxCD3 Bispecific Antibodies) for Desensitization of Hemodialysis Patients Who Are Highly Sensitized to Human Leukocyte Antigen

Session Information

  • Informational Posters
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category:

  • No subcategory defined

Authors

  • Ali, Nicole M., Department of Surgery, Transplant Institute, New York University Langone Medical Center, New York, New York, United States
  • Montgomery, Robert Avery, Department of Surgery, Transplant Institute, New York University Langone Medical Center, New York, New York, United States
  • Jordan, Stanley C., Transplant Immunology Laboratory and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Reed, Elaine F., Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States
  • Knechtle, Stuart J., Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
  • Redfield, Robert R., Transplant Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States
  • Labriola-Tompkins, Emily, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Harari, Olivier A., Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Norton, Thomas D., Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Boyapati, Anita, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Mcintyre, Debra Ag, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Perlee, Lorah T., Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Rodriguez Lorenc, Cristina Karen, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Carpenter, Stephen M., Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Kroog, Glenn Scott, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
  • Singh, Nikhil, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States
Description

Despite recent efforts to improve donor kidney allocation for highly sensitized patients, many fail to receive a transplant and waitlist mortality remains high. There is a need for effective desensitization regimens that can facilitate donor transplantation by reducing the risk of antibody-mediated rejection in highly sensitized recipients.
B-cell maturation antigen (BCMA) x cluster of differentiation 3 (CD3) bispecific antibodies have shown effective depletion of plasma cells and immunoglobulins in patients with relapsed/refractory multiple myeloma. In the context of desensitization, we hypothesize that plasma cell depletion may reduce transplant-precluding alloantibody levels with less rebound than existing desensitization strategies.
In a multicenter US-based dose escalation Phase 1 and proof-of-concept study (NCT05092347), we are investigating a single cycle (3 doses over 15 days) of BCMAxCD3 monotherapy for desensitization of patients with calculated panel-reactive antibody (cPRA) levels ≥99.9 (or >98 in patients with ≥5 years on the transplant waitlist). Two different BCMAxCD3 bispecific antibodies (REGN5459 or REGN5458) with different CD3 affinity will be evaluated.
The primary objective is to assess the safety and tolerability of REGN5459 and REGN5458 to reduce human leukocyte antigen (HLA) antibody levels in highly sensitized patients with chronic kidney disease, assessed over 6 months. Secondary objectives include determining dosing regimen(s) that result in a clinically meaningful reduction of anti-HLA alloantibody levels, the effect on cPRA levels and circulating immunoglobulin isotypes, pharmacokinetics, and immunogenicity.
In a companion study (NCT05106387), patients enrolled in NCT05092347 who receive a kidney transplant will be followed for 1 year to assess rates of adverse events, graft survival, rates and classification of rejection, and emergence of anti-HLA alloantibodies.