Axatilimab for Chronic Graft-Versus-Host Disease After Failure of at Least Two Prior Systemic Therapies: Results of a Phase I/II Study

Carrie L. Kitko, Mukta Arora, Zachariah Defilipp, Mohammad Abu Zaid, Antonio Di Stasi, Vedran Radojcic, Courtney B. Betts, Lisa M. Coussens, Michael L. Meyers, Hope Qamoos, Peter Ordentlich, Vinit Kumar, Christine Quaranto, Aaron Schmitt, Yu Gu, Bruce R. Blazar, Trent P. Wang, Amandeep Salhotra, Iskra Pusic, Madan JagasiaStephanie J. Lee

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


PURPOSEChronic graft-versus-host disease (cGVHD) remains the major cause of late morbidity after allogeneic hematopoietic cell transplantation. Colony-stimulating factor 1 receptor (CSF-1R) dependent macrophages promote cGVHD fibrosis, and their elimination in preclinical studies ameliorated cGVHD. Axatilimab is a humanized monoclonal antibody that inhibits CSF-1R signaling and restrains macrophage development.PATIENTS AND METHODSThis phase I (phI)/phase II (phII) open-label study ( identifier: NCT03604692) evaluated safety, tolerability, and efficacy of axatilimab in patients age 6 years with active cGVHD after 2 prior systemic therapy lines. Primary objectives in phI were to identify the optimal biologic and recommended phII dose and in phII to evaluate the overall (complete and partial) response rate (ORR) at the start of treatment cycle 7.RESULTSForty enrolled patients (17 phI; 23 phII) received at least one axatilimab dose. In phI, a dose of 3 mg/kg given once every 4 weeks met the optimal biologic dose definition. Two dose-limiting toxicities occurred at the 3 mg/kg dose given once every 2 weeks. At least one treatment-related adverse event (TRAE) was observed in 30 patients with grade 3 TRAEs in eight patients, the majority known on-target effects of CSF-1R inhibition. No cytomegalovirus reactivations occurred. With the 50% ORR at cycle 7 day 1, the phII cohort met the primary efficacy end point. Furthermore, the ORR in the first six cycles, an end point supporting regulatory approvals, was 82%. Responses were seen in all affected organs regardless of prior therapy. Fifty-eight percent of patients reported significant improvement in cGVHD-related symptoms using the Lee Symptom Scale. On-target activity of axatilimab was suggested by the decrease in skin CSF-1R expressing macrophages.CONCLUSIONTargeting profibrotic macrophages with axatilimab is a therapeutically promising novel strategy with a favorable safety profile for refractory cGVHD.

Original languageEnglish (US)
Pages (from-to)1864-1875
Number of pages12
JournalJournal of Clinical Oncology
Issue number10
StatePublished - Apr 1 2023

Bibliographical note

Funding Information:
Supported by Syndax Pharmaceuticals, Inc. Individual investigators were also supported by the funding from the National Institutes of Health (B.R.B.: P01CA142106, P01AI056299, and R37AI34495; V.R.: K08HL145116; L.M.C.: U01CA224012 and U2CCA233280), the Knight Cancer Institute, and the Brenden-Colson Center for Pancreatic Care at Oregon Health & Science University (L.M.C.). T.P.W. is a K12 Scholar supported by the National Cancer Institute of the National Institutes of Health under Award No. K12CA226330.

Publisher Copyright:
© 2023 American Society of Clinical Oncology.

PubMed: MeSH publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase I
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural


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