A phase 2 trial of CD24Fc for prevention of graft-versus-host disease

Author:

Magenau John1,Jaglowski Samantha2ORCID,Uberti Joseph3,Farag Sherif S.4,Riwes Mary Mansour1,Pawarode Attaphol1,Anand Sarah1,Ghosh Monalisa1,Maciejewski John1,Braun Thomas5,Devenport Martin6,Lu Susan7,Banerjee Bhramori7,DaSilva Carolyn7,Devine Steven8,Zhang Mei-Jie9,Burns Linda J.9,Liu Yang610,Zheng Pan610ORCID,Reddy Pavan1

Affiliation:

1. 1Transplantation and Cellular Therapy Program, Rogel Cancer Center, University of Michigan, Ann Arbor, MI

2. 2The James Cancer Hospital and Solove Research Institute, Ohio State University, Columbus, OH

3. 3Karmanos Cancer Center, Hudson-Webber Cancer Research Center, Detroit, MI

4. 4Blood and Bone Marrow Stem Cell Transplant and Immune Cell Therapy Program, Indiana University, Indianapolis, IN

5. 5Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI

6. 6OncoImmune, Inc, Rockville, MD

7. 7Merck & Co, Inc, Rahway, NJ

8. 8National Marrow Donor Program, Minneapolis, MN

9. 9Center for International Blood and Marrow Transplant Research, Milwaukee, WI

10. 10Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD

Abstract

Abstract Patients who undergo human leukocyte antigen–matched unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation (HSCT) with myeloablative conditioning for hematologic malignancies often develop acute graft-versus-host disease (GVHD) despite standard calcineurin inhibitor–based prophylaxis in combination with methotrexate. This trial evaluated a novel human CD24 fusion protein (CD24Fc/MK-7110) that selectively targets and mitigates inflammation due to damage-associated molecular patterns underlying acute GVHD while preserving protective immunity after myeloablative conditioning. This phase 2a, multicenter study evaluated the pharmacokinetics, safety, and efficacy of CD24Fc in combination with tacrolimus and methotrexate in preventing acute GVHD in adults undergoing MUD HSCT for hematologic malignancies. A double-blind, placebo-controlled, dose-escalation phase to identify a recommended dose was followed by an open-label expansion phase with matched controls to further evaluate the efficacy and safety of CD24Fc in preventing acute GVHD. A multidose regimen of CD24Fc produced sustained drug exposure with similar safety outcomes when compared with single-dose regimens. Grade 3 to 4 acute GVHD–free survival at day 180 was 96.2% (95% confidence interval [CI], 75.7-99.4) in the CD24Fc expansion cohort (CD24Fc multidose), compared with 73.6% (95% CI, 63.2-81.4) in matched controls (hazard ratio, 0.1 [95% CI, 0.0-0.6]; log-rank test, P = .03). No participants in the CD24Fc escalation or expansion phases experienced dose-limiting toxicities (DLTs). The multidose regimen of CD24Fc was well tolerated with no DLTs and was associated with high rates of severe acute GVHD–free survival after myeloablative MUD HSCT. This trial was registered at ClinicalTrials.gov as #NCT02663622.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. From mechanism to therapy: the journey of CD24 in cancer;Frontiers in Immunology;2024-05-31

2. Checkpoint CD24 function on tumor and immunotherapy;Frontiers in Immunology;2024-02-29

3. CD24Fc to DAMPen GVHD;Blood;2024-01-04

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